dinoprost and dorzolamide

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

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

To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily.. Prospective multicenter, randomized, double-masked, crossover comparison study.. Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days.. Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial.. This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.

Topics: Antihypertensive Agents; Cross-Over Studies; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome; Visual Acuity

To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension.. This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy.. Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101).. Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Chemotherapy, Adjuvant; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Timolol

To investigate the clinical characteristics of docosanoid derivative, isopropyl unoprostone in the treatment of primary open angle glaucoma (POAG).. In 17 patients (22 eyes) with POAG we analysed prospectively the effect of Rescula upon intraocular pressure, aqueous flare, pupil size, ocular signs and symptoms. Patients were followed up every 2 weeks for at least 8 weeks with complete ocular examination. Concomitant topical therapeutics were used in the study: 0.5% Timolol--group I (16 eyes), and 0.5% Timolol + 2% Dorzolamide--group II (6 eyes).. Mean (+/- SD) pretreatment pressure was 24.7 +/- 4.3 mm Hg in group I and it was reduced by 3.7 mm Hg (13.5%) (p < 0.05) at the end of the follow up. In group I Rescula was very effective (delta T% > 25%) in 6/16 eyes (37.5%) and it was ineffective (delta T% < 10%) in the same number of eyes. In group II pretreatment pressure was 24.8 +/- 2.6 mm Hg and it was reduced by 2.6 mm Hg (10.6%) (p = 0.1). Rescula induced no elevation of the aqueous flare during the treatment. No effect on pupil size was observed, either. Eye stinging/conjunctival hyperaemia was noted in 2/17 patients and punctate epitheliopathy in 1 patient (5.9%) that caused discontinuation of drops.. Unoprostone produced significant additive effect to Timolol. Thus, it may be a valuable option for adjunctive therapy. However, interindividual differences need to be considered, as in some patients the response was insignificant.

Topics: Administration, Topical; Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Timolol

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

Long-term use of drugs that suppress aqueous humor formation, such as timolol and dorzolamide, or that redirect aqueous humor outflow from the trabecular meshwork, such as prostaglandin F2alpha analogues, could cause underperfusion of the trabecular meshwork and a secondary decrease in outflow facility. We investigated the mechanism of suppression of aqueous humor formation by timolol in monkey eyes by measuring aqueous humor ascorbate levels. We also determined whether suppression of aqueous humor formation with and without redirection of aqueous humor away from the trabecular meshwork could lead to a subsequent reduction in outflow facility, and whether this reduction was correlated with increased fibronectin levels in anterior chamber aqueous humor. In cynomolgus monkeys, unilateral dose/aqueous humor formation response curves were generated for timolol, dorzolamide, and a combination of timolol + dorzolamide. Aqueous humor formation and/or outflow facility were measured in both eyes after approximately four days, four weeks and seven weeks of twice daily treatment with 3.5 microg timolol + 1.0 mg dorzolamide to one eye and 30% DMSO to the other. In some monkeys, 5 microg prostaglandin F2alpha-isopropyl ester (PG) was added to timolol + dorzolamide for 4-week treatments. Intraocular pressure and corneal endothelial transfer coefficients (k(a)) were also measured at four weeks. Aqueous humor fibronectin levels were determined in four monkeys after approximately 9.5 weeks of timolol + dorzolamide treatment. Aqueous humor formation, intraocular pressure, and aqueous humor ascorbate levels were also determined in rhesus monkeys at baseline and after a single unilateral topical administration of 25 microg timolol. Compared to baseline for the same eye, aqueous humor formation was significantly decreased in treated eyes at all doses of timolol and at 1.8 and 4 mg dorzolamide. Compared to the opposite control eye, aqueous humor formation was lower in treated eyes after 3.5 and 5 microg timolol and after all doses of dorzolamide. Aqueous humor formation after treatment with 3.5 microg timolol + 1.0 mg dorzolamide was decreased in treated vs. control eyes, after four days and was suppressed in both treated and control eyes after four weeks of treatment, but not when PG was added. There was no difference in k(a) values with or without the addition of PG. Intraocular pressure was significantly lower in both treated and control eyes vs. baseline after approximatel

Topics: Adrenergic beta-Antagonists; Animals; Antihypertensive Agents; Aqueous Humor; Ascorbic Acid; Carbonic Anhydrase Inhibitors; Dinoprost; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fibronectins; Macaca fascicularis; Macaca mulatta; Sulfonamides; Thiophenes; Timolol

To evaluate the ocular factors contributing to keratoepitheliopathy in glaucoma patients treated with or without anti-glaucomatous eyedrops, and the influences of each anti-glaucomatous eyedrop to keratoepitheliopathy.. The presence and severity of keratoepitheliopathy was investigated in 193 eyes of 110 glaucoma patients. The ocular factors examined were the status of the lipid layer of the tear fluid as assessed by a specular reflection video-recording system, tear volume assessed by Schirmer's test, and tear film stability assessed by tear break-up time. The influences of combined anti-glaucomatous eyedrops and each anti-glaucomatous eyedrops to keratoepitheliopathy were investigated.. The overall occurrence of superficial punctate keratitis was 29.0%. Superficial punctate keratitis was more frequently observed in patients who used more than two anti-glaucomatous eyedrops (35.9%) than in those who used without (19.7%) and one (30.9%). Results of Schirmer's test and break-up time were worse in patients who used combined medication. The occurrence of superficial punctate keratitis in patients who used timolol (46.2%) was significantly more frequent than in those who used carteolol (4.2%). Severity of superficial punctate keratitis and break-up time in patients who used timolol were significantly worse than in those who used carteolol. There were no differences of keratoepitheliopathy and ocular factors between patients who used latanoprost and unoprostone.. The usage of multiple anti-glaucomatous eyedrops induces keratoepitheliopathy by reducing the tear volume and the tear film stability. Carteolol may be used more safely for corneal epithelium.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carteolol; Dinoprost; Drug Therapy, Combination; Epithelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Keratitis; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prostaglandins F, Synthetic; Risk Factors; Sulfonamides; Tears; Thiophenes; Timolol

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