Thomas Mundorf

Effects of carteolol and timolol on plasma lipid profiles in older women with ocular hypertension or primary open-angle glaucoma

PURPOSE To determine the effect on serum lipid levels of carteolol hydrochloride 1.0% or timolol maleate 0.5% given twice a day to women age 60 years and older with primary open-angle glaucoma or ocular hypertension. METHOD We included 112 patients in this double-masked, randomized, multicenter trial. Fasting clinical laboratory studies were evaluated at baseline and at 12 weeks. Patients were instructed not to change their dietary, alcohol consumption, or exercise habits during the study. RESULTS For the carteolol group, the high-density lipoprotein (HDL) and total cholesterol/high-density lipoprotein (TC/HDL) ratio at baseline of 50.1 +/- 1.5 mg/dl and 4.7 +/- 0.2 changed by the 12-week visit to 51.3 +/- 1.9 mg/dl (P = .25) and 4.6 +/- .02 (P = .47), respectively. For the timolol maleate group, the baseline HDL and TC/HDL ratio of 53.6 +/- 2.2 mg/dl and 4.4 +/- 0.2 changed to 50.2 +/- 1.9 mg/dl (P < .001) and 4.7 +/- 0.2 (P = .001), respectively, at the 12-week visit. Carteolol patients showed no significant change from baseline, whereas the HDL (P < .001) and TC/HDL ratio decreased (P = .001) significantly in the timolol maleate group. There also was a significant difference in the change from baseline at 12 weeks between carteolol and timolol maleate groups for the HDL and TC/HDL ratio (P = .01 and .012, respectively). No differences in TC, low-density lipoprotein (LDL), or triglycerides (TG) or in changes from baseline were observed between groups at 12 weeks (P > .05). At 12 weeks, no differences were observed between carteolol and timolol maleate groups in intraocular pressure or safety (P > .05), except that patients given carteolol demonstrated fewer solicited ocular symptoms (P = .007). CONCLUSIONS Carteolol appears to be neutral in its effect on serum lipid levels, whereas timolol maleate adversely affects the HDL and TC/HDL ratio in women age 60 years and older with ocular hypertension or primary open-angle glaucoma.

Pemirolast potassium 0.1% ophthalmic solution is an effective treatment for allergic conjunctivitis : a pooled analysis of two prospective, randomized, double-masked, placebo-controlled, phase III studies

Patients with allergic conjunctivitis may experience several debilitating symptoms, particularly ocular itching. The objective of this study was to evaluate the efficacy and safety of pemirolast potassium 0.1% ophthalmic solution (Alamast trade mark ), a novel mast-cell stabilizer, for preventing ocular manifestations of seasonal allergic conjunctivitis. A pooled analysis was performed of data derived from 2 prospective, randomized, double-masked, placebo-controlled, multicenter phase III clinical trials of pemirolast potassium 0.1% in patients with a history of allergic conjunctivitis. Patients having a positive bilateral response to conjunctival allergen challenge (CAC) with ragweed antigen (N = 274) were randomized to receive pemirolast potassium 0.1% or placebo QID, beginning approximately 1-2 weeks before the onset of ragweed season and continuing until after the first killing frost (12-17 weeks duration). Patients recorded their daily evaluations of ocular itching in a diary. After the allergy season, patients underwent a second CAC. Evaluable patients (n = 265) recorded a total of 21,491 patient-days of ocular itching data during allergy season. In every 7-day or 14-day period, patients treated with pemirolast potassium 0.1% reported more days without any ocular itching compared with patients receiving placebo. Differences favoring pemirolast potassium 0.1% were statistically significant in 63% (10/16) of all 7-day periods (p < or = 0.046) and 88% (7/8) of all 14-day periods (p < or = 0.016). After the allergy season, pemirolast potassium 0.1% was significantly superior to placebo in relieving CAC-induced ocular itching, with relief occurring as early as 3 minutes after allergen challenge (p < or = 0.034). Pemirolast potassium 0.1% was well tolerated and had a safety profile similar to that of placebo. In conclusion, pemirolast potassium 0.1% is effective and safe in preventing ocular itching in patients with allergic conjunctivitis during allergy season.

