dorzolamide and Glaucoma

Since their introduction the local carbonic anhydrase inhibitors (CAH) dorzolamide and brinzolamide have become well established in the drug therapy of glaucoma. They lower intraocular pressure (IOP) by blocking specifically carbonic anhydrase in the ciliary epithelium and thereby the secretion of aqueous humor. The IOP lowering effect is comparable with that of beta-blockers, but less than that of prostaglandin agonists. Because of their specific mode of action they produce an additive pressure lowering effect with any other glaucoma drug. Therefore they are ideal for being combined with other drugs. In addition, CAH may improve perfusion of the posterior eye. Preliminary results in glaucoma patients under dorzolamide therapy suggesting a reduction in the risk of progression due to enhanced blood flow need further confirmation.

Topics: Animals; Antihypertensive Agents; Aqueous Humor; Carbonic Anhydrase Inhibitors; Ciliary Body; Drug Combinations; Glaucoma; Humans; Intraocular Pressure; Ophthalmic Solutions; Retinal Vessels; Sulfonamides; Thiazines; Thiophenes

Glaucoma is the leading cause of irreversible blindness in industrialized countries and comprises a group of diseases characterized by progressive optic nerve degeneration. Glaucoma is commonly associated with elevated intraocular pressure due to impaired outflow of aqueous humor resulting from abnormalities within the drainage system of the anterior chamber angle (open-angle glaucoma) or impaired access of aqueous humor to the drainage system (angle-closure glaucoma). Oxidative injury and altered antioxidant defense mechanisms in glaucoma appear to play a role in the pathophysiology of glaucomatous neurodegeneration that is characterized by death of retinal ganglion cells. Oxidative protein modifications occurring in glaucoma serve as immunostimulatory signals and alter neurosupportive and immunoregulatory functions of glial cells. Initiation of the apoptotic cascade observed in glaucomatous retinopathy can involve oxidant mechanisms and different agents have been shown to be neuroprotective. This review focuses on the molecular mechanisms of oxidant injury and summarizes studies that have investigated novel free radical scavengers in the treatment of glaucomatous neurodegeneration.

Topics: Animals; Antioxidants; Apoptosis; DNA; Free Radical Scavengers; Ginkgo biloba; Glaucoma; Humans; Lipid Peroxidation; Oxidative Stress; Protein Carbonylation; Resveratrol; Stilbenes; Sulfonamides; Thiophenes

Topically applied carbonic anhydrase inhibitors (CAIs) in eye drop solutions are commonly used to treat glaucoma. However, local eye irritation and multiple daily administrations may hamper their clinical usefulness. Aqueous eye drop formulations that improve their topical bioavailability and reduce their eye irritation can improve their clinical efficacy. Earlier studies showed that dorzolamide and closely related CAIs are more effectively delivered into the eye from acidic eye drop solutions than from comparable neutral solutions. Consequently, dorzolamide was marketed as an aqueous pH 5.6 eye drop solution (Trusopt(®) , Merck). Later, it was shown that increasing the pH of the eye drops from pH 5.6 to physiologic pH significantly reduced their local irritation. Earlier attempts to use cyclodextrins (CDs) as ocular penetration enhancers in dorzolamide eye drop solutions failed since; although the CDs were able to enhance the aqueous solubility of dorzolamide, increasing the pH from 5.6 to physiologic pH reduced the ability of the drug to permeate into the eye. Later, it was discovered that formulating the drug as aqueous dorzolamide/γCD eye drop microparticle suspension resulted in significant bioavailability enhancement. The solid dorzolamide/γCD microparticles are mucoadhesive and release dorzolamide into the aqueous tear fluid for extended time period. Consequently, sustained high dorzolamide concentrations in aqueous humour and various eye tissues were observed after single administration of the aqueous dorzolamide/γCD eye drop microsuspension. The microsuspension has a potential of being developed into a once-a-day eye drop product. This article reviews the physicochemical properties of dorzolamide, its permeation characteristics and topical bioavailability.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Aqueous Humor; Biological Availability; Carbonic Anhydrase Inhibitors; Drug Delivery Systems; Glaucoma; Humans; Ophthalmic Solutions; Sulfonamides; Thiophenes

Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension.. An evidence-based review of clinical trials of dorzolamide and brinzolamide was undertaken to determine an effect of these medications on visual function (primarily visual field) in open-angle glaucoma and ocular hypertension. Using the keywords 'dorzolamide' and 'brinzolamide', all articles describing trials of these medications reporting on visual acuity, contrast sensitivity and visual field from September 1966 to July 2009 were found in MEDLINE and EMBASE databases. No information from other sources was included in this review.. A relatively modest number of trials was identified, where impact of therapy on one or more of the visual function modes was reported. In the studies of less than 1 year duration (3 days to 1 year, 23 studies) in all but three studies treatment with topical CAIs did not influence visual function, in two studies with dorzolamide some improvement in the contrast sensitivity was observed and in one open-label retrospective no-control-group study with dorzolamide visual field indices improved significantly. A different picture was seen in long-term studies, which were designed and powered to detect changes in visual field. One large study (European Glaucoma Prevention Study) with dorzolamide versus placebo failed to detect significant protective effect of the drug on glaucoma occurrence in ocular hypertensives. Several interesting aspects of this study are discussed in detail. The other two long-term studies reported on the superiority of adding dorzolamide over timolol therapy alone, and the superiority of the combination of dorzolamide and timolol over brinzolamide and timolol in terms of improving ocular blood flow (retrobulbar Color Doppler Imaging--CDI parameters) as well as in terms of visual field preservation in glaucoma patients over 4 to 5 years.. For the first time one study could demonstrate that an improvement in ocular blood flow in the long run results in preservation of visual field in glaucoma patients. Dorzolamide, combined with the beta-blocker timolol, seems to be superior in this regard to brinzolamide plus timolol.

Topics: Administration, Topical; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Ocular Hypertension; Sulfonamides; Thiazines; Thiophenes; Visual Fields

To evaluate the intraocular pressure (IOP)-lowering effects of adjunctive medications when added to 0.005% latanoprost taken once daily.. Pertinent publications were identified through systematic searches of PubMed, Embase, and the Cochrane Controlled Trials Register. Randomized clinical trials with over 85% of patients presenting with primary open-angle glaucoma or ocular hypertension who were treated with the combination treatment of latanoprost were selected. The pooled additional IOP-lowering effects at 1-3 months after a run-in phase of at least 2 weeks on 0.005% latanoprost once daily were calculated using the random effects model.. Nine randomized clinical trials were included. The mean pooled IOP reductions were 3.3 mm Hg (95% CI: 2.1-4.5) at trough and 4.4 mm Hg (95% CI: 3.4-5.4) at peak when adding 0.5% timolol once daily, 2.6 mm Hg (95% CI: 1.9-3.3) at trough and 3.8 mm Hg (95% CI: 2.5-5.2) at peak when adding 0.1/0.15% brimonidine twice daily, 2.6 mm Hg (95% CI: 1.7-3.4) at trough and 3.1 mm Hg (95% CI: 2.6-3.6) at peak when adding 2% dorzolamide twice daily, 2.4 mm Hg (95% CI: 2.0 -2.8) at trough and 2.7 mm Hg (95% CI: 2.2-3.2) at peak when adding 0.5% timolol twice daily, and 2.8 mm Hg (95% CI: 1.5-4.1) at trough and 1.8 mm Hg (95% CI: 1.2-2.3) at peak when adding 1% brinzolamide twice daily.. The addition of brimonidine, dorzolamide, timolol, or brinzolamide can further lower IOP in eyes being treated with latanoprost. Timolol 0.5% once daily might be the most effective adjunctive medication.

Topics: Aged; Antihypertensive Agents; Brimonidine Tartrate; Databases, Factual; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Optic Nerve Diseases; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiazines; Thiophenes; Timolol

Fixed combinations represent a combination of two ocular hypotensive agents into one single ophthalmic solution. Current commercially available fixed combinations used in glaucoma treatment include Combigan, Cosopt, Xalcom, Duotrav and Ganfort. Statistically significant superiority of the ocular hipotensive efficacy of the fixed combinations vs monotherapy with the two individual constituents is present connected with Cosopt and Xalcom. It also exists vs timolol ophthalmic solution relative to Combigan, Duotrav and Ganfort but is missing within these fixed combinations vs brimonidine, travatan and bimatoprost respectively. A slight reduction, that is clinically and statistically insignificant relative to fixed combination efficacy vs the nonfixed combinations (e.g. concomitant but separate administration of the two individual components) is acceptable when this is balanced by potential benefits of the fixed combinations therapy (improved tolerability and convenience,increased compliance,cost and time economies,decreased washout effect and reduced exposure to preservatives).

Topics: Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Cloprostenol; Drug Combinations; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Travoprost; Treatment Outcome

To systematically review the literature on the efficacy and harm of prostaglandin analogues (PGAs) compared to brimonidine and dorzolamide in treating elevated intraocular pressure (IOP).. Keywords were searched in major literature databases to identify relevant randomised clinical trials (RCTs) of PGAs for ophthalmic use. The study quality of RCTs was assessed using the Jadad scale. Outcomes assessed included reduction in IOP in individual patients, adverse events (AEs) and withdrawals due to AEs.. Eight unique RCTs evaluating a total of 1,722 individuals were included in this systematic review. Analysis did not show a significant reduction in the mean IOP from patients receiving latanoprost compared with those receiving brimonidine (WMD = -1.04; p = 0.30). On the other hand, the latanoprost group showed a significant reduction in mean IOP compared to the dorzolamide group (WMD = -2.64; p<0.00001). The number of ocular AEs (excluding hyperaemia) was significantly higher in the brimonidine group compared with the latanoprost group (RR = 0.66; p = 0.0005).. Latanoprost was found to be significantly superior to dorzolamide but not brimonidine. However, ocular adverse events were significantly fewer in latanoprost users than in brimonide users. Neither travoprost nor bimatoprost was compared to dorzolamide or brimonidine in the present literature.

Topics: Adult; Aged; Antihypertensive Agents; Brimonidine Tartrate; Female; Glaucoma; Humans; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Quinoxalines; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Treatment Outcome

The aim of this research is to describe one of the most frequent ophthalmology disease-glaucoma and to look at their neurodegenerative nature and methods to stop disease. We use neuroprotection in glaucoma from a short time but despite of ethiological reasons neuroprotection seems to be one of the main mechanism to slow their progression. This research is talking about new opinions about neuroprotection in glaucoma and their epidemiology and etiology.

Topics: Betaxolol; Brimonidine Tartrate; Disease Progression; Glaucoma; Guanidines; Humans; Memantine; Neuroprotective Agents; Quinoxalines; Sulfonamides; Thiophenes

Brimonidine and dorzolamide are intraocular pressure (IOP)-lowering medications most commonly used in second-line treatment of glaucoma and ocular hypertension.. An evidence-based review of comparative clinical trials of brimonidine and dorzolamide was undertaken to determine the relative efficacy and safety of these drugs in reducing IOP. Using the keywords 'brimonidine' and 'dorzolamide', all articles describing such trials from September 1966 to July 2007 were found in MEDLINE and EMBASE.. In all identified studies, brimonidine and dorzolamide were both found to provide significant IOP reduction from treated or untreated baseline levels. Results of eight trials reported to date indicate that brimonidine produced either a lower treated IOP or greater pressure reduction from baseline than dorzolamide at one or more measured timepoints, and provided comparable IOP lowering over all other measurements. Differences between the IOP reductions provided by brimonidine and dorzolamide were more pronounced when the medications were used adjunctively with other classes of drugs. Six other trials showed similar efficacy, and one additional monotherapy study showed lower IOP with dorzolamide treatment. Ocular burning was noted with dorzolamide more than any other adverse event with either drug. Trials ranged widely in duration of therapy and the time of day IOP measurements were taken, and many were too small for sufficient statistical power.. Brimonidine and dorzolamide are both efficacious and reasonably well tolerated. Possible overall distinctions in efficacy were obscured by differences in study designs and treatment regimens, but adjunctive therapy with brimonidine may reduce IOP as effectively or more effectively than adjunctive or fixed combination dorzolamide therapy. In certain patients with glaucoma and ocular hypertension brimonidine may be a better choice than dorzolamide for second-line treatment.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Clinical Trials as Topic; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Male; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome

Normal tension glaucoma is a clinical condition in which the optic nerve is pathologically excavated and the visual field is disturbed. Nevertheless it has been assumed that intraocular pressure plays a role in the progression of visual field defects in this disease, but other, mainly vascular factors, have been discussed as well.. The objective of this review is to assess the effects of medical and surgical treatments for normal tension glaucoma.. Trials were identified from the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register), MEDLINE, EMBASE and BIOSIS Previews. Bibliographies of identified trials were searched to find additional trials. In addition, investigators and pharmaceutical companies were contacted. Date of last search: January 2001.. This review includes randomised controlled trials in which medical or surgical interventions were compared to no treatment, placebo or other treatment in people with normal tension glaucoma. Two reviewers independently assessed the full text copies of the possibly relevant trials. Trial quality was assessed according to the methods set out in Section 6 of the Cochrane Reviewers' Handbook (Clarke 2000).. Data were extracted by two reviewers and results were compared for differences. Discrepancies were resolved by discussion. The heterogeneity of interventions, follow-up periods and outcomes did not allow for statistical combinations of the study results.. According to the selection criteria on visual field loss, eight studies were included in this review. Only three studies focussed on patient relevant outcomes. In one trial a beneficial effect of lowering intraocular pressure was found, but only if data were corrected for cataract development. In two small studies a beneficial effect on visual field loss of brovincamine, a calcium antagonist was reported.. In one study the effect of intraocular pressure lowering on visual field outcome was only significant when data were corrected for cataract development. The results for calcium antagonists are promising, but larger trials have to be performed. Studies that focussed on reduction of intraocular pressure or haemodynamic variables are not necessarily relevant for the outcome in people with normal tension glaucoma.

Topics: Antihypertensive Agents; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol; Vincamine

Despite treatment, glaucoma patients may still suffer vision loss because of inadequate control of intraocular pressure or late presentation. This article reviews the latest evidence supporting a reappraisal of first-line treatment in the management of glaucoma, including a review of latanoprost, recently approved for first-line treatment of glaucoma and ocular hypertension.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Cloprostenol; Dinoprost; Drug Therapy, Combination; Glaucoma; Humans; Latanoprost; Lipids; Prostaglandins; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Travoprost

Dorzolamide is a carbonic anhydrase inhibitor for topical ophthalmic application. It is used in the treatment of glaucoma to lower the intraocular pressure. After absorption via the cornea and stroma, it inhibits carbonic anhydrase in the ciliary process, which leads to a reduction of aqueous humour production and therefore to the desired therapeutic effect. In the systemic circulation, dorzolamide is bound mainly to carbonic anhydrase in red blood cells. It is slowly metabolised to N-de-ethyldorzolamide, which in turn is also stored in red blood cells. The very slow elimination (half-life >4 months) of both substances takes place via the renal route. However, the inhibition of carbonic anhydrase in red blood cells is moderate in the course of a topical treatment, avoiding systemic adverse effects. This review summarises the pharmacokinetic and pharmacodynamic properties of dorzolamide and its metabolite in eye tissues and in the systemic circulation.

Topics: Administration, Topical; Animals; Aqueous Humor; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Ciliary Body; Cornea; Erythrocytes; Glaucoma; Humans; Intraocular Pressure; Isoenzymes; Ophthalmic Solutions; Sulfonamides; Thiophenes

Significant advances have recently been achieved in the development of topical glaucoma medications. The primary advantage of a topical preparation is the reduced incidence of adverse systemic effects attributable to a given drug compared to its systemically administered counterpart. However, the strong protective barrier of the eye forces topical ophthalmic preparations to be highly concentrated and in some cases, they have the potential to produce unwanted systemic effects, particularly in smaller animals. Oral carbonic anhydrase inhibitors are commonly associated with adverse effects in both humans and animals. Two recently developed topical carbonic anhydrase inhibitors, dorzolamide and brinzolamide, have shown promise in reducing intraocular pressure in animals and systemic side effects are apparently limited with their use. The topical alpha2-agonist apraclonidine, on the other hand, effectively reduces intraocular pressure in cats and dogs, but in its currently available form is likely to induce unwanted systemic effects. Latanoprost is a topical prostaglandin F2alpha analog that has proven effective in reducing intraocular pressure in dogs and horses, but while systemic side effects have not yet been reported, this topical preparation may exacerbate pre-existing or concurrent ocular inflammatory disease.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Clonidine; Dog Diseases; Dogs; Glaucoma; Humans; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiazines; Thiophenes

Topical carbonic anhydrase inhibitors are a novel addition to the armamentarium of medical glaucoma treatment; dorzolamide has been available since 1995 and brinzolamide since 1998. They lower intraocular pressure by inhibiting carbonic anhydrase, a key enzyme for aqueous humor formation. Intraocular pressure-lowering activity of the substances appears to be the same and is similar to that of most other agents, but it does not reach the activity of the unselective beta-blocker timolol or the prostaglandin latanoprost. On concomitant treatment, additivity is reached with all other topical agents. A possible improvement of blood flow may offer an additional benefit, but its significance for the long-term outcome for human glaucoma remains to be shown. Side effects are mostly local. A more physiologic pH of brinzolamide appears to be advantageous.

Topics: Antihypertensive Agents; Aqueous Humor; Blood Flow Velocity; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Dose-Response Relationship, Drug; Eye; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiazines; Thiophenes

A review of the literature has identified 10 agents causing contact dermatitis among topically administered drugs for glaucoma. These agents include beta-blockers (timolol, befunolol, betaxolol, levobunolol, carteolol, metipranolol), a carbonic anhydrase inhibitor (dorzolamide), a parasympathomimetic (pilocarpine), and sympathomimetics (dipivefrin, apraclonidine). Patch testing has been documented in certain individuals as well as cross sensitization and reactivity. Systemic reactions to these topically applied medications have been briefly noted.

Topics: Dermatitis, Allergic Contact; Epinephrine; Glaucoma; Humans; Ophthalmic Solutions; Pilocarpine; Sulfonamides; Thiophenes; Timolol

There was a time gap of over 40 years between the demonstrated oral effectiveness of acetazolamide in lowering the intraocular pressure (IOP) of glaucoma patients and the introduction of a topical carbonic anhydrase (CA) inhibitor. This is due to the fact that CA-II, the isoenzyme which most likely plays an important role in the production of aqueous humor in humans, must be essentially inhibited by 100% to elicit a pharmacological response. The lack of success with earlier attempts to obtain a topical agent stems from an inability to attain and maintain a sufficiently high intraocular concentration of drug to achieve the required inhibition of CA. Dorzolamide and brinzolamide are two topical CA inhibitors which are currently available to treat ocular hypertension and/or glaucoma. Dorzolamide is a very potent inhibitor of CA-II and its site of action is local within the eye. Like oral CA inhibitors, topically applied dorzolamide lowers IOP by decreasing the production of aqueous humor. The drug is used in monotherapy as a 2% solution administered three times daily. Its ocular hypotensive effect is comparable to that of timolol at peak but is somewhat less at trough. The IOP lowering effect of timolol is enhanced by the twice daily administration of 2% dorzolamide either concomitantly or in combination. Topically applied dorzolamide is generally well tolerated and had a low drop-out rate in clinical studies. The most frequent ocular adverse experience is burning and/or stinging. Corneal and lenticular problems have generally not been encountered with long-term therapy with dorzolamide. Topically applied dorzolamide penetrates directly to the posterior segment of the eye and its presence is consistent with the initial report that dorzolamide increases retinal blood flow velocity in patients with normal tension glaucoma. The most frequent systemic adverse experience is a transient bitter taste. Biochemical changes indicative of the systemic inhibition of CA have not been observed in monotherapy studies lasting up to 2 years. This is in harmony with the inability of dorzolamide at steady-state to saturate CA in the red blood cell and the failure to detect its presence in plasma. A 1% suspension of brinzolamide is comparable to 2% dorzolamide in lowering IOP, both drugs being administered three times daily. Although brinzolamide has a lower incidence of burning/ stinging, it elicits more blurred vision.

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Clinical Trials as Topic; Forecasting; Glaucoma; Humans; In Vitro Techniques; Sulfonamides; Thiazines; Thiophenes

Dorzolamide, on the basis of its pharmacological profile and lack of undesirable side effects in safety assessment studies together with the fact that it could be formulated in solution at 2%, underwent extensive clinical studies. Early clinical studies in the development of dorzolamide have been described elsewhere (Maren, 1995; Serle and Podos, 1995). In a 1-year study in which a comparison was undertaken in patients for intraocular pressure lowering effects between 2% dorzolamide administered three times daily, 0.5% betaxolol twice daily, and 0.5% timolol twice daily, the peak reductions in intraocular pressure were 23, 21, and 25%, respectively. Tachyphylaxis did not develop to dorzolamide nor were electrolyte and/or systemic side effects encountered (Strahlman et al., 1995). The latter is consistent with results of a pharmacokinetic study in humans in which plasma levels of dorzolamide were lower than the limit of detection (5 ng/ml) at a time when the red blood cell content of dorzolamide had reached steady state which was appreciably less than the red blood cell content of the enzyme (Biollaz et al., 1995). Patients taking 0.5% timolol twice daily received either 2% dorzolamide twice daily or 2% pilocarpine four times daily for 6 months and the additional reductions in intraocular pressure elicited by dorzolamide and pilocarpine were very similar. However, pilocarpine usage resulted in a higher discontinuation rate (Strahlman et al., 1996). In a separate study in which dorzolamide and pilocarpine were compared at these dosage schedules, patients preferred dorzolamide to pilocarpine by a ratio of over 7 to 1 in terms of quality of life (Laibovitz et al., 1995). In summary, the quest for a topical, ocular hypotensive, CA inhibitor, though time-consuming, was a successful one with the introduction of dorzolamide into general clinical practice.

Topics: Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Sulfonamides; Thiophenes

Glaucoma is in most of cases initially treated with drugs, viz. beta-blocking agents, miotics, sympathicomimetics and carbonic anhydrase inhibitors. The therapy of first choice is a beta-blocking agent, but in approximately 50% of the patients treated the effect becomes inadequate with time and combination therapy is necessary. Recently, four new antiglaucomatous agents have become available: apraclonidine, brimonidine, dorzolamide and latanoprost. Apraclonidine, an alpha 2-adrenergic agonist, is indicated for brief episodes of postlaser rise of the intraocular pressure. Longer treatment may lead to tolerance. Brimonidine, another alpha 2-adrenergic agonist, is indicated for long-term treatment of glaucoma; tolerance does not often occur. Dorzolamide is a local carbonic anhydrase inhibitor which lacks the systemic side effects seen after oral administration of carbonic anhydrase inhibitors. Latanoprost, a prostaglandin F2 alpha-derivative induces an effective decrease of the intraocular pressure if administered as monotherapy and has a good efficacy when combined with other drugs lowering the intraocular pressure. The new antiglaucomatous agents are a welcome addition to the pharmacotherapy, since in many cases they make it possible to postpone or avoid surgery.

Topics: Administration, Oral; Administration, Topical; Adrenergic alpha-Agonists; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Clonidine; Drug Therapy, Combination; Female; Glaucoma; Humans; Latanoprost; Male; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes

Topics: Adenosine; Animals; Antihypertensive Agents; Cannabinoids; Drug Design; Endothelins; Glaucoma; Guanylate Cyclase; Humans; Intraocular Pressure; Neuroprotective Agents

Dorzolamide (dorzolamide hydrochloride), the first topical carbonic anhydrase (CA) inhibitor to become available for clinical use, lowers intraocular pressure (IOP) by reducing aqueous humour formation. It is formulated as a 2% eyedrop for use in the management of glaucoma and ocular hypertension. When administered 3 times daily, dorzolamide is effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Mean IOP was reduced by approximately 4 to 6 mm Hg at peak (2 hours postdose) and 3 to 4.5 mm Hg at trough (8 hours postdose) in clinical trails. A 1-year comparative study showed that the ocular hypotensive efficacy of dorzolamine 2% 3 times daily was similar to that of betaxolol 0.5% twice daily, but slightly inferior to that of timolol 0.5% twice daily. Dorzolamide has additive ocular hypotensive effects when used in conjunction with topical beta-adrenergic antagonists and was as effective as pilocarpine 2% 4 times daily as adjunctive therapy in patients receiving timolol. Dorzolamide does not appear to produce the acid-base or electrolyte disturbances and severe systemic adverse events associated with oral CA inhibitors, and unlike beta-adrenergic antagonists, it is not contraindicated in patients with asthma, reactive airways disease or heart disease. Furthermore, as CA inhibitors do not cause miosis, they may cause less interference with vision than pilocarpine or epinephrine (adrenaline). The most common adverse effects associated with dorzolamide are bitter taste and transient local burning or stinging. Conjunctivitis was the most common reason for discontinuation of dorzolamide in one large study. Thus, available data suggest that dorzolamide has potential as an alternative therapy option in patients with glaucoma or ocular hypertension who are intolerant of, or unable to receive, ophthalmic beta-adrenergic antagonists and as adjunctive therapy in patients already receiving these agents. Further efficacy and tolerability data are needed to determine the place of dorzolamide in therapy.

Topics: Absorption; Aging; Animals; Antihypertensive Agents; Aqueous Humor; Carbonic Anhydrase Inhibitors; Controlled Clinical Trials as Topic; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Quality of Life; Regional Blood Flow; Retina; Sulfonamides; Thiophenes; Tissue Distribution

Carbonic anhydrase inhibitors (CAI) have been investigated for topical administration in glaucoma therapy during the past few years. Dorzolamide is the first topical CAI to become available for clinical use. CAI's lower intraocular pressure (IOP) by the inhibition of bicarbonate secretion into the posterior chamber by the ciliary epithelium, thereby suppressing aqueous humor production and lowering the IOP. A topical CAI with ocular hypotensive efficacy is comparable with that of oral agents, but without their systemic effects would represent a major advance in medical treatment of glaucoma and ocular hypertension. Data from clinical trials with dorzolamid (Trusopt) have shown this topical carbonic anhydrase inhibitor to be comparable in efficacy to beta-blockers when used as monotherapy, and as effective as pilocarpine when used as an adjunct to beta-blocker therapy. The aim of this paper was to present the results of long-term clinical and experimental studies with dorzolamid (Trusopt).

Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase Inhibitors; Drug Interactions; Drug Therapy, Combination; Glaucoma; Intraocular Pressure; Pilocarpine; Sulfonamides; Thiophenes

Dorzolamide, a topically active carbonic anhydrase inhibitor, is an effective new glaucoma medication that creates a decrease in intraocular pressure similar to that produced by beta-blockers. When beta-blockers are contraindicated, dorzolamide may be used as a first-line therapy. It has excellent additivity with other topical ocular hypotensive medications, including beta-blockers and pilocarpine. Systemic side effects are minimal, particularly compared with those of oral carbonic anhydrase inhibitors. However, local side effects, including corneal edema in patients with borderline endothelial function, may occur. Decreased visual acuity and allergic reactions, which occur frequently, may curtail the use of dorzolamide in some patients.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Treatment Outcome

Systemically administered carbonic anhydrase inhibitors have been in clinical use since the 1950's. Their use and side effects have been reviewed extensively. Our review summarizes the development of topically administered carbonic anhydrase inhibitors in patients with glaucoma. Moreover, it documents clinical trials leading to the present choice of dorzolamide (MK-507), which is now being reviewed for worldwide approval for marketing by 1995.

