Mean intraocular pressure and progression based on corneal thickness in patients with ocular hypertension.

PURPOSE: To determine the incidence of glaucomatous progression at mean intraocular pressure (IOP) levels in patients with ocular hypertension (OHT). METHODS: A retrospective, multicentre, cohort analysis of 230 OHT patients with 5 years of follow-up evaluated for risk factors associated with progressive optic disc and visual field loss to determine the incidence of glaucomatous progression. RESULTS: Forty percent of patients with IOPs > or = 24 mmHg, 18% of patients with IOPs of 21-23 mmHg, 11% of patients with IOPs with 18-20 mmHg, and 3% of patients with IOPs of < or = 17 mmHg progressed to glaucoma. The mean IOP was 19.8+/-2.4 mmHg in the stable group and 21.7+/-2.6 mmHg in the progressed group (P=0.0004). The highest average peak IOP was 23.4+/-4.0 mmHg in the stable group and 25.2+/-3.1 mmHg in the progressed group (P=0.006). Based on the pachymetry values for central corneal thickness, patients with thinner corneas more often progressed to glaucoma (P<0.0001). A multivariant regression analysis to determine risk factors for progression was positive primarily for higher peak IOPs, older age, male gender, argon laser trabeculoplasty, visual acuity > or = 20/50, and no topical medical therapy or beta-blocker therapy prior to the study. CONCLUSIONS: IOP reduction within the normal range over 5 years of follow-up reduces the chance of progression to primary open-angle glaucoma in OHT patients.

Long-term progression at individual mean intraocular pressure levels in primary open-angle and exfoliative glaucoma.

PURPOSE: To describe progression and non-progression rates at individual mean intraocular pressure (IOP) levels for patients with primary open-angle and exfoliative glaucoma. METHODS: A meta-analysis of five previously published retrospective studies describing progression and non-progression rates at individual intraocular pressure levels over 5 or more years of follow-up. All patients had primary open-angle (four studies) or exfoliative glaucoma (one study). RESULTS: This meta-analysis included 822 patients of whom 655 (80%) had primary openangle glaucoma and 167 (20%) had exfoliative glaucoma. In total, 220 patients progressed (27%), while 602 (73%) remained stable over 5 years. The mean IOP was 20.0 for progressed and 17.1 mmHg for stable patients (p=0.0004). The peak IOP was 29.1 for progressed and 23.6 mmHg for stable patients (p=0.0014). At an IOP level >18 mmHg, 49% of patients remained stable; at 18 mmHg, 78%; between 13 and 17 mmHg, 82%; and <13 mmHg, 96%. Additional factors associated with progression were older age (p=0.0004) and exfoliative glaucoma (p=0.0001). However, multivariant regression analysis identified only mean IOP as a risk factor for progression (p=0.039). CONCLUSIONS: This study suggests that maintaining an IOP well within the normal range over 5 years in patients with primary open-angle or exfoliative glaucoma helps to prevent glaucomatousprogression.

The clinical validity of the treatment satisfaction survey for intraocular pressure in ocular hypertensive and glaucoma patients.

PURPOSE: To provide initial validation of the Treatment Satisfaction Survey-Intraocular Pressure (TSS-IOP) quality-of-life survey that analyses specific issues related to side effects, patient satisfaction, and compliance. METHODS: A prospective, observational cohort of 250 consecutive patients with primary open-angle glaucoma or ocular hypertension was administered the TSS-IOP survey. RESULTS: Factors that correlated with patient satisfaction included perceived effectiveness of the medicine (F=7.47, P<0.001), ocular irritation (F=6.06, P<0.001), conjunctival hyperaemia (F=4.40, P<0.001), ease of use (F=8.52, P<0.001), and convenience of use (F=6.90, P<0.001). Patient compliance, acceptance of their illness, and knowledge of glaucoma were also related to perceived effectiveness of the medicine (P<0.001), ease of use (P<0.05) and convenience (P<0.001). Physician ratings of patient pressure control, side effects, and instillation problems also were significantly correlated to patient satisfaction (R=0.13-0.26, P=0.05-0.001). The physician ratings of patient compliance, however, were not significantly related to any dimension of patient satisfaction (P>0.05). Among monotherapy prostaglandin treatments, latanoprost demonstrated statistically greater satisfaction than bimatoprost or travoprost regarding conjunctival hyperaemia (P<0.05) and eye irritation (P<0.01). CONCLUSIONS: This study provides initial evidence that patient satisfaction may be related to compliance, perceived effectiveness of treatment, adverse side effects, ease and convenience of use, acceptance of illness, and knowledge of glaucoma.

