dorzolamide-timolol-combination and Glaucoma

Azarga is a new fixed combination product that consists of the carbonic anhydrase inhibitor brinzolamide 1% and the betablocker timolol 0,5%. Its efficacy in lowering intraocular pressure is similar to that of Cosopt, a fixed combination that combines another carbonic anhydrase inhibitor (eg dorzolamide 2%) with the betablocker timolol 0,5%. The main difference between these two ocular hypotensive agents lies in their safety profiles with Cosopt causing more ocular discomfort to appear while instilling (burning,stinging and smarting sensations) probably due to the differences between the pH of these two fixed combinations agents. Its similar efficacy and enhanced tolerability compared with Cosopt make Azarga represent a resonable alternative for the patients who do not achieve an adequate intraocular pressure control while treating with a monotherapeutic agent.

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Combinations; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Sulfonamides; Thiazines; Thiophenes; Timolol; Treatment Outcome; Vision, Ocular

Modern fixed-combination products simplify medication dose regimen without sacrificing their effectiveness.Potential benefits of the therapy with fixed-combination products are enhanced tolerability increased convenience,better compliance,cost and time economy and removal of the wash out effect. Regarding intraocular pressure lowering effect, fixed-combination agents are superior to monotherapy with the two medication components, with the exception of Duotrav that is not superior to travoprost action.Fixed-combination products are noninferior to concomitant administration of the two components of medication (nonfixed-combination agents) relative to their ocular hypotensive efficacy with the exception of Ganfort that is however inferior to concurrent administration of both the bimatoprost and timolol.

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

The emergence of fixed-combination drugs for the treatment of glaucoma has, to some extent, changed the medical management of glaucoma. The potential benefits of these drugs include a reduction in the total number of drops and preservatives instilled per day and improved patient comfort factors, which may contribute to better compliance. Combination medications may also improve therapeutic efficacy and play an important role in controlling medication cost. However, the fixed dosing may be a disadvantage in some cases.. This review describes the composition, pharmacokinetics, mode of action, efficacy, side effects, and safety profile of fixed-combination dorzolamide-timolol and fixed-combination brimonidine-timolol.. Understanding of the pros, cons, and safety profile of two FDA approved fixed-combination antiglaucoma medication.. Fixed-combination medications may be a reasonable adjunct to prostaglandins if a large drop in the intraocular pressure (IOP) is desired and adding only one medication is unlikely to reach the target IOP range. Both mentioned drugs are effective in reducing the IOP and further clinical studies will help identify differences in efficacy between the two. The clinician must make an individualized assessment of the medication's risk-benefit profile for each patient.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Brimonidine Tartrate; Carbonic Anhydrase Inhibitors; Drug Combinations; Glaucoma; Humans; Intraocular Pressure; Patient Selection; Quinoxalines; Risk Assessment; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The fixed combination of dorzolamide and timolol (Cosopt) represents a high effective therapy and is generally well tolerated. It produces a baro-protection similarly to that caused by both the prostaglandin analogs and the other topically fixed combinations. Cosopt is the only hypotensive medication that produces a direct vasoprotection by increasing retrobulbar, choroidal, retinal and optic nerve head blood flow. Its major indication is as second line therapy e.g. after the failure of a previously given monotherapy Cosopt is also indicated as an initial therapy (first line therapy) in ocular hypertensions associated with high risk factors of conversion, in some well chosen cases of primary open-angle glaucoma (e.g. glaucomas with untreated intraocular pressure of greater than 30 mmHg), in exfoliation glaucoma as well as in the majority forms of secondary glaucoma.

Topics: Antihypertensive Agents; Drug Combinations; Evidence-Based Medicine; Glaucoma; Humans; Intraocular Pressure; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

Topically administered dorzolamide 2%/timolol 0.5% (dorzolamide/timolol ophthalmic solution; Cosopt) is a fixed combination of two ocular hypotensive drugs (the carbonic anhydrase inhibitor dorzolamide and the beta-adrenoceptor antagonist timolol) that have an additive effect on lowering intraocular pressure (IOP) when administered together. This product is indicated for the treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension (OH) who are insufficiently responsive to topical beta-adrenoceptor antagonist monotherapy. As such, it can be considered for use in individuals who, as a consequence of failing to achieve target IOP with beta-adrenoceptor antagonist monotherapy, require the addition or substitution of another class of topical antiglaucoma medication. Clinical trials have demonstrated that dorzolamide/timolol (1 drop per eye twice daily) is an effective and generally well tolerated fixed combination for lowering IOP in patients with open angle glaucoma or OH, including individuals uncontrolled on beta-adrenoceptor antagonist monotherapy. Compared with concomitant therapy with the individual components, the primary advantage of fixed combination dorzolamide/timolol is convenience.

