Oral Belzutifan Treatment in von Hippel-Lindau-Associated Retinal Haemangioblastoma: A Promising Approach

Objectives To assess the efficacy and safety of oral belzutifan in a real-world cohort of pretreated patients with von Hippel-Lindau (vHL)-associated retinal haemangioblastomas (RHs). Methods This retrospective observational study included genetically confirmed vHL patients with RHs, in whom at least one eye had been previously refractory to conventional ocular therapy. Patients received oral belzutifan (120 mg once daily) and underwent standardised ophthalmic follow-up with multimodal imaging. Tumour area was quantified on widefield colour fundus photography and red-free images using standardised image analysis. To minimize clustering bias, the largest lesion per eye was predefined for the primary analysis, with an exploratory analysis including all detected lesions. Overall ocular response (OOR) was assessed at the eye level. Safety monitoring was performed within an interdisciplinary clinical framework. Results Five patients (seven eyes, 14 RHs) were included. Significant tumour regression was observed for the largest lesion per eye (median reduction − 58% [IQR, 17–64]; p = 0.028) and across all lesions (median − 57.2% [IQR, 28.0-66.9]; p < 0.001); nine of 14 lesions showed > 20% size reduction. OOR improved in six of seven eyes; one eye was not evaluable due to pre-existing phthisis bulbi. Changes in best-corrected visual acuity and central subfield thickness were not statistically significant. No genotype-response association was identified. Drug-related adverse events were mostly mild to moderate and manageable. Conclusions Belzutifan was associated with clinically meaningful tumour regression in vHL-associated RHs that were previously mainly refractory to conventional ocular therapy, with an acceptable safety profile. Further prospective studies are warranted.