Topics: Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Ophthalmic Solutions; Sulfonamides; Thiophenes

Topics: Acetazolamide; Administration, Topical; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Methazolamide; Sulfonamides; Thiophenes

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Intraocular Pressure; Ophthalmic Solutions; Sulfonamides; Thiophenes

Topics: Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Glaucoma; Humans; Intraocular Pressure; Structure-Activity Relationship; Sulfonamides; Thiophenes

Dorzolamide hydrochloride (S,S-5,6-dihydro-4H-4-ethylamino-6-methylthieno [2,3-b]thiopyran-2-sulfonamide-7,7-dioxide HCl; MK-507; L-671,152) is a water-soluble, potent inhibitor of human carbonic anhydrase isoenzymes II and IV in vitro, the respective IC50 values being 0.18 nM and 6.9 nM. In contrast, it was found to be a much weaker inhibitor of human carbonic anhydrase isoenzyme I (IC50 value of 600 nM). The topical administration of one 50 microliters drop of 0.5%, 1% and 2% solutions of dorzolamide maximally lowered the intraocular pressure (IOP) of glaucomatous monkeys by 22%, 30% and 37%, respectively. Good ocular hypotensive activity was also observed in ocular normotensive and hypertensive rabbits. Its site of action was within the eye, and the reductions in IOP in both species was achieved via decreased aqueous humor inflow. The duration of action of 2% dorzolamide was shorter than that of 0.5% timolol in glaucomatous monkeys. The IOP lowering activity of timolol in this paradigm was enhanced by the concomitant instillation of dorzolamide. Both acutely and repeatedly administered 2% dorzolamide did not decrease regional ocular blood flow in the rabbit, and the topical instillation of the drug had no adverse effects on the eye of rabbits, dogs and monkeys. Dorzolamide has been approved in a number of countries for use in patients with ocular hypertension or open-angle glaucoma.

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Dogs; Drug Combinations; Drug Evaluation, Preclinical; Glaucoma; Intraocular Pressure; Macaca; Ophthalmic Solutions; Rabbits; Sulfonamides; Thiophenes; Timolol

Glaucoma is a potentially blinding disease. The goal of glaucoma therapy is to reduce intraocular pressure to a predetermined target level. There are currently 5 classes of compounds used for the medical management of glaucoma. Four classes that appear promising for the long term management of glaucoma are in different phases of clinical investigation, and include the topically active carbonic anhydrase inhibitors, selective alpha 2-adrenergic agonists, prostaglandins and ethacrynic acid. The topically active carbonic anhydrase inhibitor dorzolamide (MK-507) is effective and well tolerated in clinical trials of up to 1 year's duration. Animal studies have demonstrated that this drug lowers intraocular pressure by reducing aqueous humour formation. The selective alpha 2-adrenergic agonists, brimonidine and apraclonidine, have been shown to be effective in reducing intraocular pressure in the short term. Long term effectiveness of these agents is under investigation. Prostaglandins (PG) of the PGF2-alpha isopropylester series caused marked reductions of intraocular pressure in laboratory and clinical trials. The newest prostaglandin analogue, latanoprost (PhXA41), effectively lowered intraocular pressure and was well tolerated in clinical trials of up to 4 weeks' duration. Prostaglandins reduce intraocular pressure by enhancing uveoscleral outflow. Ethacrynic acid enhanced traditional outflow facility and lowered intraocular pressure when applied topically or intracamerally in laboratory studies and clinical trials. Corneal adverse effects of ethacrynic acid have been noted. Reformulation of ethacrynic acid ointment may resolve this problem. These 4 classes of compounds will enhance our options for the medical management of glaucoma. They may be used instead of or in combination with some of the drugs currently in use, and may be better tolerated.

Topics: Administration, Topical; Adrenergic alpha-Agonists; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Clonidine; Ethacrynic Acid; Glaucoma; Humans; Latanoprost; Prostaglandins; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes

Posterior capsular opacification is treated using neodymium-doped yttrium aluminium garnet laser capsulotomy that leads to increased intraocular pressure. Here, we compare the effects of dorzolamide hydrochloride + timolol maleate versus brimonidine on intraocular pressure. We also investigate their side effects after neodymium-doped yttrium aluminium garnet laser capsulotomy. In these patients, there are no prior studies comparing the results of these two drugs.. Ninety patients with posterior capsule opacification contributed to the study. They received yttrium aluminium garnet laser capsulotomy. After yttrium aluminium garnet laser capsulotomy, they were randomized into three groups. Group 1 received dorzolamide hydrochloride + timolol maleate; Group 2 took brimonidine; and Group 3, the control group, took no drug. Group 1 took dorzolamide hydrochloride + timolol maleate eye drops 1. Brimonidine had a similar side effect profile to the fix combination. Intraocular pressure on the first (. We suggest that brimonidine and a combination of dorzolamide + timolol are similarly effective at reducing eye pressure for routine cases. In cases where intraocular pressure attacks might be at higher risk, using the dorzolamide + timolol combination would be more appropriate.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Capsule Opacification; Glaucoma; Humans; Intraocular Pressure; Lasers, Solid-State; Neodymium; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol; Yttrium

To investigate the corneal epithelial and limbal epithelial alterations in patients under topical glaucoma treatment using anterior segment-OCT (AS-OCT) and to determine the changes of the limbal region due to the preservatives and glaucoma drugs, that can progress to limbal stem cell deficiency (LSCD). Limbal thickness was measured by AS-OCT to evaluate limbal cell deficiency.. Forty-seven patients using topical medication for glaucoma, and 48 control subjects were enrolled in this matched case-control study. The patients were divided into four groups according to the treatment regimens. Group 1: One-drug regimen, Group 2: Two-drug regimen, Group 3: Three-drug regimen, Group 4: Four-drug regimen For the ocular surface evaluation; tear break-up time with standard fluorescein sodium sterile strip application, Schirmer test-I, Ocular Surface Disease Index Questionnaire, and AS-OCT were performed.. A total of 95 subjects were included: 47 eyes of 47 patients with glaucoma medication and 48 eyes of 48 healthy subjects. There was a statistically significant difference between patients and controls according to BUT, SCH, and OSDI (. Using at least one glaucoma drug caused limbal area injury, changed ocular surface measurements, and significantly reduced the limbal epithelial thickness where the stem cells reside. The limbal epithelial thickness measurement by AS-OCT seems to be an innovative, non-invasive, and promising technique for detecting and staging corneal damage in topical glaucoma therapy.

Topics: Aged; Antihypertensive Agents; Benzalkonium Compounds; Brimonidine Tartrate; Case-Control Studies; Epithelium, Corneal; Female; Glaucoma; Humans; Latanoprost; Limbus Corneae; Male; Middle Aged; Ophthalmic Solutions; Preservatives, Pharmaceutical; Single-Blind Method; Sulfonamides; Thiophenes; Timolol; Tomography, Optical Coherence

Central corneal thickness (CCT) may increase over time in children affected by primary congenital glaucoma and treated with latanoprost for at least 30 months.. The purpose of this study was to investigate CCT modification over time in a population of primary pediatric glaucoma (PPG) patients prescribed a monotherapy of latanoprost.. The present paper reports the results of a post hoc analysis on patients enrolled in the Glaucoma Italian Pediatric Study (GIPSy). Children affected by PPG, with a postsurgical intraocular pressure between 22 and 26 mm Hg and treated with latanoprost monotherapy for at least 30 months were eligible for the analysis. CCT variation from baseline was investigated over the follow-up using univariable and multivariable longitudinal linear mixed models. The impact of age, sex, and intraocular pressure on CCT variation were evaluated taking into account the interaction of each variable with time.. Twenty-seven eyes (20 patients) were included in the analysis. Mean duration of latanoprost treatment was 36.6 months (SD 2.5) and mean CCT at baseline was 551 μm (SD 37.7). A significant increase of CCT over time was revealed by multivariable analysis, taking into account the impact of age at baseline and its interaction with time (P=0.03). The interaction between age and time was significant (P=0.04), indicating that older age at baseline was associated with lower increase of CCT over time. No variation of CCT was found in univariable analysis (P=0.28).. In this population of PPG patients treated with latanoprost for at least 30 months, CCT significantly increased over time, when the impact of age and its interaction with time were considered.

Topics: Administration, Topical; Adolescent; Age of Onset; Antihypertensive Agents; Child; Child, Preschool; Cornea; Corneal Pachymetry; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Italy; Latanoprost; Long-Term Care; Male; Organ Size; Sulfonamides; Thiophenes; Time Factors; Tonometry, Ocular

To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery.. Children with primary pediatric glaucoma with postsurgical intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure.. A total of 37 patients (61 eyes) were analyzed. The mean age of the patients was 4.1 years (SD: 3.8). In total, 43 eyes were included in the efficacy analysis. A total of 33 eyes (76.7%; 95% confidence interval, 61.4-88.2) were considered responders: 19 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to central corneal thickness at the time of surgery and the age at the time of surgery. IOP reduction was 9.7 mm Hg (SD: 2.6) for latanoprost, 8.4 mm Hg (SD: 1.5) for the latanoprost/dorzolamide combination, and 9.3 mm Hg (SD: 2.5) for the dorzolamide monotherapy. None of the patients was withdrawn because of adverse events.. Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children after surgery. Nonresponders were mainly patients with early presentation of the disease.

Topics: Antihypertensive Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Italy; Latanoprost; Male; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Tonometry, Ocular; Treatment Outcome

To investigate the efficacy of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery.. Single arm, prospective, interventional multicenter study. Primary pediatric glaucoma patients younger than 13 years after a single surgical procedure with IOP between 22 and 26 mmHg were considered eligible. At baseline, patients were allocated to latanoprost monotherapy once daily. Depending on intraocular pressure (IOP) reduction at first visit, the patients were allocated to one of three groups: continuation of latanoprost monotherapy, addition of dorzolamide twice daily, or switch to dorzolamide three times daily. The same approach for allocation in medication groups was used in all subsequent visits. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered non-responders and withdrawn. Study treatment and patient follow-up will continue for 3 years or until treatment failure. The primary endpoint is the percentage of responders. Secondary endpoints are time to treatment failure and frequency of adverse events.. A total of 37 patients (69 eyes) were enrolled. The mean age was 4.0 ± 3.8 years, the female/male ratio was 1/1.7, and the majority of patients were Caucasian. Eighty percent of patients had bilateral glaucoma. Goniotomy was the most frequently performed surgery (38.6%), followed by trabeculotomy (22.8%), trabeculectomy (21.1%), and trabeculectomy plus trabeculotomy (17.5%). The baseline IOP was 23.6 ± 1.5 mmHg.. The study population is representative of patients frequently encountered after the first surgery for primary pediatric glaucoma. The study will produce evidence on the medium-term efficacy of a defined pharmacological approach.

Topics: Antihypertensive Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Italy; Latanoprost; Male; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Treatment Outcome

To evaluate the effect of early aqueous suppressant treatment on Ahmed glaucoma valve (AGV) surgery outcomes.. Randomized clinical trial.. Ninety-four eyes of 94 patients with refractory glaucoma.. After AGV implantation, 47 cases (group 1) received topical timolol-dorzolamide fixed-combination drops twice daily when intraocular pressure (IOP) exceeded 10 mmHg, whereas 47 controls (group 2) received conventional stepwise treatment when IOP exceeded target pressure.. Main outcome measures included IOP and success rate (6 mmHg < IOP < 15 mmHg and IOP reduction of at least 30% from baseline). Other outcome measures included best-corrected visual acuity, complications, and hypertensive phase frequency.. Groups 1 and 2 were both followed up for a mean of 45±11.6 and 47.2±7.4 weeks, respectively (P = 0.74). Mixed model analysis revealed a significantly greater IOP reduction in group 1 at all intervals (P<0.001). At 1 year, the cases exhibited a significantly higher success rate (63.2% vs. 33.3%; P = 0.008) and reduced hypertensive phase frequency (23.4% vs. 66.0%; P<0.001).. Early aqueous suppressant treatment may improve AGV implantation outcomes in terms of IOP reduction, success rate, and hypertensive phase frequency.

Topics: Adult; Antihypertensive Agents; Aqueous Humor; Carbonic Anhydrase Inhibitors; Drug Combinations; Female; Glaucoma; Glaucoma Drainage Implants; Humans; Intraocular Pressure; Logistic Models; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Timolol; Visual Acuity

To describe the study design and baseline factors of the Heidelberg Retina Tomograph ancillary study within the EGPS. Furthermore, to examine the relationship between HRT optic disc topographic measurements and baseline demographic and ocular factors.. Four hundred and eighty-nine ocular hypertensive participants were included. Each participant completed HRT imaging at least annually. The associations between HRT measurements and IOP, central corneal thickness (CCT), baseline photographic estimates of vertical CDR ratio (CDR), asymmetry between the two eyes in CDR ratio and baseline visual field indices were assessed using regression analysis.. Associations between HRT measurements and vertical CDR by photographs were found for almost all stereometric optic disc parameters in both univariate and multivariate analysis. The strongest association was found between vertical CDR measurements and disc, cup and rim area; cup and rim volume, CDR area, linear CDR, mean and maximum cup depth and cup shape measure (all p < 0.0001). In multivariate analysis, pattern standard deviation (PSD) and HRT disc area had significant associations with several HRT optic disc measurements. Furthermore, CCT was significantly associated with reference height and the glaucoma probability score (GPS, outside normal limits).. The EGPS is the first multicentre, placebo-controlled randomized clinical trial to use HRT for monitoring optic disc changes in participants with ocular hypertension. We found strong associations between stereophotographic vertical CDR estimates, HRT disc area, PSD and several HRT parameters. We found, furthermore, that the parameters reference height and GPS were significantly related to central corneal thickness.

Topics: Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmoscopy; Optic Disk; Optic Nerve Diseases; Research Design; Sulfonamides; Thiophenes; Tomography; Tonometry, Ocular; Visual Acuity; Visual Fields

The goal of glaucoma management is to reduce intraocular pressure (IOP) and maintain it at a level compatible with the health of the optic nerve. New therapies are constantly being sought. Topical instillation of levobunolol 0.5%, alone or with dorzolamide 2%, has a hypotensive effect on the IOP in healthy dogs, and levobunolol combined with dorzolamide produces a stronger hypotensive effect than the combination of timolol and dorzolamide. All animals tolerate these topical medications well with no signs of discomfort, and no ocular side effects have been observed. Levobunolol, alone or in combination with dorzolamide, induces bradycardia, as does timolol with dorzolamide.

Topics: Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase Inhibitors; Cross-Over Studies; Dogs; Drug Combinations; Drug Therapy, Combination; Female; Glaucoma; Heart Rate; Intraocular Pressure; Levobunolol; Male; Sulfonamides; Thiophenes; Timolol

To compare the efficacy and safety of latanoprost against a fixed combination of dorzolamide and timolol in eyes with elevated intraocular pressure (IOP) or glaucoma and anterior or intermediate uveitis.. Fifty-eight patients with anterior or intermediate uveitis and elevated IOP or glaucoma presented or followed up in the Ocular Inflammation and Immunology Service of General Hospital of Athens were randomly assigned to receive treatment either with latanoprost (30) or with dorzolamide/timolol (28). The main outcome measures were inflammatory relapses and IOP response to treatment.. Ten patients (34%) in the latanoprost group and sixteen patients (57%) in the dorzolamide/timolol group experienced relapses of anterior uveitis (p = 0.93). There was no statistical difference between the two groups in respect of inflammatory relapses (p = 0.21). Twenty-one patients were followed up before starting latanoprost. The number of recurrences of anterior uveitis per patient per year before treatment with latanoprost was 0.82 +/- 1.2. The rate of relapses per patient per year after starting latanoprost was 0.39 +/-0.7 for these patients (p = 0.038). After 1 year of treatment, intraocular pressure was dropped from 27.8 +/- 8.4 mmHg to 18.6 +/- 5.3 mmHg (p < 0.001) in the latanoprost group and from 28.2 +/-8.1 mmHg to 22.6 +/-10.1 mmHg (p < 0.001) in the dorzolamide/timolol group. Four patients during treatment with latanoprost and five patients during treatment with dorzolamide/timolol developed macular edema.. Latanoprost is safe and equally effective to a fixed combination of dorzolamide and timolol in the treatment of uveitic glaucoma.

Topics: Adult; Antihypertensive Agents; Drug Combinations; Female; Follow-Up Studies; Glaucoma; Gonioscopy; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Prostaglandins F, Synthetic; Recurrence; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome; Uveitis, Anterior; Uveitis, Intermediate; Visual Acuity

To evaluate intraocular pressure (IOP) and ocular allergy after replacement of 1 of 2 adjunctive therapy regimens (fixed-combination dorzolamide/timolol or dorzolamide/timolol plus brimonidine) with fixed-combination brimonidine/timolol in glaucoma patients treated with ongoing prostaglandin analog (PGA) therapy.. This prospective, nonrandomized, open-label study involved patients on dorzolamide 2%/timolol 0.5% and a PGA who needed lower IOP and patients on brimonidine, dorzolamide 2%/timolol 0.5%, and a PGA who wanted to simplify their treatment regimens. After the baseline evaluation, patients were continued on the PGA and their other IOP-lowering medications were replaced with brimonidine 0.2%/timolol 0.5%. IOP was measured at baseline and months 1 and 3.. In patients who replaced dorzolamide/timolol with brimonidine/timolol (n = 45), the mean (SD) IOP was 15.9 (1.4) mm Hg at baseline, 13.3 (0.9) mm Hg after 1 month (P < 0.001 vs. baseline), and 13.3 (1.0) mm Hg after 3 months (P < 0.001 vs. baseline). In patients who replaced both brimonidine and dorzolamide/timolol with brimonidine/timolol (n = 15), the mean (SD) IOP was 15.9 (5.2) mm Hg at baseline, 13.8 (1.8) mm Hg after 1 month (P = 0.053 vs. baseline), and 13.8 (1.4) mm Hg after 3 months (P = 0.079 vs. baseline). Allergy was reported in 5 patients previously treated with dorzolamide/timolol and 1 patient previously treated with brimonidine plus dorzolamide/timolol.. For patients on multiple-drug therapy including a PGA, replacement of dorzolamide/timolol with brimonidine/timolol may help achieve a lower IOP, while replacement of brimonidine plus dorzolamide/timolol with brimonidine/timolol may help achieve as low an IOP with fewer medications.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Drug Combinations; Drug Hypersensitivity; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Time Factors; Timolol

To measure central corneal thickness (CCT) within the participants of the European Glaucoma Prevention Study (EGPS). This study was designed to test if lowering intraocular pressure (IOP) by means of dorzolamide is able to prevent or delay conversion from ocular hypertension to glaucoma.. Randomized, double-masked, controlled, observational clinical trial.. Eight hundred fifty-four of 1077 ocular hypertensive participants within the EGPS were investigated. Four hundred twenty-nine patients were treated with dorzolamide and 425 patients received placebo.. Treatment with dorzolamide or placebo (the vehicle of dorzolamide) in 1 or both eyes.. Central corneal thickness as measured by ultrasound pachymetry (DGH-500 Pachette; DGH Technologies, Exton, PA). The CCT measurements were obtained in the morning before measuring IOP. Five measurements were taken from each eye of each patient within 5 minutes of application of anesthetic eye drops.. Mean CCT was 572.6+/-37.4 microm (range, 458.5-695.6 microm). The CCT was higher in younger patients, male patients, and diabetic patients. Mean CCTs for the 429 patients receiving dorzolamide were 574.2+/-38.48 microm (range, 458.5-695.6 microm) and 571.0+/-36.21 microm (469.7-690.1 microm) for the 425 patients receiving placebo (P = 0.205). Central corneal thickness did not correlate with refraction, baseline IOP, or systemic hypertension.. Central corneal thickness measurements within the EGPS were greater than those reported in other studies of normal eyes without ocular hypertension. Larger CCT measurements correlated with male gender, younger age, and diabetes.

Topics: Adult; Age Factors; Aged; Cornea; Diabetes Complications; Double-Blind Method; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sex Factors; Sulfonamides; Thiophenes; Ultrasonography

In previous analyses of primary efficacy data from two randomized clinical trials, standard dosing regimens of the dorzolamide/timolol fixed combination (COSOPT) and latanoprost (XALATAN) were shown to have equivalent efficacy with regard to reduction in mean daytime diurnal intraocular pressure (IOP). We performed additional post hoc analyses of pooled data from these studies to compare further the efficacy of the two treatments. The studies used identical 3-month, parallel group, randomized, observer-masked and patient-masked, multicenter designs. Patients with a baseline IOP > or = 24 mm Hg were randomized to either the 2% dorzolamide/0.5% timolol combination eye drops twice daily (n = 273) or 0.005% latanoprost eye drops once daily (n = 271). The IOP measurements were made at 8 AM, 10 AM, 2 PM, and 4 PM at the baseline visit and then on each of the 3 monthly assessment days. The following measures were analyzed on a post hoc basis: 1) percentages of patients meeting target levels of IOP reduction; 2) mean IOP reduction in those patients with high IOP (> or =30 mmHg) at baseline; 3) mean IOP at each of the assessment time points during a day. A total of 259 patients in the dorzolamide/timolol group and 268 patients in the latanoprost group were included in the efficacy analysis. At 3 months, both treatments showed similar efficacy with regard to the percentages of patients who achieved target levels of IOP reduction (e.g., 40% IOP reduction in 15% of dorzolamide/timolol combination patients and 13% of latanoprost patients), mean IOP reduction in those patients with high IOP at baseline (dorzolamide/ timolol combination, 12.5 mmHg, latanoprost, 12.6 mmHg), and mean IOP at each time point during the day. By the measures used in this analysis, the dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP in patients with ocular hypertension or glaucoma.

Topics: Double-Blind Method; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To evaluate dorzolamide hydrochloride in patients younger than 6 years who have an elevated intraocular pressure or glaucoma.. A 3-month, controlled, randomized, double-masked, multicenter, clinical trial. Patients were randomized to 2% dorzolamide 3 times daily or timolol maleate gel-forming solution (0.25% for patients <2 years and 0.5% for patients > or =2 but <6 years) once daily plus placebo twice daily. If the intraocular pressure was not controlled through monotherapy, younger patients received concomitant dorzolamide 3 times daily and 0.25% timolol gel-forming solution once daily and older patients received a fixed combination of 2% dorzolamide and 0.5% timolol twice daily. The primary safety variable was the proportion of patients who discontinued therapy for a drug-related adverse experience. Intraocular pressure reduction was a secondary measure.. One younger patient (1.8%) of 56 randomized to dorzolamide discontinued concomitant therapy because of bradycardia. Two older patients (3.0%) of 66 discontinued dorzolamide because of ocular adverse experiences. The most frequent ocular adverse experiences were discharge and ocular hyperemia (younger cohort) and ocular hyperemia and burning/stinging (older cohort). At week 12, the mean change in intraocular pressure for dorzolamide was statistically significant from baseline (-7.3 mm Hg [-20.6%] and -7.1 mm Hg [-23.3%]) in the younger and older cohorts, respectively; P<.001 for both.. Dorzolamide was generally well tolerated and demonstrated efficacy for up to 3 months in patients younger than 6 years.

Topics: Antihypertensive Agents; Child, Preschool; Double-Blind Method; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

To compare the intraocular pressure (IOP) lowering effect of concomitant administration of 0.5% timolol and 2% dorzolamide and a fixed combination dorzolamide-timolol (Cosopt) To critically evaluate discrepancies between phase 3 clinical trials and prior replacement studies.. A prospective, randomized, controlled clinical trial and a prospective, non-randomized comparative replacement trial.. In a national multicentre trial, 131 patients were randomized to dorzolamide-timolol or a topical carbonic anhydrase inhibitor (CAI) and non-selective beta-blocker following a 1-month run-in using the separate components. Peak (maximal drug effect) and trough (minimal drug effect) IOPs were measured at baseline and 1 month after treatment. The replacement therapy study enrolled 404 consecutive glaucoma patients using a non-selective beta-blocker and dorzolamide and changed treatment to the fixed combination. Mean IOPs at the same time of day were compared before and 1 month after changeover.. The main outcome measure was IOP, comparing baseline and on-therapy measurements at study conclusion between the two arms of the randomized trial and before and after switching therapy in the replacement trial.. In the randomized trial, the mean baseline peak and trough IOPs were 18.4 and 21.0 mmHg in the group randomized to combination therapy and 17.6 and 19.8 mmHg in the dual drug group. After randomization and treatment for four weeks, the peak and trough IOPs were 17.6 and 19.5 mmHg in the combination group and 17.3 and 19.0 mmHg in the concomitant group. The percentage change in IOP was -3.2% at peak and -6.5% at trough for the combination and -0.3 and -3.2% for the concomitant group. These differences did not show statistical significance. In the replacement study, mean baseline IOP was 19.4 mmHg. Four weeks after initiation of treatment on the fixed combination, a significant additional IOP reduction of 1.7 mmHg (-8.8%) was observed (P < 0.0001). Overall, 81% of eyes exhibited equal or lower IOP on the fixed combination compared with concomitant therapy.. The results of the randomized trial indicate that the fixed combination dorzolamide-timolol (Cosopt) was as effective as its components in controlling IOP, confirming results seen in phase 3 clinical trials. However, in the replacement study, utilization of the combination drug offered a statistically significant additional IOP reduction (P < 0.0001), which duplicates results from previous replacement studies.

Topics: Aged; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Combinations; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Male; Prospective Studies; Sulfonamides; Thiophenes; Timolol

Histological changes of, in particular, collagen and extracellular matrix after administration of topical prostaglandin F(2alpha)(PGF (2alpha)) analogues have been reported. In view of this observation, we investigated the influence of PGF(2alpha) analogues on the central corneal thickness.. In a non-randomized, controlled, cross-sectional study, 403 eyes from 208 consecutive patients were examined: 149 eyes (normals/controls) and 79 with ocular hypertension (OHT), 119 eyes with primary open angle glaucoma (POAG) and 56 eyes with normal tension glaucoma (NTG). One experienced ophthalmologist measured the central corneal thickness (CCT) using ultrasound pachymetry (Tomey AL-2000, sequence of 5 measurements with an SD < 3 microm). The central corneal power was measured with the Zeiss keratometer. Depending on the topical treatment, the patients were classified into 4 groups: A) PGF(2alpha) analogues (n = 78), B) carbonic anhydrase inhibitors (n = 26), C) combination of PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (n = 41), D) none of these drugs (n = 258). T tests and multiple linear regression analyses were used for statistical analysis.. CCT was decreased significantly (p < 0.01 each) in eyes treated with PGF(2alpha) analogues (group A: 529 +/- 34 microM), in comparison with the untreated and non-glaucomatous eyes (part of group D: 542 +/- 35 microM, n = 148), untreated glaucomatous/OHT eyes (part of group D: 563 +/- 37 microM, n = 110), eyes treated with carbonic anhydrase inhibitors (group B: 561 +/- 32 microm) and eyes with a topical application of both PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (group C: 555 +/- 48 microM. No correlation was found between CCT and diagnosis (OHT, POAG, NTG, control), gender, central corneal power, and intraocular pressure in a multivariate analysis.. The present findings suggest that the topical application of prostaglandin F(2alpha) analogues onto the cornea reduces the central corneal thickness significantly. These changes might be attributed to effects of PGF(2alpha) analogues on the extracellular matrix of the corneal stroma via upregulation of matrix metalloproteinases. In clinical practice, corneal thinning under local PGF (2)(alpha) analogue treatment could result in underestimation of intraocular pressure levels as measured by applanation tonometry.

