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Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders., Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma., Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma., Exposures: Genetic variants associated with primary open-angle glaucoma., Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data., Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry., Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.

Purpose: To study the relationship between primary open-angle glaucoma (POAG) in a cohort of patients of African descent (AD) and serum vitamin D levels., Methods: A subset of the AD and glaucoma evaluation study III (ADAGES III) cohort, consisting of 357 patients with a diagnosis of POAG and 178 normal controls of self-reported AD, were included in this analysis. Demographic information, family history, and blood samples were collected from all the participants. All the subjects underwent clinical evaluation, including visual field (VF) mean deviation (MD), central cornea thickness (CCT), intraocular pressure (IOP), and height and weight measurements. POAG patients were classified into early and advanced phenotypes based on the severity of their visual field damage, and they were matched for age, gender, and history of hypertension and diabetes. Serum 25-Hydroxy (25-OH) vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). The association of serum vitamin D levels with the development and severity of POAG was tested by analysis of variance (ANOVA) and the paired t -test., Results: The 178 early POAG subjects had a visual field MD of better than -4.0 dB, and the 179 advanced glaucoma subjects had a visual field MD of worse than -10 dB. The mean (95% confidence interval [CI]) levels of vitamin D of the subjects in the control (8.02 ± 6.19 pg/ml) and early phenotype (7.56 ± 5.74 pg/ml) groups were significantly or marginally significantly different from the levels observed in subjects with the advanced phenotype (6.35 ± 4.76 pg/ml; p = 0.0117 and 0.0543, respectively). In contrast, the mean serum vitamin D level in controls was not significantly different from that of the subjects with the early glaucoma phenotype (p = 0.8508)., Conclusions: In this AD cohort, patients with advanced glaucoma had lower serum levels of vitamin D compared with early glaucoma and normal subjects.

Purpose: To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III., Design: Cross-sectional, case-control study., Participants: Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States., Methods: Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review., Main Outcome Measures: Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded., Results: The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients., Conclusions: With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To find genetic contributions to glaucoma in African Americans., Design: Cross-sectional, case-control study., Participants: One thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine., Methods: MegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs)., Main Outcome Measures: Primary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946)., Results: Eighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r 2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P < 3×10 -8 ). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10 -5 ) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10 -5 ) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10 -5 ) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively., Conclusions: A novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: Cortisol is involved in the regulation of intraocular pressure (IOP). This study aimed to assess the effect of 11β-hydroxysteroid-dehydrogenase type 1 (11βHSD1) inhibition by oral administration of RO5093151 on IOP., Methods: The exposure of key ocular compartments following oral administration was assessed in rabbits. An adaptive, randomised, placebo-controlled study gated by a Bayesian decision criterion was performed in 35 patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Following a 7-day placebo-controlled run-in period, 200 mg twice daily RO5093151 or placebo (4:1) were administered for 7 days. The extent of 11βHSD1 inhibition was assessed by the ratio of urinary tetrahydrocortisol (5α and 5β)/tetrahydrocortisone (THF/THE). Time-matched IOP assessments were performed., Results: A high distribution of RO5093151 into the rabbit eye was observed. In humans, a high and sustained inhibition of 11βHSD1 was shown by the decrease of THF/THE from 0.9 at baseline to 0.18 on day 7. There was no statistically significant difference in change of IOP from baseline. In the 'worse eye', the adjusted least square mean change from baseline was -2.7 mm Hg (95% CI -4.2 to -1.2) and -2.9(95% CI -5.9 to 0.1) in the RO5093151 and placebo group, respectively., Conclusions: Despite high inhibition of 11βHSD1 and expected moderate to high tissue distribution in ocular tissues, a 7-day treatment with a high oral dose of RO5093151 did not result in a clinically meaningful effect on IOP in patients with POAG or OHT., Competing Interests: Competing interests: DS, CS, AP, SF-R, DH and PJ were employees of F. Hoffmann La Roche Ltd. The study was funded by Roche Pharmaceutical Research and Early Development.

