Geographic atrophy (GA) can cause significant vision loss in age-related macular degeneration (AMD) patients and has garnered increased research attention of late now that there are medical treatments available. However, these are currently limited to anti-complement drugs, which are limited by their efficacy in delaying progression, with significant complication risk still a possibility. The precursor to dopamine, levodopa (L-dopa), may be an interesting therapeutic option, as it is already associated with reduced development of neovascular AMD.

In a new study, researchers investigated if levodopa was associated with reduced likelihood of new-onset GA. The retrospective investigation included eyes with dry AMD without GA and one to five years of follow-up. Two groups of eyes were formed: those exposed to levodopa before or on the date of diagnosis for non-neovascular AMD without GA and those not exposed to L-dopa.

Levodopa can reduce oxidative stress in RPE cells, which is just one potential mechanism for which the dopamine precursor may be protecting against GA. Photo: Wendy Harrison, OD, PhD. Click image to enlarge.

After propensity score matching, 2,532 controls and 844 levodopa exposed eyes remained that were matched well for age, sex, AMD severity, AREDS2 use and smoking status. Upon analysis, it was found that levodopa exposure indeed was associated with a significantly reduced likelihood of new-onset GA detection. Over one to five years, L-dopa exposure culminated to be a 32% risk reduction. Consequently, this finding underscores the idea that exposure to levodopa may reduce the likelihood of GA development.

In their paper for Eye and Vision, the authors expand upon potential mechanisms that may explain this effect in the discussion of their paper. One possibility may be explained by exogenous L-dopa dilating choroidal vasculature, as patients with Parkinson’s disease who take levodopa have been observed to have greater choroidal thickness when compared with age-matched controls without the condition. Choriocapillaris loss is predictive of drusen accumulation and progression, so levodopa may be improving choriocapillaris perfusion via choroidal dilation.

Another observation is that Parkinson’s patients have inner retinal atrophy when compared with controls. It’s possible that inner retinal atrophy leads to greater perfusion of the outer retina from retinal circulation, improving relative ischemia and preventing GA.

The authors also point out that GA development was, on average, longer in eyes exposed to levodopa , being 2.1 years, when compared with controls, with development averaging 1.7 years. They also identify one protective factor that was found, which was younger age. Both intermediate AMD and AREDS2 use were risk factors for new-onset GA detection.

These results are promising, prompting the authors to write that, “since complement pathway inhibitors, such as pegcetacoplan or avacincaptad pegol, only reduce GA growth by 15% to 20% and have the potential for devastating complications like occlusive retinal vasculitis, alternative treatments to prevent GA onset are important for the future of dry AMD treatment.”

They surmise that “future studies will additionally investigate if L-DOPA can reduce progression of early AMD to intermediate AMD.”