William C. Stewart

Efficacy and Safety of Bimatoprost in Patients with Elevated Intraocular Pressure: A 30-Day Comparison with Latanoprost

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.

Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications.

Purpose: To determine the prevalence of ocular surface disease (OSD) in patients with glaucoma using topical intraocular pressure (IOP)-lowering therapy. Methods: This prospective observational study enrolled patients with primary open-angle glaucoma or ocular hypertension who were on a topical IOP-lowering medication regimen. Enrolled patients completed the ocular surface disease index (OSDI) and OSDI scores (0-100, with 0 representing no symptoms) were calculated for each patient. Medical history, demographics, and concomitant medication information were also collected. Results: Overall, 630 patients from 10 sites participated. Of these, 305 patients (48.4%) had an OSDI score indicating either mild (n = 134, 21.3%), moderate (n = 84, 13.3%), or severe (n = 87, 13.8%) OSD symptoms. OSDI scores were significantly different between patients with and without a prior diagnosis of dry eye syndrome (25.2 ± 15.4 vs 15.4 ± 15.8, respectively; P = 0.0036) and between patients who did and did not use artificial tears at the time of study participation (23.0 ± 15.6 vs 15.3 ± 15.8, respectively; P = 0.0046). Mean OSDI scores varied significantly with the number of topical IOP-lowering medications used, with higher (more severe) OSDI scores in patients using multiple IOP-lowering medications. Specifically, patients on a single medication had a mean OSDI score of 12.9 ± 13.1, which was significantly lower than those of patients on 2 (16.7 ± 17.0; P = 0.007) or 3 medications (19.4 ± 18.1; P = 0.0001). Conclusions: OSD is prevalent among medically treated patients with glaucoma. The severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used.

Factors Associated With Visual Loss in Patients With Advanced Glaucomatous Changes in the Optic Nerve Head

We evaluated factors associated with decreased or stable visual function in 72 patients with primary open-angle glaucoma and complete cupping of the optic disk who were followed up five years or more. We found a significantly lower mean (15.4 +/- 2.7 mm Hg) and peak (24.5 +/- 6.9 mm Hg) intraocular pressure in those patients whose vision remained stable vs those whose vision decreased (21.3 +/- 3.2 and 39.2 +/- 11.0 mm Hg, respectively) (t-test, P < .001). Additionally, the variance of each patients individual intraocular pressure readings measured during the follow-up period was lower in the group with stable vision (4.5 mm Hg) than in those in whom vision decreased (9.0 mm Hg) (F test, P < .001). Stepwise discriminant analysis disclosed that mean intraocular pressure, variance of an individuals intraocular pressure measurements over time, history of argon laser trabeculoplasty, and compliance with therapy discriminated 92.9% of patients (52 of 56) whose vision remained stable and 87.5% of patients (14 of 16) whose vision decreased. Reduction of intraocular pressure and compliance with therapy are important in patients with complete glaucomatous cupping of the optic disk.

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.

Comparison of 24-hour intraocular pressure reduction with two dosing regimens of latanoprost and timolol maleate in patients with primary open-angle glaucoma.

PURPOSE To compare the 24-hour diurnal ocular hypotensive efficacy of two dosing regimens of latanoprost, once daily (8 AM or 10 PM), vs timolol maleate, twice daily. METHODS We measured six diurnal intraocular pressure curves (6 AM, 10 AM, 2 PM, 6 PM, 10 PM, and 2 AM) in one randomly selected eye of 34 Greek patients newly diagnosed with primary open-angle glaucoma. The first diurnal curve was an untreated baseline. Patients began taking timolol 0.5%, twice daily, for 2 months. Patients were randomly assigned to latanoprost 0.005% given at 8 AM or 10 PM for 1 month and then changed to the other dosing regimen for 1 month. A diurnal curve was performed after each dosing period. RESULTS The baseline diurnal pressure for all 34 subjects was 23.1 +/- 3.7 mm Hg. The average intraocular pressures at 6 AM for patients who were given latanoprost in the evening (17.9 +/- 2.9 mm Hg) was statistically lower than that in patients given timolol solution (20.1 +/- 2.5 mm Hg, P = .003); however, patients who were given timolol demonstrated a similar diurnal intraocular pressure (19.1 +/- 2.8 mm Hg) to both morning (18.8 +/- 3.7 mm Hg) and evening doses (18.8 +/- 3.6 mm Hg) of latanoprost (P =.329). When the two latanoprost dosages were compared directly, evening administration provided a statistically lower intraocular pressure at 10 AM (P = .0001) and morning administration at 10 PM (P = .0001). This study had an 80% power to exclude a 1.2-mm Hg difference between groups. CONCLUSIONS This study indicates that in a small population, both latanoprost and timolol are effective in lowering intraocular pressure throughout a 24-hour period; however, latanoprost is most effective in the 12-hour to 24-hour period after administration.

Semiconductor diode laser transscleral cyclophotocoagulation in patients with glaucoma.