Safety and efficacy of bimatoprost 0.03% versus timolol maleate 0.5%/dorzolamide 2% fixed combination.

PURPOSE: To determine the efficacy and safety of bimatoprost given every evening versus the dorzolamide/timolol fixed combination (DTFC) given twice daily in open-angle glaucoma and ocular hypertensive patients. METHODS: A double-masked, three-center, prospective, randomized, crossover comparison with two 8-week treatment periods following a 4-week medicine free washout period. Diurnal curve intraocular pressures (IOPs) were taken at 08:00 (trough) and 10:00 and 16:00 hours. RESULTS: A total of 35 patients were enrolled and 32 completed all evaluations. The diurnal untreated baseline intraocular pressures was 24.8 +/- 2.4 mmHg. On the last day of treatment the mean diurnal intraocular pressures was 17.4 +/- 2.9 for bimatoprost and 18.1 +/- 2.8 mmHg for DTFC (p = 0.35). The individual time points for intraocular pressures were not statistically different between groups. Both groups statistically reduced the intraocular pressures from baseline for each time point and for the diurnal curve (p < 0.05). Regarding ocular safety and tolerability, there was more conjunctival hyperemia with bimatoprost (n = 15) than with DTFC (n = 7, p = 0.013) and more burning and stinging with DTFC (n = 12) than with bimatoprost (n = 0, p = 0.0005). Few systemic adverse events were recorded and there was no statistical difference between groups for any individual event (p > 0.05). CONCLUSIONS: This study indicates that the intraocular pressures are lowered to a statistically similar amount with DTFC compared to bimatoprost in open-angle glaucoma and ocular hypertensive patients.

Brimonidine 0.2% vs unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily. METHODS: In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period. RESULTS: In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey. CONCLUSION: Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.

Brimonidine purite 0.15% versus dorzolamide 2% each given twice daily to reduce intraocular pressure in subjects with open angle glaucoma or ocular hypertension.

BACKGROUND/AIMS: To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects. METHODS: In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period after a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (IOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period. RESULTS: The baseline diurnal IOP was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolamide. The trough IOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal IOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p = 0.46). Dorzolamide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events. CONCLUSIONS: This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide.

Efficacy and safety of the latanoprost/timolol maleate fixed combination vs concomitant brimonidine and latanoprost therapy.

AIMS: To evaluate the efficacy and safety of latanoprost/timolol maleate fixed combination (LTFC) given once daily vs the concomitant therapy of brimonidine twice daily and latanoprost once daily in primary open-angle glaucoma or ocular hypertensive subjects. METHODS: A prospective, double-masked, active-controlled comparison in which qualified subjects had all glaucoma medicines discontinued for 1 month and then were randomized to either LTFC or brimonidine and latanoprost concomitant therapy for 6 weeks. They were then switched to the other treatment regimen. The intraocular pressure (IOP) was measured at 0800, 1200, and 1600 h at baseline and at the end of Periods 1 and Period 2. RESULTS: In 32 subjects, the diurnal curve of the untreated IOP of 26.0+/-3.4 decreased to 17.8+/-2.5 on LTFC and 17.2+/-2.8 mmHg on brimonidine and latanoprost (P=0.31). At 0800 and 1600 h, the IOPs were statistically similar between the groups (P>0.05). At 1200 h the latanoprost and brimonidine treatment IOP was statistically lower (16.2+/-3.2) than LTFC (18.0+/-2.8 mmHg). However, the reduced IOP from untreated baseline was not statistically different at each time point and for the diurnal curve for each therapy (P<0.05). Safety was similar between groups for both solicited and unsolicited side effects (P>0.05). CONCLUSION: This study suggests that LTFC and concomitant therapy of brimonidine and latanoprost provide statistically similar diurnal IOP reduction from an untreated baseline.

Additive efficacy of unoprostone isopropyl 0.12% (rescula) to latanoprost 0.005%.

