Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration

Murray H. Brilliant, Kamyar Vaziri, Thomas B. Connor, Stephen Schwartz, Joseph J. Carroll, Catherine A. McCarty, Steven J. Schrodi, Scott J. Hebbring, Krishna Kishor, Harry W Flynn, Andrew A. Moshfeghi, Darius M. Moshfeghi, M. Elizabeth Fini, Brian S. McKay

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25 Scopus citations

Abstract

Background Age-related macular degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell type involved in AMD, the retinal pigment epithelium, expresses a G protein-coupled receptor that, in response to its ligand, L-DOPA, up-regulates pigment epithelia-derived factor, while down-regulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD. Methods We used retrospective analysis to compare the incidence of AMD between patients taking vs not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (approximately 17,000 and approximately 20,000) and the Truven MarketScan outpatient and databases (approximately 87 million) patients. We used International Classification of Diseases, 9th Revision codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription. Results In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3, and 71.3 in 3 independent retrospective cohorts. Age-related macular degeneration occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (odds ratio 0.78; confidence interval, 0.76-0.80; P

Original languageEnglish (US)
Pages (from-to)292-298
Number of pages7
JournalAmerican Journal of Medicine
Volume129
Issue number3
DOIs
StatePublished - Mar 1 2016

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Keywords

  • Age-related macular degeneration (AMD)
  • GPR143
  • L-DOPA
  • Movement disorder
  • Parkinson's disease
  • Retinal pigment epithelium (RPE)
  • Retrospective study

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Brilliant, M. H., Vaziri, K., Connor, T. B., Schwartz, S., Carroll, J. J., McCarty, C. A., Schrodi, S. J., Hebbring, S. J., Kishor, K., Flynn, H. W., Moshfeghi, A. A., Moshfeghi, D. M., Fini, M. E., & McKay, B. S. (2016). Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration. American Journal of Medicine, 129(3), 292-298. https://doi.org/10.1016/j.amjmed.2015.10.015