Short-term efficacy of apraclonidine hydrochloride added to maximum- tolerated medical therapy for glaucoma

Purpose We determined whether the addition of topical apraclonidine hydrochloride to eyes that are receiving maximal medical therapy but still have inadequate intraocular pressure control and that are scheduled to undergo surgery could adequately decrease intraocular pressure, postponing the need for further intervention. Methods We performed a prospective, 90-day, multicentered, placebo-controlled, double-masked parallel study. We enrolled one eye each of 174 glaucoma patients with inadequate intraocular pressure control who were on maximally tolerated medical therapy. We continued to administer maximum medical therapy for glaucoma. Study medications were either apraclonidine hydrochloride 0.5% or placebo (apraclonidines vehicle). Patients were instructed to take the study medication every eight hours. We measured intraocular pressure, change in intraocular pressure from baseline, and the number of eyes requiring surgery after the addition of study medication. Results Fifty-two (60%) of 86 patients treated with apraclonidine maintained adequate intraocular pressure control throughout the study and avoided surgery, compared with 28 (32%) of 88 patients treated with placebo (P Conclusion Apraclonidine appeared to be safe in all eyes and efficacious in some eyes. It significantly lowered intraocular pressure when used in combination with maximally tolerated medical therapy, which delayed or prevented further glaucoma surgery for at least 90 days in 52 (60%) of 86 treated patients.

Efficacy and safety of ketotifen fumarate 0.025% in the conjunctival antigen challenge model of ocular allergic conjunctivitis

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.

Evaluation of the comfort of Alphagan® P compared with Alphagan® in irritated eyes

The tolerability of brimonidine tartrate 0.15%—referred to as bromonidine-Purite® 0.15% in this study—was compared with brimonidine tartrate 0.2% in irritated eyes of healthy volunteers as well as patients with glaucoma or ocular hypertension (N=20) in a 2-week, single-center, randomized, double-masked, crossover study. Participants were evaluated at days 0, 7, 11, and 15. At day 0, they were exposed to a controlled adverse environment (CAE), in which humidity, temperature, and airflow was regulated, for up to 90 minutes. Participants who reported a sufficient level of bilateral ocular discomfort during exposure to the CAE were enrolled in this study and received 1 drop of brimonidine-Purite 0.15% in 1 eye and 1 drop of brimonidine tartrate 0.2% in the contralateral eye. Immediately following instillation, participants were asked to indicate their preference for either study medication. The study medications were not used between days 0 and 7. From day 7 to 10, participants administered either drug bilaterally. On day 11, the treatment was crossed over, and participants were asked to compare the preferred medication with their previous regimen. They continued to administer the drug bilaterally twice daily until day 15, when the preferred medication was again compared with the previous regimen. Following CAE exposure at visit 1, 70.6% of the participants preferred brimonidine-Purite 0.15% over brimonidine tartrate 0.2% and indicated that it was significantly more comfortable than brimonidine tartrate 0.2% (P=.009). When given brimonidine-Purite 0.15% first before switching to brimonidine tartrate 0.2%, 80% of participants preferred brimonidine-Purite 0.15% (P=.012). When given brimonidine tartrate 0.2% first before switching to brimonidine-Purite 0.15%, 85% preferred brimonidine-Purite 0.15% (P=.001). The results of this study suggest that brimonidine-Purite 0.15% is significantly more comfortable than brimonidine tartrate 0.2% in patients with irritated eyes.