Topics: Drug Combinations; Glaucoma; Humans; Ocular Hypertension; Ophthalmic Solutions; Sulfonamides; Thiophenes; Timolol; Vision, Ocular

To demonstrate that preoperative treatment for 28 days with topical dorzolamide/timolol is non-inferior (Δ = 4 mm Hg) to oral acetazolamide and topical dexamethasone (standard therapy) in terms of intraocular pressure (IOP) reduction 3 and 6 months after trabeculectomy in glaucoma patients.. Sixty-two eyes undergoing trabeculectomy with mitomycin C were included in this monocentric prospective randomized controlled study. IOP change between baseline and 3 months post-op was defined as the primary efficacy variable. Secondary efficacy variables included the number of 5-fluorouracil (5-FU) injections, needlings, suture lyses, preoperative IOP change, hypertension rate and change of conjunctival redness 3 and 6 months post-op. Safety was assessed based on the documentation of adverse events.. Preoperative treatment with topical dorzolamide/timolol was non-inferior to oral acetazolamide and topical dexamethasone in terms of IOP reduction 3 months after trabeculectomy (adjusted means -8.12 mmHg versus -8.30 mmHg; Difference: 0.18; 95% CI -1.91 to 2.26, p = 0.8662). Similar results were found 6 months after trabeculectomy (-9.13 mmHg versus -9.06 mmHg; p = 0.9401). Comparable results were also shown for both groups concerning the classification of the filtering bleb, corneal staining, and numbers of treatments with 5-FU, needlings and suture lyses. More patients reported AEs in the acetazolamide/dexamethasone group than in the dorzolamide/timolol group.. Preoperative, preservative-free, fixed-dose dorzolamide/timolol seems to be equally effective as preoperative acetazolamide and dexamethasone and has a favourable safety profile.

Topics: Acetazolamide; Aged; Antihypertensive Agents; Dexamethasone; Drug Combinations; Female; Fluorouracil; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preoperative Care; Prospective Studies; Sulfonamides; Thiophenes; Timolol; Trabeculectomy; Treatment Outcome

To compare initial glaucoma therapy with medications and trabeculectomy in southern India.. Patients aged ≥ 30 years newly diagnosed with glaucoma were randomized to trabeculectomy with 5-fluorouracil or medical therapy. Subjects with best-corrected vision <6/18 due to cataract underwent phacoemulsification (phaco/intraocular lens, IOL). Intraocular pressure (IOP), vision and visual function were assessed at 12 months.. Patients assigned to medications and surgery received the expected therapy in 86% (172/199) and 64% (126/199) of cases, respectively. Forty patients (20%) assigned to surgery refused any treatment and 33 (17%) received medications. Among 199 patients randomized to medications, 52 (26.1%) underwent phaco/IOL, as did 89/199 (43.7%) of patients randomized to trabeculectomy. Baseline parameters of the two groups did not differ, nor did 1-year follow-up rates (medication 65%, trabeculectomy 58%, P = 0.15). Final IOP was lower with randomization to trabeculectomy (16.3 ± 5.1 mmHg) than medication (18.8 ± 6.7 mmHg, P < 0.0001). In regression models, randomization to trabeculectomy (P < 0.0001) was associated with lower IOP, and simultaneous trabeculectomy and cataract surgery was associated with higher IOP (P = 0.008) than trabeculectomy alone. Subjects receiving Phaco/IOL had significantly better final acuity (P < 0.0001) and visual function (P = 0.035), despite concurrent glaucoma treatment. Final visual acuity was worse in those receiving trabeculectomy in addition to cataract surgery, but this was of borderline significance (P = 0.06).. Trabeculectomy lowered IOP significantly more than medical treatment, but with slightly greater loss of visual acuity. Combined phaco/IOL and trabeculectomy improved visual acuity with substantial IOP lowering.

Topics: Aged; Antihypertensive Agents; Antimetabolites, Antineoplastic; Brimonidine Tartrate; Drug Combinations; Female; Fluorouracil; Glaucoma; Humans; India; Intraocular Pressure; Latanoprost; Lens Implantation, Intraocular; Male; Middle Aged; Phacoemulsification; Prospective Studies; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol; Tonometry, Ocular; Trabeculectomy; Visual Acuity

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

To compare the efficacy and safety of topical bimatoprost (LUMIGAN; Allergan, Inc., Irvine, CA) once daily with that of topical combined timolol and dorzolamide (Cosopt; Merck and Co, Inc., Whitehouse Station, NJ) twice daily.. Prospective, randomized, double-masked, multicenter clinical trial.. One hundred seventy-seven patients with a diagnosis of glaucoma or ocular hypertension and inadequate control of intraocular pressure (IOP) after at least 2 weeks of topical timolol maleate 0.5% monotherapy.. Patients were randomized to receive bimatoprost 0.03% once daily (n = 90) or combined timolol 0.5% and dorzolamide 2% twice daily (n = 87) over a 3-month period.. Intraocular pressure, the primary end point, was measured at 8 AM and 10 AM at baseline, week 1, and months 1, 2, and 3, and also at 4 PM and 8 PM at baseline and month 3.. Bimatoprost provided significantly greater IOP lowering compared with combined timolol and dorzolamide. At the 8 AM measurements, bimatoprost lowered mean IOP 6.8 mmHg to 7.6 mmHg from baseline, whereas combined timolol and dorzolamide lowered mean IOP 4.4 to 5.0 mmHg from baseline (P<0.001). At the last follow-up, patients had better diurnal IOP control with bimatoprost than combined timolol and dorzolamide. At 8 AM at the 3-month visit, the percentages of patients achieving IOPs of