Purpose: To evaluate the safety and ocular hypotensive efficacy of 4 trabodenoson doses administered twice daily over 14 or 28 days in subjects with ocular hypertension or primary open-angle glaucoma (POAG)., Methods: In this multicenter, randomized, double-masked, placebo-controlled, dose-escalation Phase 2 study, patients received unilateral topical twice-daily trabodenoson (50, 100, or 200 mcg) or placebo for 14 days, or 500 mcg trabodenoson or placebo for 28 days. Ocular and systemic safety and tolerability were assessed by examinations, clinical and laboratory studies. Intraocular pressure (IOP) was assessed using Goldmann tonometry., Results: Trabodenoson was well tolerated; no clinically meaningful ocular or systemic side effects were identified. Trabodenoson produced a dose-dependent IOP reduction. IOP reductions in the 500 mcg group were significantly greater than placebo at all time points at Day 28. Mean IOP reductions from diurnal baseline ranged from -3.5 to -5.0 mmHg with a mean change of -4.1 mmHg in the 500 mcg group compared -1.0 to -2.5 mmHg with a mean change of -1.6 mmHg for the placebo group, and the Day 28 drop was significantly greater than at Day 14 (P = 0.0163) indicating improvement in IOP lowering with longer treatment time. IOP remained significantly reduced 24 h after the final 500 mcg dose (P = 0.048)., Conclusion: Twice-daily ocular doses of trabodenoson, from 50 to 500 mcg, were well tolerated and showed a dose-related decrease in IOP that was statistically significant and clinically relevant at 500 mcg in patients with ocular hypertension or POAG., Competing Interests: Author Disclosure Statement J.S.M. is a consultant and member of the Inotek Scientific Advisory Board; R.A.B., W.M., and C.C.R. are employees and own stock and stock options of Inotek Pharmaceuticals; N.S. is a consultant; K.N.S. and H.D. have no competing financial interests.

