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

Abstract

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.

Keywords: Lindau; benign tumours; clinical genetics; haemangioblastoma; retina; von Hippel - Lindau.

Figure 1

Peripheral retinal haemangioblastoma with dilated and tortuous feeding vessels, surrounded by detachment and exudation that extends into the macula.

Figure 2

Line graph showing the regression rate of treated haemangioblastomas relative to the number of tumours arised during follow‐up. In both genotypic categories, the regression rate was 100% if merely one or two tumours arised. Missense mutation carriers showed a faster decrease of the regression rate when tumour number increased.

Figure 3

Bar graph showing the distribution of the initial and last recorded best‐corrected visual acuities between genotypic categories. Whereas missense mutation carriers started with a better visual acuity in best‐ and worse‐seeing eye, at last recorded visit a larger percentage of severe visual impairment is observed in this genotypic category.