Levodopa Positively Affects Neovascular Age-Related Macular Degeneration - 17/12/20
, Robert W. Snyder, MD, PhD e, fAbstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Age-related macular degeneration (AMD), Carbidopa-levodopa, GPR143, L-DOPA, nAMD, Neovascular AMD, Prospective study, Retinal pigment epithelium, Wet AMD
Plan
| Funding: Snyder Biomedical Corporation (RWS) financially supported the clinical trials. NEI RO1-EY026544 (BSM) supported other aspects of the study. |
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| Conflict of Interest: The authors TCF, RWS, BSM, and CGJ certify that they have affiliation or involvement in an organization or entity with a financial interest in the subject matter or materials discussed in this manuscript. Snyder Biomedical Corporation has licensed patent (No. US9173862 B2, inventors: Brian S. McKay and John A. Martens) entitled “Methods and Compositions for Treating and Identifying Compounds to Treat Age-Related Macular Degeneration.” A patent (application no. 62/799,444) is pending, entitled “Compositions and Methods for Treating or Limiting Development of Age-Related Macular Degeneration,” filed January 31, 2020 (inventors: RWS and BSM). RWS is founder and president of Snyder Biomedical Corporation. RWS, TCF, and CGJ are shareholders in Snyder Biomedical Corporation. The authors BMB, CAC, and AGF certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. |
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| Authorship: All authors had access to the data and had a role in writing, reviewing, and approving the manuscript. |
Vol 134 - N° 1
P. 122 - janvier 2021 Retour au numéro
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