The effect of oral belzutifan on retinal hemangioblastomas in von Hippel-Lindau syndrome.

Objective: To assess the effect of belzutifan, a first-in-class oral hypoxia-inducible factor 2α inhibitor, on retinal hemangioblastoma (RH) outcomes.

Subjects/methods: This is a single-centre retrospective cohort study of patients with confirmed von Hippel-Lindau syndrome (VHLS) and RH. Subjects were taking oral belzutifan for renal cell carcinoma, central nervous system hemangioblastoma, or pancreatic neuroendocrine tumours. Patients were assessed for ophthalmic structural, functional, and therapeutic outcomes for >11 months. Patient demographics, VHL genotype, visual function, behaviour of pre-existing RH, number of new lesions, systemic features, and drug-related adverse events were recorded.

Results: Sixteen patients (30 eyes) taking oral belzutifan were identified. The mean age was 37 ± 9 years. The proportion of type 1 VHLS was 87.5%, with large (≥1 exon) VHL deletions (81.3%) being the most common. No new RHs developed during the treatment period. The mean final visual acuity was 0.4 ± 1.0 logMAR, with 80% retaining a visual acuity of 0.3 logMAR or better in at least 1 eye (81.3% bilateral).

Conclusions: In patients with VHLS, oral belzutifan resulted in stability of pre-existing RH and no new RH developed during the treatment period. Early use of belzutifan may be a therapeutic avenue to prevent RH development and blindness in patients with VHLS when compared with destructive/ablative alternatives, particularly for posterior or juxtapapillary lesions.