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Brennan Michael Boyd, Timothy Fagan, Anna G. Figueroa, Brian S McKay, Robert W Snyder; Short Term Effects of Carbidopa-Levodopa in Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2019;60(9):356.
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A large retrospective cohort study shows that carbidopa-levodopa therapy delays the onset of AMD by 8 years. The retinal pigment epithelium responds to L-DOPA activation of GPR143 in vitro with up-regulation of pigment epithelium-derived factor and down-regulation of vascular endothelial growth factor (VEGF). This is the initial report on a prospective, proof of concept study to test our hypothesis that carbidopa-levodopa has a positive therapeutic effect on wet AMD.
We designed a clinical trial and filed an IND with the FDA for use of carbidopa-levodopa to treat wet AMD. Following informed consent, 8 patients with newly diagnosed wet AMD, naïve to anti-VEGF injections, were started on either carbidopa-levodopa 25-100 qhs or tid and followed weekly for 4 weeks. Patients included 3 males and 5 females, ages 63-87, and were all diagnosed by an Ophthalmologist within 1 week before study enrollment. Best corrected visual acuity (VA) was measured using an ETDRS protocol, and subjective vision changes were assessed using a survey. SD-OCT measurements of central retinal thickness (CRT) and retinal fluid were obtained. If at any time there was evidence of significant worsening, patients were referred for an anti-VEGF injection. Due to the small sample size and ethical issues of withholding treatment, a placebo group was not used.
All 8 enrolled patients finished the trial; 1 was excluded from the analysis for requiring an anti-VEGF injection. VA improved by 2-7 letters in 4/7, was unchanged in 1 and worsened by 1 and 4 letters in 2/7. CRT decreased by 1-18 μm in 7/7. Retinal fluid decreased by 33-75% in 5/7 and was unchanged in 2/7. Subjective vision survey remained stable in 7/7. No drug-related adverse events were reported. Patient response to carbidopa-levodopa did not differ with respect to dosage, age, gender, time since diagnosis or baseline values for the variables measured.
Our results support our hypothesis that carbidopa-levodopa has a positive effect on wet AMD, as 5/7 patients were improved or stable with respect to VA, CRT, retinal fluid and subjective vision, whereas deterioration would be expected in patients not treated with anti-VEGF injections. These early findings warrant further investigation into the possibility of repurposing carbidopa-levodopa, an FDA approved drug, as an adjunctive treatment for wet AMD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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