We used the semiconductor diode laser to perform transscleral cyclophotocoagulation in 14 patients with glaucoma. Laser settings used for this procedure were 990 milliseconds, 100-microns spot size, and 1,200 mW of power. Applications were placed 1 mm posterior to the surgical corneoscleral limbus and 1 mm defocused toward the ciliary body. The mean preoperative intraocular pressure was 34.8 +/- 13 mm Hg, and the mean intraocular pressure six months after a single treatment session was 24.3 +/- 18 mm Hg (P greater than .001, paired t-test). The mean number of glaucoma medications decreased from 2.2 preoperatively to 1.4 postoperatively. Complications included conjunctival burns and uveitis in 14 patients, and pain in one patient. These results suggested that semiconductor diode transscleral cyclophotocoagulation may be useful as a treatment to reduce the intraocular pressure in patients with glaucoma.

The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in open-angle glaucoma or ocular hypertension

PURPOSE To evaluate the efficacy and safety of latanoprost 0.005% given topically every evening versus brimonidine 0.2% given topically twice daily in primary open-angle glaucoma or ocular hypertensive patients. METHODS This was a multicenter, crossover, double-masked comparison. After a 28-day treatment-free period, patients with primary open-angle glaucoma or ocular hypertension were randomized for 6 weeks to brimonidine or latanoprost and then crossed over to the opposite treatment. At baseline and after each treatment period, patients underwent intraocular pressure measurements every 2 hours from 08:00 to 20:00. RESULTS In 33 patients the mean baseline trough (08:00) was 23.2 +/- 2.1 mm Hg and the diurnal curve pressure was 19.8 +/- 2.7 mm Hg. The trough and diurnal intraocular pressures for brimonidine were 19.6 +/- 3.4 mm Hg and 17.6 +/- 2.2 mm Hg, respectively. Brimonidine statistically reduced the pressure from baseline at each time point except hours 10 and 12 (P =.14 and P =.21, respectively). For latanoprost, the trough and diurnal pressures were 16.2 +/- 2.9 mm Hg and 15.4 +/- 2.5 mm Hg, respectively, and the pressure was statistically reduced at each time point (P <.001) and for the diurnal curve (P <.001). When compared directly, the intraocular pressure level for latanoprost was lower than brimonidine for the diurnal pressure and at each time point (P <.05). One patient was discontinued early from latanoprost treatment because of eyelid swelling; also, latanoprost caused more hyperemia than brimonidine (P =.04). CONCLUSION This study suggests latanoprost dosed daily in the evening statistically reduces intraocular pressure more during daytime and evening hours than brimonidine dosed twice daily. Brimonidine may not consistently decrease the pressure 10 and 12 hours past dosing from nontreated levels.

Latanoprost Treatment for Glaucoma: Effects of Treating for 1 Year and of Switching From Timolol

PURPOSE To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Intraocular Lens Complications Requiring Removal or Exchange

Intraocular lens (IOL)-related complications are caused primarily by mechanical trauma, inflammatory or infectious complications, or optical problems. Complications may occur at the time of surgery or be the result of an ongoing postoperative process. Mechanical and inflammatory injury may produce corneal decompensation, cystoid macular edema, hyphema, uveitis, and glaucoma, causing reduced vision and in some cases chronic pain. Optical problems may be due to a wrong power of the IOL or to postoperative decentration or dislocation of the lens. Ophthalmologists should be aware of the indications for IOL removal or exchange in those patients who have ongoing IOL-induced injury or impairment. Removal or exchange of an IOL frequently involves a complex decision-making process and is often associated with immense technical challenge. Various medical and surgical treatments may be tried to correct IOL problems before the decision is made to remove or exchange the lens.

A Comparison of Once-daily Morning Vs Evening Dosing of Concomitant Latanoprost/Timolol

PURPOSE To evaluate morning vs evening once daily concomitant latanoprost 0.005%/timolol maleate 0.5% therapy in ocular hypertensive or primary open-angle glaucoma patients. DESIGN Prospective single-center double-masked crossover comparison. METHODS Patients who responded to timolol maleate 0.5% given twice daily were randomized to either evening or morning dosing of concomitant latanoprost 0.005% and timolol maleate 0.5% therapy for 7 weeks. Twenty-four hour diurnal curve intraocular pressure (IOP) testing was performed following each period. RESULTS Thirty-six patients completed this study. There was a significant reduction at each time point in the 24-hour diurnal curve of both evening (17.1 +/- 2.7 mm Hg) and morning (17.3 +/- 3.1 mm Hg) dosed latanoprost/timolol maleate compared with timolol maleate given twice daily (21.1 +/- 3.3 mm Hg) (P <.0001). When the morning and evening dosing groups were compared directly, the 06:00 time point was statistically lower with evening dosing (16.4 +/- 2.3 mm Hg) vs morning dosing (17.9 +/- 2.8 mm Hg) (P =.01). Overall, a trend existed for greater daytime reduction with night-time dosing of the concomitant therapy, whereas morning dosing tended to give lower night-time pressures. There was a significantly lower mean range of diurnal pressure with evening (3.6 mm Hg) vs morning (4.3 mm Hg) dosing (P =.02). No differences in adverse events existed between the treated arms. CONCLUSIONS This study suggests that latanoprost and timolol maleate, both given once daily in the morning or evening, effectively reduce the IOP for the 24-hour diurnal curve when compared with timolol maleate twice daily.