Purpose: Improving adherence to manage elevated intraocular pressure (IOP) remains an unmet need. A topical bimatoprost ocular insert was compared with twice-daily timolol eye drops in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) treated for 6 months., Design: Parallel-arm, multicenter, double-masked, randomized, controlled trial., Participants: One hundred thirty adult OAG or OHT patients., Methods: Eligible patients were randomized 1:1 to receive a bimatoprost insert plus artificial tears twice daily or a placebo insert plus timolol (0.5% solution) twice daily for 6 months after a screening washout period. Diurnal IOP measurements (at 0, 2, and 8 hours) were obtained at baseline; weeks 2, 6, and 12; and months 4, 5, and 6. Key eligibility included washout IOP of 23 mmHg or more at time 0, IOP of 20 mmHg or more at 2 and 8 hours, and IOP of 34 mmHg or less at all time points; no prior incisional surgery for OAG or OHT; and no known nonresponders to prostaglandins., Main Outcome Measures: The primary efficacy end point examined the difference in mean change from baseline in diurnal IOPs (point estimate, 95% confidence interval) across 9 coprimary end points at weeks 2, 6, and 12 comparing the bimatoprost arm with the timolol arm using a noninferiority margin of 1.5 mmHg. Secondary end points were diurnal IOP measurements at months 4, 5, and 6 and adverse events (AEs)., Results: A mean reduction from baseline IOP of -3.2 to -6.4 mmHg was observed for the bimatoprost group compared with -4.2 to -6.4 mmHg for the timolol group over 6 months. The study met the noninferiority definition at 2 of 9 time points but was underpowered for the observed treatment effect. Adverse events were consistent with bimatoprost or timolol exposure; no unexpected ocular AEs were observed. Primary retention rate of the insert was 88.5% of patients at 6 months., Conclusions: Clinically relevant reduction in mean IOP was observed over 6 months with a bimatoprost ocular insert and seems to be safe and well tolerated. The topically applied bimatoprost insert may provide an alternative to daily eye drops to improve adherence, consistency of delivery, and reduction of elevated IOP., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: This study evaluates the contribution of the individual components of an investigational non-β-antagonist fixed combination of brinzolamide, 1%, and brimonidine, 0.2%. This study and its sister study provide the first randomized data showing the intraocular pressure (IOP)-lowering activity and the toxicity profile of this novel topical antihypertensive fixed combination., Objective: To compare IOP-lowering efficacy of fixed-combination brinzolamide, 1%, and brimonidine, 0.2%, with that of its components in patients with open-angle glaucoma or ocular hypertension., Design: In this phase 3, double-masked, parallel-group, multicenter study, eligible patients were randomized 1:1:1 to treatment with fixed-combination brinzolamide, 1%, and brimonidine, 0.2%; brinzolamide, 1%; or brimonidine, 0.2%, 3 times daily for 3 months., Setting: Sixty-six academic and private practice study sites throughout the United States., Participants: A total of 660 adults with a clinical diagnosis of open-angle glaucoma or ocular hypertension from a referred sample were enrolled. Thirty-four patients discontinued participation due to treatment-related nonserious adverse events., Intervention: Topical administration of study medication (fixed-combination brinzolamide, 1%, and brimonidine, 0.2%; brinzolamide, 1%; or brimonidine, 0.2%) 1 drop 3 times daily for 3 months., Main Outcomes and Measures: Mean IOP at the 3-month visit at all time points (8 AM, 10 AM, 3 PM, and 5 PM)., Results: A total of 660 patients were enrolled. Baseline mean IOP values were similar among treatment groups at all 4 time points. At 3 months, the mean IOP of the brinzolamide-brimonidine group (16.3-19.8 mm Hg) was significantly lower than that of either the brinzolamide group (19.3-20.9 mm Hg; P ≤ .002) or the brimonidine group (17.9-22.5 mm Hg; P < .001) across all time points. One of 10 serious adverse events (chest pain, brinzolamide group) was judged as treatment related. A total of 129 patients experienced at least 1 treatment-related adverse effect (brinzolamide-brimonidine, 22.9%; brinzolamide, 18.6%; and brimonidine, 17.3%; P = .31), most of which were ocular., Conclusions and Relevance: This registrational study provides evidence that the fixed combination of brinzolamide, 1%, and brimonidine, 0.2%, can safely and effectively lower IOP in patients with open-angle glaucoma or ocular hypertension, showing significantly superior IOP-lowering activity compared with either brinzolamide or brimonidine monotherapy while providing a safety profile consistent with that of its individual components., Trial Registration: clinicaltrials.gov Identifier: NCT01297517.

Purpose: To determine the duration of action of ketotifen 0.025% eye drops vs placebo taken as single or multiple doses in an allergen challenge model., Design: Two randomized, multicenter, double-masked, contralateral placebo-controlled studies, one a single-dose and one a multiple-dose study., Methods: Two conjunctival provocation tests (CPTs) were initially conducted to confirm reproducibility of subject responses in both studies. Subjects in study 1 (n = 87) received single doses of ketotifen in one eye and placebo in the other 15 minutes, 6 hours, and 8 hours before CPT. Subjects in study 2 (n = 85) received ketotifen or placebo once 8 hours before CPT. Single-dose efficacy results were used to further qualify a subject as a responder. Responders were re-randomized to a 4-week twice daily dosing regimen with a CPT 8 hours after the final dose. In both studies, ocular symptoms were assessed at three time points 3 to 15 minutes after challenge. There were no significant differences in adverse events between groups., Results: For both studies, ocular itching and vascular injection were significantly reduced (P <.003) at all time points after instillation of ketotifen, with a maximum reduction at 7 minutes postchallenge. In study 2, chemosis, tearing, and lid swelling were also assessed and were significantly reduced (P <.008) after instillation of ketotifen., Conclusions: Ketotifen 0.025% eye drops were safe and statistically effective in preventing ocular itching, injection, and other signs and symptoms of allergic conjunctivitis at 15 minutes, 6 hours, and 8 hours after a single dose and at 8 hours after the final dose of a 4-week twice daily regimen.

