Levodopa Positively Affects Neovascular Age-Related Macular Degeneration

Area of Science:

• Ophthalmology
• Pharmacology
• Cell Biology

Background:

• Age-related macular degeneration (AMD) is a leading cause of blindness globally.
• Neovascular AMD (nAMD), an advanced form, involves excess vascular endothelial growth factor (VEGF) driving abnormal blood vessel growth and fluid leakage, causing 90% of AMD-related vision loss.
• Retinal pigment epithelial cell dysfunction and G protein-coupled receptor 143 (GPR143) signaling are implicated in AMD pathogenesis, with levodopa shown to downregulate VEGF via GPR143.

Purpose of the Study:

• To evaluate the safety and efficacy of carbidopa-levodopa in patients with newly diagnosed neovascular AMD (nAMD).
• To assess the impact of levodopa on visual acuity and anatomical outcomes in nAMD patients.
• To determine if levodopa can reduce the need for anti-VEGF therapies in nAMD management.

Main Methods:

• An open-label pilot study involving two cohorts of nAMD patients.
• Cohort 1: Newly diagnosed, anti-VEGF treatment-naïve patients treated with ascending levodopa doses for 6 months.
• Cohort 2: Patients previously treated with anti-VEGF injections, also treated with ascending levodopa doses for 6 months.

Main Results:

• Levodopa was safe and well-tolerated, with significant reduction in retinal fluid (29% in the first month) and sustained improvement in visual acuity (4.7-4.8 letters at 6 months) in both cohorts.
• Levodopa therapy delayed the need for anti-VEGF injections.
• A 52% reduction in the requirement for anti-VEGF injections was observed in Cohort 2.

Conclusions:

• Levodopa demonstrates efficacy in treating nAMD, improving vision and reducing retinal fluid.
• Pharmacological targeting of GPR143 with levodopa presents a potential new therapeutic strategy for nAMD.
• Further studies are warranted to confirm these findings and explore levodopa's role in nAMD treatment.