Dataset Information

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.

SUBMITTER: Hsu J

PROVIDER: S-EPMC7118620 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundClinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.MethodsIn a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.ResultsBevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.ConclusionsAt 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).