Objective: To compare the efficacy and safety of a fixed combination of 0.005% latanoprost and 0.5% timolol maleate administered once daily vs monotherapy with either 0.005% latanoprost once daily or 0.5% timolol twice daily., Methods: Patients with either primary or secondary open-angle glaucoma or ocular hypertension participated in a 6-month, randomized, double-masked, multicenter study with 3 parallel treatment groups. The double-masked period was preceded by a 2- to 4-week "run-in" treatment with timolol. Subjects could receive fixed combination therapy during a 6-month open-label extension., Main Outcome Measure: The difference between groups in mean diurnal intraocular pressure reduction in study eye(s) from baseline through 6 months of treatment., Results: Overall, 418 patients were enrolled in the study; 332 completed the open-label phase. Diurnal intraocular pressure levels were similar at baseline, but at week 26, they were 19.9 +/- 3.4 mm Hg in the fixed combination therapy group, 20.8 +/- 4.6 mm Hg in latanoprost-treated patients, and 23.4 +/- 5.4 mm Hg in timolol-treated patients (data are given as mean +/- SD). The mean change from baseline was greater among patients receiving fixed combination therapy compared with each monotherapy group (P<.01). Fixed combination therapy effectively lowered intraocular pressure levels for up to 1 year. All treatments were well tolerated., Conclusion: The combination of 0.005% latanoprost and 0.5% timolol administered once daily is effective and well tolerated for up to 12 months.

Background: Many physicians recommend either brimonidine or latanoprost as firstline therapy for chronic open-angle glaucoma or ocular hypertension. However, a search of MEDLINE indicates that there have been few head-to-head comparisons of the 2 monotherapies in a clinical setting., Objective: This study compared the clinical efficacy and tolerability of brimonidine 0.2% twice daily with those of latanoprost 0.005% once daily as monotherapy in patients with open-angle glaucoma or ocular hypertension., Methods: In this 3-month, multicenter, double-masked, parallel-group, 4-visit study, treatment-naive and previously treated patients with open-angle glaucoma or ocular hypertension and bilateral intraocular pressure (IOP) after washout of between 22 and 34 mm Hg were randomized to receive either brimonidine or latanoprost. Patients who had received previous treatment with either study drug were excluded from the study. The primary outcome measure was response rate, defined as the percentage of patients achieving > or = 20% reduction in IOP from baseline to month 3. Secondary outcome measures were mean IOP reduction from baseline to month 3 and clinical success, defined as the investigator's recommendation that the patient continue using the assigned study medication., Results: A total of 127 patients (55 treatment naive) were enrolled, 66 in the brimonidine group and 61 in the latanoprost group. After 3 months of treatment, 80% of patients in the brimonidine group and 74% of patients in the latanoprost group had achieved > or = 20% reduction in IOP from baseline. The mean reduction in IOP from baseline at month 3 was 6.8 mm Hg with brimonidine and 6.5 mm Hg with latanoprost (27.8% vs 27.0%, respectively). Among treatment-naive patients, a significantly higher percentage of brimonidine-treated patients achieved > or = 20% decrease in IOP compared with latanoprost-treated patients (88% vs 59%, respectively; P = 0.01). In previously treated patients, a higher percentage of the latanoprost group achieved > or = 20% reduction in IOP compared with the brimonidine group (88% vs 74%, respectively); however, the difference was not statistically significant. Significantly more patients in the brimonidine group achieved clinical success at month 3 compared with patients in the latanoprost group (91% vs 74%; P = 0.01)., Conclusions: At peak effect, brimonidine twice daily was as effective as latanoprost once daily in lowering IOP. In treatment-naive patients, latanoprost was associated with a significantly higher rate of nonresponse after 3 months of treatment compared with brimonidine. This suggests that brimonidine may be the more reliable choice for first-line therapy of newly diagnosed open-angle glaucoma or ocular hypertension. In previously treated patients, however, latanoprost provided greater mean IOP reduction than did brimonidine. Significantly more patients achieved clinical success with brimonidine monotherapy than with latanoprost monotherapy.

