Risks of Retinal Vascular Occlusions with the Systemic Use of Tyrosine Kinase Inhibitors.

purposeCentral retinal vein occlusion (CRVO) and retinal perfusion defects have been described as potential risks associated with systemic tyrosine kinase inhibitor (TKI) therapy, but current evidence is limited to case reports. Therefore, this study aimed to better characterize any associations between systemic TKIs and the risks of retinal artery occlusion (RAO) and retinal vein occlusion (RVO).

designRetrospective cohort study using multi-institutional electronic health records across the United States.

participantsAdults with cancer diagnoses and no prior history of retinal vascular occlusions or maculopathy, based on International Classification of Diseases (ICD) encounter diagnosis codes, were included. Patients with prescriptions for TKIs with and without anti-VEGF activities were created, and were each compared with matched control patients with non-TKI antineoplastic prescriptions.

methodsThe study and control cohorts were propensity score-matched 1:1 based on demographic factors, comorbidities, other antineoplastic therapy, and cancer stages. The matched cohorts were then compared for having new-onset ICD encounter diagnosis codes of any RAO, central RAO, branch RAO, CRVO, and branch RVO (BRVO).

main outcome measuresLifetime risks of RAO, central RAO, branch RAO, RVO, CRVO, and BRVO were compared via risk ratios (RRs). Rates of these outcomes within 3 years of antineoplastic initiation were also evaluated via hazard ratios (HRs). Differences in the outcome measures were considered statistically significant if the 95% confidence interval (CI) was ≤0.9 or ≥1.1.

resultsWhile the anytime-risks of having RAOs and RVOs were comparable between the anti-VEGF TKI cohort and controls (each n = 6728), the anti-VEGF TKI cohort had a significant hazard of having CRVO within 3 years of TKI initiation (HR = 2.86, CI = 1.44-5.69). In contrast, while the non-anti-VEGF TKI cohort (n = 17 185) had a lower anytime-risk of having RAO (RR = 0.61, CI = 0.45-0.83) and BRVO (RR = 0.51, CI = 0.36-0.71) compared with the non-TKI controls (n = 17 185), there was no difference in the HR among outcomes between the 2 cohorts.

conclusionsAlthough non-anti-VEGF TKIs may have a more favorable safety profile with respect to BRVO and RAO compared with other antineoplastic therapies, patients initiating anti-VEGF TKIs may warrant closer ophthalmological monitoring for the incidence of CRVO during the first few years of treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.