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Double-Blind Method; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Lipids; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol

This study assessed the clinical risk factors for periorbital dermatitis (PD) after using dorzolamide/timolol eye drops in a total of 1282 glaucoma patients. Both the PD(+) group and the PD(-) group were evaluated using clinical data such as age, sex, dosing duration, presence of benzalkonium chloride (BAK) in the formulation, ocular surgery history (e.g. cataract or glaucoma operations), height, weight, personal history of systemic hypertension, smoking, alcohol consumption, intraocular pressure, best-corrected visual acuity (BCVA), central corneal thickness, axial length, and visual field index (VFI). Univariate analyses showed that shorter dosing duration, higher rate of BAK-included cases, worse BCVA, worse VFI, more systemic hypertension history, and more ocular surgery history were more associated with the PD(+) group than the PD(-) group. The BAK(-) group showed a lower PD rate than the BAK-included group, which was supported by the Kaplan-Meier analysis (log-rank test, p = 0.0014). Multivariate analyses revealed that the probability of PD increased by 8 times if they had a history of ocular surgery and increased by 2.3% when the VFI decreased by 1% (Cox's hazard regression test, p < 0.001). Therefore, a preservative-free dorzolamide/timolol can benefit the subjects for those who had ocular surgery or who have worse VFI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Child; Dermatitis; Drug Combinations; Female; Glaucoma; Humans; Male; Middle Aged; Ophthalmic Solutions; Preservatives, Pharmaceutical; Risk Factors; Sulfonamides; Thiophenes; Timolol; Young Adult

Topics: Aged; Antihypertensive Agents; Cataract; Drug Combinations; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Ophthalmic Solutions; Optic Disk; Referral and Consultation; Retinal Pigment Epithelium; Sulfonamides; Thiophenes; Timolol; Tomography, Optical Coherence; Visual Fields

Studies have reported that intraocular pressure (IOP) might change markedly during hemodialysis. We report the case of a 34-year-old Nigerian female with a 3-year history of chronic kidney disease secondary to chronic glomerulonephritis who presented with acute symptomatic elevation of IOPs following hemodialysis. She had no ocular complaints immediately before undergoing hemodialysis. She presented with a history of pain, redness, and mild blurring of vision in the left eye about 15 min after hemodialysis. Examination revealed circumciliary injection, shallow anterior chambers, and closed angles on gonioscopy in both the eyes. She was treated with pilocarpine (4%) four times daily and dorzolamide/timolol (2%/0.5%) twice daily combination eye drops with subsequent relief of symptoms and IOP reduction from an initial 48 and 74 mmHg to 10 and 12 mmHg for the right and left eyes, respectively. This case highlights the need for sensitization and awareness among renal physicians and ophthalmologists of the possibility of extremely high IOP during or immediately following hemodialysis. It also emphasizes the importance of gonioscopy and treatment of at-risk patients with narrow angles before hemodialysis.

Topics: Adult; Drug Combinations; Female; Glaucoma; Glaucoma, Angle-Closure; Glomerulonephritis; Gonioscopy; Humans; Intraocular Pressure; Ophthalmic Solutions; Pilocarpine; Renal Dialysis; Renal Insufficiency, Chronic; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome; Visual Acuity

Supplementation with Mirtogenol® improves the retinal microcirculation and reduces intraocular pressure (IOP) in ocular hypertension, when administrated either alone or in association with an ophthalmic solution (latanoprost). In this study, microcirculatory parameters (perfusion of the circle of Zinn-Haller and retinal circulation) and oxidative stress were tested to assess the effects of Mirtogenol® plus traditional antihypertensive drugs in patients with elevated IOP.. 88 otherwise healthy patients with increased IOP were followed-up in a supplement registry for 12 weeks. Three groups received; (a) dorzolamide-timolol plus Mirtogenol®; (b) latanoprost drops plus Mirtogenol® or (c) latanoprost only. Oral supplementation consisted of two tablets/day of Mirtogenol® (80 mg of bilberry extract, Mirtoselect® plus 40 mg of Pycnogenol®). IOP, retinal blood flow, perfusion of the circle of Zinn-Haller, and oxidative stress were measured during the registry period.. The three study groups were comparable; IOP and ocular blood flow velocity at inclusion were also comparable. Over the study period the decrease in IOP and the improvements in retinal microcirculation were statistically significant for all management groups, with a marginally more evident benefit in Mirtogenol®+latanosprost-treated patients. At 12 weeks, the altered perfusion at the circle of Zinn-Haller was improved in all groups; patients using Mirtogenol® showed a better perfusional pattern compared with subjects using only latanoprost. A reduction in oxidative stress was observed in supplemented subjects at the end of the study period; no significant change was seen in non-supplemented patients. All managements were well-tolerated without side effects.. Supplementation with Mirtogenol®, in addition to local ophthalmic treatments, is safe and may contribute as a supplementary management to reach a normal IOP and ocular microcirculatory parameters.

