Abstract
Purpose :
Levodopa, a byproduct of melanin synthesis, is an agonist of the G-protein coupled receptor 143 (GPR143), which is expressed by the retinal pigment epithelium. GPR143 agonism increases the expression of anti-angiogenic pigment epithelial derived factor and decreases the expression of pro-angiogenic vascular endothelial growth factor and exosomes. Prior studies have shown there is reduced risk of developing neovascular age-related macular degeneration (AMD) in patients taking levodopa. However, it remains unclear whether levodopa has an association with the development of advanced non-neovascular AMD, including geographic atrophy (GA). We investigated the odds of new-onset GA in patients with and without levodopa exposure.
Methods :
We retrospectively analyzed data from the Vestrum Health Retina Database between January 2014 and July 2023. We identified patients with and without levodopa exposure who underwent an eye examination and were diagnosed with non-neovascular AMD. We determined the incidence of new-onset GA and foveal GA in the 1-5 year follow-up period. We additionally collected age, sex, smoking status, AMD severity, and AREDS use. Multivariable logistic regression analysis was performed to investigate the association between levodopa exposure and new-onset GA.
Results :
We identified 1065, 730, 447, 277, and 136 eyes with non-neovascular AMD who were exposed to levodopa at Years 1-5 respectively. We found 153494, 100847, 65449, 40223, and 20674 control non-neovascular AMD eyes at Years 1-5. At Year 1, no significant differences in GA rates were detected. Levodopa exposure reduced the rates of any new-onset GA by 51% at Year 2 (p=0.013), 52% at Year 3 (p=0.017), 49% at Year 4 (p=0.039), and 61% at Year 5 (p=0.041). Levodopa exposure decreased foveal GA rates by 58% at Year 2 (p=0.055), 71% at Year 3 (p=0.035), and 66% at Year 4 (p=0.068).
Conclusions :
Levodopa exposure is associated with reduced conversion to GA and foveal GA. Since levodopa is also associated with decreased odds of new-onset neovascular AMD, a randomized, placebo-controlled clinical trial to investigate if levodopa can reduce the risk of advanced AMD should be considered.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.