Purpose: To compare the safety and efficacy of bimatoprost and latanoprost in patients with primary open-angle glaucoma or ocular hypertension., Methods: This was a 30-day, multicenter, double-masked, randomized, clinical trial. Patients (n = 64) diagnosed with primary open-angle glaucoma or ocular hypertension were randomly assigned to receive bimatoprost 0.03%, latanoprost 0.005%, or vehicle topically in both eyes once daily, in the evening, for 29 days. The primary endpoint was the reduction in IOP from baseline on day 14 and day 29. Secondary outcome measures included eye examinations and safety parameters., Results: Bimatoprost and latanoprost significantly lowered IOP from baseline (p <.001). Bimatoprost lowered IOP more than latanoprost at every timepoint measured (bimatoprost: 25-34% reduction, 5.9-8.9 mm Hg; latanoprost: 20-31% reduction, 4.4-7.9 mm Hg), although the between-group differences did not reach statistical significance. Over the 12-hour course of IOP measurements on day 29, bimatoprost provided better diurnal IOP control than latanoprost (p =.0378, area under the curve of diurnal IOP reductions, 1-way ANOVA with pairwise t-test). Both treatment regimens were safe and well tolerated, with no significant between-group differences in reports of specific adverse events. The most common side effect was conjunctival hyperemia, which was similarly apparent in the bimatoprost and latanoprost treatment groups., Conclusions: At the end of this 30-day trial, once-daily bimatoprost 0.03% provided better diurnal IOP control than latanoprost and was safe and well tolerated in patients with ocular hypertension and glaucoma.

Objective: To evaluate whether a fixed combination of 2% dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily., Design: Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension., Participants and Intervention: In the masked phase, 242 patients received either the dorzolamide-timolol combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the dorzolamide-timolol combination twice daily for up to 9 months., Main Outcome Measures: The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments., Results: During 3 months of treatment, the dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0, 20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures., Conclusions: The IOP-lowering effect of the dorzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.

Purpose: To compare the efficacy and safety of timolol hemihydrate 0.5% (Betimol, Ciba Vision Ophthalmics, Duluth, Georgia) vs timolol maleate gel-forming solution 0.5% (Timoptic-XE, Merck, Blue Bell, Pennsylvania), both given every morning added to latanoprost 0.005% given every evening., Methods: A multicenter, randomized, crossover comparison was performed in patients with primary open-angle glaucoma or ocular hypertension. After at least a 4-week run-in period with latanoprost 0.005% (Xalatan, Pharmacia & Upjohn, Kalamazoo, Michigan), both eyes from 30 patients (60 eyes) were randomly assigned to one of the two adjunctive therapies, timolol hemihydrate or timolol maleate gel for 6 weeks. At the end of the first period, the study medicine was discontinued for a 2-week washout period. Patients then received the opposite medication for the second 6-week period. This study had an 80% power to exclude a 1-mm Hg difference between groups., Results: The baseline intraocular pressure after 1 month of latanoprost treatment only for all 30 subjects was 20.8 +/- 2.6 mm Hg. After 6 weeks of timolol hemihydrate, the 24-hour trough intraocular pressure was 17.5 +/- 3.4 mm Hg, and for timolol maleate gel, 17.9 +/- 3.5 mm Hg (P = .74). The peak level 2 hours after dosing for timolol hemihydate was 16.4 +/- 2.6 mm Hg, and for timolol maleate gel, 16.8 +/- 3.8 mm Hg (P = .84). No patient was discontinued from the study because of lack of efficacy. No differences were observed between treatments in visual acuity, anterior segment findings, or adverse events., Conclusions: Once-daily beta-blocker therapy is an effective ocular hypotensive adjunctive treatment 24 hours after dosing when added to latanoprost, for which timolol hemihydrate 0.5% solution and timolol maleate gel 0.5% appear equally effective and safe.

