Effect of Adjuvant Topical Dorzolamide-Timolol vs Placebo in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial

Abstract

Importance: Some eyes with neovascular age-related macular degeneration (AMD) have persistent exudation despite frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. Adjuvant therapies that further reduce edema may improve vision outcomes.

Objective: To compare the short-term effect of topical dorzolamide-timolol vs placebo in eyes with neovascular AMD that have persistent exudation following intravitreal anti-VEGF injections.

Design, setting, and participants: Randomized placebo-controlled clinical trial with enrollment from March 1, 2017, through October 30, 2018. Multicenter trial at 4 clinical sites in the United States. Sixty-three patients with neovascular AMD who had persistent exudation despite intravitreal anti-VEGF injections at 4-week, 5-week, or 6-week intervals.

Interventions: Patients were randomized to use dorzolamide-timolol or artificial tears for the study duration. They continued to receive the same anti-VEGF drug at the same interval as the 2 visits before enrollment for 3 additional study visits.

Main outcomes and measures: The primary outcome measure was change in mean central subfield thickness on optical coherence tomography from baseline to visit 3 (approximately 3 months). Secondary measures included change in mean maximum subretinal fluid height, mean maximum pigment epithelial detachment height, and mean visual acuity (VA).

Results: This trial included 52 patients. All 27 patients (100%) assigned to dorzolamide-timolol and 23 of 25 (92%) assigned to placebo were analyzed for the primary outcome. Mean (SD) age was 78.4 (7) years, and 34 of 50 patients (68%) were women. Mean (SD) injections were 20.5 (14) (range, 4-58) before enrollment. Mean (SD) baseline logMAR VA was 0.361 (0.26) (approximate Snellen equivalent, 20/50). Comparing the dorzolamide-timolol with placebo group from baseline to visit 3, mean (SD) change in central subfield thickness (primary outcome) was -36.6 (54) μm vs 1.7 (52.3) μm (difference, 30.8; 95% CI, 0.3-61.3; P = .04); secondary outcomes: maximum PED height was -39.1 (65) μm vs 1.1 (16) μm (difference, 39.6; 95% CI, 9.6-69.6; P = .01) and change in VA from baseline to visit 3 was -2.3 (5) vs 0.3 (1) letters (difference, 2.6 letters; 95% CI, -1.9 to 7.1 letters; P = .78).

Conclusions and relevance: These findings suggest use of dorzolamide-timolol in patients with neovascular AMD with persistent exudation resulted in anatomic but not visual acuity improvements compared with placebo at approximately 3 months. Additional clinical trials with longer follow-up and larger sample sizes presumably would be needed to determine the role, if any, of dorzolamide-timolol in neovascular AMD.

Trial registration: ClinicalTrials.gov Identifier: NCT03034772.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hsu reported grants from Roche/Genentech and Santen and grants and personal fees from Ophthotech outside the submitted work. Dr Wolfe reported grants and personal fees from Allergan, Genentech, Novartis, and Regeneron outside the submitted work. Dr Chen reported grants from Genentech and Regeneron outside the submitted work. Dr Jenkins reported personal fees from Genentech outside the submitted work. Dr Garg reported personal fees from Bausch Health, Johnson and Johnson, and Topivert and grants from Allergan, Aerpio, and Apellis outside the submitted work. Dr Ho reported grants and other support from Regeneron and Genentech during the conduct of the study. Dr Chiang reported grants from Regeneron, grants and nonfinancial support from Genentech and Apellis, and personal fees from Recens Medical and Orbit Biomedical outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram Showing Randomization and Treatment of Study Patients

Figure 2.. Distribution of Changes in Mean Optical Coherence Tomography Parameters Including Central Subfield Thickness (A), Maximum Pigment Epithelial Detachment Height (B), Maximum Subretinal Fluid Height (C), and Central Foveal Thickness (D) in Eyes With Neovascular Age-Related Macular Degeneration Receiving Intravitreal Anti–Vascular Endothelial Growth Factor With Adjuvant Topical Dorzolamide-Timolol vs Placebo

P values were obtained using analysis of covariance, with adjustment for baseline optical coherence tomography parameter and type of anti–vascular endothelial growth factor therapy used. Error bars represent standard deviation.