Ophthalmol Retina. 2026 Apr;10(4):353-361. doi: 10.1016/j.oret.2025.12.004.
Summary
Levodopa exposure reduced conversion from non-exudative AMD to nAMD. Suggests that RCT should be considered. Retrospective, SOURCE database.
Abstract
Objective: There is a need for therapies that delay neovascular age-related macular degeneration (AMD) progression. Levodopa (L-DOPA) and dopamine receptor D2 (DRD2) agonists have been proposed as potential agents. We investigated the association between dopamine agonist (DA) exposure and conversion to neovascular AMD using the Sight Outcomes Research Collaborative (SOURCE) database.
Design: Retrospective cohort analysis from SOURCE.
Participants: Eyes with non-neovascular AMD at the early or intermediate stage.
Methods: We included eyes with a diagnosis of early- or intermediate-stage AMD in 1 eye. We excluded eyes with new exposure to L-DOPA or DRD2 agonist after the time of non-neovascular AMD diagnosis or when a variable of interest was unknown. Propensity score matching was performed, and survival analysis with Cox proportional hazard models was conducted in 3 separate analyses: (1) eyes with no DA exposure versus eyes exposed to any DA; (2) eyes with no DA exposure versus eyes with exposure to DRD2 agonist; and (3) eyes with no DA exposure versus eyes with exposure to L-DOPA.
Main outcome measures: Adjusted hazard ratios of any (1) DA exposure, (2) DRD2 agonist exposure, and (3) L-DOPA exposure in association with conversion to new-onset neovascular AMD.
Results: There was a 47% reduced likelihood of conversion to neovascular AMD in eyes exposed to L-DOPA compared with those without DA exposure over 5 years (P = 0.028). There was no association between exposure to any DA or exposure to DRD2 agonist and conversion to neovascular AMD.
Conclusions: Levodopa exposure was associated with reduced conversion from non-neovascular AMD to new-onset neovascular AMD. A randomized clinical trial to study whether L-DOPA decreases the development of neovascular AMD should be considered.