PURPOSE: To evaluate the safety and efficacy of adding unoprostone isopropyl 0.12% vs placebo both given twice daily to latanoprost 0.005% given every evening. METHODS: We treated 41 patients with primary open-angle glaucoma or ocular hypertension with latanoprost 0.005% for 1 month and then randomized each to either placebo or unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at baseline (time of randomization) and after 8 weeks of treatment. RESULTS: Twenty patients were treated in the placebo group and 21 in the unoprostone isopropyl group. After 8 weeks of treatment in the placebo group, the trough intraocular pressure at 08:00 and the diurnal pressure were 20.4 +/- 3.2 and 19.1 +/- 2.2 mm Hg, respectively. In the unoprostone isopropyl group the pressures were 19.4 +/- 3.3 and 18.0 +/- 1.7 mm Hg (P =.22 and P =.042), respectively. However, eyes with a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm Hg greater reduction at trough (P <.01) and a 2.1 mm Hg greater decrease in diurnal pressure (P =.030) after adding unoprostone isopropyl (n = 14 eyes) compared with placebo (n = 16 eyes; P <.001). In addition, the range of the pressures throughout the diurnal curve was reduced from 2.7 mm Hg on latanoprost alone to 1.4 mm Hg after adding unoprostone isopropyl. Adverse events were similar between groups, and no patients were discontinued because of safety reasons. CONCLUSIONS: This study suggests that unoprostone isopropyl can safely improve the diurnal curve characteristics in patients who continue to have an elevated pressure on latanoprost 0.005% alone.

Factors associated with long-term progression or stability in primary open-angle glaucoma.

PURPOSE: To evaluate long-term risk factors for progression or stability in patients with primary open-angle glaucoma. METHOD: We retrospectively included consecutively reviewed patients who had primary open-angle glaucoma for at least 5 years in this multicenter trial. Historical and clinical factors in these patients were evaluated for their association with stability or progression of the glaucoma. RESULTS: We included 218 patients in this study; of these, 34 progressed over an average length of follow-up of 45.5 +/- 30.0 months, and 184 were stable over an average of 72.8 +/- 18.3 months. The mean intraocular pressure over the follow-up period for the progressed group was 19.5 +/- 3.8 mm Hg and for the stable group 17. 2 +/- 3.1 mm Hg (P =.001). The average standard deviation of individual intraocular pressures was greater in the progressed group (5.1 mm Hg) than the stable group (3.9 mm Hg, P =.012). Baseline characteristics indicating a greater potential to progress were a larger cup-to-disk ratio (P <.001), a greater number of medications (P =.02), older age (P.007), and worse visual acuity (P =.003). However, no difference was observed in pressure levels that prevented progression in these subpopulations compared with the total sample size. CONCLUSIONS: This study suggests that lowering the intraocular pressure is important in the treatment of primary open-angle glaucoma to help prevent long-term progression. Lowering the pressure, however, is not uniformly effective in preventing progression. Additionally, risk factors for progression do not further help identify pressure levels that prevent worsening of glaucoma.

Brimonidine 0.2% versus dorzolamide 2% each given three times daily to reduce intraocular pressure.

PURPOSE: To evaluate the efficacy and safety of brimonidine compared with dorzolamide given three times daily as monotherapy in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In a double-masked, multicenter, crossover comparison in 40 patients, qualified patients were washed out from their previous medication and randomized to dorzolamide 2% or brimonidine 0.2% for the first 6-week treatment period. Patients then were washed out for 2 weeks and started on the opposite medication for the second 6-week period. RESULTS: Baseline intraocular pressure for all 40 subjects (76 eyes) was 24.1 +/- 2.0 mm Hg. This study found that the 8:00 AM trough intraocular pressure after 6 weeks of therapy for dorzolamide was 20. 7 +/- 3.1 mm Hg and for brimonidine 20.8 +/- 3.2 mm Hg (P =.99). The peak intraocular pressure (2 hours after dosing) for dorzolamide was 18.6 +/- 3.4 mm Hg and for brimonidine 17.8 +/- 2.7 mm Hg (P =.10 ). Dorzolamide caused more stinging upon instillation (P <.01) and brimonidine more itching (P =.01). No statistical differences existed between groups for systemic adverse events. Six patients, all on brimonidine, were discontinued from a treatment period early. Of these, two were discontinued for inadequate pressure control, two with dizziness and fatigue, one with ocular pain, and one for lifestyle reasons (P =.07). CONCLUSIONS: This study found similar efficacy and safety between monotherapy treatment with dorzolamide or brimonidine when each was given three times daily to patients with ocular hypertension or primary open-angle glaucoma.

