CC BY-NC-ND 4.0 · Klin Monbl Augenheilkd
DOI: 10.1055/a-2501-8628
Klinische Studie

Morphology of Retinal Hemangioblastoma in von Hippel-Lindau Disease Revealed by Optical Coherence Tomography Angiography

Morphologie von retinalen Hämangioblastomen bei Von-Hippel-Lindau-Erkrankung dargestellt durch optische Kohärenztomografie-Angiografie
Yannik Laich
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Stefan J. Lang 
2   Department of Ophthalmology, University Hospital Brandenburg, Brandenburg Medical School, Brandenburg an der Havel, Germany
,
Andreas Glatz
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Navid Farassat
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Felicitas Bucher
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Simone Nuessle 
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Daniel Böhringer
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Wolf Alexander Lagrèze
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Spyridon Sideris
3   Jules Bordet Institute, Medical Oncology Department, University Hospital of Brussels, Brussels, Belgium
,
Peter Maloca
4   Medical Practice for Ophthalmology Priv.-Doz. Dr. med. Peter Maloca, Luzern, Switzerland
5   Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
,
Clemens Lange
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
6   Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany
,
Thomas Reinhard
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Hansjürgen Agostini
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Michael Reich 
1   Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
7   Augenärzte am Städel, Medical Practice for Ophthalmology, Frankfurt am Main, Germany
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Abstract

Background To characterize different growth patterns of retinal hemangioblastomas (RHs) in patients with von Hippel-Lindau disease (VHLD) using swept-source optical coherence tomography angiography (SS-OCTA).

Methods Single-center observational cross-sectional study. SS-OCTA B-scans were centered over primary treatment-naïve RHs to display the perfusion in the inner, middle, and outer areas (IA, MA, OA). Distinctive growth patterns were characterized using K-means cluster analysis of the flow signal.

Results Annual screening of 201 patients with VHLD revealed 49 patients with 85 RHs (41 recurrent, 44 primary treatment-naïve RHs). High-quality SS-OCTA images were available for 24 primary RHs and were pooled with scans of the treatment-naïve form of 6 recurrent RHs, which were taken at a prior visit, for further analysis. Out of 30 primary RHs, 18 were located juxtapapillary (jRH) and 12 peripherally (pRH). K-means cluster analysis distinguished seven exophytic (23.3%, 2 jRH, 5 pRH), nine endophytic (30%, 6 jRH, 3 pRH), and fourteen sessile (46.7%, 10 jRH, 4 pRH) growth patterns. Fractions of the flow signal in the IA, MA, and OA were 7.3 ± 3.3%, 89.3 ± 5.0%, and 3.4 ± 3.5% for exophytic RHs, 22.2 ± 7.4%, 65.6 ± 7.3%, and 12.1 ± 8.2% for sessile RHs, and 65.4 ± 5.7%, 26.6 ± 4.9%, and 8.0 ± 6.1% for endophytic RH.

Conclusion OCTA contributes to further elucidating the morphology of RHs as a useful complementary diagnostic tool that can help to provide customized therapeutic approaches in the future and thus improve the effectiveness of RH treatment.

Zusammenfassung

Hintergrund Ziel der Studie ist die Charakterisierung unterschiedlicher Wachstumsmuster von retinalen Hämangioblastomen (RHs) bei Patienten mit Von-Hippel-Lindau-Krankheit (VHLD) mittels Swept-Source optischer Kohärenztomografie-Angiografie (SS-OCTA).

Methoden Monozentrische Querschnittsstudie. SS-OCTA-B-Scans von primären, unbehandelten RHs wurden erstellt, um die Perfusion in den inneren, mittleren und äußeren Bereichen (IA, MA, OA) der RH darzustellen. Charakteristische Wachstumsmuster wurden mithilfe einer K-Means-Cluster-Analyse des Flusssignals ermittelt.

Ergebnisse Bei jährlichen Screenings von 201 Patienten mit VHLD wurden bei 49 Patienten 85 RHs (41 rezidivierende, 44 primäre, unbehandelte RHs) detektiert. SS-OCTA-Scans von 24 primären RHs wurden zusammen mit Aufnahmen der unbehandelten Form von 6 rezidivierenden RHs, die bei einem früheren Besuch erhoben wurden, zur weiteren Analyse zusammengeführt. Von den 30 primären RHs waren 18 juxtapapillär (jRH) und 12 peripher (pRH) gelegen. Mittels K-Mittel-Cluster-Analyse wurden sieben exophytische (23,3%, 2 jRH, 5 pRH), 9 endophytische (30%, 6 jRH, 3 pRH) und 14 sessile (46,7%, 10 jRH, 4 pRH) Wachstumsmuster unterschieden. Die jeweiligen Anteile des Flusssignals in der IA, MA und OA betrugen 7,3 ± 3,3%, 89,3 ± 5,0%, 3,4 ± 3,5% für exophytische RHs, 22,2 ± 7,4%, 65,6 ± 7,3%, 12,1 ± 8,2% für sessile RHs und 65,4 ± 5,7%, 26,6 ± 4,9%, 8,0 ± 6,1% für endophytische RHs.

