Levodopa Positively Affects Neovascular Age-Related Macular Degeneration.
BACKGROUND
Age-related macular degeneration (AMD) is a common cause of blindness worldwide. Neovascular AMD (nAMD) is an advanced form of the disease, in which excess vascular endothelial growth factor (VEGF) induces growth of new blood vessels that leak fluid, accounting for 90% of vision loss in AMD. Dysfunction of the retinal pigment epithelium likely initiates AMD. Retinal pigment epithelial cells express a G protein-coupled receptor, GPR143, which downregulates VEGF in response to levodopa. Anti-VEGF therapy effectively treats nAMD, suggesting that excessive VEGF activity drives the pathology.


METHODS
In an open-label pilot study, in patients with newly diagnosed nAMD and naïve to anti-VEGF injections (Cohort-1), the effects of carbidopa-levodopa on vision and anatomic outcomes were evaluated for 4 weeks. Then patients were followed 5 months further with ascending levodopa doses. Patients previously treated with anti-VEGF injection therapy (Cohort-2) were also treated with ascending levodopa doses and evaluated for 6 months.


RESULTS
Levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29% (P = .02, n = 12) without anti-VEGF treatment. Through 6 months the decrease in retinal fluid was sustained, with a mean frequency of 0.38 injections/month. At month 6, mean visual acuity improved by 4.7 letters in Cohort-1 (P = .004, n = 15) and by 4.8 letters in Cohort-2 (P = .02, n = 11). Additionally, there was a 52% reduction in the need for anti-VEGF injections in Cohort-2 (P = .002).


CONCLUSIONS
Our findings suggest efficacy and support the pharmacological targeting of GPR143 with levodopa for the treatment of nAMD in future studies.
['Figueroa|Anna G|AG|', 'Boyd|Brennan M|BM|', 'Christensen|Cory A|CA|', 'Javid|Cameron G|CG|', 'McKay|Brian S|BS|', 'Fagan|Timothy C|TC|', 'Snyder|Robert W|RW|']
D000368:Aged D000369:Aged, 80 and over D002230:Carbidopa D015331:Cohort Studies D015259:Dopamine Agents D004338:Drug Combinations D005260:Female D006801:Humans D007980:Levodopa D008268:Macular Degeneration D008297:Male D008875:Middle Aged D010865:Pilot Projects D016896:Treatment Outcome
Age-related macular degeneration (AMD) Neovascular AMD nAMD Retinal pigment epithelium GPR143 Carbidopa-levodopa L-DOPA Prospective study Wet AMD