Topics: Administration, Ophthalmic; Adult; Antihypertensive Agents; Blood Flow Velocity; Drug Combinations; Female; Flavonoids; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Microcirculation; Middle Aged; Oxidative Stress; Prostaglandins F, Synthetic; Retina; Sulfonamides; Thiophenes; Timolol; Treatment Outcome

The purpose of this study is to determine the effect of various commonly used antiglaucoma eye drops on inflammatory mediators such as the platelet activating factor (PAF).. Various intraocular pressure (IOP) lowering drops were tested to examine their inhibitory effect on PAF. Multiple eye drops were tested in washed rabbit platelets (WRPs) in order to determine the interaction between these eye drops and the inhibition of PAF in the PAF-induced platelet aggregation model. In addition, we examined the eyedrops' effect on PAF-metabolism, through in vitro analysis on PAF basic metabolic enzymes (PAF-CPT, lyso PAF-AT, and PAF-AH).. Latanoprost (Xalatan) was found to be the most potent in inhibiting PAF, suggesting that it is the most effective in decreasing IOP amongst the eye drops tested. Conversely, dorzolamide hydrochloride-timolol (Cosopt) exhibited the least anti-PAF action.. This is the first study examine the relationship between PAF activity and glaucoma medication. Potency in PAF inhibition may be related to drop efficacy.

Topics: Animals; Disease Models, Animal; Drug Combinations; Glaucoma; Intraocular Pressure; Ophthalmic Solutions; Platelet Activating Factor; Platelet Aggregation; Rabbits; Sulfonamides; Thiophenes; Timolol

We investigated the transcorneal penetration of commercial ophthalmic formulations containing timolol maleate in rabbit eyes.. One drop (30 μL) of each ophthalmic solution (Xalacom(®), DuoTrav(®), Cosopt(®), and Timoptol(®)) was administered to the conjunctival sac of the rabbits' eyes and the timolol maleate aqueous humor concentration was measured by high-performance liquid chromatography 15, 60, 120, and 240 min after the completion of administration. The effect of timolol ophthalmic solution pH (5.7-6.8) on ocular penetration was also examined.. The concentration [Cmax (μg/mL)] of timolol maleate, found in each of the 4 ophthalmic solutions, penetrated to the aqueous humor was as follows: DuoTrav>Cosopt>Timoptol>Xalacom. The concentration of timolol maleate penetrated to the aqueous humor was highest with solutions in the vicinity of pH 6.8.. The concentration of timolol maleate penetrated to the aqueous humor was highest in DuoTrav followed by Cosopt, Timoptol, and Xalacom, and the pH and Benzalkonium chloride (BAK) concentration of the ophthalmic solution were believed to be factors that influenced this phenomena.

Topics: Animals; Benzalkonium Compounds; Chromatography, Liquid; Cloprostenol; Cornea; Drug Combinations; Eye; Glaucoma; Male; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F, Synthetic; Rabbits; Sulfonamides; Thiophenes; Timolol

Optic nerve atrophy caused by abnormal intraocular pressure (IOP) remains the most common cause of irreversible loss of vision worldwide. The aim of this study was to determine whether topically applied IOP-lowering eye drugs affect retinal ganglion cells (RGCs) and retinal metabolism in a rat model of optic neuropathy. IOP was elevated through cauterization of episcleral veins, and then lowered either by the daily topical application of timolol, timolol/travoprost, timolol/dorzolamide, or timolol/brimonidine, or surgically with sectorial iridectomy. RGCs were retrogradely labeled 4 days prior to enucleation, and counted. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization mass spectrometry, Western blotting, and immunohistochemistry allowed the identification of IOP-dependent proteomic changes. Genomic changes were scrutinized using microarrays and qRT-PCR. The significant increase in IOP induced by episcleral vein cauterization that persisted until 8 weeks of follow-up in control animals (p<0.05) was effectively lowered by the eye drops (p<0.05). As anticipated, the number of RGCs decreased significantly following 8 weeks of elevated IOP (p<0.05), while treatment with combination compounds markedly improved RGC survival (p<0.05). 2D-PAGE and Western blot analyses revealed an IOP-dependent expression of crystallin cry-βb2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects.

