Jeanette A. Stewart

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.

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.

Ocular Surface Disease in Patients with Ocular Hypertension and Glaucoma

Purpose: To review the prevalence, diagnosis, causes, and treatment of ocular surface disease (OSD) in patients with ocular hypertension or primary open-angle glaucoma. Methods: A review of the literature pertaining to OSD and glaucoma. Results: Recent studies indicate that OSD demonstrates an overall prevalence in glaucoma of 42% (range 20–59%) and is severe in 36% (range 14–66%). Further, the prevalence appears to increase with the greater the number of glaucoma drugs prescribed. Symptoms and signs are non-specific to the anterior surface of the eye and are thought to result from allergic, toxic, or pro-inflammatory conditions. However, the specific causes remain incompletely described, but may result from the benzalkonium chloride (BAK) preservative or occasionally the ocular hypotensive active molecule itself. Additionally, anterior segment ocular diseases might be causative, such as allergy, blepharitis, dry eye, and eyelid anatomical abnormalities. Treatment may consist of using preservative-free or non-BAK preserved glaucoma medications. Also, although unproven specifically in glaucoma patients, treatment of associated diseases of the anterior surface might reduce signs and symptoms. Conclusions: OSD is common in treated glaucoma patients causing symptoms and signs that may impact on a patient’s quality of life. Treatment is directed towards any underlying disease process and the use of preservative-free or non-BAK-preserved glaucoma preparations.

Efficacy, safety, and improved tolerability of travoprost BAK-free ophthalmic solution compared with prior prostaglandin therapy

Purpose To evaluate the efficacy, safety and tolerability of changing to travoprost BAK-free from prior prostaglandin therapy in patients with primary open-angle glaucoma or ocular hypertension. Design Prospective, multi-center, historical control study. Methods Patients treated with latanoprost or bimatoprost who needed alternative therapy due to tolerability issues were enrolled. Patients were surveyed using the Ocular Surface Disease Index (OSDI) to evaluate OSD symptoms prior to changing to travoprost BAK-free dosed once every evening. Patients were re-evaluated 3 months later. Results In 691 patients, travoprost BAK-free demonstrated improved mean OSDI scores compared to either latanoprost or bimatoprost (p < 0.0001). Patients having any baseline OSD symptoms (n = 235) demonstrated significant improvement after switching to travoprost BAK-free (p < 0.0001). In 70.2% of these patients, symptoms were reduced in severity by at least 1 level. After changing medications to travoprost BAK-free, mean intraocular pressure (IOP) was significantly decreased (p < 0.0001). Overall, 72.4% preferred travoprost BAK-free (p < 0.0001, travoprost BAK-free vs prior therapy). Travoprost BAK-free demonstrated less conjunctival hyperemia than either prior therapy (p < 0.0001). Conclusions Patients previously treated with a BAK-preserved prostaglandin analog who are changed to travoprost BAK-free have clinically and statistically significant improvement in their OSD symptoms, decreased hyperemia, and equal or better IOP control.

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.

Peak Intraocular Pressure and Glaucomatous Progression in Primary Open-Angle Glaucoma

PURPOSE To evaluate the effect of 24-h peak intraocular pressure (IOP) on the progression of primary open-angle glaucoma (POAG) and the 24 h time points that best predict peak pressure. METHODS A retrospective analysis of clinical data evaluating long-term glaucomatous progression in patients with POAG who were previously in a 24-h study of the authors (IOP readings at 2/6/10 A.M. and 2/6/10 PM); had ≥3 treated 10 A.M. (±1 h) IOP measurements over 5-years after an untreated 24-h baseline; and had a treated 24-h curve with a 10 A.M. IOP±2 mmHg within the 10 A.M. mean IOP over 5-years. RESULTS We included 98 nonprogressed and 53 progressed patients with POAG (n=151). The mean 24-h peak IOP (mmHg) was 19.9±2.7 for progressed and 18.3±2.0 for nonprogressed patients (P<0.001). Progressed patients also showed a higher mean 24-h IOP. Generally, patients with a mean or peak daytime (readings at 10 A.M., 2 and 6 P.M.) or 24-h peak IOP of ≤18 remained nonprogressed in 75%-78% of cases. Further, measuring IOP at night found a higher peak in only 20% of cases, which was ≤2 of the daytime peak in 98% of cases. A multivariate regression analysis showed only 24-h peak IOP as an independent risk factor for progression (P=0.002). CONCLUSIONS This study suggests that daytime peak IOP may be clinically important in predicting long-term glaucomatous progression. Further, daytime peak IOP may assist, as much as daytime mean IOP and, in most cases, 24-h peak IOP, in helping to guide long-term treatment in POAG.

Intraocular pressure control over 24 hours using travoprost and timolol fixed combination administered in the morning or evening in primary open‐angle and exfoliative glaucoma

Purpose:  To evaluate intraocular pressure (IOP) control over 24 hours using travoprost and timolol fixed combination (TTFC) administered in the morning or evening in primary open‐angle and exfoliative glaucoma.

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

PurposeTo 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.MethodsA prospective, observational cohort of 250 consecutive patients with primary open-angle glaucoma or ocular hypertension was administered the TSS-IOP survey.ResultsFactors 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).ConclusionsThis 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.

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.

Cost-effectiveness of Treating Ocular Hypertension

PURPOSE To assess the cost-effectiveness of treating ocular hypertension (OHT) in the United States. DESIGN A Markov model was constructed to perform a cost-effectiveness analysis. PARTICIPANTS Patients with OHT. METHODS The health states considered were stable OHT and glaucoma. Practice patterns for the model were derived from the Ocular Hypertension Treatment Study (OHTS), and transition probabilities were derived from previous literature. Specific unit costs used for medications, patient visits, and diagnostic and therapeutic procedures were obtained from Blue Cross/Blue Shield. The time horizon was 5 years. Costs were discounted at 3% per annum. MAIN OUTCOME MEASURE Long-term cost effectiveness of treating OHT to prevent the development of glaucoma. RESULTS The incremental cost-effectiveness ratio (ICER) for all OHT patients to prevent 1 case from progressing to primary open-angle glaucoma was