Topics: Acetazolamide; Administration, Topical; Adult; Aged; Carbonic Anhydrase Inhibitors; Cloprostenol; Collagen; Cornea; Corneal Topography; Cross-Sectional Studies; Dinoprost; Drug Therapy, Combination; Extracellular Matrix; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Travoprost; Ultrasonography

The aim of this study was to evaluate the long-term follow-up of patients who were changed to latanoprost from previous glaucoma therapies.. Primary open-angle, exfoliative or chronic angle-closure glaucoma, or ocular hypertensive patients who switched to latanoprost therapy with a 2-year follow-up, were evaluated for efficacy, safety, and continuance of therapy.. In 1,571 patients, the intraocular pressure (IOP) across all treatment groups of 21.3 +/- 4.1 was reduced to 17.6 +/- 3.2 mm Hg after switching to latanoprost. Latanoprost reduced the IOP from previous monotherapies, including nonselective beta-adrenergic blockers, topical carbonic anhydrase inhibitors, alpha-adrenergic agonists and pilocarpine (p < 0.0001) and adjunctive therapies, including the fixed combinations of dorzolamide and timolol, pilocarpine and timolol, and pilocarpine and metipranolol, and the unfixed combination of dorzolamide and timolol and dorzolamide and clonidine (p < 0.0028). Latanoprost further reduced the IOP across all diagnostic groups (p < 0.0001). The most common ocular adverse event was ocular irritation (n = 25; 1.6%), which was also the most common reason given for patients who discontinued latanoprost because of an adverse event (n = 20; 1.3%).. The mean IOP was maintained at an acceptable level throughout the 2-year follow-up period on latanoprost. Latanoprost generally provides further reduction of IOP when switched from previous mono- and adjunctive therapies, with a low rate of side effects and discontinuations.

Topics: Aged; Antihypertensive Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Germany; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Pilocarpine; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Time Factors; Timolol; Treatment Outcome

Topics: Administration, Topical; Antihypertensive Agents; Betaxolol; Clonidine; Epinephrine; Glaucoma; Humans; Intraocular Pressure; Levobunolol; Prospective Studies; Sulfonamides; Thiophenes; Visual Field Tests

We investigated the dose-escalation profile of dorzolamide used in combination with other antiglaucoma agents in patients with primary glaucoma and ocular hypertension. In a prospective, open-label study, 78 patients received dorzolamide 0.5% in addition to other topical antiglaucoma agents for > or =4 weeks. The concentration of dorzolamide was then escalated to 1.0% and intraocular pressure (IOP) measured every 4 weeks for 12 weeks. Dose escalation of dorzolamide from 0.5% to 1.0% resulted in a significant reduction in IOP throughout the 12 weeks of treatment at the higher dose. Mean baseline IOP was 19.7 mmHg. At 4, 8, and 12 weeks after dose escalation, mean IOP had decreased to 17.8 (-9.4%), 17.6 (-10.8%), and 17.5 (-10.7%) mmHg. No serious drug-related adverse effects were reported. These results indicate that dose escalation of dorzolamide from 0.5% to 1.0% is effective and well tolerated as adjunctive therapy for patients in whom IOP is insufficiently controlled by combination therapy.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Adult; Aged; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Irritants; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins; Sulfonamides; Thiophenes; Time Factors

To compare hypotensive effect of latanoprost versus timolol-dorzolamide association on patients with glaucoma.. We studied 102 eyes in 52 patients with intraocular pressure (IOP) higher than 21 mmHg, previously treated with a betablocker. Patients were divided in two groups. Treatment was changed on group 1 (51 eyes in 27 patients) to a timolol-dorzolamide association. Group 2 (51 eyes in 27 patients) changed treatment to latanoprost. After determination of previous IOP, readings were taken at 1, 3 and 8 months later.. Both groups showed a decrease in IOP levels: Group 1, 5.6 mmHg and Group 2, 8.5 mmHg. Association between timolol and dorzolamide reached the highest hypotensive effect after the first month of treatment and remained constant during the rest of the study period. Latanoprost showed a maximal effect after the third month of treatment and maintained its effect all through the study as well. Latanoprost behaved similar to associated timolol-dorzolamide not showing significant differences during the first month of treatment. Significant differences appeared at third and eighth month favoring latanoprost (p<0.005 and p<0.001 respectively).. There was a similarity in efficacy of both treatments. However, after the third month latanoprost became more effective than the timolol-dorzolamide association.

Topics: Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma; Humans; Latanoprost; Male; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

The alpha-adrenergic agonist brimonidine and the carbonic anhydrase inhibitor dorzolamide have been studied both as monotherapy and in combination with beta-blockers in the treatment of glaucoma and ocular hypertension; however, a MEDLINE literature search failed to reveal any clinical studies directly comparing these 2 agents as adjunctive therapy.. The purpose of this study was to compare the intraocular pressure (IOP)-lowering efficacy of brimonidine and dorzolamide as adjunctive therapy to beta-blockers in adult patients with glaucoma or ocular hypertension.. In a prospective, investigator-masked, multicenter, parallel-design clinical trial, adult patients whose IOP was inadequately controlled with topical beta-blocker therapy were randomly assigned to receive brimonidine 0.2% twice daily or dorzolamide 2% 3 times daily as adjunctive therapy for 3 months. Efficacy was determined by the reduction in IOP from baseline. After 1 month of adjunctive treatment, patients who failed to meet a target 15% reduction in IOP at peak drug effect were crossed over to the other study medication.. A total of 106 patients were treated. Approximately 70% (74/106) of the patients were white, and 61.3% (65/106) had a diagnosis of open-angle glaucoma. Mean baseline IOP (ie, with beta-blocker monotherapy) was comparable between treatment groups (approximately 21 mm Hg). After 1 month of adjunctive treatment, the mean daily IOP reduction was significantly greater with brimonidine (4.40 mm Hg, 20.4%) than with dorzolamide (3.0 mm Hg, 14.4%, P = 0.033). At peak drug effect at month 1, the mean IOP reduction was significantly greater in the brimonidine group (5.95 mm Hg, 27.6%) than in the dorzolamide group (4.11 mm Hg, 19.7%; P = 0.007). Significantly more patients treated with brimonidine (44/51, 86.3%) than with dorzolamide (29/47, 61.7%) achieved the target 15% reduction in IOP at month 1 (P = 0.005). At month 3, the mean daily IOP reduction and the mean IOP reduction at peak drug effect were not significantly different in the 2 treatment groups. The mean daily IOP reduction was 4.98 mm Hg in the brimonidine group and 3.15 mm Hg in the dorzolamide group (P = 0.092). At peak drug effect, the mean IOP reduction was 6.39 mm Hg with brimonidine and 4.06 mm Hg with dorzolamide. The incidence of adverse events leading to discontinuation was 9.3% (5/54) in the brimonidine group (depression, 2; allergic conjunctivitis, 1; dry mouth and tearing, 1; dermatitis, 1) and 9.8% (5/51) in the dorzolamide group (ocular burning and stinging, 2; ocular itch, 1; gastrointestinal complaints, 1; lack of tolerance for beta-blocker, 1), with no significant difference between groups.. In this trial, brimonidine 0.2% twice daily produced greater mean decreases in IOP and was effective in more patients than dorzolamide 2% 3 times daily when used as adjunctive therapy to beta-blockers.

Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Down-Regulation; Female; Glaucoma; Humans; Immunologic Factors; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quality of Life; Quinoxalines; Sulfonamides; Thiophenes

To investigate whether dorzolamide alters corneal hydration control in patients with glaucoma or ocular hypertension.. Pachymetry, tonometry, and endothelial cell density were measured by a masked observer in 19 subjects with bilateral glaucoma or ocular hypertension. They were treated with 2% dorzolamide in one eye, and with saline in the other, before wearing contact lenses under patched eyes. Corneal thickness, measured each 30 minutes up to 4.5 hours after contact lens removal, enabled estimation of percentage recovery per hour and time for 95% of corneal thickness recovery for both eyes. Seven patients repeated this test after 1 year of dorzolamide use, and their results were compared with those of the preceding year.. After induction of hypoxic corneal edema, there was no significant difference between paired corneas in swelling levels (60.0+/-11.8 and 59.8+/-12.9 microm) (P = .94), time to 95% recovery (440.6+/-255.8 and 445.4+/-186.7 minutes) (P = .93), and percentage recovery per hour (38.1%+/-10.9% and 36.1%+/-9.6%) (P = .40). Subjects followed up after 1 year of dorzolamide use did not differ significantly in values of endothelial cell density, percentage recovery per hour, or time to 95% recovery from those obtained a year before. One subject developed persistent corneal edema after his stress test in the eye treated with dorzolamide.. There is no significant difference in the recovery from induced corneal edema after either a short-term or 1-year use of dorzolamide in patients with glaucoma or ocular hypertension with a normal corneal endothelium. One patient had persistent corneal edema after the stress test was performed on the dorzolamide-treated eye.

Topics: Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Cell Count; Contact Lenses; Cornea; Corneal Edema; Double-Blind Method; Endothelium, Corneal; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Sulfonamides; Thiophenes; Tonometry, Ocular

The first topically active carbonic anhydrase inhibitor, dorzolamide, was developed to circumvent the adverse systemic effects of oral carbonic anhydrase inhibitors. However, its use has been associated with ocular discomfort.. The present study examined the acceptability of brinzolamide, as measured by patients' ratings and stated preferences, in patients with glaucoma previously treated with dorzolamide in the clinical practice setting.. This was a prospective, open-label, noncomparative study conducted shortly after the approval of brinzolamide. Ophthalmologists in private practice in the continental United States were asked to select patients currently using dorzolamide as their sole or combination therapy for glaucoma. Patients underwent a screening assessment in which they were asked to rate their ocular comfort with dorzolamide on a scale from 1 to 6. Brinzolamide was then substituted for dorzolamide, and patients returned for a follow-up visit approximately 1 to 3 months later. At this visit, patients were asked about ocular comfort, their preferred medication, and whether they thought ocular comfort influenced their adherence to treatment. Intraocular pressure (IOP) was measured at both visits.. Valid visit dates (ie, both baseline and follow-up dates) were available for 447 of 501 patients from 68 of 73 sites (range, 1-40 patients per site). Because not all measurements were available for all patients at each visit, the sample size varied for each measurement. Demographic data were not available. The switch to brinzolamide resulted in a mean decrease in IOP of approximately 0.8 mm Hg (P < 0.001, paired t test). Sixty-nine percent of patients (274/397) reported an improvement of > or =1 grade in their comfort rating with brinzolamide versus dorzolamide. The mean (+/- SD) improvement in comfort rating was 1.43 +/- 1.48 grades (P < 0.001, Wilcoxon rank sum test). When patients were asked whether their adherence to treatment was affected by the occurrence of burning and stinging, 43% (173/399) answered affirmatively. Fifty-nine percent (251/424) preferred brinzolamide to dorzolamide. At the end of the study, based on patient preference, physician judgment, and other factors, 73% of responding patients (301/410) continued with brinzolamide therapy.. In this study, the switch from dorzolamide to brinzolamide resulted in overall improvements in comfort and ocular hypotensive efficacy. However, studies using a more rigorous randomized, controlled, crossover design are needed to support these observations.

Topics: Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Intraocular Pressure; Patient Satisfaction; Prospective Studies; Sulfonamides; Thiazines; Thiophenes

To compare the intraocular pressure (IOP) lowering effect of fixed combination dorzolamide 2% and timolol 0.5% therapy to that of concomitant administration of a topical beta-blocker and dorzolamide.. Seventy-four consecutive glaucoma patients were changed from a regimen including a topical beta-blocker and dorzolamide to the fixed combination dorzolamide-timolol in 1 eye, with the other eye used as the control. The average IOP readings before and 1 month after the change were compared.. The mean baseline IOP in the entire study population was 19.4 +/- 4.2 mm Hg in the study eyes and 16.9 +/- 4.2 mm Hg in the control eyes. Four weeks after the medication change, the mean IOP was 17.3 +/- 3.9 mm Hg in the study eyes (P <.001) and 16.1 +/- 4.1 mm Hg in the control eyes (P =.02). The difference between the mean IOP change of 2.1 mm Hg in the study eyes and 0.8 mm Hg in the control eyes was found to be statistically significant (P =.01).. These findings suggest that the fixed combination dorzolamide-timolol therapy achieves additional lowering of the intraocular pressure compared with the concomitant administration of a beta-blocker and dorzolamide.

Topics: Adrenergic beta-Antagonists; Aged; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Male; Ophthalmic Solutions; Prospective Studies; Sulfonamides; Thiophenes; Timolol

To evaluate the effect of dorzolamide on ocular blood flow in normal and glaucomatous eyes.. Twenty-six eyes with documented open-angle glaucoma of 26 patients and 13 normal control eyes of 8 age-matched subjects were included in this study. All eyes underwent color Doppler imaging for measuring peak-systolic velocity, end-diastolic velocity, and resistance index in the ophthalmic and central retinal arteries and the maximal and minimal velocities in the central retinal vein. Eyes were grouped in control and initial and advanced glaucoma categories. Measurements were made in all groups before and after application of topical dorzolamide. Intragroup comparisons between baseline and dorzolamide conditions were made using paired Student's t-test. Intergroup comparisons under baseline conditions between normal and glaucomatous eyes were made by using the one-way ANOVA test. Statistical significance was set at P < 0.05.. The peak-systolic velocity of the central retinal artery in glaucomatous eyes and the end-diastolic velocity of the ophthalmic and central retinal arteries in all groups were significantly higher after application of dorzolamide. The minimal velocity of the central retinal vein showed significantly higher values after dorzolamide, whereas the maximal velocity remained unchanged. The peak-systolic velocity of the ophthalmic artery in all groups and the peak-systolic velocity of the central retinal artery in normal eyes also remained unchanged. The resistance index was significantly lower in the ophthalmic and central retinal arteries in all groups after dorzolamide. The intraocular pressure was significantly reduced in all groups after dorzolamide. Under baseline conditions normal control eyes and glaucomatous eyes showed differences in various measurements. Peak-systolic velocity was significantly lower in glaucomatous eyes than in normal control eyes with the exception of the ophthalmic artery in the initial glaucoma group. End-diastolic velocity was lower in glaucomatous eyes than in control eyes in both arteries. Maximal and minimal velocities of the central retinal vein were lower in glaucomatous eyes than in normal control eyes. Resistance index was higher in glaucomatous eyes than in normal control eyes in the ophthalmic artery but not in the central retinal artery.. Most hemodynamic parameters of intraocular and periocular vessels improve after application of topical dorzolamide in both normal control and glaucomatous eyes. Dorzolamide should be regarded as a useful drug for treatment of glaucoma not only because it reduces intraocular pressure but also because it improves the ocular blood supply.

Topics: Aged; Carbonic Anhydrase Inhibitors; Eye; Glaucoma; Hemodynamics; Humans; Intraocular Pressure; Middle Aged; Reference Values; Regional Blood Flow; Sulfonamides; Thiophenes; Ultrasonography

The purpose of this study was to determine how a topical carbonic anhydrase inhibitor, dorzolamide, alters visual function and ocular blood flow in persons with normal-tension glaucoma. Eighteen normal tension glaucoma patients, after washout of other ocular medications, were treated for four weeks with 2% dorzolamide, three times daily. A control group of eleven other normal-tension glaucoma patients received placebo eye drops. Patients were studied before treatment, and after two and four weeks of treatment. Each study included assessment of central visual function (contrast sensitivity), intraocular pressure (IOP), and several aspects of ocular hemodynamics, including measures of retinal arteriovenous passage time, retinal arterial and venous diameters, and flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries. Dorzolamide significantly reduced IOP at two and four weeks (each p<0.01), and at the same time increased contrast sensitivity at both three and six cycles per degree (each p<0.05). Neither of these variables changed significantly in the control group. Dorzolamide also accelerated retinal arteriovenous passage time of fluorescein dye, at constant retinal arterial and venous diameters (p<0.05), but failed to change flow velocities in any retrobulbar vessel. The ability of dorzolamide to improve contrast sensitivity in persons with normal-tension glaucoma may be related to either IOP reduction or altered ocular perfusion.

Topics: Blood Pressure; Carbonic Anhydrase Inhibitors; Double-Blind Method; Glaucoma; Heart Rate; Humans; Ocular Physiological Phenomena; Regional Blood Flow; Sulfonamides; Thiophenes; Visual Acuity

The purpose of this study was to evaluate the drop characteristics of newer glaucoma medicines compared to timolol solution and timolol gel forming solution (Timoptic-XE, Merck). We evaluated latanoprost 0.005% (2.5 ml bottle), brimonidine 0.2%, apraclonidine 0.5%, dorzolamide 2%, timolol solution 0.5% (5 and 10 ml bottles), and timolol gel forming solution 0.5% (5 ml bottle) in 14 patients with primary open-angle glaucoma or ocular hypertension. Each patient placed 10 drops onto an analytical scale (one drop every 10 seconds) for all ten preparations. Patients then attempted to instill 10 drops of a tear replacement solution into their ocular cul-de-sac. Medication bottles were weighed before and after patients dispensed from the bottle and then after the bottle was emptied. Weights were converted to volume using the density of the medicine. A statistical difference existed between groups for mean drop volume with latanoprost having the smallest drop volume (.0273 +/- .004 ml) (P<0.005). All manufacturers filled correctly or overfilled their bottles with product and had <10% of medicine wasted. Patients instilled 77.9% of the tear solution correctly. When dosed according to labeling, latanoprost had the lowest cost of therapy at $0.87 daily compared to the other newly released medications (range $1.05 to $1.40). Latanoprost was more expensive, however, than timolol maleate solution or gel (range $0.45 to $0.54 per day). Latanoprost therapy is less expensive per day than dorzolamide, brimonidine or apraclonidine, but more expensive than timolol maleate. Cost per day could be further reduced by limiting medicine wastage upon instillation, however.

Topics: Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Gels; Glaucoma; Humans; Latanoprost; Prostaglandins F, Synthetic; Quinoxalines; Solutions; Sulfonamides; Thiophenes; Timolol

Topics: Carbonic Anhydrase Inhibitors; Cornea; Glaucoma; Humans; Ocular Hypertension; Sulfonamides; Thiophenes

To determine whether the effectiveness of dorzolamide changes when the drug is used under routine clinical conditions versus the more ideal conditions of a clinical trial.. A total of 118 eyes of 65 patients were assessed. Nine patients (15 eyes) received dorzolamide only, 41 patients (74 eyes) received dorzolamide as an "add-on" medication, and 15 patients (29 eyes) received dorzolamide as a substitute for an oral carbonic anhydrase inhibitor.. At 1 month the intraocular pressure (IOP) had decreased from 23.5 to 19.9 mm Hg in the patients receiving dorzolamide only, from 18.6 to 16.4 mm Hg in the patients receiving dorzolamide as an add-on medication, and from 17.7 to 16.0 mm Hg in the patients receiving dorzolamide as a substitute for an oral carbonic anhydrase inhibitor. Similar decreases in IOP were present at 3 and 6 months. Local drug reactions occurred in 3 patients. Five patients stopped treatment because of severe symptoms of nausea and prostration.. Under routine clinical conditions, dorzolamide was effective as a sole medication and as an add-on medication. It was at least as effective as oral acetazolamide. Local drug reactions sometimes occurred, as did systemic reactions.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Child; Drug Administration Routes; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Miotics; Sulfonamides; Thiophenes; Treatment Outcome

Our purpose was to compare, in a crossover design,the hypotensive effect of oral acetazolamide (Diamox) and topical dorzolamide (Trusopt) in patients with pediatric glaucoma.. All patients less than 18 years old who were switched from acetazolamide to dorzolamide without other intervention were reviewed. Intraocular pressures were obtained with either a Tono-Pen (Mentor Ophthalmics, Santa Barbara, Calif.) or applanation tonometer. Minimum follow-up times on acetazolamide and on dorzolamide were 1 month (mean 12.2 +/- 19.7 months) and 2 months (mean 8.2 +/- 5.1 months), respectively. The average dose of acetazolamide was 9.9 +/- 1.8 mg/kg/day.. Eleven eyes (11 patients) were included. Indications for crossover from oral to topical carbonic anhydrase inhibitor (CAI) therapy were intolerance to acetazolamide (6 eyes) and surgical intervention in the fellow eye (5 eyes). The mean age at the time of crossover was 7.4 +/- 3.0 years. A comparison of intraocular pressure (IOP) before addition of a CAI was made in 8 eyes. The mean IOP off of a CAI was 27.8 +/- 4.9 mm Hg. The mean 10P was reduced to 18.5 +/- 4.3 mm Hg on acetazolamide (mean percent IOP reduction 35.7% +/- 15.6%, p < 0.01) and to 22.2 +/- 5.4 mm Hg on dorzolamide (mean percent IOP reduction 27.4% +/- 17.1%, p < 0.01). All 11 eyes showed an increase in IOP when switched from acetazolamide to dorzolamide, with a mean increase of 3.7 +/- 2.5 mm Hg (20.2% -/+ 13.7%, p < 0.01). Five eyes have remained controlled on dorzolamide and a topical beta-blocker. Five eyes required further intervention for the control of glaucoma. One eye was switched back to acetazolamide for better IOP control.. Although not as effective as oral acetazolamide, topical dorzolamide causes a significant IOP reduction in this group of pediatric glaucoma patients and appears to be well tolerated.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Carbonic Anhydrase Inhibitors; Child; Child, Preschool; Cross-Over Studies; Female; Glaucoma; Humans; Intraocular Pressure; Male; Sulfonamides; Thiophenes

The purpose of the study is to compare the efficacy and safety profile of 2.0% dorzolamide (three times daily) and 0.5% timolol (twice daily) for up to 6 months in patients with glaucoma or ocular hypertension associated with pseudoexfoliation. The additive effects of dorzolamide and timolol in patients requiring add-on therapy also was evaluated.. This was a double-masked, randomized, parallel comparison study at 15 Scandinavian sites. One hundred eighty-four patients with pseudoexfoliation and either glaucoma or ocular hypertension who were 21 to 85 years of age were studied. The treatment groups were 2.0% dorzolamide three times daily and 0.5% timolol maleate twice daily.. At 6 months, the mean percent reduction in intraocular pressure of 2% dorzolamide and 0.5% timolol was 24% and 29%, respectively, at morning peak and 21% and 23%, respectively, at afternoon trough. The additional intraocular pressure-lowering effect of adding 2.0% dorzolamide twice daily to patients receiving timolol was 14% and 15%, at peak and trough, respectively. There were no differences between treatment groups in the incidence of clinical adverse experiences, and dorzolamide was not associated with the systemic adverse effects typically ascribed to the use of oral carbonic anhydrase inhibitors.. Two percent dorzolamide (three times daily) was effective and well tolerated in patients with glaucoma or ocular hypertension associated with pseudoexfoliation over the course of 6 months; 0.5% timolol (twice daily) had a greater level of intraocular pressure-lowering activity than did dorzolamide, although the difference between the two treatments became less pronounced during the study period. Finally, 2.0% dorzolamide (twice daily) produced additional lowering of intraocular pressure when given with 0.5% timolol (twice daily).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Exfoliation Syndrome; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

The aims of the following study were to compare the efficacy of Dorzolamide 1% eye drops with systemic Acetazolamide on the ocular pressure diurnal curve in patients with maximal medical therapy. Three ocular pressure curve were performed in glaucomatous patients, already receiving maximal medical therapy. After a baseline curve, patients were pretreated either with Dorzolamide 1% eye drops or 250 mg Acetazolamide tablets in a double-blind cross-over study. Dorzolamide 1% eye drops and 250 mg Acetazolamide tablets significantly reduced intraocular pressure (IOP) at 2 and 4 h after pretreatment. Both treatments caused a significantly additional decrease of IOP despite maximal medical therapy. Dorzolamide 1% eye drops is as effective as Acetazolamide tablets in reducing the IOP curve. Topical carbonic anhydrase inhibitors may represent an additional and safer treatment for those patients with uncontrolled medical glaucoma.

Topics: Acetazolamide; Adult; Aged; Aged, 80 and over; Aging; Carbonic Anhydrase Inhibitors; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Eye Color; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Sulfonamides; Thiophenes

Since the introduction of carbonic anhydrase inhibitors, a topical preparation has been sought to avoid the complications of systemic medication while retaining the effect of lowering intraocular pressure. Recently, a topical carbonic anhydrase inhibitor, MK-507, has been found superior to others and introduced for multicentre clinical trial.. As part of an international multicentre trial, we compared MK-507 with beta blockers for one year in 20 patients with raised intraocular pressure, both as monotherapy and in combination.. Twelve patients with a mean peak pressure of 31.9 +/- 6.8 mmHg (range, 22 to 49 mmHg) off all medication received MK-507. After two weeks, mean peak pressure was 24.7 +/- 6.1 mmHg (range, 14 to 41 mmHg)--a 22.6% fall in pressure. Six of these patients had a mean peak pressure of 27.8 +/- 6.4 mmHg (range, 21 to 41 mmHg), a fall of 19.2% from day one and were given timolol as add-on therapy. This resulted in a fall to 19.1 +/- 2.8 (range, 15 to 24 mmHg) at year one, a fall of 31.3% after add-on. Four patients on timolol and four on betaxolol gave similar falls in pressure with an additional fall when MK-507 was used as add-on therapy.. MK-507 demonstrated its effectiveness as an ocular hypotensive agent in this trial of patients with an unusually high rise in pressure. It showed a hypotensive effect roughly equivalent to beta blockers. It is likely that either a topical carbonic anhydrase inhibitor or a cardioselective beta blocker will be the medication of first choice in newly diagnosed glaucoma.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Australia; Betaxolol; Carbonic Anhydrase Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

Two Shih-Tzu dogs with atopic dermatitis presented with delayed periocular dermatitis (PD) following the instillation of dorzolamide and dorzolamide/timolol combination eyedrops; the development of dermatologic signs took 94 and 104 d in cases 1 and 2, respectively. Hypersensitivity to anti-glaucoma eyedrops was highly suspected, and treatment was discontinued. Delayed PD was significantly relieved in cases 1 and 2, at days 155 and 64 after discontinuation, respectively. In this study, the clinical characteristics and progression of delayed PD were described to inform clinicians who may encounter this rare side effect.

