Associations between Systemic Tyrosine Kinase Inhibitors and Development of Age-Related Macular Degeneration in Patients with Cancer

Document Type

Article

Publication Title

Ophthalmology Retina

Abstract

Purpose To evaluate the association between systemic tyrosine kinase inhibitor (TKI) therapy and the risk of age-related macular degeneration (AMD) onset, and whether this relationship varies by anti-VEGF activity of TKIs. Design Retrospective cohort study using a large deidentified electronic health records research platform. Participants Patients ≥50 years old with cancer encounter diagnoses were divided into groups with (treatment) and without (control) systemic TKI prescription codes and followed for incident AMD diagnosis. Methods Landmarked time-to-event analyses were performed at 1, 3, and 5 years postcancer diagnosis. Treatment and control groups were propensity score matched, followed from the landmark date until incident International Classification of Diseases 10 (ICD-10) AMD encounter diagnosis, death, or last recorded clinical encounter and compared using hazard ratios (HRs) for incident AMD. A 3-arm subanalysis was also performed by stratifying TKIs by anti-VEGF activity, comparing the TKI-with-anti-VEGF and TKI-without-anti-VEGF subgroups to the control group and to each other. Main Outcome Measures Hazard ratios for an incident ICD-10 AMD encounter diagnosis code after the landmark date. Significance was defined as 95% confidence interval (CI) <0.9 and >1.1. Results Across landmark analyses, TKI prescriptions were not consistently associated with the hazard of receiving a new ICD-10 AMD encounter diagnosis code compared with matched controls: 1 year (HR = 0.97; 95% CI = 0.85, 1.12), 3 years (HR = 0.90; 95% CI = 0.78, 1.05), and 5 years (HR = 0.81; 95% CI = 0.69, 0.96). In the subanalysis, the TKI-with-anti-VEGF subgroup showed significant reduction only at the 5-year landmark (HR = 0.60; 95% CI = 0.40, 0.89). The TKI-without-anti-VEGF subgroup demonstrated no significant association between systemic TKI exposure and the hazard of receiving a new ICD-10 AMD encounter diagnosis code at any time point: 1 year (HR = 0.98; 95% CI = 0.84, 1.15), 3 years (HR = 0.97; 95% CI = 0.82, 1.15), and 5 years (HR = 0.87; 95% CI = 0.73, 1.05). In contrast, across analyses, TKI prescriptions were consistently associated with increased hazards of mortality and fewer ophthalmology encounters. Conclusions This explorative study found that TKI prescriptions are not associated with incident AMD diagnosis. These findings do not support a population-level protective effect of systemic TKIs on AMD risk. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

DOI

10.1016/j.oret.2026.02.018

Publication Date

1-1-2026

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