Schlussfolgerung Die OCTA bietet als ergänzendes diagnostisches Verfahren einen wertvollen Beitrag zur weiteren Aufklärung der Morphologie von RHs. Sie kann zukünftig zur Entwicklung individuellerer therapeutischer Ansätze beitragen und dadurch die Effektivität der Behandlung von RH bei VHLD verbessern.

Conclusion

Already known:

OCTA has been described as a useful tool for early RH detection, classification of single lesions, and post-treatment monitoring; however, its use in systematically classifying RH flow patterns across a broad patient sample remains unexplored. This study examines whether RH growth patterns correlate with flow patterns in OCTA.

Newly described:

There is a correlation between the flow patterns measured by OCTA and the three distinct RH morphologies–endophytic, sessile, and exophytic–in both juxtapapillary RHs and peripheral RHs. Given the critical role of tumor morphology in determining treatment approaches, OCTA scan data could support more tailored therapeutic strategies for RHs, potentially enhancing the visual prognosis for patients with VHLD in the future.

Keywords

retinal hemangioblastoma - morphology - von Hippel-Lindau disease - optical coherence tomography angiography - OCTA

Schlüsselwörter

retinale Hämangioblastome - Morphologie - Von-Hippel-Lindau Erkrankung - optische Kohärenztomografie-Angiografie - OCTA

