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Year : 2009  |  Volume : 2  |  Issue : 2  |  Page : 82-85 Table of Contents   

A case of von Hippel-Lindau disease with exudative maculopathy

Vitreoretinal Division, Department of Ophthalmology, Al-Hussein Hospital, King Hussein Medical Center, Amman, Jordan

Date of Web Publication30-Jun-2009

Correspondence Address:
Basel T Ba'arah
Post Box: 2327, Amman - 11181
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-620X.53038

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Von Hippel-Lindau (VHL) disease is a rare multisystem familial tumor syndrome of autosomal dominant inheritance. Hallmark lesions include retinal, cerebellum and spinal cord hemangioblastomas, renal cell carcinomas, adrenal pheochromocytomas, angiomatous or cystic lesions of the kidneys, pancreas, and epididymis. We report a case of VHL disease in a 26-year-old patient who presented with exudative macular edema. Ocular and systemic studies revealed the presence of retinal and central nervous system hemangioblastomas, adrenal pheochromocytoma, multiple pancreatic, and kidney cysts. The retinal angiomas were successfully treated with argon laser photocoagulation and cryotherapy.

Keywords: Argon laser, cryotherapy, hemangioblastoma, von Hippel-Lindau disease

How to cite this article:
Ba'arah BT. A case of von Hippel-Lindau disease with exudative maculopathy. Oman J Ophthalmol 2009;2:82-5

How to cite this URL:
Ba'arah BT. A case of von Hippel-Lindau disease with exudative maculopathy. Oman J Ophthalmol [serial online] 2009 [cited 2022 Jan 27];2:82-5. Available from: https://www.ojoonline.org/text.asp?2009/2/2/82/53038

   Introduction Top

Von Hippel-Lindau disease (VHL) is a multisystem familial tumor syndrome predisposing to various benign or malignant tumors: central nervous system (CNS) and retinal hemangioblastomas (RHB), renal cell carcinoma (RCC) and cysts, pancreatic tumors and cysts, pheochromocytoma, and endolymphatic sac tumors. [1],[2],[3] RHB occurs in 43% to 67% of patients with VHL. [4],[5],[6] They can be asymptomatic for years and may even regress spontaneously, but usually they grow and cause visual impairment. [4],[7] One of the RHB complications is exudative maculopathy. Dollfus H, [8] reported its presence in 15% of VHL disease cases. In this report, we present a case of unilateral decrease of vision due to macular exudation as the initial manifestation of VHL disease, and summarize the ocular and systemic clinical features, along with treatment measures.

   Case Report Top

A 26-year-old man presented with painless decrease of vision in the right eye. His best corrected visual acuity was 20/200 in the right eye and 20/20 in the left. The intraocular pressure was within normal limits. The results of bilateral biomicroscopic examination of anterior segments were unremarkable. Right eye fundus examination with 78-diopter noncontact lens revealed significant macular edema with lipid exudates [Figure 1]. In addition, two lesions in the superior retina were noticed; one large (3.0 mm) with a globular reddish appearance, dilated feeding vessel and tortuous draining vein [Figure 2]; and another small (1.2 mm) with a moderately enlarged and tortuous draining vessel, which is a characteristic for RHB [Figure 3]. Two small peripheral RHBs were seen in the left eye. Fluorescien angiography showed a progressive hyperfluorescence with late leakage of fluorescien into surrounding retina [Figure 4] and [Figure 5]. Systemic studies, including magnetic resonance imaging of the brain, renal ultrasonography, and computed tomography of the abdomen revealed brain stem tumor invading medulla oblongata, right adrenal gland tumor (pheochromocytoma) and multiple pancreatic and kidney cysts.

Detailed family history revealed that his father had died from cerebral vascular accident at the age of 54; he was treated for uncontrolled blood pressure, but was not investigated for possible presence of adrenal gland tumor.

On the basis of clinical and investigational findings, the diagnosis of VHL disease was made.

Argon laser photocoagulation was used to treat the small (≤1.5 mm) hemangiomas. Large size (500 micron), low intensity (250 mW), and long duration (0.5 sec) laser burns were applied directly on the RHB. As for the large hemangioma, a combination therapy of laser photocoagulation and cryopexy was used. Laser burns were directly applied on the RHB and the feeding artery. This resulted in complete regression of RHBs with formation of chorioretinal scar [Figure 6]. After six months, the macular edema with exudates regressed and the visual acuity improved to 20/40 in the right eye [Figure 7]. During the next two years follow-up time, no new RHB were observed. In the third year of observation, the patient underwent right adrenalectomy and he died the day after surgery from uncontrolled internal bleeding.