Topics: Animals; Dermatitis, Atopic; Dermatitis, Perioral; Dog Diseases; Dogs; Glaucoma; Ophthalmic Solutions

Topics: Carbonic Anhydrase Inhibitors; Eye; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions

Topics: Carbonic Anhydrase Inhibitors; Eye; Glaucoma; Glaucoma, Open-Angle; Humans

A 62-year-old woman with mild myopia presented to her local optometrist for a routine examination and was found to have intraocular pressure (IOP) of 30 mm Hg in both eyes and cupped nerves. She had a family history of glaucoma in her father. She was started on latanoprost in both eyes and was referred for a glaucoma evaluation. On initial evaluation, her IOP was 25 mm Hg in the right eye and 26 mm Hg in the left eye. Central corneal thickness measured 592 µm in the right eye and 581 µm in the left eye. Her angles were open to gonioscopy without any peripheral anterior synechia. She had 1+ nuclear sclerosis with a corrected distance visual acuity (CDVA) of 20/25 in the right eye and 20/30- in the left eye and uncorrected near visual acuity of J1+ in each eye. Her nerves were 0.85 mm in the right eye and 0.75 mm in the left eye. Optical coherence tomography (OCT) showed retinal nerve fiber layer thinning and a dense superior arcuate scotoma into fixation in her right eye, and superior and inferior arcuate scotomas in her left eye (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202307000-00019/figure1/v/2023-06-26T195222Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202307000-00019/figure2/v/2023-06-26T195222Z/r/image-tiff, Supplemental Figures 1 and 2, available at http://links.lww.com/JRS/A882 and http://links.lww.com/JRS/A883). She was successively trialed on fixed combination brimonidine-timolol, dorzolamide, and netarsudil, in addition to her latanoprost, but her IOP remained in the mid- to upper 20s in both eyes. The addition of acetazolamide lowered the pressure to 19 mm Hg in both eyes, but she tolerated it poorly. Methazolamide was also attempted with similar side effects. We elected to perform left eye cataract surgery combined with 360-degree viscocanaloplasty and insertion of a Hydrus microstent (Alcon Laboratories, Inc.). Surgery was uncomplicated with IOP of 16 mm Hg on postoperative day 1 with no glaucoma medications. However, by postoperative week 3, IOP returned to 27 mm Hg, and despite restarting latanoprost-netarsudil and finishing her steroid taper, IOP remained at 27 mm Hg by postoperative week 6. Brimonidine-timolol was added back to her left eye regimen and at postoperative week 8, IOP had elevated to 45 mm Hg. Maximizing her therapy with the addition of topical dorzolamide and oral methazolamide brought her IOP back down to 30 mm Hg. At that point, the decision was made to proceed with trabeculectomy of the left eye. The trabeculectomy was un

Topics: Adolescent; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Latanoprost; Methazolamide; Middle Aged; Timolol; Treatment Outcome; United States

In this study, we aimed to assess the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) thinning relationships with dry eye development monitoring and underestimated measurement of intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients treated with timolol, dorzolamide, and brimonidine.. This longitudinal cohort study included 106 patients with POAG. All patients underwent a detailed ophthalmic examination. In addition, CET, CST, and CCT were measured using anterior segment optical coherence tomography (AS-OCT). Subsequently, the cohort was divided into three groups based on the therapy administered. The Tomec group received monotherapy with benzalkonium chloride (BAK)-preserved timolol + dorzolamide fixed combination. The Alphagan group received monotherapy with purite-preserved brimonidine, and the Combigan group received monotherapy with BAK-preserved timolol + brimonidine fixed combination.. CET, CST, and CCT did not show a statistically significant decrease in the Alphagan group (p>0.05). However, the Tomec and Combigan groups showed significantly reduced measurements, except for stromal thickness (p<0.05). Finally, a significant positive correlation was found between changes in tear break-up time (TBUT) and CET during the follow-up period (r = 0.637, p = 0.001).. CET and CCT thinning were higher in the Tomec and Combigan groups than in the Alphagan group. Furthermore, although CCT reduction was significant in the Tomec and Combigan groups, its effect on IOP underestimation was approximately 1%. Furthermore, the positive correlation between CET and TBUT suggests that CET measurement with AS-OCT may also be useful in dry eye monitoring.

Topics: Brimonidine Tartrate; Brimonidine Tartrate, Timolol Maleate Drug Combination; Dry Eye Syndromes; Glaucoma; Glaucoma, Open-Angle; Humans; Longitudinal Studies; Photochemotherapy; Photosensitizing Agents; Timolol; Tomography, Optical Coherence

We report a one-pot procedure for the synthesis of asymmetrical ureido-containing benzenesulfonamides based on in situ generation of the corresponding isocyanatobenezenesulfonamide species, which were trapped with the appropriate amines. A library of new compounds was generated and evaluated in vitro for their inhibition properties against a representative panel of the human (h) metalloenzymes carbonic anhydrases (EC 4.2.1.1), and the best performing compounds on the isozyme II (i.e.,

Topics: Animals; Benzenesulfonamides; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Drug Design; Glaucoma; Intraocular Pressure; Male; Models, Molecular; Protein Binding; Rabbits; Structure-Activity Relationship; Sulfonamides

Impaired ocular blood flow is an important risk factor in the pathogenesis of open-angle glaucoma (OAG). Studies have reported that dorzolamide 2% may be effective in improving ocular blood flow (OBF) in OAG patients. The objective of this study was to determine the efficacy of dorzolamide 2% (DORZOX, Cipla Ltd.) in improving retrobulbar blood flow in an Indian setting.. The study was conducted as an interventional pilot project in 24 healthy subjects and 19 OAG patients. Baseline OBF measurements were done for all glaucoma patients with color Doppler imaging (CDI). Baseline ocular perfusion pressure (OPP) was calculated for all participants. Glaucoma patients were given dorzolamide 2% thrice daily for 12 weeks. The primary efficacy endpoints were mean changes in the CDI parameters of the retrobulbar vessels and OPP posttreatment. The secondary endpoint was mean change in the intraocular pressure (IOP) and adverse events, if any.. In comparison to healthy subjects, glaucoma patients displayed significantly reduced baseline OPP (P = 0.002). Treatment with dorzolamide 2% for 12 weeks led to a significant increase in OPP (P < 0.001) and a significant increase in end diastolic velocity (EDV) in all major ophthalmic arteries like ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA) (P < 0.001, P = 0.04, and P = 0.0075, respectively). A significant reduction in the intraocular pressure (IOP; P = 0.007) was observed posttreatment, with no adverse events reported.. Dorzolamide 2% significantly improved parameters such as the EDV and OPP in major ophthalmic arteries. This pilot study shows promising results on using dorzolamide for treating Indian patients with OAG.

Topics: Carbonic Anhydrase Inhibitors; Glaucoma; Glaucoma, Open-Angle; Humans; Pilot Projects

To examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians.. A survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection.. Responses from 199 veterinary ophthalmology clinicians were evaluated. While a large variety of topical anti-hypertensive drugs and protocols were used, the most commonly used medications were aqueous humor production suppressors such as dorzolamide 2.0% ophthalmic solution, timolol 0.5% ophthalmic solution, and a combination product containing both drugs. Latanoprost 0.005% ophthalmic solution was used infrequently for prophylaxis by comparison. The majority of respondents do not use concurrent anti-inflammatory medications (61.22%), although a sizeable minority used prednisolone acetate, dexamethasone, or ketorolac as prophylactic treatment. Systemically administered ocular anti-hypertensive agents were rarely used. Only 40% of respondents used neuroprotectant agents; the most commonly prescribed were the calcium channel blocker amlodipine and the nutraceutical Ocu-Glo™. Recommended intervals between re-examination by the clinician ranged from one month to one year, with most re-evaluations occurring every 3 to 6 months. The majority of respondents recommended more frequent assessments of IOP at intervals between once monthly and once every 3 months.. Data analysis of medical therapy for the normotensive fellow eye of dogs previously diagnosed with primary glaucoma suggests that there is a great need for well-designed, prospective, controlled, multi-center studies to determine which protocols have the greatest efficacy in delaying an overt attack in the previously normotensive eye in dogs with a genetic predisposition to glaucoma. Prospective studies utilizing a carbonic anhydrase inhibitor such as dorzolamide and a prostaglandin analogue such as latanoprost would be reasonable as these two drugs are widely used in the treatment of overt glaucoma and would allow for an exploration of the impact of different mechanisms of action of lowering IOP on the pathophysiology of primary glaucoma.

Topics: Animals; Dog Diseases; Dogs; Female; Glaucoma; Health Care Surveys; Male; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

In patients with normal-tension glaucoma (NTG), topical dorzolamide might enhance the vessel density (VD), topical carteolol decreased the VD in the inferior-temporal peripapillary retina, whereas topical brimonidine did not change the VD.. Topical antiglaucoma medications may improve ocular perfusion pressure or microcirculation in the optic nerve head. The study evaluated responses of retinal VD to topical carteolol, brimonidine, and dorzolamide in NTG using optical coherence tomography angiography.. This is a retrospective, nonrandomized, comparative study. The study included 131 individuals (77 men, 54 women) diagnosed with NTG, without systemic medication use, who visited the glaucoma clinic of Chang Gung Memorial Hospital, Taiwan, between January 2019 and May 2020. If both eyes were diagnosed with NTG, only the right eye was included. Of these, there were 80 carteolol-treated eyes, 27 brimonidine-treated eyes, and 24 dorzolamide-treated eyes. We studied the response of optical coherence tomography angiography parameters and retinal nerve fiber layer (RNFL) thickness to drugs, 6 months after treatment.. In dorzolamide-treated eyes, increases in the peripapillary superficial retinal VD, especially in the superior-nasal area, were significant; however, no RNFL thickness changes were observed. In contrast, the superficial retinal VD decreased at the inferior-temporal peripapillary area, and RNFL thickness decreased in the inferior-nasal peripapillary area of carteolol-treated eyes. Finally, in brimonidine-treated eyes, changes in either VD parameters or RNFL thickness were not significant.. Topical dorzolamide possibly enhanced the VD of the peripapillary retina in NTG eyes. On the contrary, topical carteolol possibly decreased VD in the inferior-temporal peripapillary retina. Finally, in cases treated with topical brimonidine, peripapillary microcirculation remained unchanged. The study shows preliminary results and future large-scale studies are needed to confirm findings.

Topics: Angiography; Brimonidine Tartrate; Carteolol; Female; Fluorescein Angiography; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Nerve Fibers; Retinal Ganglion Cells; Retinal Vessels; Retrospective Studies; Sulfonamides; Thiophenes; Tomography, Optical Coherence; Visual Fields

The design of three dual-tailed sulfonamide series

Topics: Animals; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Catalytic Domain; Crystallography, X-Ray; Drug Design; Glaucoma; Humans; Intraocular Pressure; Male; Molecular Structure; Protein Binding; Rabbits; Structure-Activity Relationship; Sulfonamides

Topics: Animals; Cornea; Drug Compounding; Drug Stability; Gamma Rays; Gels; Glaucoma; Liposomes; Male; Permeability; Rabbits; Sterilization; Sulfonamides; Thiophenes

In the present study, bioadhesive polymeric nanoparticles for ocular delivery of dorzolamide hydrochloride (DRZ) were formulated using derivatized Leucaena leucocephala galactomannan (LLG). The carboxymethyl (CMLLG) and amine derivative (AMLLG) of LLG were synthesized and used for the preparation of nanoparticles. The preparation method was optimized using 2-factor, 3-level central composite experimental design. The optimized nanoparticles were characterized by FTIR, DSC, SEM, TEM and XRD studies. The results of in vitro release studies and ex vivo transcorneal permeation studies revealed sustained release and higher corneal permeation as compared to conventional formulation of DRZ. The optimized nanoparticles were found to reduce the intra ocular pressure (IOP) for prolonged period of time when compared to conventional eye drops. Overall, the present study suggests a promising role of bioadhesive polymeric nanoparticles for ocular drug delivery in glaucoma treatment.

Topics: Adhesiveness; Animals; Drug Carriers; Drug Liberation; Eye; Fabaceae; Galactose; Glaucoma; Goats; Mannans; Nanoparticles; Permeability; Sulfonamides; Thiophenes

Eye drops containing hydrophilic drugs are commonly used to reduce intraocular pressure (IOP) in glaucoma patients, but compliance to the treatement is commonly reduced by frequent dosing and eventual systemic side effects. Sustained-release drug delivery systems, such as ocular inserts, can reduce dosing, limit systemic exposure, reduce side effects, and, then, improve patient adherence to therapy. Here, we developed and evaluated chitosan/hydroxyethyl cellulose-based ocular inserts for sustained release of dorzolamide, a hydrophilic drug. Dorzolamide inserts (DI) were produced by solvent/casting method and characterized by various physicochemical techniques. Pharmacokinetics studies were performed using scintigraphic images and ex vivo biodistribution. The effectiveness of inserts was tested in glaucomatous rats. Characterization studies showed that the drug strongly interacted with the polymeric matrix, but in vitro results showed that DI took only 3 h to release 75% of dorzolamide entraped. However, scintigraphic images and ex vivo biodistribution studies revealed that more than 50% of

Topics: Animals; Cellulose; Chitosan; Delayed-Action Preparations; Drug Delivery Systems; Eye; Glaucoma; Intraocular Pressure; Male; Ophthalmic Solutions; Polymers; Rats; Rats, Wistar; Sulfonamides; Thiophenes; Tissue Distribution

Timolol is a non-cardioselective beta blocker and has different combined ophthalmic dosage forms for treatment of glaucoma. This research introduce an HPLC method for the separation of three drugs used in combination with timolol simultaneously by applying isocratic mobile phase system in a single run and the same detection wavelength with short time. The drugs included in the separation procedures are; dorzolamide, brinzolamide, and brimonidine. The HPLC method was carried out through a single mobile phase system, which contains acetonitrile: 0.05M phosphate buffer at the ratio of 30:70, respectively at pH 3.5 and wavelength of 220nm. The method, regarding its simplicity allows determination of the studied drugs simultaneously using single run in about 8minutes. The method was rectilinear in the ranges of concentration: 1.25-25μg/mL for timolol, 4-80μg/mL for dorzolamide, 5-50μg/mL for brinzolamide and 2-20μg/mL for brimonidine. Different factors affecting the separation are thoroughly studied. The developed method was validated based on the official guidelines and the results were compared statistically with previously published methods and showed non-significant difference.

Topics: Adrenergic beta-Antagonists; Brimonidine Tartrate; Chromatography, High Pressure Liquid; Drug Combinations; Drug Compounding; Glaucoma; Limit of Detection; Ophthalmic Solutions; Reference Standards; Reproducibility of Results; Sulfonamides; Thiazines; Thiophenes; Timolol

Topics: Acrylic Resins; Administration, Ophthalmic; Animals; Antihypertensive Agents; Cornea; Drug Carriers; Drug Evaluation, Preclinical; Drug Liberation; Gels; Glaucoma; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intraocular Pressure; Male; Ophthalmic Solutions; Rabbits; Sulfonamides; Swine; Thiophenes

The combination of a β-adrenergic receptors (AR) blocker and a carbonic anhydrase (CA, EC 4.2.1.1) inhibitor in eye drops formulations is one of the most clinically used treatment for glaucoma. A novel approach consisting of single-molecule, multitargeted compounds for the treatment of glaucoma is proposed here by designing compounds which concomitantly interact with the β-adrenergic and CA targets. Most derivatives of the two series of benzenesulfonamides incorporating 2-hydroxypropylamine moieties reported here exhibited striking efficacy against the target hCA II and XII, whereas a subset of compounds also showed significant modulation of β

Topics: Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Disease Models, Animal; Drug Design; Drug Evaluation, Preclinical; Glaucoma; Humans; Intraocular Pressure; Male; Molecular Targeted Therapy; Rabbits; Receptors, Adrenergic, beta; Structure-Activity Relationship

This work presents a simple, sensitive, and generic HPLC-diode-array detection method for the simultaneous determination of six drugs prescribed for the treatment of open-angle glaucoma and ocular hypertension. The investigated drugs include brimonidine tartarate (BMN), acetazolamide (AZA), brinzomaide (BZA), dorzolamide HCl (DZA), levobunolol HCl (LVB), and timolol maleate (TIM). Efficient chromatographic separation was achieved using a Thermo Hypersil BDS C18 column (4.6 × 250 mm, 5 µm) with a mobile phase consisting of phosphate buffer pH 5 and acetonitrile in a ratio of 78 + 22. The flow rate was 1 mL/min, and quantification was based on measuring peak areas at 298 nm for TIM and 254 nm for the other drugs. Peaks were perfectly resolved, with retention times at 3.06, 3.87, 4.53, 5.78, 7.31, and 10.78 min for BMN, AZA, DZA, TIM, LVB, and BZA respectively. The developed method was validated according to International Conference on Harmonization guidelines with respect to system suitability, linearity, ranges, accuracy, precision, robustness, and LODs and LOQs. The proposed method showed good linearity in the ranges of 2-80, 2.5-100, 2.5-100, 5-200, 3.75-150, and 1.75-70 µg/mL for BMN, AZA, DZA, TIM, LVB, and BZA, respectively. LODs were 0.20-1.01 μg/mL for the analyzed compounds. Applicability of the proposed method to real-life situations was assessed through the analysis of five different pharmaceutical formulations, and satisfactory results were obtained.

Topics: Acetazolamide; Antihypertensive Agents; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Chromatography, High Pressure Liquid; Glaucoma; Humans; Levobunolol; Sulfonamides; Thiophenes; Timolol

Topical carbonic anhydrase inhibitors (CAI), used for treatment of glaucoma, are generally regarded as safe and unconnected with systemic side effects. We report an unusual case of fatigue, metabolic acidosis, and normocytic anaemia associated with ocular administration of the CAI, dorzolamide, in a patient with impaired renal function. In chronic kidney disease, where CAI elimination may be decreased, and patients prone to develop metabolic acidosis, systemic absorption of ocular administered CAI could lead to rare, but potentially serious adverse reaction, that are a consequence of inhibition of extraocular carbonic anhydrase isoenzymes.

Topics: Acidosis; Administration, Ophthalmic; Anemia; Carbonic Anhydrase Inhibitors; Fatigue; Glaucoma; Humans; Male; Middle Aged; Renal Insufficiency; Sulfonamides; Thiophenes

Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher Cmax, [Formula: see text] and [Formula: see text] at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt®. The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action.

Topics: Animals; Aqueous Humor; Biological Availability; Delayed-Action Preparations; Drug Compounding; Glaucoma; Half-Life; Intraocular Pressure; Male; Nanostructures; Ophthalmic Solutions; Particle Size; Permeability; Phosphatidylcholines; Rabbits; Sulfonamides; Thiophenes

Glaucoma is the second cause of blindness worldwide. Frequent administration of traditional topical dosage forms may lead to patient incompliance and failure of treatment. Our study aims to formulate proniosomal gel formulations that sustain the release of the water-soluble anti-glaucoma drug Dorzolamide-HCl (Dorz). Proniosomal gel formulations were prepared using coacervation phase separation method according to a 5

Topics: Animals; Biological Availability; Chemistry, Pharmaceutical; Cholesterol; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Eye; Gels; Glaucoma; Intraocular Pressure; Liposomes; Male; Ophthalmic Solutions; Particle Size; Rabbits; Sulfonamides; Surface-Active Agents; Thiophenes

Topics: Acidosis; Administration, Topical; Anesthesia, General; Animals; Carbonic Anhydrase Inhibitors; Dog Diseases; Dogs; Female; Glaucoma; Sulfonamides; Thiophenes

Topics: Acetazolamide; Adrenergic beta-Antagonists; Adult; Capillaries; Carbonic Anhydrase Inhibitors; Cryosurgery; Diagnosis, Differential; Female; Glaucoma; Humans; Port-Wine Stain; Sulfonamides; Thiophenes; Timolol; Vascular Malformations

To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma.. Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice under isoflurane anesthesia using magnetic resonance imaging. Ocular blood flow was measured at baseline, and 1 and 2 hours after topical dorzolamide. Intraocular pressure was measured using a rebound tonometer in a subset of animals at the same time points.. Baseline IOP in the 4-month-old DBA/2J mice and C57BL/6 mice was not significantly different (P > 0.05), and IOP in both groups was less than in the 9-month-old DBA/2J mice (P < 0.05 for both). Compared to baseline, dorzolamide reduced IOP at 1 and 2 hours after dorzolamide in the 4- (P < 0.05) and 9-month-old (P < 0.01) DBA/2J mice, but not in the C57BL/6J mice (P > 0.05). Baseline retinal blood flow was lower in the 4-month and 9-month-old DBA/2J mice compared with the 4-month-old C57BL/6J mice (P < 0.05). Baseline choroidal blood flow in the 9-month-old DBA/2J mice was less than in the C57BL/6J mice (P < 0.05). Compared with baseline, both retinal and choroidal blood flow increased at 1-hour post-dorzolamide and remained elevated 2 hours later in the 9-month-old DBA/2J mice (P < 0.05).. Dorzolamide lowers IOP and raises retinal and choroidal blood flow in older DBA/2J mice, consistent with the study hypothesis.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Choroid; Disease Models, Animal; Glaucoma; Intraocular Pressure; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Regional Blood Flow; Retina; Sulfonamides; Thiophenes; Treatment Outcome

Topical medications that inhibit the enzyme carbonic anhydrase (CAI) are widely used to lower intraocular pressure in glaucoma; however, their clinical efficacy is limited by the requirement for multiple-daily dosing, as well as side effects such as blurred vision and discomfort on drop instillation. We developed a biodegradable polymer microparticle formulation of the CAI dorzolamide that produces sustained lowering of intraocular pressure after subconjunctival injection. Dorzolamide was ion paired with sodium dodecyl sulfate (SDS) and sodium oleate (SO) with 0.8% and 1.5% drug loading in poly(lactic-co-glycolic acid) (PLGA), respectively. Encapsulating dorzolamide into poly(ethylene glycol)-co-poly(sebacic acid) (PEG3-PSA) microparticles in the presence of triethylamine (TEA) resulted in 14.9% drug loading and drug release that occurred over 12 days in vitro. Subconjunctival injection of dorzolamide-PEG3-PSA microparticles (DPP) in Dutch belted rabbits reduced IOP as much as 4.0 ± 1.5 mmHg compared to untreated fellow eyes for 35 days. IOP reduction after injection of DPP microparticles was significant when compared to baseline untreated IOPs (P < 0.001); however, injection of blank microparticles (PEG3-PSA) did not affect IOP (P = 0.9). Microparticle injection was associated with transient clinical vascularity and inflammatory cell infiltration in conjunctiva on histological examination. Fluorescently labeled PEG3-PSA microparticles were detected for at least 42 days after injection, indicating that in vivo particle degradation is several-fold longer than in vitro degradation. Subconjunctival DPP microparticle delivery is a promising new platform for sustained intraocular pressure lowering in glaucoma.

Topics: Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Ethylamines; Female; Glaucoma; Intraocular Pressure; Lactic Acid; Male; Oleic Acid; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rabbits; Sodium Dodecyl Sulfate; Sulfonamides; Thiophenes

The antiglaucoma drugs dorzolamide (1) and brinzolamide (2) lower intraocular pressure (IOP) by inhibiting the carbonic anhydrase (CA) enzyme to reduce aqueous humor production. The introduction of a nitric oxide (NO) donor into the alkyl side chain of dorzolamide (1) and brinzolamide (2) has led to the discovery of NO-dorzolamide 3a and NO-brinzolamide 4a, which could lower IOP through two mechanisms: CA inhibition to decrease aqueous humor secretion (reduce inflow) and NO release to increase aqueous humor drainage (increase outflow). Compounds 3a and 4a have shown improved efficacy of lowering IOP in both rabbits and monkeys compared to brinzolamide (2).

Topics: Animals; Carbonic Anhydrase Inhibitors; Drug Design; Glaucoma; Intraocular Pressure; Male; Nitric Oxide Donors; Rabbits; Sulfonamides; Thiazines; Thiophenes

A new series of dithiocarbamates (DTCs) was prepared from primary/secondary amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, and carbon disulfide. The compounds were investigated for the inhibition of four mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is, the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient hCA I inhibitors (off-target isoform for both applications), efficiently inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering properties in an animal model of glaucoma, with a two times better efficiency compared to the clinically used sulfonamide dorzolamide.

Topics: Animals; Antihypertensive Agents; Carbon Disulfide; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Disease Models, Animal; Glaucoma; Humans; Intraocular Pressure; Male; Molecular Docking Simulation; Morpholines; Piperazines; Piperidines; Quinuclidines; Rabbits; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Thiocarbamates; Thiophenes

Two new sulfonamides incorporating arylsulfonylureido moieties were complexed with gamma cyclodextrin (γ-CD), hydroxypropyl-gamma cyclodextrin (HPγ-CD), hydroxypropyl-beta cyclodextrin (HPβ-CD) and hydroxyethyl-beta cyclodextrin (HEβ-CD) in order to obtain drug formulations with effective topical intraocular pressure (IOP) lowering effects, in an animal model of glaucoma. The HPγ-CD was the best solubilizing agent for the two sulfonamides and its complexes were characterized in detail and administered to rabbits with eye hypertension of 45-50 mmHg. The peak IOP lowering was observed after 1h post-administration and was of 36-37 mmHg. A low IOP pressure (of around-35 mmHg) was then maintained for the next 24h post-administration, which has not been observed before with any IOP lowering drug.

Topics: Administration, Topical; Animals; Benzenesulfonamides; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Chemistry, Pharmaceutical; Cyclodextrins; Disease Models, Animal; Glaucoma; Humans; Intraocular Pressure; Male; Rabbits; Solubility; Sulfonamides

This study was carried out to evaluate the drug prescribing, utilization pattern and adverse drug reactions recording associated with drugs prescribed to glaucoma patients.. A total of 50 glaucoma patients were included in the study, based on inclusion and exclusion criteria. All the observations were recorded in drug utilization and ADR recording documentation form.. Out of 50 patients suffering from glaucoma, 38 patients (76%) were diagnosed open angle glaucoma, 4 patients (8%) closed angle glaucoma and 8 patients (16%) post-operative respectively. There were 19 patients (38%) males and 31 patients (62%) were females. The age range between 41-50 years had the maximum number of patients 15 (30%). A total of 17 patients (34%) had family history of glaucoma. Timolol was prescribed to 34 patients (68%), followed by dorzolamide 18 patients (36%) and acetazolamide 14 patients (28%). A total of 32 patients (64%) were prescribed single drug therapy whereas 18 patients (36%) were on multiple drug therapy. A total of 25 patients (50%) reported ADR. In the present study, latanoprost was associated with maximum number of ADRs 9 patients (18%) followed by acetazolamide 7 patients (14%), dorzolamide 4 patients (8%), then timolol 3 patients (6%) and pilocarpine 2 patients (4%). According to Naranjo scale, in 6 patients (24%) the ADR were unlikely, 12 patients (48%) were given possible score, 3 patients (12%) were given probable score, and 4 patients (16%) were given definite scores.. In the present study, the maximum patients were in the age group of 41-50 years. The most commonly prescribed drugs were timolol followed by dorzolamide, acetazolamide. Latanoprost was associated with maximum number of ADRs.

Topics: Acetazolamide; Adult; Adverse Drug Reaction Reporting Systems; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Female; Glaucoma; Hospitals, University; Humans; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

We report the case of a 6-year-old boy with Sturge-Weber syndrome and unilateral glaucoma in his left eye. He was born with a port wine mark involving his upper left eyelid. On ultra-widefield fluorescein angiography, he was found to have several vein-to-vein anastomoses in his left retina. To our knowledge, this is the first documentation of retinal vein-to-vein anastomoses in Sturge-Weber syndrome.

