Using TKI Drugs as Anti-VEGF Fine for BRVO Risk, Dicey for CRVO

Although TKIs without anti-VEGF properties may have a more favorable safety profile with respect to BRVO and RAO compared to other antineoplastic therapies, patients initiating TKIs with such properties may warrant closer monitoring for the incidence of CRVO during the first few years of treatment. Photo: Jessica Haynes, OD. Click image to enlarge. Recently, systemic tyrosine kinase inhibitor therapy, typically an anti-cancer regimen, has gained attention as a potential treatment for retinal diseases such as diabetic macular edema (DME) and age-related macular degeneration (AMD). In this context, TKIs inhibit vascular endothelial growth factor receptors, functioning similarly to anti-VEGF agents that are currently the standard therapy for various exudative retinal diseases. Still, it remains unclear whether these observations reflect a true association with TKIs or were caused by comorbidities or patient-specific risk factors. To address these gaps, researchers analyzed large cohorts of patients on TKIs to determine the risk of having retinal vein occlusions (RVOs) and retinal artery occlusions (RAOs). They also investigated the potential role of anti-VEGF properties of systemic TKIs in retinal vascular occlusions through stratified analysis based on the anti-VEGF activity of TKIs.The researchers determined that, while the overall risk of RVOs with systemic TKI use is low and may even be associated with a lower risk of branch retinal vein occlusion (BRVO) and RAO for non-anti-VEGF TKIs, anti-VEGF TKIs were associated with a significantly higher hazard of having central retinal vein occlusion (CRVO) within the first three years of initiation.“TKIs without anti-VEGF properties had no such association with acute retinal vascular events and instead were associated with a lower lifetime risk of BRVO and RAO, which may reflect their potential benefit against malignancy-associated retinal thrombosis compared to non-TKI antineoplastics,” the study authors wrote in their paper.In the study, which was published in Ophthalmology Retina, lifetime risks of RAO, central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), RVO, CRVO and BRVO were compared via risk ratios (RRs). Rates of these outcomes within three years of antineoplastic initiation were also evaluated via hazard ratios (HRs).While the anytime-risks of having RAOs and RVOs were comparable between the anti-VEGF TKI cohort and controls (each n=6,728), the anti-VEGF TKI cohort had a significant hazard of having CRVO within three years of TKI initiation (HR=2.86). In contrast, while the non-anti-VEGF TKI cohort (n=17,185) had a lower anytime-risk of having RAO (RR=0.61) and BRVO (RR=0.51) compared to the non-TKI controls (n=17,185), there was no difference in the HR among outcomes between the two cohorts.The researchers suggested that the observed elevated hazards of CRVO in the anti-VEGF cohort should not be interpreted as a result of VEGF receptor inhibition alone, but rather the combined disruption of the mitogen-activated protein kinase pathway signaling axis—and potentially other pathways—from such off-target inhibition.“Although inhibition of the mitogen-activated protein kinase pathway offers oncologic and anti-neovascular benefits, it also downregulates factors critical for endothelial repair while inducing pro-atherogenic surface adhesion molecules and the coagulation cascade, ultimately promoting prothrombotic and atherosclerotic states with endothelial and pericyte dysfunction,” the researchers pointed out.Whether the potential short-term risk of CRVO from TKI extends to intraocular TKI therapy for retinal pathologies remains to be elucidated. According to the study team, prospective studies using retinal imaging and more stringent control against confounders would help refine these implications of this explorative study and further inform monitoring strategies for patients initiating TKI therapy.Click here for the journal source. Jeong H, Yue SC, Kaelber DC, et al. Risks of retinal vascular occlusions with the systemic use of tyrosine kinase inhibitors. Ophthalmol Retina. March 4, 2026. [Epub ahead of print].  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.