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Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors
Kwang Min Woo1, M Abdallah Mahrous1, Donald J D'Amico1
1Department of Ophthalmology, Weill Cornell Medical College, 1305 York Avenue, 11Th Floor, New York, NY, 10021, USA.
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.
Insights
This study found no significant association between antiretroviral therapy (zidovudine, lamivudine, abacavir) and age-related macular degeneration (ARMD) in HIV patients. Further research with larger cohorts is recommended for definitive conclusions on ARMD subtypes.
Area of Science:
- Ophthalmology
- Pharmacology
- Infectious Diseases
Background:
- P2X7 receptor (P2X7R) activation is implicated in age-related macular degeneration (ARMD).
- Nucleoside reverse transcriptase inhibitors (NRTIs) like zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) inhibit P2X7R and show promise in animal models of ARMD.
Purpose of the Study:
- To investigate the clinical association between chronic NRTI therapy (AZT, 3TC, ABC) and ARMD.
- To determine if P2X7R-inhibiting antiretrovirals impact ARMD prevalence in HIV patients.
Main Methods:
- Retrospective cohort study comparing HIV patients with and without NRTI use, and non-HIV controls.
- Fundus examination and spectral domain optical coherence tomography (SD-ODT) used to assess ARMD prevalence.
Main Results:
- No statistically significant difference in early-intermediate ARMD prevalence between HIV patients with and without NRTI history (p=0.887).
- No significant difference in geographic atrophy or exudative ARMD prevalence between HIV patients with NRTI history and non-HIV controls.
Conclusions:
- Chronic use of AZT, 3TC, and ABC did not show a significant effect on early-intermediate ARMD, geographic atrophy, or exudative ARMD in this cohort.
- Larger studies with detailed medication histories are necessary to confirm these findings, particularly for geographic atrophy and exudative ARMD.
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