Topics: Animals; Biomarkers; Crystallins; Disease Models, Animal; Drug Combinations; Gene Expression Profiling; Gene Expression Regulation; Glaucoma; Intraocular Pressure; Ophthalmic Solutions; Optic Nerve Diseases; Proteome; Proteomics; Rats; Real-Time Polymerase Chain Reaction; Retina; Retinal Ganglion Cells; Sulfonamides; Thiophenes; Timolol

ABSTRACT.:. Malfunction of retinal blood flow or oxygenation is believed to be involved in various diseases. Among them are retinal vessel occlusions, diabetic retinopathy and glaucoma. Reliable, non-invasive technology for retinal oxygen measurements has been scarce and most of the knowledge on retinal oxygenation comes from animal studies. This thesis describes human retinal oximetry, performed with novel retinal oximetry technology. The thesis describes studies on retinal vessel oxygen saturation in (1) light and dark in healthy volunteers, (2) central retinal vein occlusion, (3) branch retinal vein occlusion, (4) central retinal artery occlusion, (5) diabetic retinopathy, (6) patients undergoing glaucoma surgery and (7) patients taking glaucoma medication.. The retinal oximeter (Oxymap ehf., Reykjavik, Iceland) is based on a fundus camera. An attached image splitter allows the simultaneous capture of four images of the same area of the fundus. Two images are used for further analysis, one acquired with 586 nm light and one with 605 nm light. Light absorbance of retinal vessels is sensitive to oxygen saturation at 605 nm but not at 586 nm. Measurement of reflected light at these wavelengths allows estimation of oxygen saturation in the main retinal vessels. This is performed with custom-made analysis software.. LIGHT AND DARK: After 30 min in the dark, oxygen saturation in retinal arterioles of healthy volunteers was 92 ± 4% (mean ± SD, n = 15). After 5 min in 80 cd/m(2) light, the arteriolar saturation was 89 ± 5%. The decrease was statistically significant (p = 0.008). The corresponding values for retinal venules were 60 ± 5% in the dark and 55 ± 10% in the light (p = 0.020). Similar results were found after alternating 5 min periods of darkness and light. In a second experiment (n = 19), a significant decrease in retinal vessel oxygen saturation was found in 100 cd/m(2) light compared with darkness but 1 and 10 cd/m(2) light had no significant effect. CENTRAL RETINAL VEIN OCCLUSION: In patients with central retinal vein occlusion, the mean saturation in affected retinal venules was 49 ± 12%, while the mean value for venules in the fellow eye was 65 ± 6% (mean ± SD, p = 0.003, n = 8). The retinal arteriolar saturation was the same in affected (99 ± 3%) and the unaffected (99 ± 6%) eyes. The venous oxygen saturation showed much variation between affected eyes. BRANCH RETINAL VEIN OCCLUSION: Median oxygen saturation in venules affected by branch retinal vein occlusion was 59% (range, 12-93%, n = 22), while it was 63% (23-80%) in unaffected venules in the affected eye and 55% (39-80%) in venules in the fellow eye. The difference was not statistically significant (p > 0.05). There was a significant difference between affected arterioles (median 101%; range, 89-115%) and unaffected arterioles (95%, 85-104%) in the affected eye (p < 0.05, n = 18). CENTRAL RETINAL ARTERY OCCLUSION: In a patient with a day's history of central retinal artery occlusion due to temporal arteritis, the mean arteriolar saturation was 71 ± 9% and 63 ± 9% in the venules. One month later, after treatment with prednisolone, the mean arteriolar saturation was 100 ± 4% and the venous saturation 54 ± 5%. DIABETIC RETINOPATHY: When compared with healthy volunteers (n = 31), patients with all categories of diabetic retinopathy had on average 7-10 percentage points higher saturation in retinal arterioles (p < 0.05 for all categories, n = 6-8 in each category). In venules, the saturation was 8-12 percentage points higher (p < 0.05 for all categories). GLAUCOMA SURGERY: Oxygen saturation in retinal arterioles increased by 2 percentage points on average (p = 0.046, n = 19) with surgery, which lowered intraocular pressure from 23 ± 7 mmHg (mean ± SD) to 10 ± 4 mmHg (p < 0.0001). No other significant cha. Dual wavelength oximetry can be used to non-invasively measure retinal vessel oxygen saturation in health and disease. The results indicate that retinal vessel oxygen saturation is (1) increased in the dark, (2) lower in venules affected by central retinal vein occlusions, (3) variable in branch retinal vein occlusion, (4) lower in retinal arterioles in central retinal artery occlusion, (5) increased in diabetic retinopathy, (6-7) mildly affected by glaucoma surgery or dorzolamide.

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Case-Control Studies; Dark Adaptation; Diabetic Retinopathy; Drug Combinations; Female; Glaucoma; Humans; Light; Male; Middle Aged; Oximetry; Oxygen; Regional Blood Flow; Retinal Artery Occlusion; Retinal Vein Occlusion; Retinal Vessels; Sulfonamides; Thiophenes; Timolol; Young Adult

This work compares the concentration of active ingredients and preservatives in commonly used brand name versus generic glaucoma medications.. Active ingredient and benzalkonium chloride (BAK) concentrations in brand name latanoprost and dorzolamide-timolol were each compared to two generic counterparts using liquid chromatography-mass spectrometry at baseline and after exposure to 25°C and 50°C for 30 days. Micro flow imaging was used to quantify particulate material greater than one micron in diameter.. Brand name formulations contained active ingredients and BAK in concentrations that were generally in agreement with their package inserts at baseline. The two generic formulations of latanoprost contained baseline levels of active ingredients that were 10% greater than their labeled value. Generic latanoprost formulations had significant loss of active ingredient concentration after exposure to 25°C and 50°C for 30 days. Both generic and brand name dorzolamide-timolol appeared relatively resistant to degradation. BAK concentrations remained stable at 25°C but decreased in some bottles at 50°C. Bottles of both generic medications had higher levels of particulate matter compared to brand name versions.. Exposure to temperatures at the high end of the labeled value may lead to a significant decrease in concentration of active ingredients in generic formulations that could influence clinical efficacy. Re-evaluation of intraocular pressure lowering efficacy may be indicated in glaucoma patients switching from brand name to generic formulations.

