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Karimi S, Arabi A, Shahraki T, Safi S. Von Hippel-Lindau Disease and the Eye. JOVR [Internet]. 2020Feb.3 [cited 2024Apr.25];15(1):78–94. Available from: https://knepublishing.com/index.php/JOVR/article/view/5950
https://doi.org/10.18502/jovr.v15i1.5950
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authors
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Saeed Karimi
Saeed Karimi
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Ophthalmology, Torfeh Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
-
Amir Arabi
Amir Arabi
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Ophthalmology, Torfeh Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
-
Toktam Shahraki
Toktam Shahraki
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Ophthalmology, Torfeh Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
-
Sare Safi
Sare Safi
Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Published Date
- Feb 3, 2020
Von Hippel-Lindau Disease and the Eye
Abstract
Retinal hemangioblastoma (also referred to as retinal capillary hemangioma) is a benign lesion originating from the endothelial and glial components of the neurosensory retina and optic nerve head. Historically known as a manifestation of the von Hippel- Lindau (VHL) disease, it can be seen as an isolated finding or in association with some rare ocular conditions. In addition to characteristic ophthalmoscopic features, results of numerous ancillary tests including angiography, ultrasound, optical coherence tomography, and genetic tests may support the diagnosis and differentiate it from similar conditions. Because of serious life-threatening complications of VHL disease, every ocular approach to retinal hemangioblastomas should be in relationship with additional multidisciplinary diagnostic and therapeutic efforts. In addition, any patient with actual or probable diagnosis of VHL disease should be screened for ocular involvement. Unfavorable visual loss can occur early, and ocular complications of VHL range from exudative retinopathy to tractional retinal detachment, neovascular glaucoma, and phthisis bulbi. Accordingly, various treatment methods have been tested with overall acceptable responses, including photocoagulation, cryotherapy, photodynamic therapy, plaque radiotherapy, vitrectomy, and more novel intra-vitreal injections of anti-vascular endothelial growth factors and propranolol.
Keywords:
Diagnosis, Retinal Capillary Hemangioma, Treatment, Von Hippel-Lindau
References
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2. Resche F, Moisan JP, Mantoura J, de Kersaint-Gilly A, Andre MJ, Perrin-Resche I, et al. Haemangioblastoma, haemangioblastomatosis, and von Hippel-Lindau disease. Adv Tech Stand Neurosurg 1993;20:197–304.
3. Jesberg DO, Spencer WH, Hoyt WF. Incipient lesions of von Hippel-Lindau disease. Arch Ophthalmol 1968;80:632–640.
4. Webster AR, Maher ER, Bird AC, Gregor ZJ, Moore AT. A clinical and molecular genetic analysis of solitary ocular angioma. Ophthalmology 1999;106:623–629.
5. Niemela M, Lemeta S, Sainio M, Rauma S, Pukkala E, Kere J, et al. Hemangioblastomas of the retina: impact of von Hippel-Lindau disease. Invest Ophthalmol Vis Sci 2000;41:1909–1915.
6. Lasave AF, Deromedis P. Solitary retinal capillary hemangioma in a patient with bilateral chorioretinal coloboma. Retin Cases Brief Rep 2017;13: 320–323.
7. Shields JA, Shields CL, Deglin E. Retinal capillary hemangioma in Marshall-Stickler syndrome. Am J Ophthalmol 1997;124:120–122.
8. Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS. A review of Von Hippel-Lindau syndrome. J Kidney Cancer VHL 2017;4:20–29.
9. Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, et al. von Hippel-Lindau disease. Lancet 2003;361:2059–2067.
10. Maher ER, Iselius L, Yates JR, Littler M, Benjamin C, Harris R, et al. Von Hippel-Lindau disease: a genetic study. J Med Genet 1991;28:443–447.
11. Binderup ML, Jensen AM, Budtz-Jorgensen E, Bisgaard ML. Survival and causes of death in patients with von Hippel-Lindau disease. J Med Genet 2017;54:11–18.
12. Chou A, Toon C, Pickett J, Gill AJ. von Hippel-Lindau syndrome. Front Horm Res 2013;41:30–49.
13. Melmon KL, Rosen SW. Lindau’s disease. Review of the literature and study of a large kindred. Am J Med 1964;36:595–617.
14. Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, et al. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 1988;332:268–269.
15. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science1993;260:1317–1320.
16. Gossage L, Eisen T, Maher ER. VHL, the story of a tumour suppressor gene. Nat Rev Cancer 2015;15:55–64.
17. Hascoet P, Chesnel F, Jouan F, Le Goff C, Couturier A, Darrigrand E, et al. The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of protumorigenic genes including TGFB1 and MMP13. Oncotarget 2017;8:75989–76002.
18. Schoenfeld A, Davidowitz EJ, Burk RD. A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. Proc Natl Acad Sci USA 1998;95:8817–8822.
19. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygendependent proteolysis. Nature 1999;399:271–275.
20. Min JH, Yang H, Ivan M, Gertler F, Kaelin WG, Jr, Pavletich NP. Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition in signaling. Science 2002;296:1886–1889.
21. Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 1999;15:551–578.
22. Bohling T, Hatva E, Kujala M, Claesson-Welsh L, Alitalo K, Haltia M. Expression of growth factors and growth factor receptors in capillary hemangioblastoma. J Neuropathol Exp Neurol. 1996;55:522–527.
23. Reifenberger G, Reifenberger J, Bilzer T, Wechsler W, Collins VP. Coexpression of transforming growth factoralpha and epidermal growth factor receptor in capillary hemangioblastomas of the central nervous system. Am J Pathol 1995;147:245–250.
24. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, et al. Role of HIF-1alpha in hypoxiamediated apoptosis, cell proliferation and tumour angiogenesis. Nature 1998;394:485–490.
25. Kaelin WG, Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002;2:673–682.
26. Knudson AG, Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68:820–823.
27. Sgambati MT, Stolle C, Choyke PL, Walther MM, Zbar B, Linehan WM, et al. Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents. Am J Hum Genet 2000;66:84–91.
28. Wu P, Zhang N, Wang X, Li T, Ning X, Bu D, et al. Mosaicism in von Hippel-Lindau disease with severe renal manifestations. Clin Genet 2013;84:581–584.
29. Stolle C, Glenn G, Zbar B, Humphrey JS, Choyke P, Walther M, et al. Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum Mutation 1998;12:417–423.
30. Zbar B, Kishida T, Chen F, Schmidt L, Maher ER, Richards FM, et al. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Hum Mutation 1996;8:348–357.
31. Beroud C, Joly D, Gallou C, Staroz F, Orfanelli MT, Junien C. Software and database for the analysis of mutations in the VHL gene. Nucleic Acids Res 1998;26:256–258.
32. Czyzyk-Krzeska MF, Meller J. von Hippel-Lindau tumor suppressor: not only HIF’s executioner. Trends Mol Med 2004;10:146–149.
33. Wittstrom E, Nordling M, Andreasson S. Genotypephenotype correlations, and retinal function and structure in von Hippel-Lindau disease. Ophthalmic Genet 2014;35:91–106.
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