Automated Perimetry, Tonometry, and Questionnaire in Glaucoma Screening

To evaluate the sensitivity and specificity of various portions of the glaucoma screening process, 145 participants underwent complete ophthalmic examinations. A weighted questionnaire was 20% (2 patients) and 36% (5 suspects) sensitive for the glaucoma patients and glaucoma suspects, respectively. Tonometry alone was 20% (2 patients) and 7% (1 suspect) sensitive for glaucoma patients and glaucoma suspects, respectively. Automated perimetry of the central 30 degrees and nasal periphery identified nine (90%) of the glaucoma patients and five (36%) of the glaucoma suspects. The presence of increased intraocular pressure was not by itself very useful, but when perimetry or tonometry was used, 10 (100%) of the glaucoma group was identified. We recommend that automated suprathreshold perimetry and tonometry be performed in glaucoma screening.

Timolol Hemihydrate vs Timolol Maleate to Treat Ocular Hypertension and Open-Angle Glaucoma

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.

Ocular hypotensive efficacy of brimonidine 0.15% as adjunctive therapy with latanoprost 0.005% in patients with open-angle glaucoma or ocular hypertension.

This study was undertaken to evaluate the ocular hypotensive efficacy of brimonidine Purite® 0.15% (Alphagan® P 0.15%; Allergan, Inc., Irvine, Calif) given as adjunctive therapy with latanoprost 0.005% (Xalatan®; Pfizer Inc., New York, NY) to patients with open-angle glaucoma or ocular hypertension. In this multicenter, open-label, prospective evaluation, the intraocular pressure (IOP) of the 43 enrolled patients was ≥18 mm Hg after at least 6 wk of latanoprost monotherapy. The primary outcome measure was IOP at peak drug effect (10 am, or approximately 2 h after the morning dose of brimonidine 0.15%). IOP at trough drug effect (8 am, or approximately 12 h after the evening dose of brimonidine) was also measured. Baseline IOP was 21.9 (±2.3) mm Hg. After 1 mo of treatment, additional mean IOP reductions from latanoprost-treated baseline values were 5.8 mm Hg (26%) at peak drug effect (P < .001) and 3.3 mm Hg (15%) at trough (P < .001). At the month 2 visit, additional mean IOP reductions from latanoprost-treated baseline values were 5.1 mm Hg (23%) at peak drug effect (P < .001) and 2.0 mm Hg (9%) at trough (P=.002). Brimonidine Purite 0.15% provided statistically significant additional reductions in IOP from latanoprost-Transmission and reproduction of this material in whole or part without prior written approval are prohibited. treated baseline values. These findings suggest that brimonidine Purite 0.15% is an efficacious adjunctive therapy in patients given latanoprost who require additional lowering of IOP.

Efficacy of Bimatoprost 0.03 Percent in Untreated Glaucoma and Ocular Hypertension Patients: Results From a Large Community-Based Clinical Trial

PURPOSE To evaluate the intraocular pressure- (IOP-) lowering efficacy of bimatoprost 0.03% (Lumigan, Allergan, Inc.) monotherapy in the treatment of patients with glaucoma or ocular hypertension not currently using ocular hypotensives. METHODS Open-label, community-based, multicenter evaluation. Patients (n = 6767) who, according to their physicians, required IOP lowering were prescribed bimatoprost for 2 months. Subgroup analyses of the results, stratified by treatment history and use of concomitant medications, were performed. This report focuses on the subgroup of patients that was not being treated with antiglaucoma medications at baseline (n = 1946, 29%). All of these patients were placed on bimatoprost monotherapy. RESULTS The mean IOP at the untreated baseline was 23.8 mmHg. Bimatoprost provided a mean IOP reduction of 7.5 mmHg (30%, p < 0.001) from baseline after 2 months of monotherapy. Further, bimatoprost allowed patients to achieve low target pressures. For example, 41.5% of patients achieved target IOPs of < or =15 mmHg after 2 months of bimatoprost monotherapy, and 75.8% of patients reached IOPs of < or =18 mmHg. The most commonly reported adverse event was conjunctival hyperemia (7.9%). CONCLUSION Bimatoprost monotherapy was well tolerated and reduced IOP by an average of 30% in a large population of untreated patients.