Topics: Antihypertensive Agents; Benzalkonium Compounds; Chromatography, High Pressure Liquid; Drug Combinations; Drug Contamination; Drug Stability; Drug Storage; Drugs, Generic; Glaucoma; Latanoprost; Prescription Drugs; Preservatives, Pharmaceutical; Prostaglandins F, Synthetic; Sulfonamides; Tandem Mass Spectrometry; Thiophenes; Timolol

We report a 9-month-old boy with bilateral pseudoptosis associated with elevated IOP. The patient had previously undergone bilateral trabeculectomies and Ahmed tube placement and right cataract extraction and penetrating keratoplasty. At presentation, the right eye IOP was 24 mm Hg and the left eye IOP was 32 mm Hg. Approximately 2 weeks after dorzolamide was added to the treatment regimen for the left eye, the mother reported that the ptosis had resolved. We suggest several explanations for the resolution of the ptosis.

Topics: Anterior Eye Segment; Antihypertensive Agents; Blepharoptosis; Drug Combinations; Eye Abnormalities; Eye Diseases, Hereditary; Glaucoma; Humans; Infant; Intraocular Pressure; Male; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular

We evaluated the cytotoxicity of antiglaucoma ophthalmic solutions preserved with the same concentration of benzalkonium chloride (BAK) in four cultured corneal and conjunctival cell lines. The viability of cell cultures was determined following the exposure of cells to timolol maleate, dorzolamide, and their fixed combination, Kosoputo(®) (MSD, a Japanese formulation of Cosopt(®) (Merck)), and two commercially available eyedrop solutions, 0.5% Timpotol(®) (containing 0.5% timolol maleate, MSD) and 1% Trusopt(®) (containing 1% dorzolamide, MSD) for varying exposure times and at various dilutions using the MTT and neutral red assays. All the three commercially available eyedrop solutions tested in this study were preserved with 0.005% BAK. The toxicity of each solution was compared using the % cell viability score (CVS) . Cell viability was also subjected to statistical analysis using ANOVA, Dunnett's multiple comparison tests and a chi-square test. %CVS50/%CVS40/80s for the tested solutions were 53/-13 for 0.5% Timoptol(®), 100/88 for preservative-free 0.5% timolol maleate, 50/ -10 for 1% Trusopt(®), 72/100 for preservative-free 1% dorzolamide, and 44/-17 for Kosoputo(®). The results of statistical analysis were consistent to them. In conclusion, Kosoputo(®) had greater cytotoxicity than each component; however, in actual use it may have the advantages of reduced toxicity (side effect) due to reduced instillation frequency, and better patient adherence to the treatment regimen as well as a comparable pressure reduction effect.

Topics: Animals; Benzalkonium Compounds; Cattle; Cell Line; Cell Survival; Conjunctiva; Cornea; Drug Combinations; Glaucoma; Humans; Ophthalmic Solutions; Preservatives, Pharmaceutical; Rabbits; Sulfonamides; Thiophenes; Timolol

We evaluated the in vitro cytotoxicity of benzalkonium chloride (BAK)-containing antiglaucoma eyedrops. We prepared cell cultures of SIRC, BCE C/D-1b, RC-1, and Chang conjunctiva. The viability of cell cultures was determined using the MTT and neutral red assays. The cell viability score (CVS) was used to compare the toxicity of test solutions. %CVS50 and %CVS40/80 of each eyedrop solution were 71 and 26 for Lumigan(®) (0.002% bimatoprost with 0.005% BAK), 100 and 99 for Tapros(®) (0.0015% tafluprost, a new formula from 2010 with 0.001% BAK), 39 and -29 for 2% Trusopt(®) (2% dorzolamide with 0.0075% BAK), 28 and -43 for Xalacom(®) (latanoprost/0.5% timolol with 0.02% BAK), 88 and 66 for DuoTrav(®) (travoprost/0.5% timolol with no BAK), 36 and -35 for Cosopt(®) (2% dorzolamide/0.5% timolol with 0.0075% BAK) and 53 and -1 for Combigan(®) (0.15% brimonidin/0.5% timolol with 0.005% BAK). Only Xalacom(®) and Tapros(®) did not show an apparent decrease in %CVS as compared to the corresponding concentration of BAK. In conclusion, the cytotoxicity of tested eyedrops was dependent on BAK. Only the eyedrops containing latanoprost or tafluprost showed a reduction in the cytotoxicity of BAK.