Topics: Carbonic Anhydrase Inhibitors; Child; Fluorescein Angiography; Glaucoma; Humans; Intraocular Pressure; Male; Retinal Vein; Sturge-Weber Syndrome; Sulfonamides; Thiophenes; Vascular Fistula; Visual Acuity

6 dogs (10 eyes) with keratitis following long-term topical treatment with a carbonic anhydrase inhibitor (CAI) were evaluated. In 4 dogs (6 eyes), CAI treatment was discontinued. Three dogs (4 eyes) underwent enucleation because of end-stage corneal disease. One dog was treated differently in each eye and thus was represented in both aforementioned groups.. Following initiation of treatment with a CAI (ie, brinzolamide or dorzolamide), the median time to development of severe ocular signs was 266 days (range, 133 to 679 days). Clinically severe ocular signs included ulcerative and nonulcerative perilimbal keratitis or severe diffuse keratitis with marked vascularization. The keratitis was refractory to treatment with anti-inflammatory medications. Histologic and immunohistochemical examination of enucleated globes was performed in 3 affected dogs and in 1 dog with keratitis that recovered. Corneal lesions included 2 distinct inflammatory infiltrates with plasma cells predominating in the anterior stroma and both T cells and neutrophils in the epithelium. Stromal plasma cells and overlying epithelium exhibited strong positive immunoreactivity for IgG.. Topical CAI treatment was discontinued in 4 dogs after a median of 209 days (range, 44 to 433 days), and in these dogs, clinical improvement was evident within 2 to 4 days of CAI treatment cessation. Signs of keratitis resolved in 12 to 25 days in these 4 dogs, and median follow-up time after CAI discontinuation was 25.5 months (range, 6 to 42 months), during which time signs of corneal disease did not recur.. On the basis of this small series, presumed topical CAI-associated keratitis in dogs appeared to be an uncommon immune-mediated disease that was not responsive to corticosteroid treatment. Affected patients improved rapidly, but only after discontinuation of CAI treatment. In dogs with glaucoma, clinicians should consider the development of punctate keratopathy and severe diffuse keratitis as potential adverse effects related to topical administration of CAIs, even after previously uneventful long-term use.

Topics: Animals; Carbonic Anhydrase Inhibitors; Dog Diseases; Dogs; Female; Glaucoma; Keratitis; Male; Sulfonamides; Thiazines; Thiophenes

A series of furazan and furoxan sulfonamides were prepared and studied for their ability to inhibit human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX, and hCA XII. The simple methyl substituted products 3-5 were potent inhibitors. Differing structural modifications of these leads had differing effects on potency and selectivity. In particular, products in which the sulfonamide group is separated from the hetero ring by a phenylene bridge retained high potency only on the hCA XII isoform. The sulfonamides 3-5 exerted intraocular pressure (IOP) lowering effects in vivo in hypertensive rabbits more efficiently than dorzolamide. Some other products (39-42), although less effective in vitro hCA II/XII inhibitors, also effectively lowered IOP in two different animal models of glaucoma.

Topics: Acrylic Resins; Animals; Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Disease Models, Animal; Glaucoma; Humans; Male; Oxadiazoles; Protein Isoforms; Rabbits; Sulfonamides

In the present work polymeric nano-fiber patches was developed for the effective treatment of glaucoma using timolol maleate and dorzolamide hydrochloride as model drugs. The nano-fibers were prepared by electrospinning technique and were characterized on the basis of fiber diameter, morphology, entrapment efficiency, mucoadhesive strength, and drug release behavior, etc. Final formulations were inserted in the cul-de-sac of glaucoma induced rabbits and the efficacy of the formulation was evaluated. The results clearly indicated the potential of the developed formulation for occur drug delivery. There was a significant fall in the intraocular pressure compared to commercial eye drops.

Topics: Animals; Antihypertensive Agents; Drug Delivery Systems; Glaucoma; Nanofibers; Rabbits; Sulfonamides; Thiophenes; Timolol

The most important risk associated with glaucoma is the onset and progression of intraocular pressure. The objective of this study was to formulate in situ gel of chitosan nanoparticles to enhance the bioavailability and efficacy of dorzolamide in the glaucoma treatment. Optimized nanoparticles were spherical in shape (particle size: 164 nm) with a loading efficiency of 98.1%. The ex vivo release of the optimized in situ gel nanoparticle formulation showed a sustained drug release as compared to marketed formulation. The gamma scintigraphic study of prepared in situ nanoparticle gel showed good corneal retention compared to marketed formulation. HET-CAM assay of the prepared formulation scored 0.33 in 5 min which indicates the non-irritant property of the formulation. Thus in situ gel of dorzolamide hydrochloride loaded nanoparticles offers a more intensive treatment of glaucoma and a better patient compliance as it requires fewer applications per day compared to conventional eye drops.

Topics: Animals; Calorimetry, Differential Scanning; Carbonic Anhydrase Inhibitors; Chitosan; Glaucoma; Goats; Humans; In Vitro Techniques; Nanoparticles; Radionuclide Imaging; Sulfonamides; Thiophenes; X-Ray Diffraction

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.

Topics: Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Intraocular Pressure; Lactic Acid; Microscopy, Electron, Scanning; Nanoparticles; Ocular Hypertension; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Radionuclide Imaging; Sulfonamides; Thiophenes; Vitamin A; Vitamin E

Lowering of intra-ocular pressure is the primary pharmacologic approach for the treatment of glaucoma and a number of distinct mechanisms of action have been clinically validated. Targeting of multiple mechanisms in combination therapies has proven effective both clinically and commercially although potential improvements with regards to efficacy, tolerability and dosing frequency remain. Application of Theravance's multivalent approach to drug discovery towards linked dual-pharmacology prostaglandin F receptor (FP) agonist/carbonic anhydrase (CA)-II inhibitor compounds is described. Compound 29 exhibits weak potency (pEC(50)=5.7, IA>1.0) as an FP agonist with high binding affinity (pK(i)=8.1) to the CA-II enzyme, and has comparable corneal permeability to the CA-II inhibitor dorzolamide.

Topics: Carbonic Anhydrase Inhibitors; Drug Discovery; Glaucoma; Humans; Models, Molecular; Prostaglandins F, Synthetic; Receptors, Prostaglandin

Dithiocarbamates (DTCs) were recently discovered as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. A series of xanthates and a trithiocarbonate, structurally related to the DTCs, were prepared by reaction of alcohols/thiols with carbon disulfide in the presence of bases. These compounds were tested for the inhibition of four human (h) isoforms, hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX). Several low nanomolar xanthate/trithiocarbonate inhibitors targeting these CAs were detected. A docking study of some xanthates within the CA II active site showed that these compounds bind in a similar manner with the dithiocarbamates, coordinating monodentately to the Zn(II) ion from the enzyme active site. Several xanthates showed potent intraocular pressure lowering activity in two animal models of glaucoma via the topical administration. Xanthates and thioxanthates represent two novel, promising classes of CA inhibitors.

Topics: Animals; Antigens, Neoplasm; Carbonic Anhydrase I; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Carbonic Anhydrase IX; Carbonic Anhydrases; Catalytic Domain; Glaucoma; Humans; Intraocular Pressure; Isoenzymes; Male; Models, Molecular; Rabbits; Structure-Activity Relationship; Thiocarbamates

To investigate whether a self-reported history of allergy to sulfa-based drugs is a predictor for subsequent adverse reactions to topical carbonic anhydrase inhibitors (CAIs).. A retrospective case-controlled cohort study via chart review was performed on 1,287 patients with a diagnosis of glaucoma. The outcome measure was the development of an adverse reaction (either ocular, systemic, or both) within at least 30 days after receipt of 1 of 4 classes of topical glaucoma medications: CAIs (dorzolamide and brinzolamide), prostaglandin analogues, beta-adrenergic blockers, and alpha2-adrenergic agonists.. Patients with a self-reported history of sulfa allergy had significantly more ocular adverse reactions after the initiation of any of the topical antiglaucoma medications when compared to those patients with no reported allergies. Patients with a self-reported sulfa allergy and patients who self-reported other, nonsulfa-related allergies had similar rates of adverse reactions to most of the topical medications. The patients reporting a sulfa allergy who used topical CAIs did not have more adverse reactions compared with patients who reported having other, nonsulfa-related allergies who used topical CAIs. Self-reported sulfa-allergic patients had similar rates of adverse reactions to topical CAIs compared with topical prostaglandin analogues.. It may be safe to use a topical CAI in patients who report a history of a sulfa allergy. Patients with medication allergies of any kind may be more likely to develop allergic reactions to other, unrelated drug classes.

Topics: Administration, Ophthalmic; Adrenergic alpha-2 Receptor Agonists; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Case-Control Studies; Cohort Studies; Drug Hypersensitivity; Female; Glaucoma; Humans; Male; Middle Aged; Prostaglandins; Retrospective Studies; Sulfonamides; Thiazines; Thiophenes

To evaluate the effects of the activation of endogenous angiotensin-converting enzyme 2 (ACE2) using the compound diminazene aceturate (DIZE) in an experimental model of glaucoma in Wistar rats.. DIZE (1 mg/kg) was administered daily, either systemically or topically, and the IOP was measured weekly. To examine the role of the Mas receptor in the effects of DIZE, the Ang-(1-7) antagonist A-779 was co-administered. Drainage of the aqueous humor was evaluated by using scintigraphy. The analysis of ACE2 expression by immunohistochemistry and the counting of retinal ganglion cells (RGCs) were performed in histologic sections. Additionally, the nerve fiber structure was evaluated by transmission electron microscopy.. The systemic administration and topical administration (in the form of eye drops) of DIZE increased the ACE2 expression in the eyes and significantly decreased the IOP of glaucomatous rats without changing the blood pressure. Importantly, this IOP-lowering action of DIZE was similar to the effects of dorzolamide. The antiglaucomatous effects of DIZE were blocked by A-779. Histologic analysis revealed that the reduction in the number of RGCs and the increase in the expression of caspase-3 in the RGC layer in glaucomatous animals were prevented by DIZE. This compound also prevented alterations in the cytoplasm of axons in glaucomatous rats. In addition to these neuroprotective effects, DIZE facilitated the drainage of the aqueous humor.. Our results evidence the pathophysiologic relevance of the ocular ACE2/Ang-(1-7)/Mas axis of the renin-angiotensin system and, importantly, indicate that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma.

Topics: Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Antihypertensive Agents; Aqueous Humor; Blood Pressure; Caspase 3; Cell Count; Diminazene; Disease Models, Animal; Enzyme Activation; Fluorescent Antibody Technique, Indirect; Glaucoma; Immunoenzyme Techniques; Intraocular Pressure; Male; Nerve Fibers; Ophthalmic Solutions; Optic Nerve; Peptide Fragments; Peptidyl-Dipeptidase A; Radionuclide Imaging; Rats; Rats, Wistar; Renin-Angiotensin System; Retina; Retinal Ganglion Cells; Sulfonamides; Thiophenes; Tonometry, Ocular

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic beta-Antagonists; Antihypertensive Agents; Betaxolol; Brimonidine Tartrate; Glaucoma; Humans; Latanoprost; Neuroprotective Agents; Ophthalmic Solutions; Ophthalmology; Prostaglandins; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes

The clinically used sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor dorzolamide (DRZ), a new sulfonamide CA inhibitor also incorporating NO-donating moieties, NCX250, and isosorbide mononitrate (ISMN) (an NO-donating compound with no CA inhibitory properties) were investigated for their intraocular pressure (IOP) lowering effects in rabbits with carbomer-induced glaucoma. NCX250 was more effective than DRZ or ISMN on lowering IOP, increasing ocular hemodynamics, decreasing the inflammatory processes and ocular apoptosis in this animal model of glaucoma. NO participate to the regulation of IOP in glaucoma, having also antiapoptotic and anti-inflammatory effects. The ophthalmic artery, both systolic and diastolic velocities, were significantly reduced in NCX250-treated eyes in comparison to DRZ treated ones, suggesting thus a beneficial effect of NCX250 on the blood supply to the optic nerve. Combining CA inhibition with NO-donating moieties in the same compound offers an excellent approach for the management of glaucoma.

Topics: Acrylic Resins; Animals; Carbonic Anhydrases; Drug Evaluation, Preclinical; Enzyme Inhibitors; Glaucoma; Isosorbide Dinitrate; Male; Molecular Structure; Nitrates; Nitric Oxide; Rabbits; Sulfonamides; Thiophenes; Time Factors

Examination of the response of the retinal proteome to elevated intraocular pressure (IOP) and to the pharmacological normalization of IOP is crucial, in order to develop drugs with neuroptorective potential. We used a hereditary rat model of ocular hypertension to lower IOP with travaprost and dorzolamide applied topically on the eye surface, and examine changes of the retinal proteome. Our data demonstrate that elevated IOP causes alterations in the retinal protein profile, in particular in high-mobility-group-protein B1 (HMGB1), calmodulin, heat-shock-protein (HSP) 70 and carbonic anhydrase II expression. The changes of the retinal proteome by dorzolamide or travoprost are different and independent of the IOP lowering effect. This fact suggests that the eye drops exert a direct IOP-independent effect on retinal metabolism. Further investigations are required to elucidate the potential neuroprotective mechanisms signaled through changes of HMGB1, calmodulin, HSP70 and carbonic anhydrase II expression in glaucoma. The data may facilitate development of eye drops that exert neuroprotection through direct pharmacological effect.

Topics: Animals; Calmodulin; Carbonic Anhydrase II; Cloprostenol; Disease Models, Animal; Glaucoma; HMGB1 Protein; HSP70 Heat-Shock Proteins; Intraocular Pressure; Ophthalmic Solutions; Peptide Mapping; Proteome; Proteomics; Rats; Retina; Sulfonamides; Thiophenes; Travoprost

Several aromatic/heterocyclic sulfonamide scaffolds have been used to synthesize compounds incorporating NO-donating moieties of the nitrate ester type, which have been investigated for the inhibition of five physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms: hCA I (offtarget), II, IV and XII (antiglaucoma targets) and IX (antitumor target). Some of the new compounds showed effective in vitro inhibition of the target isoforms involved in glaucoma, and the X-ray crystal structure of one of them revealed factors associated with the marked inhibitory activity. In an animal model of ocular hypertension, one of the new compounds was twice more effective than dorzolamide in reducing elevated intraocular pressure characteristic of this disease, anticipating their potential for the treatment of glaucoma.

Topics: Animals; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Disease Models, Animal; Glaucoma; Humans; Models, Molecular; Molecular Structure; Nitric Oxide; Ocular Hypertension; Protein Isoforms; Rabbits; Sulfonamides; Thiophenes

To assess the impact of 2 strategies for initiating therapy in ocular hypertension (OH) on drug use, intraocular pressure (IOP), and blindness caused by glaucoma.. Using a simulation model, initiating therapy with timolol (strategy 1) and with latanoprost (strategy 2) was simulated for a hypothetic cohort of ocular hypertension patients with an initial IOP distribution (data of 1000 patients). Adjustment of therapy within 15 months and a subsequent lifelong follow-up, with an IOP dependent conversion to glaucoma, were modeled. The IOP lowering effect of medication (based on a meta-analysis) was applied by Monte Carlo simulation. Therapy could be maintained or changed, depending on the achieved IOP and side effects. Four drugs (latanoprost, timolol, brimonidine, dorzolamide) were used as monotherapy or in combination. Glaucoma conversion rate was based on literature.. Treatment goal was achieved in both strategies in 90% by monotherapy. This was 60% for patients with initial IOP's of 30 mm Hg. The originally prescribed medication was maintained in 66% (1) and in 77% (2). IOP decreased with approximately 34%, from 25.4 mm Hg (mean) to 16.7 mm Hg (1) and to 16.5 mm Hg (2) Blindness per person within 18.7 years of life expectancy was 0.0923 years (1) and 0.0870 years (2), which corresponds to approximately 1 month. The difference between strategies was 2 days spent in blindness per patient.. The difference in clinical effects of the strategies is small. This is largely owing to the key concept of a target pressure, which underlies both strategies.

Topics: Adult; Antihypertensive Agents; Blindness; Brimonidine Tartrate; Decision Trees; Disease Progression; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Markov Chains; Middle Aged; Models, Biological; Monte Carlo Method; Ocular Hypertension; Prostaglandins F, Synthetic; Quinoxalines; Risk Assessment; Sulfonamides; Thiophenes; Timolol

Implantable dorzolamide-loaded discs were prepared by blending poly(ε-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

Topics: Animals; Antihypertensive Agents; Biocompatible Materials; Calorimetry, Differential Scanning; Cornea; Delayed-Action Preparations; Diffusion; Drug Delivery Systems; Glaucoma; Polyesters; Polymers; Porosity; Rabbits; Regression Analysis; Sulfonamides; Tetrazolium Salts; Thiazoles; Thiophenes; X-Ray Diffraction

Implantable disks for glaucoma treatment were prepared by blending poly(ɛ-caprolactone), PCL, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) and dorzolamide. Their in vivo performance was assessed by their capacity to decrease intraocular pressure (IOP) in normotensive and hypertensive eyes. Drug mapping showed that release was complete from blend disks and the low molecular weight (MW) PCL after 1 month in vivo. The high MW PCL showed non-cumulative release rates above the therapeutic level during 3 months in vitro. In vivo, the fibrous capsule formation around the implant controls the drug release, working as a barrier membrane. Histologic analysis showed normal foreign body reaction response to the implants. In normotensive eyes, a 20% decrease in IOP obtained with the disks during 1 month was similar to Trusopt eyedrops treatment. In hypertensive eyes, the most sustained decrease was shown by the high MW PCL (40% after 1 month, 30% after 2 months). It was shown that the implants can lower IOP in sustained manner in a rabbit glaucoma model.

Topics: Animals; Antihypertensive Agents; Calorimetry, Differential Scanning; Drug Carriers; Drug Implants; Eye; Glaucoma; Intraocular Pressure; Kinetics; Microscopy, Electron, Scanning; Polyesters; Polyethylene Glycols; Propylene Glycols; Rabbits; Solubility; Sulfonamides; Surface Properties; Thiophenes

To determine the extent of fluctuation in circadian intraocular pressure (IOP) and the efficacy of topical dorzolamide 2% q 8 h in lowering IOP and blunting circadian fluctuation in IOP in glaucomatous cats.. Seven adult cats with primary congenital glaucoma (PCG).. Measurements of IOP and pupil diameter were obtained for both eyes (OU) of each cat q 4 h for 12 days. Cats were housed in a laboratory animal facility with a 12-h light:dark cycle. Baseline values were established for 2 days. For the next 5 days, placebo (1.4% polyvinyl alcohol) was administered OU q 8 h. Dorzolamide 2% was then administered OU q 8 h for a further 5 days. A multivariate mixed linear model was fitted to the data, with parameters estimated from a Bayesian perspective. The 4 am time point was selected as the reference for the purposes of comparisons.. Estimated mean IOP for the reference time point pre-treatment was symmetric (about 33 mmHg OU). In all cats, IOP was significantly lower during the diurnal phase, relative to the 4 am measurements, with highest IOP observed 2-6 h after the onset of the dark phase. Circadian fluctuations in IOP were dampened during the treatment period. There was a significant decrease in IOP in all cats during the dorzolamide treatment period (estimated mean for the treatment period reference = 17.9 mmHg OU).. Topical dorzolamide 2% q 8 h is effective in reducing IOP and IOP fluctuation in cats with PCG.

Topics: Administration, Ophthalmic; Animals; Carbonic Anhydrase Inhibitors; Cat Diseases; Cats; Circadian Rhythm; Female; Glaucoma; Intraocular Pressure; Male; Sulfonamides; Thiophenes

In clinical practices, solution of dorzolamide hydrochloride (DH) and timolol maléate (TM) is recommended for the treatment of glaucoma. However, low drug-contact time and poor ocular bioavailability of drugs due to drainage of solution, tear turnover and its dilution or lacrimation limits its uses. In addition, systemic absorption of TM may induce undesirable cardiovascular side effects. Chitosan (CS) is a polycationic biodegradable polymer which provides sustained and local delivery of drugs to the ocular sites. Hyaluronic acid (HA) also provides synergistic effect for mucoadhesion in association with chitosan. In the present study, hyaluronic acid modified chitosan nanoparticles (CS-HA-NPs) loaded with TM and DH were developed and characterized. The CS-HA-NPs were evaluated for size, shape, zeta potential, entrapment efficiency, and mucoadhesive strength. The in vitro release study was also performed in PBS pH 7.4. The ocular irritation potential of CS-HA-NPs was estimated using draize test on albino rabbits. A significant reduction in IOP level was obtained using CS-HA-NPs as compared to plain solution of drug and a comparable higher reduction in IOP level was observed as to CS-NPs. These results suggest that HA potentialy enhance the mucoadhesiveness and efficiency of CS-NPs and may be promising carrier for ocular drug delivery.

Topics: Adrenergic beta-Antagonists; Animals; Biological Availability; Carbonic Anhydrase Inhibitors; Chitosan; Drug Carriers; Glaucoma; Hyaluronic Acid; Nanoparticles; Rabbits; Sulfonamides; Thiophenes; Timolol

The clinical efficacy of rituximab therapy in systemic mucosa-associated lymphoid tissue (MALT) lymphoma with both periocular and intraocular involvement is described. Ophthalmic examination and radiologic imaging demonstrated tumor with bilateral periorbital, lacrimal, and subconjunctival infiltration, a pseudohypopyon in one eye, and extensive systemic lymph node involvement. Lymph node biopsy confirmed the pathologic findings of a low-grade MALT lymphoma. The patient had a complete remission within 3 months of starting rituximab therapy. A recurrence 6 months later remitted with a second round of rituximab therapy and the patient remained tumor-free at 1 year.

Topics: Androstadienes; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Brimonidine Tartrate; Drug Therapy, Combination; Eye Neoplasms; Female; Glaucoma; Humans; Latanoprost; Loteprednol Etabonate; Lymphoma, B-Cell, Marginal Zone; Middle Aged; Parotid Neoplasms; Prostaglandins F, Synthetic; Quinoxalines; Rituximab; Sulfonamides; Thiophenes; Timolol

Antibiotic and non-antibiotic sulphonamides are often prescribed. Although chemical differences make cross-reactivity rare, reactions may be severe in patients allergic to sulphur. Adverse reactions are common with sulphonamides but low platelets and skin changes are rarely associated with eye-drops for glaucoma. A woman treated with dorzolamide and timolol presented with disseminated eruption. On admission, her physical examination was unremarkable except for the skin changes and severe thrombocytopaenia was detected. Skin biopsy showed hyperkeratosis, acanthosis, perivascular and periadnexal infiltrates with no vasculitis. After discontinuation of eye-drops, the eruption improved but low platelets persisted. Skin changes reappeared with use of dapsone which suggested sulphonamide cross-reactivity.

Topics: Anti-Infective Agents; Antihypertensive Agents; Biopsy; Dapsone; Drug Eruptions; Female; Glaucoma; Humans; Liver Function Tests; Middle Aged; Ophthalmic Solutions; Platelet Count; Sulfonamides; Thiophenes; Thrombocytopenia; Timolol

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.

Topics: Animals; Aqueous Humor; Carbonic Anhydrase Inhibitors; Cornea; Drug Delivery Systems; Drug Stability; Emulsions; Eye Diseases; Glaucoma; Hydrogen-Ion Concentration; Irritants; Male; Nanoparticles; Ophthalmic Solutions; Osmolar Concentration; Particle Size; Rabbits; Rheology; Solubility; Sulfonamides; Surface Tension; Thiophenes; Viscosity

To evaluate the effect of instilled amino acid L-arginine.HCl and combination of two antiglaucomatics (Trusopt with Xalatane mixture) on the physiological intraocular pressure IOP in rabbits.. Into the left conjunctival sac of 5 female rabbits of the New Zealand White species was instilled the mixture of 2% Trusopt (Dorsolamidi hydrochlorici) with 0.005% Xalatane (Latano-prostum) and after the one week break, the 10% L-arginine.HCl in 2% Trusopt with 0.005% Xalatane mixture. The IOPs were measured in 0, 5, 15, 30, 60, 120, 180, 240 min. and 24 hours after the instillation. The right eyes were used as controls.. 1. The combination of two antiglaucomatics in comparison with the control eye decreased significantly the IOP value already after 15 min. The major decrease of the IOP (6.5 mm Hg) was observed after 240 min. After 24 hours, the effectiveness was not significant. 2. After instillation of the 10% L-arginine.HCl in 2% Trusopt with 0.005% Xalatane mixture, during the next 24 hours, the biphasic decrease of the IOP was established. The maximum of the effectiveness of this mixture is after 30 min (decrease by 5.1 mm Hg). The evidence of the effect was present also after 24 hour (decrease by 2.5 mm Hg). The mean value of the IOP of the control eyes in both groups of experiments in course of 24 hours was stable and was at the initial values.. The combination of two antiglaucomatics (Trusopt with Xalatane mixture) was used. The effect of those two substances is not separate or additive but acts as a newly formed substance. In the structures of the eye, this new substance has only poor interaction with the free amino acids of the conjunctival sac in vivo. After in vitro interaction of the L-arginine.HCl and combination of two antiglaucomatics (Trusopt with Xalatane mixture), a new bioactive substance with stronger effect on physiologic IOP values was produced.

Topics: Animals; Antihypertensive Agents; Arginine; Drug Combinations; Female; Glaucoma; Intraocular Pressure; Latanoprost; Prostaglandins F, Synthetic; Rabbits; Sulfonamides; Thiophenes

Erythema multiforme may be a mild condition (erythema multiforme minor), or it may be a severe, possibly life-threatening condition (erythema multiforme major or Stevens-Johnson syndrome). Dorzolamide is a carbonic anhydrase inhibitor, which reduces intraocular pressure by suppressing aqueous production. In this paper we report on a patient who developed erythema multiforme following the use of topical dorzolamide.

Topics: Administration, Topical; Aged, 80 and over; Anti-Inflammatory Agents; Carbonic Anhydrase Inhibitors; Cataract Extraction; Drug Eruptions; Erythema Multiforme; Female; Glaucoma; Humans; Hydrocortisone; Sulfonamides; Thiophenes; Visual Acuity

To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis.. Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte-colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays.. In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group.. This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis.

Topics: Administration, Topical; Aged; Amides; Antihypertensive Agents; Bimatoprost; Brimonidine Tartrate; Carteolol; Case-Control Studies; Chemokines; Cloprostenol; Cytokines; Dose-Response Relationship, Immunologic; Drug Therapy, Combination; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Lipids; Male; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Tears; Thiophenes; Timolol

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Crystallization; Crystallography, X-Ray; Glaucoma; Humans; Molecular Conformation; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Olfaction Disorders; Sulfonamides; Thiophenes

Topics: Conjunctivitis; Female; Genital Diseases, Female; Glaucoma; Humans; Middle Aged; Ophthalmic Solutions; Stevens-Johnson Syndrome; Sulfonamides; Thiophenes

To compare the effectiveness and associated costs of travoprost versus a fixed combination of dorzolamide + timolol as first-line therapy for glaucoma according to data collected by the United Kingdom General Practitioner Research Database (UK-GPRD).. Patients with a diagnosis of ocular hypertension, glaucoma, or who had been treated topically by surgery or laser therapy were selected. Patients starting first-line treatment with travoprost or a fixed dorzolamide + timolol combination were included. Times to treatment failure were compared with an adjusted Cox model.. Cost and treatment failure defined as a prescription change (adding or removing a topical treatment, or initiating laser therapy or surgery).. 56 612 patients were extracted from the database and 39 808 patients received at least one topical prescription for IOP-lowering (intraocular pressure) therapy. Of these, 639 were treated with travoprost and 387 with dorzolamide + timolol, as first-line therapies. No significant difference was found between patient characteristics. Patients were aged 70.0 years and 48.5% were male. At 1 year, treatment failure was experienced by 30.4% of patients receiving travoprost and 49.4% receiving dorzolamide + timolol (p < 0.001). The hazard ratio for failure was 0.79 (p < 0.03) less with travoprost, after adjusting on age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management were significantly (p < 0.001) lower with travoprost ( pound198.31) than with dorzolamide + timolol ( pound312.21).. This retrospective costs and consequences analysis study showed that travoprost is more efficient than dorzolamide + timolol as first-line therapy for glaucoma patients. Patients continued longer with first-line treatment when prescribed travoprost at a lower cost.

