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

JAMA Ophthalmol. 2020 May 1;138(5):560-567. doi: 10.1001/jamaophthalmol.2020.0724.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use
  • Chemotherapy, Adjuvant
  • Choroidal Neovascularization / diagnostic imaging
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / physiopathology
  • Drug Combinations
  • Exudates and Transudates
  • Female
  • Humans
  • Intraocular Pressure / physiology
  • Intravitreal Injections
  • Macular Edema / diagnostic imaging
  • Macular Edema / drug therapy
  • Macular Edema / physiopathology
  • Male
  • Ophthalmic Solutions
  • Placebos
  • Single-Blind Method
  • Sulfonamides / therapeutic use*
  • Thiophenes / therapeutic use*
  • Timolol / therapeutic use*
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Wet Macular Degeneration / diagnostic imaging
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / physiopathology


  • Angiogenesis Inhibitors
  • Drug Combinations
  • Ophthalmic Solutions
  • Placebos
  • Sulfonamides
  • Thiophenes
  • dorzolamide-timolol combination
  • Timolol

Associated data

  • ClinicalTrials.gov/NCT03034772