Topics: Animals; Benzalkonium Compounds; Cattle; Cell Line; Cell Survival; Drug Combinations; Glaucoma; Humans; Ophthalmic Solutions; Preservatives, Pharmaceutical; Rabbits; Sulfonamides; Thiophenes; Timolol

The combination of anti-glaucoma eye drops is frequently used in clinical treatment, and it is known that the combination can cause corneal damage. Recently, an anti-glaucoma combination eye drops is developed, and the treatment by the combination eye drops is expected to enhance quality of life. However, effects of the combination eye drops on corneal epithelial cell damage have not been clarified. In this study, we investigated the corneal epithelial cell damage of commercially available anti-glaucoma combination eye drops, such as Xalacom® (latanoprost/timolol maleate combination eye drops), Duotrav® (travoprost/timolol maleate combination eye drops) and Cosopt® (dorzolamide hydrochloride/timolol maleate combination eye drops) using the human corneal epithelial cell (HCE-T). The cytotoxicity in Xalacom® was higher than that in Xalatan® (eye drops containing latanoprost) and Timoptol® (eye drops containing timolol maleate), and the benzalkonium chloride (BAC) and timolol maleate were related to cytotoxicity in Xalacom®. The cytotoxicity in Duotrav® and Cosopt® was lower than that in Timoptol®. The Duotrav® is preserved with a non-BAC system (POLYQUAD, polidronium chloride). Therefore, it was suggested that the POLYQUAD related to the low cytotoxicity in Duotrav®. On the other hand, the D-mannitol reduced the cytotoxicity by BAC in this study. This result suggested that the cytotoxicity in Cosopt® was reduced by D-mannitol. The Duotrav® and Cosopt® may be less damaging to the ocular surface of glaucoma patients receiving long-term eye drop therapy in compared with the combination of anti-glaucoma eye drops.

Topics: Antihypertensive Agents; Cells, Cultured; Cloprostenol; Cornea; Drug Combinations; Epithelial Cells; Glaucoma; Humans; In Vitro Techniques; Latanoprost; Mannitol; Ophthalmic Solutions; Polymers; Preservatives, Pharmaceutical; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Travoprost

The aim of this study was to assess the effectiveness of dorzolamide-timolol (DT) in the management of open-angle glaucoma (OAG) and ocular hypertension.. An open-label, 12-week, multicenter, Canadian study was conducted. Patients with untreated OAG or ocular hypertension received DT for 12 weeks to reduce intraocular pressure (IOP). If target IOP was not reached after the first 6-week treatment period, a prostaglandin (PG) (latanoprost) was added for the remaining 6 weeks. Primary outcome measures were changes in IOP from baseline to 6 and 12 weeks of treatment, and secondary outcome measures included the proportion of patients achieving target IOP and the proportion of patients achieving therapeutic response defined as a reduction of 5.0 mmHg or 20% in IOP from baseline. IOP values were the mean of 2 measures taken before and at least 2 h after patients administered the study medication.. A total of 164 patients were enrolled. Mean [standard deviation (SD)] population age was 63.0 (12.3) years and 53.0% of the patients were men. At week 6, the mean (SD) absolute and percent change in IOP for the total population was (-11.1) (4.9) and (-36.4)% (13.9%), respectively, and 92.1% of the patients achieved a reduction in IOP of at least 5 mmHg. Therapeutic target was achieved by 136 (82.9%) patients (DT subgroup) at 6 weeks, whereas 28 (17.1%) patients were changed to a combination therapy of DT and latanoprost [DT plus PG (DT & PG) subgroup]. Between weeks 6 and 12, DT was effective in sustaining the IOP within therapeutic target, whereas addition of latanoprost reduced the IOP of the DT & PG subgroup by an additional 6.3 mmHg or 22.1% (20.1%). At week 12, patients in the DT subgroup experienced a clinically and statistically significant mean (SD) decrease in IOP from a baseline of 12.2 mmHg or 40.4% (11.9%) (P < 0.001), whereas these values corresponded to 13.4 mmHg and 39.7% (15.7%) (P < 0.001), respectively, in the DT & PG subgroup. The proportion of patients who achieved therapeutic response during the entire 12-week study period was over 82%. Treatment-related adverse events (AEs) were reported by 19 (14.0%) patients in the DT subgroup and by 6 (21.4%) patients in the combination subgroup. Eye disorders and nervous system disorders were among the most common treatment-related AEs in both subgroups. No serious AEs were reported during the study period.. DT alone and DT in combination with a PG are effective in significantly reducing IOP in patients with untreated OAG or ocular hypertension. The treatment was safe and well tolerated with a low incidence of AEs.