Topics: Aged; Antihypertensive Agents; Cloprostenol; Cost-Benefit Analysis; Databases, Factual; Drug Combinations; Drug Costs; Female; Glaucoma; Humans; Male; Physicians, Family; Sulfonamides; Thiophenes; Timolol; Travoprost; United Kingdom

Copayments are common measures intended to control drug expenditures and promote rational prescribing. In Finland, new antiglaucoma drugs start with a high copayment, but once sufficient clinical experience is available, they are reevaluated and can receive a lower copayment status.. This study assessed the effect of changes in copayment level on the adoption of 2 antiglaucoma drugs.. A retrospective analysis was performed from 1997 to 2001 using the Finnish national register of reimbursed drug purchases, which covers approximately 98% of all antiglaucoma drug purchases in the country. There were 172,293 purchases of dorzolamide (plain or combined with timolol) and 281,377 purchases of latanoprost. An interrupted time-series design from approximately 30 months before and 20 months after the change in copayment was used in the analysis. The main outcome measures were the numbers of defined daily doses (DDDs) purchased and the monthly numbers of patients who purchased the study drugs for the first time before and after the change in copayment.. A substantial increase in consumption of both dorzolamide and latanoprost was seen immediately after the introduction of the lower copayment. The monthly consumption of dorzolamide was 60,713 DDDs higher and the monthly consumption of latanoprost was 49,330 DDDs higher than expected according to the utilization trend during the higher copayment period. Twelve months later, the observed consumption of dorzolamide was 109% higher and that of latanoprost was 21% higher than if the copayment had remained the same. The number of new patients using the study drugs peaked within 2 months of the lower copayment, but the amount consumed per patient per day remained quite stable.. Decreasing the copayment of a new antiglaucoma drug to the same level as the copayments of alternative drugs accelerated the adoption of these new products in Finland.

Topics: Carbonic Anhydrase Inhibitors; Data Collection; Data Interpretation, Statistical; Drug Utilization; Finland; Glaucoma; Humans; Insurance, Health, Reimbursement; Latanoprost; Models, Statistical; Prostaglandins; Prostaglandins F, Synthetic; Regression Analysis; Sulfonamides; Thiophenes

Disturbed ocular haemodynamics are discussed to contribute to the pathogenesis of glaucoma. Up to now there is no method available allowing direct determination of blood flow, which is the most relevant dimension for studies on haemodynamics. In this study, volumetric colour Doppler imaging (vCDI) is evaluated systematically in glaucoma patients.. A Siemens Elegra ultrasound set-up with a linear 7.5 MHz probe was used for all CDI measurements. For vCDI, the cross-sectional area of a vessel and the flow velocity is determined. From both these parameters blood flow can be calculated. Ocular pulse amplitude (OPA) was assessed by the method of Langham using a pneumatic applanation tonometer.. (1) Velocity measurements using CDI in the ophthalmic artery and central retinal artery were highly reproducible (n=20). In contrast, reproducibility of vCDI measurements was low (n=20). Reproducibility improved if five vCDI measures were averaged. (2) Results from two different CDI-operators did not differ regarding the velocity measurements, but there was a difference in vCDI measurements (n=20). (3) Results from vCDI did not correlate with measurements of OPA in 69 patients. (4) In 15 patients, vCDI failed to detect changes of ocular perfusion induced by the application of dorzolamide.. vCDI is not applicable in ophthalmology at present.

Topics: Adult; Antihypertensive Agents; Blood Flow Velocity; Glaucoma; Humans; Middle Aged; Observer Variation; Ophthalmic Artery; Regional Blood Flow; Reproducibility of Results; Retinal Artery; Sulfonamides; Thiophenes; Ultrasonography, Doppler, Color

The aim of this study was to estimate the effects of various antiglaucoma drugs including betaxolol, timolol, levobunolol, brimonidine, carteolol, dipivefrin, dorzolamide, brinzolamide, latanoprost, unoprostone, and pilocarpine on intracellular free Ca2+ ([Ca2+]i) mobility in cultured bovine corneal endothelial cells. Various antiglaucoma drugs were diluted from original concentrations to 1/ 100, 1/ 1,000, and 1/ 10,000. The [Ca2+] mobility was studied by spectrofluorophotometry after loading with the ester of fura-2 (fura-2/AM). It was found that timolol (58 microM and 5.8 microM), levobunolol (171 microM, 17.1 microM, and 1.71 microM), betaxolol (162 microM, 16.2 microM, and 1.62 microM), carteolol (680 microM and 68 microM), dipivefrin (28 microM and 2.8 microM), dorzolamide (616 microM and 61.6 microM), brinzolamide (260 microM), latanoprost (1.1 microM), unoprostone (28.2 microM, 2.82 microM, and 0.282 microM), and pilocarpine (408 micro and 40.8 microM) induced a significant increase in [Ca2+]i. Nevertheless, only brimonidine (68 microM and 6.8 microM) decreased [Ca2+]i concentration significantly. Benzalkonium chloride preservative did not affect [Ca2+]i after addition of 0.001, 0.0001 and 0.00001 mg/mL to cells. These results indicate that all antiglaucoma drugs may affect the physiologic function of corneal endothelial cells through change of [Ca2+]i mobility.

Topics: Animals; Antihypertensive Agents; Betaxolol; Calcium; Endothelium, Corneal; Glaucoma; Levobunolol; Male; Rats; Rats, Sprague-Dawley; Sulfonamides; Thiophenes; Timolol

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Dermatitis, Allergic Contact; Epinephrine; Female; Glaucoma; Humans; Ophthalmic Solutions; Patch Tests; Sulfonamides; Thiophenes; Timolol

The aim of the study was to analyze changes in intraocular pressure after Nd: YAG laser capsulotomy in pseudophakic patients with glaucoma.. Intraocular pressure was recorded before, and 1 and 3 hours after YAG laser capsulotomy in 69 pseudophakic patients with glaucoma. Twenty eight patients received no therapy before capsulotomy, 21 patients received topical brimonidine 0.2%, and 20 patients received topical dorzolamide 2% 1 hour before laser capsulotomy. All patients received topical tropicamide 1% and tetracaine 0.5%. Nd: YAG laser posterior capsulotomy was performed using inverted-U technique to make a 3-4 mm diameter capsulotomy. After capsulotomy, all eyes received topical fluorometholone for 10 days.. A pressure rise was greater in patients without any therapy before YAG laser capsulotomy. Eight patients with glaucoma showed intraocular pressure rise of 5 mm Hg, and 2 patients pressure rise of 10 mm Hg after laser capsulotomy. A reduction of intraocular pressure rise was found in patients who received dorzolamide 2% or brimonidine 0.2%, only 1 patient in each group developed a pressure rise of 5 mm Hg. In all patients a significant pressure rise developed within the first hour.. It is difficult to compare different studies due to different techniques of cataract surgery and different intraocular lense material and design. Barnes showed that 6 of 29 (21%) developed a pressure rise of 5 mm Hg, and 1 of 29 (3%) patients a pressure rise of 10 mm Hg. In our study, 29% of patients had a pressure rise of > or =5 mm Hg, and 7% of patients had a rise of > or =10 mm Hg after laser capsulotomy. These results may be associated with a large proportion of extracapsular cataract extraction (71%) versus phacoemulsification (29%) in our patients.. Pretreatment with dorzolamide 2% or brimonidine 0.2% reduce the intraocular pressure rise after Nd: YAG laser capsulotomy in pseudophakic patients with glaucoma.

Topics: Administration, Topical; Antihypertensive Agents; Brimonidine Tartrate; Cataract Extraction; Glaucoma; Humans; Intraocular Pressure; Laser Therapy; Lens Capsule, Crystalline; Preoperative Care; Pseudophakia; Quinoxalines; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Brimonidine Tartrate; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Quinoxalines; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The effect of adding oral to topical carbonic anhydrase inhibitors in the management of pediatric glaucoma is unknown.. We undertook a retrospective analysis of children with a diagnosis of glaucoma before the age of 16 years who initially were treated with topical dorzolamide or dorzolamide-timolol combination and then treated with oral acetazolamide. Children who had uveitic glaucoma or who had ocular surgery within 3 months before or during oral acetazolamide therapy were excluded. Various methods of intraocular pressure (IOP) measurement were used in the study. However, in each case, the IOP was measured using the same technique, once at the last visit before the addition of oral acetazolamide and once at the first examination after the addition of oral acetazolamide.. Twenty-two patients were included in the study with an age range of 8 months to 15 years. Seventeen children were boys. Oral acetazolamide treatment was via a daily dose (13.3 to 30 mg/kg, mean 22.5 mg/kg), and duration (6 to 31 days, mean 18.1 days). The intraocular pressure (mean +/- SD) before acetazolamide (32.2 +/- 6.5 mm Hg) was significantly different than after acetazolamide (21.8 +/- 6.3 mm Hg) with a mean difference of 10.36 mm Hg (p < 0.0001) and a mean decrease in IOP of 29.6%.. The addition of oral acetazolamide to topical dorzolamide may provide additional reduction in IOP in some children already being treated with topical carbonic anhydrase inhibitors. This possible additive effect has not been observed in adults treated with a combination of topical and systemic carbonic anhydrase inhibitors.

Topics: Acetazolamide; Administration, Oral; Administration, Topical; Adolescent; Carbonic Anhydrase Inhibitors; Child; Child, Preschool; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma; Humans; Infant; Intraocular Pressure; Male; Retrospective Studies; Sulfonamides; Thiophenes; Tonometry, Ocular

The inhibition of a newly cloned human carbonic anhydrase (CA, EC 4.2.1.1), isozyme XII (hCA XII), has been investigated with a series of sulfonamides, including some clinically used derivatives (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and sulpiride, or indisulam, a compound in clinical development as antitumor drug), as well as the sulfamate antiepileptic drug topiramate. Some simple amino-/hydrazine-/hydroxy-substituted aromatic/heterocyclic sulfonamides have also been included in the study. All types of activity have been detected, with several medium potency inhibitors (K(I)s in the range of 34-220 nM), whereas ethoxzolamide and several halogenated sulfanilamides showed stronger potency, with K(I)s in the range of 11-22 nM. The antiglaucoma sulfonamides used clinically, except dichlorophenamide, which is a moderate inhibitor (K(I) of 50 nM), as well as topiramate, indisulam, and sulpiride behave as very potent hCA XII inhibitors, with K(I)s in the range of 3.0-5.7 nM. Several subnanomolar inhibitors (K(I)s in the range of 0.30-0.85 nM) have also been detected. Compounds with excellent selectivity against hCA XII over hCA II have been found, showing selectivity ratios in the range of 177.7-566.7. Apparently, hCA XII is a target of the antiglaucoma sulfonamides, and potent hCA XII inhibitors may be developed/used for the management of hypoxic tumors, together with inhibitors of the other tumor-associated isozyme, CA IX.

Topics: Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Drug Design; Glaucoma; Humans; Isoenzymes; Structure-Activity Relationship; Sulfonamides

A new series of thioureido-substituted sulfonamides were prepared by reacting 4-isothiocyanato- or 4-isothiocyanatoethyl-benzenesulfonamide with amines, hydrazines, or amino acids bearing moieties that can lead to an enhanced hydrosolubility, such as 2-dimethylamino-ethylamine, fluorine-containing aromatic amines/hydrazines, an aminodiol, heterocyclic polyamines (derivatives of morpholine and piperazine), 4-aminobenzoic acid, or natural amino acids (Gly, Cys, Asn, Arg, and Phe). The new compounds showed good inhibitory properties against three physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, with K(I)s in the range of 24-324 nM against the cytosolic isoform CA I, of 6-185 nM against the other cytosolic isozyme CA II, and of 1.5-144 nM against the transmembrane isozyme CA XII. Some of the new derivatives were also very effective in reducing elevated intraocular pressure in hypertensive rabbits as a glaucoma animal model. Considering that this is the first study in which potent CA II/CA XII inhibitors are designed and investigated in vivo, it may be assumed that the target isozymes of the antiglaucoma sulfonamides are indeed the cytosolic CA II and the transmembrane CA XII.

Topics: Animals; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Disease Models, Animal; Drug Design; Glaucoma; Intraocular Pressure; Rabbits; Structure-Activity Relationship; Sulfonamides

Since its introduction in 1996, brimonidine tartrate 0.2% ophthalmic solution (Alphagan, Allergan) twice daily has become established as an effective intra ocular pressure-lowering treatment. While the efficacy of Alphagan cannot be questioned, we gained the clinical impression that the drug has an unacceptably high rate of allergy. Of greater concern, we suspected that patients suffering from local Alphagan allergy had a higher rate of allergy to subsequently used topical preparations. We analysed data from a large scale study of glaucoma patients to establish whether our suspicions were correct.. We have created a database of the entire glaucoma treatment histories for consecutive patients attending a single consultant's clinics (DMIM) at Glasgow Royal Infirmary between May 1999 and September 2001. All have undergone medical treatment for primary open angle glaucoma, ocular hypertension, or normal tension glaucoma. Patients with any other form of glaucoma, and patients in whom a full record of treatment was not available were excluded from the study.. Alphagan was discontinued due to allergy on 73 per 100,000 patient treatment days. This was a far higher frequency than for other preparations. In patients allergic to both Alphagan and another preparation (Timoptol, Trusopt and Xalatan), the mean interval between the first and second allergy was shorter when Alphagan allergy occurred first. This was statistically significant in Timoptol and Trusopt cross-reactivity.. Alphagan has high allergenicity, and may increase the likelihood of allergy to subsequently used preparations.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Cross Reactions; Drug Administration Schedule; Drug Hypersensitivity; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Longitudinal Studies; Male; Middle Aged; Ophthalmic Solutions; Quinoxalines; Retrospective Studies; Sulfonamides; Thiophenes; Timolol

This study sought to elucidate the effects of timolol and dorzolamide on intraocular pressure (IOP) and retinal ganglion cell (RGC) death in an experimental model of glaucoma in rat.. Mild elevation of IOP was induced in rats by intracameral injection of India ink and subsequent laser trabecular photocoagulation. IOP was measured before the surgical procedures and weekly thereafter. Timolol (0.5%), timolol XE (0.5%), dorzolamide (1%), and artificial tears (vehicle) were topically applied daily. Retinal sections were prepared for histology to determine RGC number.. Timolol, timolol XE, and dorzolamide induced a significant reduction in IOP (p<0.05) and counteracted the reduction in RGC number that occurred in vehicle treated glaucomatous eyes (p<0.05). The coefficient of correlation between RGC number and IOP was significant in the dorzolamide treated group (r = -0.908, p<0.005), but not in other groups (p>0.05).. Both timolol formulation and dorzolamide reduced IOP and protected RGCs in a rat model of experimental glaucoma. It cannot be ruled out that timolol might protect RGCs by additional mechanisms other than simply lowering of IOP.

Topics: Animals; Antihypertensive Agents; Cell Count; Cell Survival; Cytoprotection; Disease Models, Animal; Glaucoma; Intraocular Pressure; Male; Ophthalmic Solutions; Rats; Rats, Wistar; Retinal Ganglion Cells; Sulfonamides; Thiophenes; Timolol

Topics: Antihypertensive Agents; Female; Glaucoma; Humans; Latanoprost; Middle Aged; Ophthalmic Solutions; Prostaglandins F, Synthetic; Stevens-Johnson Syndrome; Sulfonamides; Thiophenes; Timolol

This study was designed to evaluate the effects of a dorzolamide-timolol combination or dorzolamide on retinal ganglion cell (RGC) density and intraocular pressure (IOP) in glaucomatous eyes of adult rats.. Glaucoma was induced in the right eye of adult Wistar rats by episcleral venous occlusion. One experimental group was administered dorzolamide 2%-timolol 0.5% combination eye drops, while the other experimental group was administered dorzolamide 2% eye drops. Control groups had surgery without drug administration. Drug application was initiated either 2 weeks before surgery (Group A), from the day of surgery (Group B), 2 weeks after surgery (Group C), or 4 weeks after surgery (Group D). RGCs were labeled by intratectal Fluorogold injections and counted from flat-mount preparations, and IOP was measured using Tonopen.. Both dorzolamide-timolol combination and dorzolamide, when applied topically, significantly reduced IOP and improved RGC densities in experimental eyes when compared to control eyes. Earlier initiation, as well as longer duration of drug application, resulted in higher RGC densities.. Topical application of a dorzolamide-timolol combination or dorzolamide saved RGCs to a significant extent and reduced IOP in glaucomatous rat eyes.

Topics: Animals; Antihypertensive Agents; Cell Count; Disease Models, Animal; Drug Combinations; Female; Glaucoma; Intraocular Pressure; Pilot Projects; Rats; Rats, Wistar; Retinal Ganglion Cells; Sulfonamides; Thiophenes; Time Factors; Timolol

A series of N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines was prepared by reaction of sulfanilamide with different monosaccharides in the presence of ammonium chloride. The new compounds were investigated for inhibition of the metallo-enzyme carbonic anhydrase (CA, EC 4.2.1.1), involved in aqueous humor secretion within the mammalian eye. Isozymes CA I and CA II were strongly inhibited by some of these compounds, which showed inhibition constants in the range of 510-1200 nM against CA I and 10-25 nM against CA II, similarly to clinically used sulfonamides, such as acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide. The presence of sugar moieties in these molecules induced an enhanced water solubility as compared to other sulfonamides. In hypertensive rabbits (a widely used animal model of glaucoma), two of the new compounds showed strong and long-lasting intraocular pressure (IOP) lowering, being more effective than dorzolamide and brinzolamide, the two clinically used, topically acting antiglaucoma sulfonamides with CA inhibitory properties.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Glaucoma; Hypertension; Intraocular Pressure; Male; Monosaccharides; Rabbits; Sulfanilamides

Polyfluorinated carbonic anhydrase inhibitors (CAIs) show very good inhibitory properties against carbonic anhydrase (CA) and excellent in vivo antiglaucoma properties after topical administration in rabbits. Still, the pentafluorinated compounds reported previously by this group (Scozzafava et al. J. Med. Chem. 2000, 43, 4542-4551) showed high reactivity with thiol groups of cysteine, glutathione, and presumably other proteins containing such moieties, which may lead to severe ocular side effects. Here, we report an approach for obtaining fluorinated CA inhibitors without the undesired enhanced reactivity. Thus, new compounds have been obtained by attaching moieties with reduced reactivity toward aromatic substitution reactions to the molecules of aromatic/heterocyclic sulfonamides possessing derivatizable amino moieties. The employed tails of the 2,3,5,6-tetrafluorobenzoyl, 2,3,5,6-tetrafluophenylsulfonyl, and pentafluorophenylureido types induced excellent CA inhibitory properties in the new reported sulfonamides, mainly against the isozymes involved in aqueous humor secretion, CA II and CA IV, whereas affinity for CA I was lower. Several low-nanomolar CA II inhibitors were detected, which did not react with cysteine or glutathione, in contrast to the corresponding perfluorinated compounds previously reported. These derivatives also showed a potent reduction of the intraocular pressure (IOP) in hypertensive rabbits, amounting to 13-21 mmHg at 1 h postadministration (compared to 5 mmHg obtained with dorzolamide, a clinically used drug), and the decreased IOP was maintained for 4-5 h after the administration. These compounds constitute valuable candidates for obtaining topically acting antiglaucoma CA inhibitors of a new generation, with enhanced efficacy, prolonged duration of action, and reduced side effects.

Topics: Administration, Topical; Animals; Carbonic Anhydrase I; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Carbonic Anhydrase IV; Fluorine; Glaucoma; Heterocyclic Compounds; Intraocular Pressure; Rabbits; Structure-Activity Relationship; Sulfonamides

To investigate the effects of antiglaucoma eyedrops and vehicles on the proliferation of human corneal epithelial cells.. Seven eyedrops[prostaglandin F2 alpha analogs(2), beta blockers(40), topical carbonic anhydrase inhibitor(1)], and six of the eyedrop vehicles, excluding that of Xalatan, were used. Anti-glaucoma eyedrops and vehicles were serially diluted 2-fold with culture medium(10-2,560 fold). The mixture was added to human corneal epithelial cells and incubated for 48 hrs. Cell proliferation was measured by commercial assay kit. Dye-reagents were added to the wells and incubated for 1 h at 37 degrees C. Optical density were measured at 490 nm. The dilution rate for 50% inhibition was calculated as the dilution rate of drugs or vehicles necessary to produce 50% inhibition of cell proliferation.. All drugs completely inhibited cell proliferation when the dilution rate was low. At 40-fold dilution, Trusopt and Timoptol showed a significant decrease in cell growth inhibition. On the other hand, Rescula showed almost 100% inhibition at 160-fold dilution. Above 640-fold dilution, the inhibition rate of all drugs became 50% or less and there was no significant difference between drugs. Vehicles also inhibited cell growth. The dilution rates for growth inhibition by vehicles were different from those of drugs. The dilution rate at 50% inhibition of anti-glaucoma eyedrops decreased in the following order: Rescula > Xalatan > Betoptic > Hypadil > Mikelan > Timoptol > Trusopt. The dilution rate for 50% inhibition of vehicles decreased in the following order: Rescula vehicle > Hypadil vehicle > Betoptic vehicle > Mikelan vehicle > Timoptol vehicle > Trusopt vehicle.. All anti-glaucoma eyedrops inhibited cell proliferation. These effects were stronger in prostaglandin F2 alpha analogs and weakest in Trusopt. Furthermore, the inhibition of cell proliferation was caused also by the vehicle of eyedrops, and the influence of the vehicle varied in each type of eyedrops.

Topics: Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Cell Division; Dinoprost; Epithelium, Corneal; Glaucoma; Growth Inhibitors; Humans; Ophthalmic Solutions; Sulfonamides; Thiophenes

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Drug Eruptions; Glaucoma; Humans; Leg Dermatoses; Lichenoid Eruptions; Male; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol

In this contribution publish the observation that addition of 10% L-arginin.HCl to the 2% Trusopt eye drops intensifies activity of antiglaucomatics with an important reduction of the normal intraocular pressure (IOP) in rabbits New Zealand white namely from 15 up to 240 minutes, compared with application of both substance alone. Size of the pupil was not affected. Based on our experimental results we assume that this increasing activity of Trusopt mixture with amino acid L-arginin.HCl created a new metabolite. According to our observations this metabolite caused reduction of the humor aqueous production and together with the increased of the uveo-scleral outflow leads to the striking reduction of the IOP.

Topics: Animals; Antihypertensive Agents; Arginine; Drug Combinations; Glaucoma; Intraocular Pressure; Ophthalmic Solutions; Pupil; Rabbits; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Betaxolol; Brimonidine Tartrate; Carteolol; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Neuroprotective Agents; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Treatment Outcome

Reaction of 3- and 4-carboxybenzenesulfonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulfonamide/5-imino-4-methyl-delta(2)-1,3,4-thiadiazoline-2-sulfonamide afforded two series of benzolamide analogues to which the carboxyl moiety has been derivatized as esters or amides, in order to reduce their very polar character. The new derivatives showed low nanomolar affinity for three carbonic anhydrase (CA) isozymes, CA I, II and IV, and were effective as topical antiglaucoma agents in normotensive rabbits. Efficacy of several of the new sulfonamides reported was better than that of the standard drugs dorzolamide and brinzolamide, whereas their duration of action was prolonged as compared to that of the clinically used drugs.

Topics: Administration, Topical; Animals; Benzolamide; Carbonic Anhydrase I; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Carbonic Anhydrase IV; Cattle; Esters; Glaucoma; Humans; Intraocular Pressure; Rabbits; Structure-Activity Relationship; Sulfonamides; Thiazines; Thiophenes

Topics: Adrenergic beta-Antagonists; Adult; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Eye; Female; Glaucoma; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Rheology; Risk Factors; Sulfonamides; Thiophenes; Time Factors; Timolol

In managing glaucoma through the lowering of intraocular pressure (IOP), beta-blockers (e.g. timolol) are commonly the drug of first choice, with other drugs added to control IOP such as carbonic anhydrase inhibitors (e.g. dorzolamide). The present survey was instigated to assess the COSOPT (fixed combination of topical timolol and topical dorzolamide) prescription behaviour of Swiss office-based ophthalmologists and to evaluate the IOP-lowering efficacy of COSOPT under real-life private practice conditions.. A survey was conducted in Swiss ophthalmologist practices. Ophthalmologists were asked to report their experience with COSOPT therapy prescribed to patients with glaucoma or ocular hypertension. Parameters recorded were: patient demographics, IOP, reason for choosing COSOPT, continuation of COSOPT therapy after completion of the survey and, if stopped, reason for discontinuation, and spontaneously occurring side-effects. All entries were optional. Since the purpose of this survey was to obtain a realistic picture of daily practice in Swiss ophthalmologists' offices, no guidelines with regard to measurement of IOP, time between visits and actual treatment were given.. Data of 733 patients were included in this analysis. COSOPT as sole therapy was prescribed to 538 patients (74%), whereas 120 (16%) were put on a combination regimen of COSOPT + latanoprost. The remaining 75 patients (10%) received combinations of COSOPT with other ocular hypotensives. When assessing those patients put on COSOPT alone, IOP reduction in new, previously untreated patients was 10.8 mmHg (average), 5.4 mmHg (average) in upgrades from previous monotherapy and 2.7 mmHg after switch from free combination therapy. Patients treated with a combination of COSOPT + latanoprost showed an IOP reduction of 27 mmHg (new, previously untreated patients), 7.6 mmHg (upgrades from monotherapy) and 3.8 mmHg (switches from previous free combination regimen). Therapy was continued in 89% of all patients overall and in 91% of new patients treated with COSOPT alone (first line). 6.8% stopped therapy due to side-effects.. COSOPT, the fixed combination of 0.5% timolol and 2% dorzolamide, is broadly prescribed to new, upgrade and switch patients in Switzerland. COSOPT therapy is well-tolerated and highly efficacious for patients requiring strong IOP lowering. Nine out ten patients stay on therapy after 1-2 months of treatment.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Child; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Neuroprotective Agents; Physicians' Offices; Practice Patterns, Physicians'; Prostaglandins F, Synthetic; Sulfonamides; Switzerland; Thiophenes; Timolol; Treatment Outcome

Over releasing of glutamate and cellular calcium influx always results in neuronal death. In the present study, we investigated various commercial antiglaucoma drugs including timolol (0.58 microM to 58 microM), betaxolol (1.62 microM to 162 microM), carteolol (6.8 microM to 680 microM), pilocarpine (4.08 microM to 408 microM), latanoprost (0.01 microM to 1.1 microM), dorzolamide (6.16 microM to 616 microM), brinzolamide (2.6 microM to 260 microM), brimonidine (0.68 microM to 68 microM), dipivefrin (0.28 microM to 28 microM) and preservative benzalkonium chloride on their effects to inhibit glutamate-induced intracellular free Ca(2+) ([Ca(2+)](i)) increase in cultured N1E-115 neuroblastoma cells. These drugs were diluted from original concentrations to 1/100, 1/1000 and 1/10000. The [Ca(2+)](i) mobility was studied after loading with fura-2-AM and analyzed by spectrofluorometry. It was found that betaxolol, dipivefrin and brimonidine have remarkable effects not only to inhibit the glutamate-induced [Ca(2+)](i) increase but also to decrease the basal [Ca(2+)](i). In the case of other drugs, only high concentration of timolol (58 microM) exhibited significant effect to completely prevent glutamate-induced [Ca(2+)](i) increase. Moreover, benzalkonium chloride did not exhibit any inhibitive effect. These results indicate that betaxolol, dipivefrin and brimonidine may have neuroprotective effects to inhibit the glutamate-induced over Ca(2+) influx damage.