Background and Objective: To evaluate the efficacy and safety of diclofenac 0.1% versus prednisolone acetate 1% following trabeculectomy with adjunctive mitomycin-C., Patients and Methods: The authors prospectively randomized chronic open-angle glaucoma patients who underwent trabeculectomy with adjunctive mitomycin-C to receive postoperatively either diclofenac 0.1% or prednisolone acetate 1% 4 times daily, to be tapered as inflammation resolved., Results: In the diclofenac group (n = 14), the preoperative intraocular pressure of 30.4 +/- 13.1 decreased to 12.4 +/- 6.5 mm Hg at 6 months postoperatively. In the prednisolone acetate group (n = 12), the preoperative intraocular pressure decreased from 29.1 +/- 10.4 to 12.8 +/- 4.2 mm Hg at 6 months postoperatively (P = .85). The average number of medicines used 6 months postoperatively was 0.50 +/- 0.8 in the diclofenac group and 0.24 +/- 0.6 in the prednisolone acetate group (P = .36). Adverse events were similar between groups (P = .51). One patient in the diclofenac group underwent reoperation at 1 month due to uncontrolled intraocular pressure., Conclusions: This study shows that following trabeculectomy with adjunctive mitomycin-C, a similar intraocular pressure result may be expected when either diclofenac or prednisolone acetate is prescribed postoperatively for intraocular inflammation.

Purpose: We compared the therapeutic efficacy and safety of timolol hemihydrate to timolol maleate in patients with ocular hypertension and chronic open-angle glaucoma., Methods: We conducted this three-month study as a multicentered, masked, parallel group comparison. Both the 0.25% and 0.5% concentrations were evaluated against similar concentrations of timolol maleate. Dosing was twice daily. An open-label, nine-month study followed the masked portion of the protocol, in which all patients received either 0.25% or 0.5% timolol hemihydrate. A total of 371 patients were included in both the 0.25% and 0.5% studies., Results: We found statistically similar intraocular pressures with both the 0.25% (18.3 and 18.6 mm Hg for the hemihydrate and maleate groups, respectively) and 0.5% (19.9 and 19.5 mm Hg for the hemihydrate and maleate groups, respectively) concentrations of timolol hemihydrate and timolol maleate after three months of masked treatment. Likewise, peak intraocular effect at two hours after taking the medication was statistically similar between medicines at both concentrations. Likewise, both ocular and systemic safety were similar between the maleate and hemihydrate preparations at both concentrations. In the nine-month open-label protocol, therapeutic efficacy (19.9 and 19.1 mm Hg for the 0.25% and 0.5% concentrations, respectively) and safety of timolol hemihydrate were similar to effect and safety of the three-month protocol., Conclusions: This study suggests that timolol hemihydrate had an ocular hypotensive efficacy and safety profile statistically equivalent to that of timolol maleate for up to three months of therapy. Timolol hemihydrate showed efficacy and safety similar to that observed within the first three months, for up to one year of therapy.

Thirty-two patients were randomly assigned to a treatment or a control group to determine the dose-response and duration of action of intracameral carbachol on immediate postoperative intraocular pressure after extracapsular cataract extraction using a viscoelastic substance. Patients in the treatment group received 0.5, 0.25, or 0.1 ml of 0.01% intracameral carbachol. Patients in the control group received 0.1 or 0.5 ml of balanced salt solution. Intraocular pressures of all patients were measured preoperatively and at three, six, 12, 24, and 48 hours postoperatively. The control group as a whole showed a 9.5-mm Hg intraocular pressure rise at three hours, a 10.0-mm Hg rise at six hours, a 9.0-mm Hg rise at 12 hours, and a 7.2-mm Hg rise at 24 hours postoperatively. The group treated with 0.5 ml of carbachol maintained stable intraocular pressures through the 48-hour measurement period. The groups treated with 0.25 and 0.1 ml of carbachol maintained stable intraocular pressures through 24 hours postoperatively. The differences in intraocular pressure were statistically significant for all treated groups through the 24-hour measurement.