Levodopa Use Associated with Reduced nAMD Development

Jeremy A. Lavine MD PhD

Credit: Northwestern Medicine

Levodopa is associated with reduced development of new onset neovascular age-related macular degeneration (nAMD), according to new research.¹

Data from an analysis of levodopa use showed cumulative two-year doses between ∼100-300mg per day and >∼300mg were associated with decreased odds of developing nAMD by 14% and 23%, respectively.

“A prospective, randomized clinical trial should be considered to investigate whether low-dose levodopa reduces nAMD conversion,” wrote the investigative team, led by Jeremy A. Lavine MD, PhD, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University.

Levodopa is the precursor to dopamine and physicians commonly use it as a dopamine replacement for the treatment of Parkinson disease. It is considered the most effective medication to improve the quality of life in patients with idiopathic Parkinson disease and is generally prescribed to a patient once bradykinetic symptoms become more difficult to control with other anti-parkinsonism agents.²

Recent literature from an open-label pilot study suggests the positive efficacy of levodopa for AMD by targeting ​​GPR143 in retinal pigment epithelium cells, which downregulates vascular endothelial growth factor (VEGF) cells in response to levodopa. The results indicate levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes.³

A total of 3 studies were performed and included in the current report. These included 2 retrospective analyses in the Vestrum Health Retina Database and a case-control analysis in the Merative™ MarketScan® Research Databases. The first analysis included eyes with nAMD and 2 years of follow; the second included eyes with non-neovascular AMD and 1 - 5 years of follow-up; and the third included patients aged 55 years and older with newly diagnosed nAMD matched to controls without nAMD.

The included eyes were divided into 2 groups: those exposed to levodopa before or on the date of neovascular (group 1) or non-neovascular AMD group (group 2), as well as those eyes not exposed to levodopa. Investigators extracted data on age, sex, AREDS status, dry AMD stage, smoking history, and the number of intravitreal injections at years 1 and 2 in group 1, as well as the conversation rate for nAMD at years 1 - 5 in group 2.

Investigators calculated the percentage of newly diagnosed nAMD cases and matched controls exposed to any levodopa. Then, the team determined the cumulative 2-year dose in grams (g) by tertiles (<100mg, ∼100-300mg, and >∼300mg per day). The main outcome for the first analysis was the number of intravitreal injections by unpaired t-test, while the detection of new-onset nAMD by multivariable logistic regression after adjusting for AMD risk factors was measured by the second and third analyses.

In the Vestrum Database, the analysis showed eyes with nAMD exposed to levodopa (n = 530) underwent 1 fewer intravitreal injection over 2 years, compared with control (n = 84,088 control; P = .0015). Within the same database (n = 42,081 - 203,155 control vs. 314 - 1,525 levodopa eyes), eyes with non-neovascular AMD exposed to levodopa experienced a 21% reduced risk of conversion to nAMD at year 2 (P = .029). The analysis showed the trend continued as eyes with non-neovascular AMD experienced a 35% reduced risk of conversion at years 3 - 4 (P <.001), and 28% at year 5 (P = .024).

Moreover, in the MarketScan Databases (n = 86,900 per group), the analysis showed the cumulative 2-year doses of levodopa between ∼100-300mg per day and >∼300mg were associated with decreased odds of developing nAMD by 14% (odds ratio [OR], 0.86; 95% CI, 0.75 - 0.97) and 23% (OR, 0.77; 95% CI, 0.67 - 0.87), respectively.

“Levodopa use was associated with reduced detection of new-onset neovascular AMD,” investigators wrote.

References

1. Hyman MJ, Skondra D, Aggarwal N, et al. Levodopa is associated with reduced development of neovascular age-related macular degeneration [published online ahead of print, 2023 May 3]. Ophthalmol Retina. 2023;S2468-6530(23)00198-7. doi:10.1016/j.oret.2023.04.014
2. A; GK. Levodopa (L-DOPA). National Center for Biotechnology Information. May 2, 2022. Accessed May 22, 2023. https://pubmed.ncbi.nlm.nih.gov/29489269/.
3. Figueroa AG, Boyd BM, Christensen CA, et al. Levodopa Positively Affects Neovascular Age-Related Macular Degeneration. Am J Med. 2021;134(1):122-128.e3. doi:10.1016/j.amjmed.2020.05.038