Topics: Animals; Antihypertensive Agents; Betaxolol; Brimonidine Tartrate; Calcium; Carteolol; Cell Death; Dose-Response Relationship, Drug; Epinephrine; Glaucoma; Glutamic Acid; Latanoprost; Mice; Neuroblastoma; Neurons; Neuroprotective Agents; Pilocarpine; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiazines; Thiophenes; Timolol; Tumor Cells, Cultured

Authors present comparison of the previous results on the influence of free amino acids of the aqueous humor in rabbits and human on the pH of the aqueous humor in vitro. Four clinically used antiglaucomatics were added (2% Trusopt--pH 5.33; 0,005% Xalatan--pH 6.4; 0.5% Timoptol--pH 6.80 and 1% Pilocarpine--pH 5.87) into the aquired aqueous humor of rabbits (pH 7.59) and human (pH 7.11 +/- 0.11). After their instillation pH of the aqueous humor immediately decreased towards acid levels. The pH changes after Timoptol, Xalatan and Pilocarpine showed a similar time pattern and after return to the baseline values the pH shifted to alkaline levels. In case of Trusopt instillation the pH value reached the baseline of the aqueous humor after 240 min. Almost no pH changes were recorded from 240 min up to 24 hours after all tested antiglaucomatics. From the wiev on the speed of activity and effectivity depending on time required to reach the initial pH value of the aqueous humor we to make this order: Pilocarpine>Timoptol>Xalatan>Trusopt. Comparing our results the effect of antiglaucomatics is connected with different composition and also with shift of the aqueous humor pH towards slightly alkaline level (similar effect in rabbits and human). Results presented in this work are theoretical but also practical contribution to the treatment of glaucoma. (Fig. 1, Ref. 38.).

Topics: Aged; Aged, 80 and over; Amino Acids; Animals; Antihypertensive Agents; Aqueous Humor; Carbonic Anhydrase Inhibitors; Female; Glaucoma; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Latanoprost; Male; Middle Aged; Pilocarpine; Prostaglandins F, Synthetic; Rabbits; Sulfonamides; Thiophenes; Timolol

To evaluate persistency with monotherapy in the treatment of glaucoma in patients new to pharmacological management.. This population-based, retrospective cohort study, using managed care administrative claims data, included patients who were 20 years of age and older and who initiated monotherapy with betaxolol, brimonidine, dorzolamide, latanoprost, or timolol between May 1999 and January 2001. Follow-up continued through January 31, 2001, and prescription refill records for all ocular hypotensive medications were extracted for the full 21-month study period. The primary outcome measures were discontinuation and change (switching/adding on) of the index ocular hypotensive medication. Rates of discontinuation and discontinuation/change were compared using Cox regression methods; survival curves were generated.. In all, 14,539 patients were prescribed any ocular hypotensive drug during the study period, and 2850 patients met all inclusion criteria. Patients treated with betaxolol, brimonidine, dorzolamide, or timolol were significantly (p < 0.05) more likely to discontinue and to discontinue/change the index therapy than were those treated with latanoprost. Results were confirmed in analyses adjusted for age and sex.. Patients initially treated with latanoprost monotherapy are more persistent than those who begin treatment with beta-blockers, brimonidine, or the carbonic anhydrase inhibitor dorzolamide. Greater persistency with an initial ocular hypotensive therapy may improve health outcomes and reduce long-term costs to patients and health plans by limiting the increased resource use associated with discontinuations or changes in therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Brimonidine Tartrate; Cohort Studies; Drug Utilization; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ocular Hypertension; Patient Compliance; Prostaglandins F, Synthetic; Quinoxalines; Retrospective Studies; Sulfonamides; Thiophenes

The frequent systemic side effects associated with the use of systemic carbonic anhydrase inhibitors have adversely affected the compliance to treatment in glaucoma patients, obviating their long-term use. The introduction of the topical CAI dorzolamide has further reduced their use. However, the tolerability of dorzolamide in patients who have been intolerant to systemic CAIs has not been evaluated prospectively.. To study the tolerability and efficacy of dorzolamide (a topical CAI) in a selected group of glaucoma and ocular hypertensive patients who have been intolerant to systemic CAI.. A 3 month prospective study was conducted in 39 patients. Following recruitment, patients were evaluated on the day of switching from systemic CAI to dorzolamide and for five more visits. The SF-36 health assessment questionnaire was used to evaluate changes in well-being and quality of life, and the intraocular pressure was measured periodically.. Within 4 weeks of switching from systemic CAI to dorzolamide, the mean health assessment scores improved significantly in seven of the eight categories of the SF-36, and remained generally unchanged for the rest of the study. No significant differences were noted between the mean IOP on day 0 and the following measurements throughout the 84 days of dorzolamide therapy.. In glaucoma patients who were intolerant to systemic CAI, topical CAI dorzolamide offers a similar efficacy and better tolerability.

Topics: Aged; Carbonic Anhydrase Inhibitors; Female; Glaucoma; Glaucoma, Open-Angle; Health Status Indicators; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Quality of Life; Sulfonamides; Thiophenes

In Canada, public drug plans may restrict the use of newer topical antiglaucoma agents. The goals of this retrospective study were to estimate the proportion of patients who, at the initiation of topical glaucoma therapy, had contraindications to the use of topical beta-blockers and to identify whether changes in formulary listing status (from restricted-drug list to generally available drug list) influenced the use of topical glaucoma agents in patients with contraindications to beta-blockers.. Claims databases administered by the Régie de l'assurance maladie du Quebec were used to identify incident users of beta-blockers (betaxolol and timolol) and newer antiglaucoma agents (brimonidine, dorzolamide and latanoprost) among patients aged 35 years or older. Drug claims and physician diagnoses were used to determine the prevalence of the following contraindications to the use of beta-blockers (including warnings and precautions): asthma or chronic bronchitis, diabetes, dysrhythmia and heart failure, all in the year preceding the initiation of therapy; or use of systemic beta-blockers at the time glaucoma therapy was started. The observation period was divided into 2 phases: the time during which newer agents were on the restricted-drug list (first-line use being limited to patients with contraindications to the use of beta-blockers; January 1997 to March 1999) and the time during which these agents were on the generally available drug list (that is, after reimbursement restrictions were relaxed; April 1999 to June 2000).. Of the 20 309 eligible patients, 59.8% were female, and the mean age was 72 years. Contraindications to topical beta-blocker therapy were significantly more frequent among the patients using newer antiglaucoma agents than among those using beta-blockers (71.5% vs. 55.5%, p < 0.0001). Asthma and chronic bronchitis were also more frequent among the patients using the newer agents than among those using beta-blockers (43.1% vs. 22.5%, p < 0.0001). Among the patients without contraindications to topical beta-blocker therapy, the overall proportions started on therapy with a newer agent were 22.7% when there were reimbursement restrictions and 30.0% when the restrictions were relaxed (p < 0.0001).. Among patients with contraindications to the use of beta-blockers, newer topical antiglaucoma agents were used more often than beta-blockers. Among patients without such contraindications, the use of the newer agents increased modestly when reimbursement restrictions were relaxed.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Betaxolol; Brimonidine Tartrate; Contraindications; Databases, Factual; Drug Prescriptions; Female; Glaucoma; Humans; Latanoprost; Male; Middle Aged; National Health Programs; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quebec; Quinoxalines; Retrospective Studies; Sulfonamides; Thiophenes; Timolol

Reaction of polyamino-polycarboxylic acids or their dianhydrides with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded mono- and bis-sulfonamides containing polyamino-polycarboxylic acid moieties in their molecule. The acids/anhydrides used in synthesis included IDA, NTA, EDDA, EDTA and EDTA dianhydride, DTPA and DTPA dianhydride, EGTA and EGTA dianhydride, and EDDHA, among others. All the newly prepared derivatives showed strong affinity toward isozymes I, II, and IV of carbonic anhydrase (CA). Metal complexes of the new compounds have also been prepared. Metal ions used in such preparations included di- and trivalent main-group and transition cations, such as Zn(II), Cu(II), Al(III), etc. Some of the new sulfonamides/disulfonamides obtained in this way, as well as their metal complexes, behaved as nanomolar CA inhibitors against isozymes II and IV, being slightly less effective in inhibiting isozyme I. Some of these sulfonamides as well as their metal complexes strongly lowered intraocular pressure (IOP) when applied topically, directly into the normotensive/glaucomatous rabbit eye, as 1-2% water solutions/suspensions. The good water solubility of these sulfonamide CA inhibitors, correlated with the neutral pH of their water solutions used in the ophthalmologic applications and the long duration of action of the IOP-lowering effect, makes them interesting candidates for developing novel types of antiglaucoma drugs devoid of serious topical side effects.

Topics: Animals; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Chelating Agents; Chloroform; Chromatography, High Pressure Liquid; Cornea; DNA, Complementary; Edetic Acid; Enzyme Inhibitors; Escherichia coli; Glaucoma; Humans; Hydrogen-Ion Concentration; Imino Acids; Kinetics; Male; Models, Chemical; Nitrilotriacetic Acid; Pentetic Acid; Pressure; Rabbits; Sulfonamides; Temperature; Time Factors; Ultraviolet Rays; Water

To document the clinical signs and management of primary glaucoma in Burmese cats.. A retrospective study of six affected Burmese cats, from 1996 to 2001. Procedure Six Burmese cats diagnosed with primary glaucoma were managed over periods varying from 3 months to 4.5 years. Clinical details were obtained from practice records. Gonioscopic examination of the drainage or iridocorneal angle in eyes of these affected cats was made.. Six desexed female Burmese cats (ages 7.0 to 10.5 years) presented with complaints of either unilateral (n = 4) or bilateral (n = 2) red eye, dilated pupil or enlarged eye. In one of the affected cats, one eye had been enucleated prior to the commencement of the study, thus a total of 11 eyes were examined. Clinically, all affected eyes (n = 8) had injected episcleral blood vessels and elevated intraocular pressure. Gonioscopy revealed the presence of nine narrow and two closed iridocorneal angles. Medical therapy included topical 2% dorzolamide (n = 8), 0.5% timolol maleate (n = 1), 0.005% latanoprost (n = 1) and 0.5-1.0% prednisolone acetate (n = 8). Surgery was performed in six eyes using either diode laser (n = 5) and/or cryothermy (n = 2) and one eye was eviscerated, with implantation of a prosthesis. With therapy, five affected eyes maintained vision and normal intraocular pressure, one eye remained blind with normal intraocular pressure, one eye remained blind with elevated intraocular pressure and one eye was eviscerated.. The Burmese cat may be predisposed to primary narrow-angle glaucoma. Early diagnosis and continuous antiglaucoma therapy can help control intraocular pressure and maintain vision.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Breeding; Cat Diseases; Cats; Female; Glaucoma; Latanoprost; Ophthalmic Solutions; Prednisolone; Prostaglandins F, Synthetic; Retrospective Studies; Sulfonamides; Thiophenes; Timolol

To report periorbital dermatitis as a late side effect of topical dorzolamide hydrochloride (Trusopt), a drug used to reduce intraocular pressure.. A retrospective study of 14 patients who developed periorbital dermatitis while using topical dorzolamide hydrochloride was undertaken. Six patients underwent patch testing for sensitivity to Trusopt, dorzolamide hydrochloride, and the preservative benzalkonium chloride.. The periorbital dermatitis occurred after a mean period of 20.4 weeks of commencing dorzolamide hydrochloride therapy. 13 patients had used preserved topical beta blocker treatment for a mean period of 34.2 months without complication before the introduction of dorzolamide. In eight (57.1%) the dermatitis resolved completely after discontinuing dorzolamide but in six (42.9%) resolution of the dermatitis did not occur until the concomitant preserved beta blocker was stopped and substituted with preservative free drops. Patch testing for sensitivity to Trusopt, dorzolamide hydrochloride, and benzalkonium chloride was negative.. These findings suggest that dorzolamide can cause severe periorbital dermatitis. Although the dermatitis may resolve when dorzolamide is discontinued, this does not always occur and in some patients all topical medication containing benzalkonium chloride needs to be stopped.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Eruptions; Facial Dermatoses; Female; Glaucoma; Humans; Male; Middle Aged; Retrospective Studies; Sulfonamides; Thiophenes

To investigate the possibility of corneal alterations in patients with long-term endothelial compromise with topical dorzolamide.. Retrospective descriptive study of 17 patients with penetrating keratoplasty and glaucoma associated with topical carbonic anhydrase inhibitor therapy, looking for coincidence with corneal alteration.. Classified by ethiology, type of glaucoma and control, recording previous ophthalmological surgeries, evolution time, complications and rejection episodes. Seven patients suffered a corneal decompensation, in three of them there were signs of true reject but only four cases had edema at the beginning of dorzolamide treatment, one of them recovering after stopping dorzolamide. Risk factors were previous cataract surgery, mainly aphakia, filtering surgery and previous vitrectomy.. Dorzolamide could have a potential negative effect on patients with endothelial compromise.

Topics: Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Cornea; Endothelium, Corneal; Filtering Surgery; Glaucoma; Humans; Keratoplasty, Penetrating; Male; Middle Aged; Retrospective Studies; Sulfonamides; Thiophenes; Vitrectomy

The management of glaucoma has been changed in the past decade by the introduction of new drugs. The impact of these changes on clinical care of patients was examined by examining operation and prescribing rates for glaucoma in four geographical areas of Scotland for the years 1994 to 1999.. A retrospective analysis of national health statistics: primary care prescribing data, hospital derived operation rates, consultant numbers, optometrist numbers, and eye test data, expressed by estimated population at risk of glaucoma. The outcome measures were prescribing volume and cost for glaucoma medications, and operation rates, corrected for population estimated to be at risk of glaucoma (PEG), for trabeculectomy, for Scotland as a whole, and for four geographical "regions" (north east, south east, central, and south west Scotland).. Prescribed items per 1000 population estimated to have glaucoma (PEG) increased by 24.9% between 1994 and 1999. This was above the general increase in prescribing in Scotland (17.8%). This increase varied in the four health regions evaluated (14.3% to 31.9%). Prescribing of topical beta blockers increased little (6.4%), but there was a large increase in the use of new products (topical prostaglandins, carbonic anhydrase inhibitors, and alpha(2) agonists), at the expense of miotics (47.7% fall), and older sympathomimetics. This change in prescribing pattern was accompanied by a 61.5% increase in cost (range 42.2% to 73.4% in the four regions). New drugs accounted for more than half of total glaucoma expenditure in 1999. Operation rates (corrected for PEG) fell by 45.9% (range 43.1 to 58.6%) between 1994 and 1999. Other indicators suggested increased activity in ophthalmic areas (for example, cataract operations, eye tests, numbers of optometrists and ophthalmic surgeons all increased). Within north east Scotland operation rates decreased and prescribing increased less than in other regions, both from lowest regional baseline in 1994.. The introduction of new drug classes has had dramatic effects on the prescribing of glaucoma treatments. There has been a decline in older treatments and an increase in new agents, which has been associated with a large reduction in operation rates for glaucoma in Scotland over 6 years. Comparison of prescribing and operation data indicates regional differences in healthcare delivery for glaucoma.

Topics: Administration, Topical; Adrenergic alpha-Antagonists; Adult; Aged; Aged, 80 and over; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Drug Costs; Drug Prescriptions; Glaucoma; Humans; Latanoprost; Middle Aged; Miotics; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Quinoxalines; Retrospective Studies; Scotland; Sulfonamides; Sympathomimetics; Thiophenes; Trabeculectomy

To determine the additive intraocular pressure reduction of various topical glaucoma agents used adjunctively with latanoprost.. Retrospective interventional case series.. Retrospective evaluation of 73 eyes of 73 patients with glaucoma and inadequate intraocular pressure control on latanoprost alone. Each patient received adjunctive treatment with an additional glaucoma agent (dorzolamide, brimonidine, timolol, or other beta-blockers) for 1 year.. When added to latanoprost, dorzolamide lowered intraocular pressure an additional 3.9 mm Hg (19.7%, P <.001); beta-blockers further reduced intraocular pressure by 2.0 mm Hg (12.3%, P <.001), and brimonidine further reduced intraocular pressure by 2.0 mm Hg (9.3%, P =.0011). Dorzolamide dosed twice or three times daily was as effective as adjunctive therapy with latanoprost (P =.92).. Adjunctive therapy with dorzolamide provided a statistically significant intraocular pressure reduction at 1 year in eyes that were inadequately controlled with latanoprost alone.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Antihypertensive Agents; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Drug Synergism; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Prostaglandins F, Synthetic; Quinoxalines; Retrospective Studies; Sulfonamides; Thiophenes

Reaction of diethylenetriamino pentaacetic acid (dtpa) dianhydride with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded bis-sulfonamides containing metal-complexing, polyamino-polycarboxylic acid moieties in their molecule. The corresponding mono-sulfonamide derivatives of dtpa were also obtained by an alternative method, from the free acid. Zn(II) complexes of these new sulfonamides were then prepared. Many of these derivatives showed nanomolar affinity towards isozymes I, II and IV of carbonic anhydrase (CA). Some of the best inhibitors were applied as 2% water solutions/suspensions into the eye of normotensive or glaucomatous albino rabbits, when strong and long-lasting intraocular pressure (IOP) lowering was observed.

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Intraocular Pressure; Pentetic Acid; Quantitative Structure-Activity Relationship; Rabbits; Sulfonamides; Zinc

Reaction of 4-carboxy-benzenesulfonamide or 4-chloro-3-sulfamoyl benzoic acid with carboxy-protected amino acids/dipeptides, or aromatic/heterocyclic sulfonamides/mercaptans afforded the corresponding benzene-carboxamide derivatives. These were tested as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV. Some of the new derivatives showed affinity in the low nanomolar range for isozymes CA II and IV, involved in aqueous humor secretion within the eye, and were tested as topically acting anti-glaucoma agents, in normotensive and glaucomatous rabbits. Good in vivo activity and prolonged duration of action has been observed for some of these derivatives, as compared to the clinically used drugs dorzolamide and brinzolamide. Some of the 4-chloro-3-sulfamoyl benzenecarboxamides reported here showed higher affinity for CA I than for the sulfonamide avid isozyme CA II.

Topics: Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Intraocular Pressure; Rabbits; Sulfonamides

Sulfonamides incorporating cis-5-norbornene-endo-3-carboxy-2-carboxamido moieties in their molecules were prepared by reaction of cis-5-norbornene-endo-2,3-dicarboxylic anhydride with aromatic/heterocyclic sulfonamides possessing free amino, hydrazino, or imino groups. Some of these compounds showed very good CA II and CA IV inhibitory properties, with affinities for the enzymes in the low nanomolar range. Some of the most active CA II inhibitors reported here have been formulated as aqueous solutions for topical administration as antiglaucoma agents in normotensive rabbits. Some of the derivatives incorporating cis-5-norbornene-endo-3-carboxy-2-carboxamido and aromatic sulfonamide moieties (as sodium salts) showed effective and longer lasting intraocular pressure (IOP) lowering as compared to dorzolamide, a widely used topical antiglaucoma drug. Compounds incorporating cis-5-norbornene-endo-2,3-carboximido moieties, although stronger in vitro CA inhibitors as compared to the corresponding cis-5-norbornene-endo-3-carboxy-2-carboxamido-;derivatives, showed no topical IOP lowering properties, probably due to their very poor water solubility.

Topics: Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cloning, Molecular; Escherichia coli; Glaucoma; Humans; Indicators and Reagents; Isoenzymes; Kinetics; Norbornanes; Recombinant Proteins; Structure-Activity Relationship; Sulfonamides; Thiazines; Thiophenes

To compare the reduction in intraocular pressure (IOP) by topical 2% dorzolamide to oral methazolamide (5 mg/kg) in dogs, and determine if the combination of both drugs would reduce IOP more than either drug administered alone.. Thirteen glaucomatous beagles.. Measurements, including applanation tonometry, pupil size and heart rate, were obtained at 8 am, 12 noon, and 5 pm on days 1, 3 and 5. The 5-day drug studies included placebo (0.5% methylcellulose); 2% dorzolamide administered in one eye twice daily (8 am and 5 pm), and repeated again in one eye three times (8 am, 12 noon and 5 pm) daily; methazolamide (5 mg/kg per os administered at 8 am and 5 pm); 2% dorzolamide instilled twice daily (5 days) combined with oral methazolamide on the last 3 days, and methazolamide (5 days) combined with 2% dorzolamide on the last 3 days and instilled twice daily. Statistical comparisons between drug groups included control (nondrug) eye and treated (placebo/drug) eyes for days 1, day 3 and 5.. Topical 2% dorzolamide, administered twice and three times daily, significantly decreased IOP (mean +/- SEM) in glaucomatous dogs on the first day (twice daily 7.6 +/- 2.4 mmHg, and three times daily 16.4 +/- 3.6 mmHg) that was even greater by day 5 (twice daily 10.4 +/- 2.0 mmHg, and three times daily 13.9 +/- 2.7). Oral methazolamide also significantly lowered IOP in both eyes. Oral methazolamide (administered from day 1 through to day 5) combined with 2% topical dorzolamide (instilled in the drug eye for day 3 through to day 5) also significantly lowered IOP of both eyes for all days, and for day 5 the mean +/- SEM IOP was decreased by 7.9 +/- 1.7 mmHg (methazolamide plus dorzolamide) and 7.5 +/- 2.6 mmHg (methazolamide only). Topical dorzolamide (instilled in the drug eye for day 1 through to day 5) combined with oral methazolamide (administered from day 3 through to day 5) significantly lowered IOP in the drug eye on day 1 (5 pm: 9.6 +/- 1.9 mmHg), for day 3 (11 am and 5 pm) and for all of day 5 for both eyes (5 pm: control eye 9.5 +/- 1.8 mmHg; drug eye 9.2 +/- 1.9 mmHg). Topical dorzolamide (2%) instilled three times daily produces similar IOP declines compared to the combination of oral methazolamide and 2% dorzolamide administered twice daily.. Dorzolamide (2%) instilled twice or three times daily causes significant decreases in IOP in glaucomatous dogs. Twice daily instillations caused progressive declines in IOP from day 1 to day 5. Dorzolamide (2%) combined with oral methazolamide (5 mg/kg per os twice daily) produces similar but not additional declines in IOP.

Topics: Administration, Oral; Administration, Topical; Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Dog Diseases; Dogs; Drug Administration Schedule; Female; Glaucoma; Intraocular Pressure; Male; Methazolamide; Ophthalmic Solutions; Sulfonamides; Thiophenes; Treatment Outcome

To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs.. 15 Beagles.. The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 microl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study.. In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 microl/min (43%) after treatment in the dorzolamide group.. Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma.

Topics: Administration, Topical; Animals; Aqueous Humor; Carbonic Anhydrase Inhibitors; Dogs; Female; Fluorophotometry; Glaucoma; Intraocular Pressure; Male; Random Allocation; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Conjunctivitis, Allergic; Dermatitis, Allergic Contact; Diagnosis, Differential; Glaucoma; Humans; Male; Middle Aged; Ophthalmic Solutions; Patch Tests; Sulfonamides; Thiophenes

Topics: Aged; Blepharitis; Carbonic Anhydrase Inhibitors; Conjunctivitis, Allergic; Dermatitis, Allergic Contact; Glaucoma; Humans; Male; Ophthalmic Solutions; Patch Tests; Sulfonamides; Thiophenes

Topical carbonic anhydrase inhibitors have been used since 1995 for medical glaucoma therapy, when dorzolamide was approved. In 2000, a second carbonic anhydrase inhibitor, brinzolamide, has become available in most of Europe. Both substances exhibit a comparable intraocular pressure-lowering activity, however, the side-effects are somewhat different. In the five years since its introduction, dorzolamide has had a positive risk-benefit-profile. In combination with any other topical agent, carbonic anhydrase inhibitors have an additive effect on the reduction of the intraocular pressure. Animal studies suggest that dorzolamide may improve ocular blood flow independent of the intraocular pressure; however, the significance for human glaucoma remains to be established.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Rabbits; Sulfonamides; Thiazines; Thiophenes; Time Factors; Timolol

The authors investigated the effect on pH of the aqueous humour in man (collected before surgery of senile cataract, where the pH of the aqueous humour was within the range of 6.80-7.46 (7.11 +/- 0.11), after administration of antiglaucomatic drugs with a different concentration and pH (0.005% Xalatan--pH 6.43, 0.5% Timoptol--pH 6.80, 1% Pilocarpine--pH 5.87, 2% Trusopt--pH 5.33) under conditions in vitro. All mentioned antiglaucomatic drugs immediately reduced the pH of the aqueous humour towards acid values in the following order: Trusopt-Xalatan-Pilocarpine-Timoptol. pH changes of aqueous humour after addition of Timoptol, Xalatan, Pilocarpine have the same course in time, and shift to alkaline pH values. The pH of aqueous humour after addition of Trusopt reached only during the 240th minute levels of the control aqueous humour. The pH values after all antiglaucomatic drugs did not change between 240 minutes and 24 hours. As regards the rate of activity and extent of effect in conjunction with the time when the pH of the control aqueous humour was attained the authors recorded the following order: Pilocarpine-Timoptol-Xalatan-Trusopt.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Aqueous Humor; Female; Glaucoma; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Latanoprost; Male; Middle Aged; Pilocarpine; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Reaction of aromatic/heterocyclic sulfonamides possessing free amino, imino or hydrazino moieties with 7-chloro-4-chloromethylcoumarin afforded a series of N-[(7-chloro-4-coumarinyl)-methyl]- derivatives which showed effective inhibition of three carbonic anhydrase (CA) isozymes. Topical application within the rabbit eye of some of these compounds led to effective intraocular pressure lowering due to CA inhibition within the ocular tissues, and reduced aqueous humor production.

