Abstract
Purpose
P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting.
Methods
This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD.
Results
There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p = 0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p = 0.062) and exudative AMD (p > 0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients.
Conclusion
We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.
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No funding was received for conducting the study. The authors did not receive support from any organization for the submitted work.
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This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Weill Cornell Medicine Institutional Review Board approved this study, Protocol # 22-07025078.
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Financial Interests: KDK is a consultant of Intergalactic Therapeutics.
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Woo, K.M., Mahrous, M.A., D’Amico, D.J. et al. Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors. Graefes Arch Clin Exp Ophthalmol (2024). https://doi.org/10.1007/s00417-024-06507-9
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DOI: https://doi.org/10.1007/s00417-024-06507-9