Supporting Information



Publication History

Received: 03 November 2024

Accepted: 25 November 2024

Article published online:
10 February 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Maher ER, Iselius L, Yates JR. et al. Von Hippel-Lindau disease: a genetic study. J Med Genet 1991; 28: 443-447
    CrossrefPubMedSearch in Google Scholar
  • 2 Maddock IR, Moran A, Maher ER. et al. A genetic register for von Hippel-Lindau disease. J Med Genet 1996; 33: 120-127
    CrossrefPubMedSearch in Google Scholar
  • 3 Evans DG, Howard E, Giblin C. et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 2010; 152 A: 327-332
    CrossrefPubMedSearch in Google Scholar
  • 4 Conway JE, Chou D, Clatterbuck RE. et al. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 2001; 48: 55-62
    PubMedSearch in Google Scholar
  • 5 Lonser RR, Glenn GM, Walther M. et al. von Hippel-Lindau disease. Lancet 2003; 361: 2059-2067
    CrossrefPubMedSearch in Google Scholar
  • 6 Schmidt D, Agostini HT. [Retinal angiomatosis – an ophthalmological challenge]. Klin Monbl Augenheilkd 2007; 224: 905-921
    PubMedSearch in Google Scholar
  • 7 Liang X, Shen D, Huang Y. et al. Molecular pathology and CXCR4 expression in surgically excised retinal hemangioblastomas associated with von Hippel-Lindau disease. Ophthalmology 2007; 114: 147-156
    CrossrefPubMedSearch in Google Scholar
  • 8 Chew EY. Ocular manifestations of von Hippel-Lindau disease: clinical and genetic investigations. Trans Am Ophthalmol Soc 2005; 103: 495-511
    PubMedSearch in Google Scholar
  • 9 Webster AR, Maher ER, Moore AT. Clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and correlation with germline mutation. Arch Ophthalmol 1999; 117: 371-378
    CrossrefPubMedSearch in Google Scholar
  • 10 Salama Y, Albanyan S, Szybowska M. et al. Comprehensive characterization of a Canadian cohort of von Hippel-Lindau disease patients. Clin Genet 2019; 96: 461-467
    CrossrefPubMedSearch in Google Scholar
  • 11 Wittebol-Post D, Hes FJ, Lips CJ. The eye in von Hippel-Lindau disease. Long-term follow-up of screening and treatment: recommendations. J Intern Med 1998; 243: 555-561
    CrossrefPubMedSearch in Google Scholar
  • 12 Maher ER, Yates JR, Harries R. et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990; 77: 1151-1163
    CrossrefPubMedSearch in Google Scholar
  • 13 Neumann HP, Wiestler OD. Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus. Lancet 1991; 337: 1052-1054
    CrossrefPubMedSearch in Google Scholar
  • 14 Reich M, Jaegle S, Neumann-Haefelin E. et al. Genotype–phenotype correlation in von Hippel-Lindau disease. Acta Ophthalmologica 2021; 99: e1492-e1500
    CrossrefPubMedSearch in Google Scholar
  • 15 Singh AD, Shields CL, Shields JA. von Hippel-Lindau disease. Surv Ophthalmol 2001; 46: 117-142
    CrossrefPubMedSearch in Google Scholar
  • 16 Binderup MLM, Stendell AS, Galanakis M. et al. Retinal hemangioblastoma: prevalence, incidence and frequency of underlying von Hippel-Lindau disease. Br J Ophthalmol 2018; 102 (07) 942-947
    CrossrefPubMedSearch in Google Scholar
  • 17 Gass JD, Braunstein R. Sessile and exophytic capillary angiomas of the juxtapapillary retina and optic nerve head. Arch Ophthalmol 1980; 98 (10) 1790-1797
    CrossrefPubMedSearch in Google Scholar
  • 18 McCabe CM, Flynn jr. HW, Shields CL. et al. Juxtapapillary capillary hemangiomas. Clinical features and visual acuity outcomes. Ophthalmology 2000; 107: 2240-2248
    CrossrefPubMedSearch in Google Scholar
  • 19 Jonasch E, Donskov F, Iliopoulos O. et al. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med 2021; 385: 2036-2046
    CrossrefPubMedSearch in Google Scholar
  • 20 Reich M, Glatz A, Boehringer D. et al. Comparison of Current Optical Coherence Tomography Angiography Methods in Imaging Retinal Hemangioblastomas. Transl Vis Sci Technol 2020; 9: 12
    CrossrefPubMedSearch in Google Scholar
  • 21 Lang SJ, Dreesbach M, Laich Y. et al. Zeiss PLEX Elite 9000 Widefield Optical Coherence Tomography Angiography as Screening Method for Early Detection of Retinal Hemangioblastomas in von Hippel-Lindau Disease. Transl Vis Sci Technol 2024; 13 (02) 8
    CrossrefPubMedSearch in Google Scholar
  • 22 Kashani AH, Chen CL, Gahm JK. et al. Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications. Prog Retin Eye Res 2017; 60: 66-100
    CrossrefPubMedSearch in Google Scholar
  • 23 Wang F, Zhang Q, Deegan AJ. et al. Comparing imaging capabilities of spectral domain and swept source optical coherence tomography angiography in healthy subjects and central serous retinopathy. Eye Vis (Lond) 2018; 5: 19
    CrossrefPubMedSearch in Google Scholar
  • 24 Reich M, Boehringer D, Rothaus K. et al. Swept-source optical coherence tomography angiography alleviates shadowing artifacts caused by subretinal fluid. Int Ophthalmol 2020; 40: 2007-2016
    CrossrefPubMedSearch in Google Scholar
  • 25 Lang SJ, Cakir B, Evers C. et al. Value of Optical Coherence Tomography Angiography Imaging in Diagnosis and Treatment of Hemangioblastomas in von Hippel-Lindau Disease. Ophthalmic Surg Lasers Imaging Retina 2016; 47: 935-946
    CrossrefPubMedSearch in Google Scholar
  • 26 Smid LM, van Overdam KA, Davidoiu V. et al. Classification and treatment follow-up of a juxtapapillary retinal hemangioblastoma with optical coherence tomography angiography. Am J Ophthalmol Case Rep 2019; 15: 100472
    CrossrefPubMedSearch in Google Scholar
  • 27 Kreusel KM, Bechrakis NE, Neumann HP. et al. Pars plana vitrectomy for juxtapapillary capillary retinal angioma. Am J Ophthalmol 2006; 141: 587-589
    CrossrefPubMedSearch in Google Scholar
  • 28 Saitta A, Nicolai M, Giovannini A. et al. Juxtapapillary retinal capillary hemangioma: new therapeutic strategies. Med Hypothesis Discov Innov Ophthalmol 2014; 3: 71-75
    PubMedSearch in Google Scholar
  • 29 Garcia-Arumi J, Sararols LH, Cavero L. et al. Therapeutic options for capillary papillary hemangiomas. Ophthalmology 2000; 107: 48-54
    PubMedSearch in Google Scholar
  • 30 Darr JL, Hughes jr. RP, McNair JN. Bilateral peripapillary retinal hemangiomas. A case report. Arch Ophthalmol 1966; 75: 77-81
    CrossrefPubMedSearch in Google Scholar