Topics: Amines; Animals; Aqueous Humor; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cattle; Glaucoma; Humans; Intraocular Pressure; Rabbits; Structure-Activity Relationship; Sulfonamides

Novel non-chiral 2H-thieno[3,2-e]- and [2,3-e]-1,2-thiazine-6-sulfonamide 1,1-dioxides were synthesized for evaluation as potential candidates for the treatment of glaucoma. All of the compounds prepared were potent high affinity inhibitors of human carbonic anhydrase II, Ki < 0.5 nM. Additionally, inhibition of recombinant human carbonic anhydrase IV was determined for selected compounds; these were shown to be moderate to potent inhibitors of this isozyme with IC50 values ranging from 4.25 to 73.6 nM. Of the compounds evaluated for their ability to lower intraocular pressure in naturally hypertensive Dutch-belted rabbits, 5a, 17a3, 17b1, 17b2, 17h2 and 17i1 showed significant efficacy (> 20% decrease) in this model following topical ocular administration.

Topics: Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Drug Evaluation; Glaucoma; Humans; Intraocular Pressure; Magnetic Resonance Spectroscopy; Rabbits; Sulfonamides

Reaction of perfluoroalkyl/arylsulfonyl chlorides or perfluoroalkyl/arylcarbonyl chlorides with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded compounds with the general formula C(x)()F(y)()Z-A-SO(2)NH(2), where Z = SO(2)NH, SO(3), CONH, or CO(2) and A = aromatic/heterocyclic moiety. The sulfonyl chlorides used in synthesis included: CF(3)SO(2)Cl, n-C(4)F(9)SO(2)Cl, n-C(8)F(17)SO(2)Cl, and C(6)F(5)SO(2)Cl, whereas the acyl chlorides were C(8)F(17)COCl and C(6)F(5)COCl. A total of 25 different sulfonamides have been derivatized by means of the above-mentioned perfluorosulfonyl/acyl halides. These new series of sulfonamides showed strong affinities toward isozymes I, II, and IV of carbonic anhydrase (CA). For a given sulfonamide derivatized by the above procedures, inhibitory power was greater for the alkyl/arylsulfonylated compounds, as compared to the corresponding perfluoroalkyl/arylcarbonylated ones. In vitro inhibitory activity generally increased with the number of carbon atoms in the molecule of the acylating/sulfonylating agent, with a maximum for the perfluorophenylsulfonylated and perfluorobenzoylated derivatives. Some of the prepared CA inhibitors displayed very good water solubility (in the range of 2%) and strongly lowered intraocular pressure (IOP) when applied topically, directly into the normotensive/glaucomatous rabbit eye, as 2% water solutions. The good water solubility of these new classes of CA inhibitors, correlated with the neutral pH of their solutions used in the ophthalmologic applications, makes them attractive candidates for developing novel types of antiglaucoma drugs devoid of unpleasant ocular side effects.

Topics: Administration, Topical; Animals; Aqueous Humor; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cattle; Glaucoma; Humans; Intraocular Pressure; Isoenzymes; Lung; Rabbits; Solubility; Structure-Activity Relationship; Sulfonamides; Tissue Distribution; Uvea

A series of sulfonamides has been obtained by reaction of 4-isothiocyanatobenzenesulfonamide with amines, amino acids, and oligopeptides. The new thiourea derivatives showed strong affinities toward isozymes I, II, and IV of carbonic anhydrase (CA, EC 4.2.1.1). In vitro inhibitory power was good (in the low-nanomolar range) for the derivatives of beta-phenylserine and alpha-phenylglycine, for those incorporating hydroxy and mercapto amino acids (Ser, Thr, Cys, Met), hydrophobic amino acids (Val, Leu, Ile), aromatic amino acids (Phe, His, Trp, Tyr, DOPA), and dicarboxylic amino acids as well as di/tri/tetrapeptides among others. Such CA inhibitors displayed very good water solubility (in the range of 2-3%) mainly as sodium (carboxylate) salts, with pH values of the obtained solutions being 6.5-7.0. Some of these preparations (such as the derivatives of Ser, beta-Ph-Ser, Leu, Asn, etc.) strongly lowered intraocular pressure (IOP) when applied topically, directly into the normotensive/glaucomatous rabbit eye, as 2% water solutions. It is interesting to note that not all the powerful CA inhibitors designed in the present study showed topical IOP-lowering effects (such as, for instance, the Cys and Lys derivatives, devoid of such properties) whereas the Pro, Arg, and oligopeptidyl thiourea derivatives showed reduced efficacy when administered topically. This may be due to the very hydrophilic nature of some of these compounds, whereas inhibitors with balanced hydro- and liposolubility also showed optimal in vivo effects. The interesting pharmacological properties of this new type of CA inhibitors, correlated with the neutral pH of their solutions used in ophthalmologic applications, make them attractive candidates for developing novel antiglaucoma drugs devoid of major ocular side effects.

Topics: Animals; Carbonic Anhydrase Inhibitors; Cornea; Eye; Glaucoma; Hydrogen-Ion Concentration; Intraocular Pressure; Ophthalmic Solutions; Rabbits; Solubility; Structure-Activity Relationship; Sulfonamides; Thiourea; Tissue Distribution; Water

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Diabetes Mellitus, Type 2; Glaucoma; Humans; Levobunolol; Male; Middle Aged; Mouth Mucosa; Ophthalmic Solutions; Pemphigoid, Bullous; Sulfonamides; Thiophenes; Timolol

To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide.. Domestic pigs were used as experimental animals. Oxygen tension was measured by means of a polarographic electrode in the vitreous 0.5 mm anterior to the optic disc. This entity is called the optic nerve oxygen tension. Intraocular pressure was controlled by a hypodermic needle inserted into the anterior chamber and connected to a saline reservoir.. When the intraocular pressure was clamped at 20 cm H2O optic nerve oxygen tension was 20 (5) mm Hg (n=8). Intravenous administration of dorzolamide caused an increase in optic nerve oxygen tension of 43 (8)% (n=6). Both before and after administration of dorzolamide optic nerve oxygen tension was unaffected by changes in intraocular pressure, as long as this pressure remained below 60 cm H2O. At intraocular pressures of 60 cm H(2)O and below, dorzolamide significantly increased optic nerve oxygen tension.. Intravenous administration of 500 mg dorzolamide increases the oxygen tension at the optic nerve head during acute increases in intraocular pressure.

Topics: Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Infusions, Intravenous; Intraocular Pressure; Optic Nerve; Oxygen; Sulfonamides; Swine; Thiophenes

The relation between Goldmann applanation tonometry and central corneal thickness (CCT) was investigated in several studies during the last thirty years. It was the aim of the present study to evaluate CCT in normals, patients with ocular hypertension, low-tension, and open-angle glaucomas.. CCT was measured in 135 normal eyes, 137 with ocular hypertension, 65 with low-tension, and 94 with primary and secondary open-angle glaucomas using the AL-11000-pachymeter (Tomey). The results were compared using the unpaired t-test.. CCT was significantly higher in the patients with ocular hypertension (586 +/- 43 microns) than in the normal group (566 +/- 37 microns, p < 0.0001), in low-tension glaucomas (555 +/- 46 microns, p < 0.0001), and in open-angle glaucomas (558 +/- 31 microns, p < 0.0001). The latter three groups did not differ significantly. There was no significant correlation between CCT and age, the actually measured IOP, the highest IOP in the patient's history, or the spherical equivalent.. Only patients with ocular hypertension showed a significant difference in CCT compared with normals. Pachymetry thus should be conducted in those patients to avoid overestimation of the IOP by applanation tonometry. In most of the patients with low-tension and open-angle glaucomas however, CCT regarded without other parameters (e.g. corneal or scleral rigidity) plays a minor role in detection of elevated IOP according to the results of this study.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Case-Control Studies; Cornea; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Reference Values; Sex Distribution; Sulfonamides; Thiophenes

To investigate the additive ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears to timolol in monkey eyes with laser-induced unilateral glaucoma.. Eight monkeys were used and each animal received all four combinations of drugs in a randomized fashion during the study. The washout period between each combination was at least 2 weeks. Intraocular pressure (IOP) was measured at 8:30 AM, 11:00 AM, 1:00 PM, and 3:30 PM on day 1 (untreated baseline), day 2 (timolol treatment alone), and days 3 through 5 (combination therapy with two drugs). One drop of 0.5% timolol was topically applied at 3:45 PM on day 1 and at 8:45 AM and 3:45 PM on days 2 through 5. One drop of 0.2% brimonidine or 2% dorzolamide or artificial tears was added on day 2 at 4:00 PM and at 9:00 AM and 4:00 PM on days 3 through 5, or latanoprost was added at 9:00 AM on days 3 through 5.. Compared with timolol alone, the maximal additive reduction in IOP which occurred on day 5 was 4.8 +/- 0.8 mm Hg (mean +/- standard error of the mean) with timolol plus brimonidine, 5.6 +/- 1.0 mm Hg with timolol plus dorzolamide, 4.3 +/- 1.0 mm Hg with timolol plus latanoprost, and 2.0 +/- 0.5 mm Hg with timolol plus artificial tears (P < 0.01). At all measurements, timolol plus brimonidine, timolol plus dorzolamide, and timolol plus latanoprost caused greater (P < 0.05) IOP reductions than did timolol plus artificial tears. The additive IOP-lowering effect was similar (P > 0.60) when comparing timolol plus brimonidine and timolol plus dorzolamide, timolol plus brimonidine and timolol plus latanoprost, timolol plus dorzolamide and timolol plus latanoprost at all measurements, but timolol plus dorzolamide caused a greater (P < 0.05) reduction of IOP than did timolol plus latanoprost at 0 hours on day 5.. The addition of brimonidine, dorzolamide, or latanoprost to timolol caused similar additional reductions of IOP in glaucomatous monkey eyes.

Topics: Animals; Antihypertensive Agents; Brimonidine Tartrate; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma; Intraocular Pressure; Latanoprost; Macaca fascicularis; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Random Allocation; Sulfonamides; Thiophenes; Timolol

To know, in long term, the effects in IOP of dorzolamide as adjunctive treatment to beta-blockers. To compare the hypotensory potential added to the different beta-blockers (selective, non-selective, with I.S.A.). To compare its potential as hypotensive drug versus another drugs in association to beta-blockers- pilocarpine and dipivalilepinefrina.. A descriptive-retrospective randomised study about 132 eyes with glaucoma, with 16 months of mean follow-up; divided into three groups: one of the patients treated with association to beta-blockers, and the two others patients treated with a combination of beta-blockers with pilocarpine or DPVE, in which they were substituted by dorzolamide. Student T was used for comparing the media.. The average IOP reduction was 21.48 to 18.39 mmHg, with the addiction of dorzolamide to beta-blockers. Between the different beta-blockers, the non selective showed a higher hypotensive effect in association to dorzolamide (5.23 mmHg), more than selective (3.75 mmHg), but not significantly higher than those with I.S.A. (4.29 mmHg). In substitution of pilocarpine or DPVE, in its use associated to beta-blockers, dorzolamide showed a significantly higher efficacy, with an average IOP reduction of 4.16 mmHg by pilocarpine, and 4.33 by DPVE.. Dorzolamide gets a higher hypotensive effect by adding it to patients in treatment with beta-blockers, principally with the non selective ones. In this way, it has shown a superior hypotensive effect than pilocarpine and DPVE.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma; Humans; Male; Retrospective Studies; Sulfonamides; Thiophenes; Time Factors

The purpose of this study was to estimate and evaluate costs of glaucoma therapy in Poland in 1998-2000 years.. 315 patients (591 eyes) including 364 POAG eyes and 227 PACG eyes were evaluated. Progression of the disease was measured in two modes: by changes in the optical nerve disc (c/d) and by IOP level. Duration of the study was 12 months. Total costs (e.g. number of visits, amount of medications used, surgical and laser procedures performed) were calculated on 100 eyes/12 months.. Pharmacological therapy constitutes 40-50% of the total costs in both glaucoma types. Timolol was the mostly prescribed drug in POAG, while pilocarpine led in PACG group. Dorzolamide was on the third place, but it generated the biggest part of total costs. Patients with advanced forms of the disease more frequently saw doctor on visits (average 6 visits per year); patients with elevated IOP (> 21 mm Hg) underwent surgical procedures more commonly than these with optical nerve disc changes (c/d > 0.6). The total costs of the therapy of non-advanced cases amounted 70.243 PLN on the average, while in advanced cases it reached the average of 155.230 PLN.. 1. The total cost of glaucoma therapy depends on progression of the disease. 2. The most cost-generating part is the pharmacological therapy of glaucoma.

Topics: Adult; Aged; Aged, 80 and over; Costs and Cost Analysis; Disease Progression; Female; Glaucoma; Humans; Intraocular Pressure; Laser Therapy; Male; Middle Aged; Office Visits; Pilocarpine; Poland; Sulfonamides; Thiophenes; Timolol

Reaction of 26 aromatic/heterocyclic sulfonamides containing amino, imino, hydrazino, or hydroxyl groups with Boc-Gly, Boc-Sar, TrS-Crt, or Boc-Gly-Gly (Sar = sarcosine, N-Me-Gly; Crt = creatine, N-amidinosarcosine; TrS = tritylsulfenyl; Boc = tert-butoxycarbonyl) in the presence of carbodiimide derivatives afforded after removal of the protecting groups a series of water-soluble compounds (as salts of strong acids, such as hydrochloric, trifluoroacetic, or trifluoromethanesulfonic). The new derivatives were assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA) and more precisely of three of its isozymes, CA I, II (cytosolic forms), and IV (membrane-bound form), involved in important physiological processes. Efficient inhibition was observed against all three isozymes and especially against CA II and IV (in the nanomolar range), the two isozymes known to play a critical role in aqueous humor secretion within the ciliary processes of the eye. Some of the best inhibitors synthesized were applied as 2% water solutions into the eye of normotensive or glaucomatous albino rabbits, when strong and long-lasting intraocular pressure (IOP) lowering was observed with many of them. Thus, the aminoacyl/dipeptidyl tail conferring water solubility to these sulfonamide CA inhibitors coupled with strong enzyme inhibitory properties and balanced lipid solubility seem to be the key factors for obtaining compounds with effective topical antiglaucoma activity.

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cell Membrane Permeability; Cornea; Delayed-Action Preparations; Dipeptides; Disease Models, Animal; Glaucoma; Humans; Intraocular Pressure; Isoenzymes; Models, Molecular; Rabbits; Solubility; Sulfonamides; Time Factors

Topics: Adrenergic alpha-Agonists; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Clonidine; Drug Approval; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Netherlands; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes

To describe irreversible corneal decompensation after topical dorzolamide hydrochloride (Trusopt; Merck and Co, Inc, West Point, Pennsylvania) therapy in nine patients who had histories consistent with corneal endothelial compromise.. Multicenter review of patients' charts.. Nine eyes of nine patients developed overt corneal decompensation after starting topical dorzolamide, a condition that did not resolve with drug cessation. This occurred after 3 to 20 weeks (mean, 7.8) of therapy. All nine patients had undergone intraocular surgery. Eight patients had undergone cataract surgery; three were aphakic and three had posterior chamber intraocular lenses. Two patients had anterior chamber intraocular lenses and also had undergone trabeculectomies. Four patients had undergone penetrating keratoplasties, each case complicated by episodes of corneal allograft rejection that were successfully treated. Two patients had asymptomatic Fuchs endothelial dystrophy. Seven patients have since undergone successful penetrating keratoplasties.. The reports suggest that dorzolamide can cause irreversible corneal edema in a subset of glaucoma patients with endothelial compromise. The findings suggest a rationale for research into the long-term effects of dorzolamide on the corneal endothelium.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Corneal Edema; Endothelium, Corneal; Female; Glaucoma; Humans; Intraocular Pressure; Keratoplasty, Penetrating; Male; Middle Aged; Ophthalmic Solutions; Refractive Errors; Retrospective Studies; Sulfonamides; Thiophenes; Visual Acuity

Topics: Adolescent; Adult; Aged; Carbonic Anhydrase Inhibitors; Female; Glaucoma; Humans; Kidney; Kidney Calculi; Male; Sulfonamides; Thiophenes

Dorzolamide is the first commercial topical carbonic anhydrase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of glaucoma. In a prospective, open label, uncontrolled study on 245 glaucoma patients, dorzolamide significantly lowered the intraocular pressure at least 14% when used alone or in combination with one, two, or three other antiglaucoma medications over ten weeks. There were very few adverse reactions to dorzolamide. Dorzolamide is effective and safe when used alone or in combination with other topical antiglaucoma medications for the treatment of glaucoma.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Prospective Studies; Sulfonamides; Thiophenes

Topics: Administration, Topical; Carbonic Anhydrase Inhibitors; Corneal Edema; Glaucoma; Humans; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Glaucoma; Government Agencies; Humans; Latanoprost; New Zealand; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes

The authors investigated in a group of six children with glaucoma persisting for a long time the possibility to use locally applied carbonic anhydrase inhibitor, 2% dorsolamide hydrochloride in the form of eye drops (TRUSOPT, Merck Co.). In the submitted preliminary study they evaluate the effectiveness of the drug in glaucoma in children very favourably, previous essential treatment with oral acetazolamide could be discontinued in all patients without a deleterious effect. The authors did not encounter any undesirable effects of the drug nor manifestations of intolerance calling for discontinuation of TRUSOPT treatment. This is so far the first communication on TRUSOPT treatment of child glaucoma in the available literature.

Topics: Adolescent; Carbonic Anhydrase Inhibitors; Child; Child, Preschool; Female; Glaucoma; Humans; Male; Ophthalmic Solutions; Sulfonamides; Thiophenes

Topics: Aged; Antihypertensive Agents; Glaucoma; Humans; Intraocular Pressure; Sulfonamides; Thiophenes; Trabeculectomy

To report a case of glaucomatocyclitic crisis (Posner-Schlossman syndrome) in a child.. Case report. A 13-year-old boy presented with decreased vision, photophobia, halos, and pain in the right eye.. Findings in this child were consistent with a diagnosis of Posner-Schlossman syndrome.. Glaucomatocyclitic crisis can occur in a child and must be included in the differential diagnosis of uveitis and glaucoma in pediatric patients.

Topics: Adolescent; Clonidine; Corneal Edema; Diagnosis, Differential; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Male; Pain; Prednisolone; Sulfonamides; Syndrome; Thiophenes; Timolol; Uveitis, Intermediate; Vision Disorders; Visual Acuity

Topics: Adrenergic beta-Antagonists; Aqueous Humor; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Sleep; Sulfonamides; Thiophenes; Timolol

Topics: Antihypertensive Agents; Glaucoma; Humans; Intraocular Pressure; Ophthalmic Solutions; Sulfonamides; Thiophenes

Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Corneal Diseases; Drug Therapy, Combination; Endothelium, Corneal; Glaucoma; Humans; Intraocular Pressure; Sulfonamides; Thiophenes

A series of N-hydroxy sulfonamides has been prepared by reaction of alkyl-, arylalkyl- and arylsulfonyl halides or sulfonic acid anhydrides with hydroxylamine. Structurally related inhibitors were also obtained from acyl chlorides and hydroxylamine, as well as by reaction of tosyl isocyanate with hydroxylamine, sulfamic acid and sulfamide. Inhibition of three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human; b = bovine) with the prepared compounds has been investigated. Good inhibitors, as well as compounds with moderate activity against these isozymes were detected, depending on the R group to which the SO2NHOH or CONHOH moieties were attached. Susceptibility to inhibition was generally: hCA II > bCA IV >> hCA I. Some of the new inhibitors showed very good antiglaucoma action when administered directly into the eye in experimental animals, acting as more efficient intraocular pressure lowering agents as compared to the clinical drug dorzolamide. This constitutes an encouraging result for obtaining novel antiglaucoma drugs from this class of CA inhibitors.

Topics: Acetamides; Animals; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cattle; Glaucoma; Humans; Hydroxylamines; Intraocular Pressure; Isoenzymes; Male; Rabbits; Structure-Activity Relationship; Sulfonamides; Sulfonic Acids; Thiophenes; Tosyl Compounds

Topics: Antihypertensive Agents; Dermatitis, Allergic Contact; Female; Glaucoma; Humans; Middle Aged; Ophthalmic Solutions; Patch Tests; Skin; Sulfonamides; Thiophenes

Topics: Adrenergic alpha-Agonists; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Dinoprost; Glaucoma; Humans; Quinoxalines; Sulfonamides; Thiophenes

The purpose of this study was to evaluate prospectively the value of dorzolamid as an adjunct to maximum tolerated medical therapy in glaucoma patients in whom surgery would otherwise be required.. 32 eyes of 21 patients with primary open angle glaucoma (14 patients), glaucoma in aphakia (3 patients), pigmentary glaucoma (2 patients), juvenile glaucoma (1 patient) and exfoliative glaucoma (1 patient) were included. The effect of additional dorzolamid application on intraocular pressure (IOP) was determined after 2 hours, 4 days, 4 weeks, 3 months and 6 months. After 6 months, visual fields were checked.. Average reduction of IOP in eyes in which dorzolamid was continued was determined to be 31% after 2 hours, 18.3% after 4 days, 17.9% after 4 weeks, 12.1% after 3 months and 9.7% after 6 months. 19 (59%) eyes continued to receive dorzolamid after 6 months without being operated. No progression of glaucomatous damage could be detected in these eyes. In 11 (34%) eyes, treatment with dorzolamid was discontinued. 2 patients (4 (12%) eyes) did not tolerate local side effects of dorzolamid. In 7 (22%) eyes reduction of IOP was insufficient and filtration surgery had to be performed immediately.. The results of the present study demonstrate that dorzolamid represents an alternative to an immediate surgical management in patients on maximum tolerated therapy for at least six months.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Prospective Studies; Sulfonamides; Thiophenes; Treatment Outcome

Clinical evaluation of the efficacy and innocuity of dorzolamide, the first new born topical carbonic anhydrase inhibitor.. Our retrospective analysis included 162 patients (76 men, 86 women) who were exclusively followed in our department and treated between June 96 and August 97 with dorzolamide (Trusopt 2%) administered in a minority of patients (n = 13) as the only hypotensive medication and in combination with other hypotensive drugs and/or as a substitute for acetazolamide or for miotics in the others (add on, n = 149). The mean age of the patients was 65.2 +/- 15.6 and the average follow up was 9.8 +/- 5.4 months. Dorzolamide was prescribed in various forms of glaucoma and ocular hypertension, mostly in POAG (n = 137). In bilateral treatments (n = 116/162), the eye with the most severe defect and/or the highest IOP was considered. IOP was checked along the other criteria generally followed in glaucoma patients at 1 and 3 months following the instauration of dorzolamide and then trimestrially. We considered as the initial IOP a mean value of the 2 most recent successive IOP values before instauration of dorzolamide realized at the same daytime. Patients with laser trabeculoplasty or cataract surgery during the dorzolamide treatment were disguarded.. All patients considered, the mean IOP reduction was from 21.5 mm Hg before to 19.3 mm Hg with dorzolamide at the last control. The mean IOP decrease was statistically significant and stable at all controls. The mean IOP reduction was 18.4% (4.2 mm Hg) in the monotherapy group and 12.5% (3 mm Hg) in the add on group. There were 15.3% non responders (mean IOP reduction < half of the average IOP decrease observed all patients confounded) in the monotherapy group and 26% in the add on group. Local tolerance of dorzolamide was excellent in 84%. About 15% of patients (25/162) complained of systemic side effects mostly comparable to the side effects of oral IAC. Treatment was stopped in 57 patients (35.2%) primarily due to allergic blepharoconjunctivitis (n = 12 or 7.4%), general intolerance (n = 14 or 8.6%) and insufficient IOP reduction (n = 26 or 16%).. Dorzolamide represents in our experience an effective ocular hypotensive drug but its systemic tolerance profile seems less promising than described in the literature.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbonic Anhydrase Inhibitors; Child; Female; Glaucoma; Humans; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies; Sulfonamides; Thiophenes

Topics: Administration, Topical; Aged; Carbonic Anhydrase Inhibitors; Choroid Diseases; Ciliary Body; Female; Filtering Surgery; Glaucoma; Humans; Intraocular Pressure; Ocular Hypotension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Ultrasonography; Uveal Diseases

Topics: Adult; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Intraocular Pressure; Male; Ophthalmic Solutions; Sulfonamides; Thiophenes

Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Sulfonamides; Thiophenes

The aim of this study was to set-up and validate the use of a radio-telemetry system in order to record IOP in chronic ocular hypertensive animals. The transmitter of a miniaturized radio-telemetry system was implanted in rabbits, and its catheter was tunnelled subcutaneously to the superior conjunctival sac and inserted into the midvitreous. Implantation was performed in chronic ocular hypertensive rabbits induced by an injection of alpha-chymotrypsin into the posterior chamber of the eye. The effects of 0.5% timolol maleate, 2% dorzolamide hydrochloride and 1% epinephrine were assessed and compared after topical administration in this model. Implanted radio-telemetric system into the vitreous allowed IOP measurement for more than 6 months. In this study, circadian IOP kinetic profiles were monitored in all animals over 24 h for 3 weeks. Timolol maleate was found significantly potent in reducing IOP, while changes depended on the nyctemeral period. Dorzolamide hydrochloride induced a very large IOP reduction and was found to be also well effective at night. We evidenced a biphasic time-dependent effect after topical epinephrine, with a long lasting IOP increase occurring after the administration. This change was found to be related to side effects resulting from a poor ocular tolerance of this drug in the rabbit, leading to either a complete eye closure or a higher blinking rate. By using our method, we confirmed the pressure pulses and undershoots occurring during blinking. Radio-telemetry in chronic glaucoma rabbits appears as a refined method to assess anti-glaucoma drug activity, 24 hours a day, for long-term periods in unrestrained animals, while also providing information on the ocular side effects of eye drops.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase Inhibitors; Chymotrypsin; Circadian Rhythm; Disease Models, Animal; Epinephrine; Female; Glaucoma; Intraocular Pressure; Ophthalmic Solutions; Rabbits; Sulfonamides; Telemetry; Thiophenes; Timolol

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Glaucoma; Humans; Sulfonamides; Thiophenes

L-671,152, a new potent water-soluble inhibitor of human carbonic anhydrase II in vitro, was applied topically to cynomolgus monkey eyes in which glaucoma had been produced by argon laser photocoagulation of the trabecular mesh-work. Intraocular pressure was measured at 0 hours, 0.5 hours, and hourly for 8 hours in eight eyes for 2 baseline days, 1 day receiving the vehicle and 5 days receiving therapy with 2% L-671,152 twice a day, after initial single-dose trials of various concentrations. Intraocular pressure was not significantly different comparing baseline and vehicle-treated days. Significant intraocular pressure reductions occurred from 1 to 8 hours after the first dose, and lasted for at least 16 hours after the second dose. The reduction in intraocular pressure became more pronounced from day 1 to day 5 at each time interval. The mean (+/- SEM) maximum reduction in intraocular pressure was 7.8 +/- 2.1 mm Hg on day 1 and 10.1 +/- 2.4 mm Hg on day 5 at 3 hours after administration, comparing the intraocular pressure in drug-treated and vehicle-treated eyes. L-671,152 has a longer duration of action than does previously studied MK-927 in glaucomatous monkeys. It appears to have great clinical potential.

Topics: Administration, Topical; Animals; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Female; Glaucoma; Intraocular Pressure; Laser Therapy; Macaca fascicularis; Molecular Structure; Sulfonamides; Thiophenes