Mauro Sartore, Emilia Maggio, Alfonso Massimiliano Ferrara, Umberto Basso, Grazia Pertile
Purpose: To describe a unique case of von Hippel-Lindau (VHL) disease in which a treatment-resistant juxtapapillary retinal hemangioblastoma (RH) underwent complete and sustained regression following systemic therapy with cabozantinib, a VEGFR/MET inhibitor administered for clear cell renal cell carcinoma (ccRCC). Observations: A 63-year-old woman with genetically confirmed VHL disease presented with a chronic, exudative juxtapapillary RH in the left eye, unresponsive to multiple prior therapies, including intravitreal anti-VEGF agents, corticosteroids, and vitreoretinal surgery. Despite temporary improvement after pars plana vitrectomy with epiretinal membrane peeling and focal laser photocoagulation, exudation recurred, and new RHs developed. In August 2022, the patient initiated cabozantinib for ccRCC. Within weeks, a marked reduction in juxtapapillary exudation was noted, followed by progressive and complete anatomical resolution. This response was sustained over a three-year follow-up period, during which no new RHs developed, and no ocular treatments were required. Conclusions and importance: This case describes sustained remission of a juxtapapillary RH following cabozantinib therapy, with long-term stability of peripheral retinal findings and no new lesions development. The temporal correlation and absence of concurrent ocular interventions suggest a therapeutic role for cabozantinib in modulating disease activity at the retinal level. These findings support further investigation into systemic, pathway-targeted therapies as non-ablative treatment options for RHs, particularly in anatomically critical locations where conventional treatments are limited or contraindicated.