Levodopa Improves Vision in Some Serious Macular Degeneration Cases

Tucson, AZ—A common Parkinson’s disease drug is showing promise for patients with an advanced form of age-related macular degeneration (AMD).

A report in the American Journal of Medicine described how levodopa stabilized and improved patients’ vision in a small study, while reducing the number of treatments necessary to maintain vision.

University of Arizona–led authors point out that more than 15% of the United States population over the age of 70 years has AMD, a common cause of blindness in developed nations. While neovascular AMD (nAMD), which involves fluid and blood leaking in the subretinal space of the eye, represents only 10% to 15% of all AMD cases, it is responsible for 90% of the vision loss attributed to the disease. Standard treatment requires frequent injections of agents to block excessive vascular endothelial growth factor (VEGF), but the injections are expensive and painful, although effective.

The authors point out that earlier research found that patients being treated with levodopa for movement disorders such as Parkinson’s disease were significantly less likely to develop any type of AMD. “Levodopa has a receptor (GPR143) selectively expressed on pigmented cells. This receptor can be supportive of retinal health and survival, which led to the development of our hypothesis that it may prevent or treat AMD,” explained lead investigator Robert W. Snyder, MD, PhD, of the Department of Biomedical Engineering at the University of Arizona, Tucson. 

Background information in the article describes how dysfunction of the retinal pigment epithelium likely initiates AMD, adding, “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.”

In the open-label pilot study, a group of 20 patients with newly diagnosed nAMD and naïve to anti-VEGF injections had the effects of carbidopa-levodopa on vision and anatomic outcomes evaluated for 4 weeks. Those patients were followed for another 5 months with ascending levodopa doses. Another cohort of 14 patients previously treated with anti-VEGF injection therapy were also treated with ascending levodopa doses and evaluated for 6 months.

Results indicate that levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. Researchers report that, in the first month, retinal fluid decreased by 29% (P = .02, n = 12) without anti-VEGF treatment and that, 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 the first cohort (P = .004, n = 15) and by 4.8 letters in the second (P = .02, n = 11), they note.

Additionally, there was a 52% reduction in the need for anti-VEGF injections in the second cohort, which had received them (P = .002).

“Our findings suggest efficacy and support the pharmacological targeting of GPR143 with levodopa for the treatment of nAMD in future studies,” the authors conclude.

Researchers suggest that levodopa might be unlikely as a standalone treatment in patients with newly diagnosed nAMD since 11 of the patients also required anti-VEGF injections. Yet, they point out, patients required fewer than the standard monthly treatments, and in the second group, monthly injections of anti-VEGF decreased by 52%.