March 2026

OPHTHALMOLOGY

LEVODOPA LINKED WITH LOWER RISK OF NEW‑ONSET GEOGRAPHIC ATROPHY IN PATIENTS WITH AMD

Jeremy Lavine, MD, PhD, shares key background on his recent study published in Eye and Vision.
 
Can You Provide a Brief Overview of Your Study?
This study examined whether exposure to levodopa (L‑DOPA) is associated with a reduced risk of developing geographic atrophy secondary to age‑related macular degeneration (AMD). Geographic atrophy is a major cause of vision loss in patients with dry AMD, and there are currently no approved preventive therapies.
 
We conducted a retrospective analysis using a large database of private practice retina specialists across the United States. Eligible patients had a diagnosis of dry AMD and at least one year of follow-up data. We excluded patients with missing data and those who initiated levodopa therapy after their AMD diagnosis.
 
For the analysis, we extracted demographic and clinical variables including age, sex, smoking status, AMD severity and use of eye vitamins. We then performed propensity score matching at a 3:1 ratio to ensure balance between levodopa exposed and control groups based on known risk factors for geographic atrophy. A mixed effects Cox regression model was used to calculate hazard ratios, adjusting for relevant covariates.
 
After matching, we analyzed 2,532 control eyes and 844 levodopa exposed eyes. Levodopa exposure was associated with a 32% reduction in the risk of new onset geographic atrophy, which was statistically significant.
 
What Inspired You to Pursue This Research?
Geographic atrophy remains an area of significant unmet need in AMD, as it is a common cause of irreversible vision loss and lacks preventive treatment options. This study was motivated by our prior work showing that levodopa exposure was associated with a reduced risk of progression to neovascular AMD, another major cause of vision loss in this patient population. Given these earlier findings, we wanted to explore whether a similar association existed for geographic atrophy.
 
How Does This Study Build On or Differ From Previous Research in This Area?
Previous studies have reported associations between levodopa use and a delayed age of onset of AMD overall, as well as neovascular AMD specifically. Our group has also shown that levodopa exposure is associated with reduced odds of developing new onset neovascular AMD and with decreased treatment burden in patients who already have wet AMD.
 
However, prior to this study, there were no published reports examining the relationship between levodopa exposure and geographic atrophy secondary to AMD. This analysis represents the first investigation, to our knowledge, of that specific association.
 
What Key Differences Did You Observe Between Patients Exposed to L‑DOPA and Those Who Were Not?
Using propensity score matching allowed us to closely balance the levodopa exposed and control groups with respect to all known risk factors for geographic atrophy, including age, sex, AMD severity, smoking status, eye vitamin use and duration of follow-up. Despite this careful matching, geographic atrophy remains understudied, and its underlying mechanisms are not fully understood. As a result, there may be additional, currently unknown risk factors that we could not account for.
 
What Are the Clinical Implications of the Study?
From a clinical standpoint, these findings should be considered preliminary. This was a retrospective database study, and while the association is compelling, it does not establish causality. A prospective, randomized clinical trial would be required before levodopa could be considered for widespread use as a preventive strategy in AMD.
 
Will These Results Influence Clinical Practice or Treatment Guidelines in the Near Term?
At this stage, the results are not sufficient to influence clinical practice or AMD treatment guidelines. They should instead be viewed as hypothesis generating and supportive of further investigation.
 
What’s Next for Your Research?
We are currently evaluating the association between levodopa exposure and both neovascular AMD and geographic atrophy in a separate, nonoverlapping academic database. A manuscript replicating our prior findings — showing reduced development of neovascular AMD in levodopa exposed patients — is currently under review.
 
In parallel, a basic science manuscript is also under review demonstrating that levodopa inhibits mouse models of neovascular AMD through two distinct pathways: direct binding of levodopa to the GPR143 receptor and conversion of levodopa to dopamine with subsequent activation of the dopamine D2 receptor.
 
Additionally, a randomized controlled clinical trial in Europe — LDOPA for Neovascular (Wet) Age Related Macular Degeneration (LAMDARCT) — is currently funded and underway. This trial is enrolling patients with new onset neovascular AMD and comparing levodopa with standard care. The primary endpoint is treatment burden for wet AMD, while secondary outcomes include the development of neovascular AMD and geographic atrophy in fellow eyes. These secondary outcomes will provide high quality prospective data on levodopa’s potential role as a preventive therapy in advanced AMD.
 
At this time, I plan to await the results of that trial before pursuing additional clinical trials.
Jeremy Lavine, MD, PhD, Assistant Professor of Ophthalmology and Rheumatology at Northwestern Medicine

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