Conventionally, many of the syndromes referred to as phakomatoses (“mother spot”) are grouped loosely by the common features of ocular and extraocular or systemic involvement of a congenital nature. Most, but not all, are hereditary. Except for Sturge-Weber syndrome, the phakomatoses involve the neuroretina and its circulation. For further discussion of the phakomatoses, see BCSC Section 5, Neuro-Ophthalmology, and Section 6, Pediatric Ophthalmology and Strabismus.
Von Hippel–Lindau Syndrome
The phakomatosis von Hippel–Lindau (VHL) syndrome (also called familial cerebello retinal angiomatosis) is caused by a tumor suppressor gene mutation on the short arm of chromosome 3 (3p26–p25), the inheritance of which is autosomal dominant with incomplete penetrance and variable expression. The disease is characterized by retinal and central nervous system hemangioblastomas and visceral manifestations (see BCSC Section 6, Pediatric Ophthalmology and Strabismus); the diagnosis can be confirmed with genetic testing. Central nervous system tumors include hemangioblastomas of the cerebellum, medulla, pons, and spinal cord in 20% of patients with VHL syndrome. Systemic manifestations include renal cell carcinoma, pheochromocytomas, endolymphatic sac tumors, cysts of the kidney, pancreas, and liver, and bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women). Diagnosis of a retinal hemangioblastoma warrants a systemic workup and genetic testing. Cerebellar hemangioblastoma and renal cell carcinoma are the leading causes of death in patients with VHL syndrome. Patients may incur severe disability from central nervous system lesions and their treatments.
A fully developed retinal lesion is a spherical orange-red tumor fed by a dilated, tortuous retinal artery and drained by an engorged vein (Fig 7-12). Hemangioblastomas of the optic nerve head and peripapillary region are often flat and difficult to recognize. Multiple hemangioblastomas may be present in the same eye, and bilateral involvement occurs in 50% of patients. Leakage from a hemangioblastoma may cause decreased vision from macular exudates (Fig 7-13) with or without exudative retinal detachment. Vitreous hemorrhage or tractional detachment may also occur.
Figure 7-12 Fundus photograph from a patient with von Hippel–Lindau syndrome shows a peripheral retinal hemangioblastoma with surrounding exudate and retinal detachment. The feeder arteriole and draining venule are dilated.
Figure 7-13 Ultra-wide-field fundus photograph of a patient with von Hippel–Lindau syndrome, showing retinal hemangioblastoma in the near periphery and associated exudative maculopathy.
(Courtesy of Colin A. McCannel, MD.)
Ocular management includes destructive treatment of all identified retinal hemangioblastoma with careful follow-up to detect recurrence or the development of new lesions. Successful treatment is facilitated by early diagnosis, because the lesions usually enlarge with time. Wide-angle fluorescein angiography can assist in detecting small, early lesions (Fig 7-14). Photocoagulation and cryotherapy are used to treat and destroy the angiomatous lesions directly. Photodynamic therapy with verteporfin can also be used, but the treatment effect has a limited duration because the treatment does not destroy the lesions. Successful treatment results in shrinkage of the hemangioblastoma, attenuation of the afferent vessels, and resorption of the subretinal fluid. Cryotherapy may be used to treat larger lesions, but it can cause a temporary and marked increase in the amount of exudation and sometimes exudative retinal detachment. Anti-VEGF therapy does not usually result in a meaningful, long-term treatment effect.
Figure 7-14 Wide-angle imaging of von Hippel–Lindau syndrome. A, Ultra-wide-angle fundus photography image of the left eye of a 26-year-old woman with von Hippel–Lindau syndrome. No obvious lesions are visible. B, The corresponding ultra-wide-angle fluorescein angiography image demonstrates multiple foci of leakage that are small, early retinal hemangioblastomas, some of which are not easily visible clinically or in the photograph.
(Courtesy of Colin A. McCannel, MD.)
Retinal hemangioblastomas may also occur sporadically without systemic involvement; these are termed von Hippel lesions. Another form of retinal angiomas, acquired vasoproliferative lesions, are idiopathic or, in rare cases, may be present as a late complication of ROP, retinitis pigmentosa, or other conditions. These lesions do not have the dilated feeder and draining vessels seen with hemangioblastomas.
Gaudric A, Krivosic V, Duquid G, Massin P, Giraud S, Richard S. Vitreoretinal surgery for severe retinal capillary hemangiomas in von Hippel–Lindau disease. Ophthalmology. 2011; 118(1):142–149.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.