Association between Nucleoside and Nucleotide Reverse Transcriptase Inhibitor Use and Primary Open-Angle Glaucoma Risk in All of Us

Abstract

Purpose: To assess the association between the systemic use of nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and primary open-angle glaucoma (POAG).

Design: Retrospective cohort study.

Participants: Individuals aged ≥40 years with linked electronic health record (EHR) data in the National Institutes of Health (NIH) All of Us dataset. Participants with a diagnosis of POAG before the use of NRTIs were excluded.

Methods: A cohort of 1:10 NRTI users to nonusers was created using a propensity score matching design, considering age, race, sex at birth, human immunodeficiency virus (HIV) diagnosis, hepatitis B diagnosis, and family history of POAG. A multivariable logistic regression model was used to adjust for residual imbalance. Sensitivity analyses were performed for self-reported eye doctor visits.

Main outcome measure: Diagnosis of POAG.

Results: Among the 305 441 All of Us participants aged ≥40 years with a linked EHR, we identified 718 individuals (0.24%) with NRTI use, excluding participants with a diagnosis of POAG before NRTI exposure. The rate of POAG in the NRTI users was 4.32% (N = 31). The rate of POAG in the propensity score-matched control group (N = 7180) was 2.00% (N = 144). Use of NRTI was associated with an increased risk of POAG (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.48-3.28; P < 0.001). When adjusting for residual imbalance of family history of POAG, HIV diagnosis, and hepatitis B diagnosis, use of any NRTIs remained significantly associated with an increased risk of developing POAG (OR, 1.84; 95% CI, 1.22-2.77; P = 0.004). After matching and adjusting for self-reported eye doctor visits, NRTIs remained significantly associated with POAG risk (OR, 2.30; 95% CI, 1.07-4.96; P = 0.033).

Conclusions: Use of NRTIs was associated with a higher risk of POAG with propensity score matching for covariates and adjusting for residual imbalances.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: All of Us, Nucleoside and nucleotide reverse transcriptase inhibitors; Primary open-angle glaucoma.