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 Schirmer's 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 Schirmer's 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.

RCT Entities:   Population Interventions Outcomes