Retinal haemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome

PURPOSE: Evaluation of phenotype and treatment outcome of retinal haemangioblastomas (RH) in von Hippel-Lindau (VHL) disease and correlation of these features with the genotype of VHL germline mutation carriers.

METHODS: Retrospective analysis of a longitudinal cohort of 21 VHL germline mutation carriers and RH. Clinical and genetic data were obtained to analyse the correlation of genotype with phenotype and treatment outcomes.

RESULTS: All patients were categorized in two genotypic categories: missense mutations (MM) and truncating mutations (TM). Mean follow-up duration was 16.3 years and did not differ significantly between mutation groups (p = 0.383). Missense mutations (MM) carriers (n = 6) developed more progression-related complications compared to TM carriers (n = 15) (p = 0.046). Vitreoretinal surgery was more often applied in MM carriers (p = 0.036). Moderate (visual acuity (VA)20/80 to 20/200) to severe (VA < 20/200) visual impairment was observed in 53.3% of the eyes of MM carriers and 28.1% of the eyes of TM carriers at last recorded visit.

CONCLUSION: Missense mutations in VHL patients seem to have a higher prevalence of progression-related complications. Missense mutations (MM) carriers required therefore more often vitreoretinal surgical treatment with a worse treatment outcome. Genetic analysis may play a role in determining a pro-active treatment strategy and prognosis for RH.