Topics: Aged; Drug Combinations; Eye; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Multicenter Studies as Topic; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Outcome

To compare the tolerability of commonly prescribed topical glaucoma medications by determining frequency and bother of side effects, patient satisfaction with their medication, and the chance of discontinuation of eye drops.. The tolerability of topical glaucoma medication was studied in glaucoma patients from nine hospitals. The frequency and severity of side effects was investigated together with patient satisfaction with the medication and the probability to change medication due to reported side effects. To register side effects of topical glaucoma medication, patients were requested to fill in a questionnaire based on "the Comparison of Ophthalmic Medications for Tolerability" (COMTOL) questionnaire supplemented with items based on the most frequently observed and severe side effects.. The number of patients responding was 3,333 (87%). Most patients (79%) were satisfied with their eye medication. The median score for ocular side effects was 58 on a scale ranging from 0 to 320. The probability that medication would be changed by the ophthalmologist at the next visit due to reported side effects occurring since the patients' last or last but one visit to the ophthalmologist was 9%. The most frequently prescribed drugs were timolol, latanoprost, and the fixed combinations of dorzolamide/timolol (Cosopt) and latanoprost/timolol (Xalcom). Only small differences in tolerability were found between these drugs.. The tolerability of timolol, latanoprost, and the fixed combinations of latanoprost/timolol (Xalcom) and dorzolamide/timolol (Cosopt) seem to be comparable. Patients are satisfied with their glaucoma medication and have a low chance of discontinuation of eye drops due to side effects.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Patient Compliance; Patient Satisfaction; Prostaglandins F, Synthetic; Sulfonamides; Surveys and Questionnaires; Thiophenes; Timolol

To evaluate the intraocular pressure lowering effect of the dorzolamide/timolol fixed combination (DTFC) in non-responder glaucoma patients to prostaglandin analogs/prostamides (prostas).. All glaucoma patients treated with DTFC, between June 2003 and December 2005, who were unresponsive to prostaglandin analogs/prostamides, were identified through a retrospective medical records review. A non-responder was defined as an intraocular pressure (IOP) lowering effect less than 15% compared with baseline measurement. Two 12-hour IOP diurnal curves, measured between 8:00 a.m. and 8:00 p.m. (8:00 a.m., 10:00 a.m., 12:00 noon, 2:00 p.m., 4:00 p.m., 6:00 p.m. and 8:00 p.m.), were obtained retrospectively from the records of 31 patients, the first while on prostaglandin analogs/prostamides (baseline IOP) and the second while receiving DTFC (DTFC IOP). The study outcomes were the change in mean diurnal IOP and the reduction in IOP fluctuation as a result of receiving DTFC in patients unresponsive to prostas. The IOP was evaluated by intragroup comparisons with a two-tailed paired Student's t-test. A chi-square test was adopted for analysis of categorical variables.. 31 patients were included in this retrospective study. DTFC significantly reduced IOP in the patients overall, from 25.4 (3.5) to 20.2 (1.0) mmHg, p < 0.0001. The majority of patients were diagnosed with pseudoexfoliative glaucoma (PEX) (58%; 18/31). DTFC reduced the mean IOP fluctuations over 12 hours (highest minus lowest IOP reading within the 12-hours pressure curve) from 8.6 (3.2) to 4.3 (1.4) mmHg, p < 0.0001. The most common adverse events were ocular burning (16%) and taste perversion (13%). There were no serious treatment-related adverse events.. DTFC significantly reduced the IOP in patients with glaucoma who did not respond to prostaglandin analogs/prostamides. Further research is needed to confirm these results.

Topics: Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Male; Ophthalmic Solutions; Probability; Prostaglandins, Synthetic; Retrospective Studies; Severity of Illness Index; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular; Treatment Failure; Treatment Outcome

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

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Drug Combinations; Glaucoma; Humans; Intraocular Pressure; Lipids; Ocular Hypertension; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Sulfonamides; Thiophenes; Timolol

To compare the costs of the new fixed combinations for glaucoma medical therapy.. The studied drugs were: Cosopt (5-mL bottle), Combigan (5-mL bottle) and Xalacom (2.5-mL bottle). Five bottles of each drug were obtained from pharmacies, and the medications lot numbers were recorded. To calculate the drop volume, 10 drops and 1 mL of each bottle were weighed with a digital precision scale. Drop volume was calculated by the relation between volume and weight. The cost of each bottle of medication was determined from the average retail price in Canada. The prices were obtained in Canadian dollars (dollars).. The drops of Cosopt (39.60 +/- 0.45 microL) were considerably larger than the drops of Combigan (33.75 +/- 0.60 microL) and Xalacom (30.87 +/- 0.37 microL). The average number of drops per millilitre varied from 25.25 +/- 0.29 (Cosopt) to 32.40 +/- 0.39 microL (Xalacom). Combigan presented the lowest daily cost (dollars 0.87 +/- 0.02) followed by Xalacom (dollars 1.09 +/- 0.01) and Cosopt (dollars 1.22 +/- 0.01). The average cost by year varied from dollars 316.75 +/- 5.59 (Combigan) to dollars 445.96 +/- 5.16 (Cosopt), with a total difference of dollars 129.21 per year of treatment.. There was a statistically significant difference in average drop size and cost among the three studied drugs. Combigan presented the lowest daily cost followed by Xalacom and Cosopt.

Topics: Administration, Topical; Antihypertensive Agents; Brimonidine Tartrate; Canada; Drug Combinations; Glaucoma; Humans; Latanoprost; Prostaglandins F, Synthetic; Quinoxalines; Sulfonamides; Thiophenes; Timolol