   Discussion Top

The incidence of VHL disease in northwest England is 1 in 45,000 live births. [9] The disease is a dominantly inherited familial cancer syndrome that predisposes the patient to the development of specific tumors both benign and malignant. [10] The diagnosis of VHL disease is based on family history and/or clinical presentation of hemangioma, renal cell carcinoma, pheochromocytoma, pancreatic, and visceral cysts. [11] After identification of the VHL tumor-suppressor gene on the short arm of chromosome 3 (3p25-26); the diagnosis can be supported by molecular genetic analysis. [12] RHBs are the first manifestation in approximately half of the VHL disease patients and is usually bilateral and multifocal or becomes so over the years. [13],[14] In spite of its benign nature and slow-growing course, RHB may cause sight-threatening complications such as macular exudation, retinal traction, retinal detachment, neovascular glaucoma, vitreous hemorrhage, and phthisis. [15] RHB are more commonly found in the peripheral retina. [16] The differential diagnosis of RHB includes Coat's disease, racemose hemangioma, retinal cavernous hemangioma, retinal macroaneurysm, and vasoproliferative tumor. As a diagnostic technique, fluorescein angiography plays a major role in detecting, localizing, and observing small RHBs. The visual prognosis is frequently poor in patients with VHL disease; early detection and treatment can change the visual prognosis. [17],[18] That was the case with our patient, where we started the treatment as soon as VHL disease was diagnosed. Accordingly, exudative maculopathy regressed and the vision improved. The treatment decisions are based on size and location of RHB. Careful observation is suggested for juxtapapillary and peripheral lesions less than 500 micrometer in diameter that are not associated with exudation or subretinal fluid and are not visually threatening. [19],[20] Lesions of less than 4.5 mm on diameter could be treated with argon laser, but when the lesion is more than 3.0 mm in diameter it is preferable to do cryotherapy. [21] In our case, we preferred to use both techniques in ablating the large (3.0 mm) RHB; the techniques proved to be effective in destructing it.

Other possible treatment modalities include plaque radio therapy, antiVEGF therapy, photodynamic therapy, transpupillary thermotherapy, and parsplana vitrectomy. [22],[23],[24]

Most commonly, the death of VHL disease patients is related to complications of cerebellar hemangioma and metastatic renal cell carcinoma. [25],[26],[1] Our patient died from complications related to the surgical intervention on adrenal gland tumor (pheochromocytoma) to control blood pressure.

In summary, VHL disease is an inherited and life-long disease. Family members of the patient should undergo clinical and/or molecular genetic screening while the patient should undergo annual clinical screening after ablating the RHBs. Macular edema with lipid exudates is usually an early complication of RHB. Prompt diagnosis and ablative treatment with laser and cryotherapy appears to be effective in controlling VHL disease progression in the retina and gives a favorable visual prognosis.

