July 2019
Volume 60, Issue 9
ARVO Annual Meeting Abstract  |   July 2019
Retinal hemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome
Author Affiliations & Notes
  • Anass Hajjaj
    Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands
  • Koen van Overdam
    Vitreoretinal Surgery, The Rotterdam Eye Hospital, Rotterdam, Netherlands
  • Rogier Oldenburg
    Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands
  • Annelies de Klein
    Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands
  • Emine Kilic
    Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands
  • Footnotes
    Commercial Relationships   Anass Hajjaj, None; Koen van Overdam, None; Rogier Oldenburg, None; Annelies de Klein, None; Emine Kilic, None
  • Footnotes
    Support  The Rotterdamse Stichting Blindenbelangen Grant HV/AB/B20180038
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3547. doi:https://doi.org/
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      Anass Hajjaj, Koen van Overdam, Rogier Oldenburg, Annelies de Klein, Emine Kilic; Retinal hemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3547. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Evaluating the phenotype, complications and treatment outcome of retinal hemangioblastomas (RH) and correlating these features with the genotype of Von Hippel-Lindau (VHL) germline mutation carriers.

Methods : Retrospective analysis of the medical and genetic records of 21 individuals with a VHL germline mutation and a diagnosis of RH during follow-up the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital between 1984 and 2017. Germline mutation status was correlated to the age at diagnosis of RH, phenotype, progression-related complications, visual acuity, treatment methods and treatment outcomes. Mutations were categorized in two genotypic categories: missense mutation (MM) or truncating mutations (TM). The latter included significant deletions, splice site mutations and out of frame indels.

Results : From the 21 VHL germline mutation carriers, 15 individuals had a TM and 6 individuals a MM. Prevalence of RH in VHL disease was highest in TM carriers (15 of 21, 68.2%). The mean age at baseline visit was 25.5 years. Mean age of diagnosis of RH was 25.7 years. There was no significant difference in age at baseline visit and age of onset of RH between genotypic categories (P = 0.57 and P = 0.93 , respectively). Mean follow-up duration was 16.3 years and did not differ significantly between the mutation groups (P = 0.38). Bilateral involvement was observed in 66.7% of the patients. Missense mutation (MM) carriers developed more RH (> 5 RH: 50.0% vs. 38.5%), had a larger extent of peripheral retinal involvement of ocular VHL disease (66.7% vs. 35.7% all quadrants involved) and developed more progression-related complications compared to TM carriers (100% vs. 46.7%). Complete tumor regression at last recorded visit was achieved in fifteen patients (71.4%). Moderate (VA 20/80 to 20/200) to severe (less than 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.

Conclusions : This pilot study suggests that VHL missense mutation carriers had a more complicated progression of RH than carriers of a truncating mutation. Why missense mutation cause such an effect is unknown status but DNA and RNA profiling will help us to understand the course of progression of RH in VHL disease.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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