Short-term tolerability of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in glaucoma and/or ocular hypertension: A prospective, randomized, double-masked, active-controlled, three-period crossover pilot study

OBJECTIVE The aim of this study was to compare symptoms and anterior segment tolerability with short-term (3-day) administration of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in the treatment of glaucoma and/or ocular hypertension. METHODS In this prospective, randomized, double-masked, active-controlled, 3-period crossover pilot study, eligible patients had primary open-angle, pigment-dispersion, or exfoliation glaucoma, and/or ocular hypertension in > or = 1 eye; had a best corrected visual acuity of 1.0 or better in each eye, as measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing chart; were receiving 1 glaucoma medication; and had an untreated intraocular pressure (IOP) of < or = 28 mm Hg in both eyes after washout (if required) at visit 2 (day 0). Patients were assigned to receive, in randomized order, timolol hemihydrate 0.5%, timolol in sorbate 0.5%, or generic timolol gel-forming solution 0.5%, 1 drop each morning (approximately 8 am) in the qualified eye(s) (washout IOP < or = 28 mm Hg) for 3 days. Each treatment period was separated by a 7-day washout period. At all baseline and end-of-treatment study visits, patients completed a solicited symptom survey (used for the assessment of stinging or burning [grade 0 = none to 4 = severe] and blurred or dimmed vision [grade 0 = none to 4 = severe], among other parameters) and underwent ETDRS, Goldmann applanation tonometry, slit-lamp biomicroscopy, anterior segment staining (corneal, conjunctival nasal, and conjunctival temporal staining), conjunctival hyperemia assessment, measurement of tear breakup time, and Schirmers testing with anesthesia. At end-of-treatment assessments, patients were questioned about adverse events. RESULTS Thirty patients were enrolled (15 men, 15 women; mean [SD] age, 66.3 [8.9] years; white, 19 patients, black, 11; primary open-angle glaucoma, 17; ocular hypertension, 13). Mean (SD) stinging or burning grade was significantly greater with timolol in sorbate compared with timolol hemihydrate and timolol gel-forming solution (0.9 [0.9] vs 0.4 [0.6] and 0.2 [0.6], respectively; P < 0.001). The between-treatment differences on anterior segment staining, conjunctival hyperemia, tear breakup time, and Schirmers testing with anesthesia were not significant, with the exception of the change from baseline in conjunctival nasal staining by count, which was significantly higher with timolol gel-forming solution compared with timolol hemihydrate and timolol in sorbate (3.1 [13.4] vs -2.9 [10.1] and -3.0 [8.0], respectively; P = 0.04). On the solicited symptom survey, timolol gel-forming solution was associated with a poorer mean score on blurred or dimmed vision compared with timolol hemihydrate and timolol in sorbate (0.3 [0.7] vs 0.1 [0.3] and 0.0 [0.2], respectively; P = 0.02). Mean best corrected ETDRS visual acuity immediately after instillation was significantly lower with timolol gel-forming solution compared with timolol hemihydrate and timolol in sorbate (49.6 [8.4] vs 53.0 [6.1] and 53.1 [6.7], respectively; P = 0.007). The mean 24-hour trough IOP did not differ significantly between the 3 treatments. CONCLUSIONS In this pilot study that compared the symptoms and tolerability of once-daily timolol hemihydrate 0.5%, timolol in sorbate 0.5%, and timolol gel-forming solution 0.5% in these patients with glaucoma and/or ocular hypertension, short-term (3-day) administration of timolol in sorbate was associated with more stinging or burning compared with timolol hemihydrate and timolol gel-forming solution. Timolol gel-forming solution was associated with more postinstillation blurred or dimmed vision compared with timolol hemihydrate and timolol in sorbate.