Comparison of the efficacy and safety of latanoprost 0.005% compared to brimonidine 0.2% or dorzolamide 2% when added to a topical beta-adrenergic blocker in patients with primary open-angle glaucoma or ocular hypertension.

The purpose of this study was to evaluate the ocular hypotensive efficacy and safety of latanoprost 0.005% (Xalatan, Pharmacia & Upjohn), brimonidine (Alphagan, Allergan), and dorzolamide (Trusopt, Merck Inc.) when added to a beta-blocker in patients with ocular hypertension or primary open-angle glaucoma. This was a multicenter, retrospective analysis which included all reviewed patient records in which latanoprost, brimonidine or dorzolamide were added to a beta-blocker for at least three months. Patients who were treated for less than three months, who failed therapy due to ineffectiveness of the medicine or an adverse event also were included. The study included 141 patients. Latanoprost (n = 50) showed an intraocular pressure of 16.7 +/- 3.3 mm Hg (-6.3 +/- 4.1 mm Hg, P < 0.001), brimonidine (n = 24) 17.4 +/- 4.9 mm Hg (-4.2 +/- 4.5 mm Hg, P < 0.001), and dorzolamide (n = 67) 20.1 +/- 6.1 mm Hg (-3.1 +/- 5.1 mm Hg, P < 0.001) at three months. A significant difference was observed in the absolute level of intraocular pressure (P < 0.005) and the change from baseline between groups (P < 0.005) at three months. A significant difference was observed between groups in the success rate of therapy between latanoprost (70%), brimonidine (58%) and dorzolamide (40%) (P = 0.008). No significant differences were observed between groups for rate or type of adverse events leading to discontinued therapy. This study showed that latanoprost, when added to beta-blockers, compares favorably in ocular hypotensive efficacy and is similar in safety to brimonidine and dorzolamide.

Efficacy and safety of timolol solution once daily vs timolol gel added to latanoprost.

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.

Argon laser therapy of occult recurrent hyphema from anterior segment wound neovascularization.

Recurrent hyphema is a complication of anterior segment surgery that may present with a variety of signs and symptoms. The appropriate diagnosis of this syndrome may be overlooked because its presentation is frequently delayed, and its symptoms and signs are varied and frequently evanescent. Major forms of surgical intervention have been recommended for this syndrome, but we believe that many such cases can be treated relatively simply and effectively with argon laser goniophotocoagulation using topical anesthesia. We present five cases of recurrent hyphema from neovascularization of a surgical incision.

A prospective comparison of Amvisc and Healon in cataract surgery.

A prospective, randomly assigned, double-masked study was designed to compare two solutions of sodium hyaluronate--Amvisc and Healon. All cases were planned extracapsular cataract extractions with posterior chamber intraocular lenses performed by a single surgeon in glaucomatous and nonglaucomatous eyes. Subjective performance of the products were rated in regard to ability to maintain the chamber, coat the intraocular lens, dilate the pupil, separate the leaves of the capsule, and be easily removed. Objective comparisons of intraocular pressure, anterior chamber reaction, and endothelial cell loss were also made. There was no subjective or objective difference between the two products.

Argon laser trabeculoplasty as a means of decreasing intraocular pressure from "normal" levels in glaucomatous eyes.

We conducted a retrospective study of 67 patients (85 eyes) with severe glaucoma to determine whether argon laser trabeculoplasty could reduce intraocular pressures below the "normal" range. All patients had initial intraocular pressures of less than or equal to 19 mm Hg. Success was defined as a decrease in intraocular pressure of at least 20%, no increase in medications, stable visual field, and no subsequent glaucoma surgery. After an average follow-up period of 30 months, treatment was successful in 31 cases. One half of the failures occurred by six months and 11 failures (30%) occurred after 12 months. Sixteen patients were able to decrease their medications. Two patients achieved intraocular pressures between 6 and 9 mm Hg and 20 between 10 and 12 mm Hg.