   References Top

1.Maher ER, Yates JRW, Harries R, Benjamin C, Harris R, Moore AT, et al . Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990;77:1151-63.  Back to cited text no. 1    
2.Richard S, David P, Marsot-Dupuch K, Giraud S, Bιroud C, Resche F. Central nervous system hemangioblastomas, endolymphatic sac tumors and von Hippel-Lindau disease. Neurosurg Rev 2000;23:1-22.  Back to cited text no. 2    
3.Clifford, SC, Maher, ER. Von Hippel-Lindau disease: Clinical and molecular perspectives. Adv Cancer Res 2001;82:85-105.  Back to cited text no. 3    
4.Wittebol-Post D, Hes FJ, Lips CJ. The eye in von Hippel-Lindau disease: long-term follow-up of screening and treatment: recommendations. J Int Med 1998;243:555-61.  Back to cited text no. 4    
5.Webster AR, Richards FM, MacRonald FE, Moore AT, Maher ER. An analysis of phenotypic variation in the familial cancer syndrome von Hippel-Lindau disease: evidence for modifier effects. Am J Hum Genet 1998;63:1025-35.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Webster AR, Moore AT, Maher ER. The clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and correlation with germline mutation. Arch Ophthalmol 1999;117:371-8.  Back to cited text no. 6    
7.Whitson J, Welch R, Green W. Von Hippel-Lindau disease: Case report of a patient with spontaneous regression of a retinal angioma. Retina 1986;6:253-9.  Back to cited text no. 7    
8.Dollfus H, Massin P, Taupin P, Nemeth C, Amara S, Giraud S, et al . Retinal Hemangioblastoma in von Hippel-Lindau disease: A Clinical and Molecular Study. Invest Ophthalmol Vis Sci 2002;43:3067-74.  Back to cited text no. 8    
9.Maddock I, Moran A, Maher E, Teare MD, Norman A, Payne SJ, et al. A genetic register for von Hippel-Lindau disease. J Med Genet 1996;33:120-7.   Back to cited text no. 9    
10.Couch V, Lindor NM, Karnes PS, Michels VV. Von Hippel-Lindau disease. Mayo Clin Proc 2000;75:265-72.  Back to cited text no. 10  [PUBMED]  
11.Friedrich C. Genotype-phenotype correlation in von Hippel-Lindau syndrome. Hum Mol Genet 2001;10:763-7.  Back to cited text no. 11    
12.Kreusel KM, Bornfeld N, Bender BU, Neumann L, Foerster MH, Neumann HP. Retinal capillary angioma. Clinical and molecular genetic studies. Ophthalmologe 1999;96:71-6.  Back to cited text no. 12    
13.Neumann H, Lips C, Hsia Y, Zbar B. Von Hippel-Lindau syndrome. Brain Pathol 1995;5;181-93.  Back to cited text no. 13    
14.Maher E, Kaelin W Jr. Von Hippel-Lindau disease. Medicine 1997;76:381-91.  Back to cited text no. 14    
15.Niemela M, Lemeta S, Sainio M, Rauma S, Pukkala E, Kere J, et al . Hemangioblastomas of the retina: Impact of von Hippel-Lindau disease. Inv Ophthalmol and Vis Sci 2000;41:1909-15.  Back to cited text no. 15    
16.Wong WT, Agron E, Coleman HR, Tran T, Reed GF, Csaky K, et al . Clinical characterization of retinal capillary hemangioblastomas in a large population of patients with von Hippel-Lindau disease. Ophthalmology 2008;115:181-8.  Back to cited text no. 16    
17.Moore AT, Maher ER, Rosen P, Gregor, Z, Bird, AC. Ophthalmological screening for von Hippel-Lindau disease. Eye 1991;5:723-8.   Back to cited text no. 17    
18.Schmidt D, Natt E, Neumann HP. Long-term results of laser treatment for retinal angiomatosis in von Hippel-Lindau disease. Eur J Med Res 2000;5:47-58.  Back to cited text no. 18  [PUBMED]  
19.Singh AD, Nouri M, Shields CL, Shields JA, Perez N. Treatment of retinal capillary hemangioma. Ophthalmology 2002;109:1799-806.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]
20.Junker B, Schmidt D, Agostini HT. Retinal angiomatosis. Ocular manifestation of von Hippel-Lindau disease. Ophthalmologe 2007;104:107-13.  Back to cited text no. 20    
21.Moskowitz C, Edelstein C, Oh M, Burnier Jr MN. Retinal capillary hemangioma in von Hippel-Lindau disease. Can J Ophthalmol 2005;40:192-4.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]
22.Singh AD, Shields CL, Shields JA. Von Hippel-Lindau disease. Surv Ophthalmol 2001;46:117-42.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]
23.Schmidt D. Retinal angiomatosis. Klin Monatsbl Augenheilkd 2005;222:90-109.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Bornfeld N, Kreusel KM. Capillary hemangioma of the retina in cases of von Hippel-Lindau syndrome. New therapeutic directions. Ophthalmologe 2007;104:114-8.  Back to cited text no. 24    
25.Filling-Katz MR, Choyke PL, Oldfield E, Charans L, Patronas NJ, Glenn GM, et al . Central nervous system involvement in von Hippel Lindau disease. Neurology 1991;41:41-6.  Back to cited text no. 25    
26.Neumann HP, Eggert HR, Scheremet R, Schumacher M, Mohadjer M, Wakhloo AK, et al . Central nervous system lesions in von Hippel Lindau syndrome. J Neurol. Neurosurg Psychiatry 1992;55:898-901.  Back to cited text no. 26    


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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