Retinal capillary hemangioblastoma

Retinal capillary hemangioblastoma (RCH) is a rare condition with a reported incidence of 1 in 40,000. It can be sporadic, occurring only in the retina, or it can be associated with a cerebellar and/or spinal hemangioblastoma, occurring as part of the von Hippel–Lindau (VHL) syndrome (Fig 18-5). A variety of names are used for RCH in the literature, including angiomatosis retinae and retinal capillary hemangioma, and sporadic lesions have also been called von Hippel lesions, a term meant to differentiate the nonsyndromic retinal lesions from those seen in the systemic disorder (VHL syndrome). This naming bias is historically derived: von Hippel, a German ophthalmologist, initially described the retinal lesions, and Lindau, a Swedish pathologist, recognized the overlap between the retinal and cerebellar lesions. In 1964, the term von Hippel–Lindau was adopted to recognize the contributions of both physicians and to unify the disease classification. The term retinal capillary hemangioblastoma most accurately reflects the pathogenesis of these lesions (see Chapter 11).

Figure 18-5 Retinal capillary hemangioblastoma (RCH), clinical photographs. Dilated, tortuous retinal feeder artery and draining vein emanate from the optic nerve head (A), leading to the red to orange peripheral retinal tumor (B). An optic nerve head hemangioblastoma causes traction in the macular area (C). In the early arterial phase of fluorescein angiography, the lesion is hyperfluorescent (D). E, Fundus photograph from a 48-year-old woman with von Hippel–Lindau syndrome, multiple cerebellar hemangioblastomas, and a typical-appearing RCH. F, Fluorescein angiogram from the same patient in part D demonstrates focal hyperfluorescence without leakage.

(Parts A and B courtesy of Robert H. Rosa Jr, MD; parts C and D courtesy of Tero Kivelä, MD; parts E and F courtesy of Mary Aronow, MD, Massachusetts Eye and Ear Infirmary.)

Although RCH may rarely be present at birth, the lesions typically are acquired and are usually diagnosed in the second to third decades of life. RCH may occur as a single lesion or as multiple ones. The lesions appear as red to orange tumors arising within the retina with large-caliber, tortuous afferent and efferent retinal blood vessels (see Fig 18-5A, B, E, F). As the lesions occur postnatally, leakage and exudation are common. Associated yellow-white retinal and subretinal lipid exudates, often involving the fovea, and exudative retinal detachments may occur. Atypical variations include tumors arising from the optic nerve head (see Fig 18-5C) and in the retinal periphery, where vitreous traction may elevate the tumor from the surface of the retina (see Fig 18-5B). FA demonstrates rapid arteriovenous transit (see Fig 18-5D, F), with immediate filling of the feeding arteriole, subsequent filling of the numerous fine blood vessels that constitute much of the tumor, and drainage by the dilated venule. Massive leakage of dye into the tumor and vitreous can occur.

RCHs are a common disease manifestation of VHL syndrome, wherein cerebellar and/or spinal hemangioblastomas may develop in patients but are less common. The VHL gene, which is located on chromosome 3, is mutated in the syndrome. Mutations in VHL cause overproduction of VEGF and other hypoxia-inducible factors, leading to the development of highly vascular tumors. A number of other tumors and cysts may develop in patients with this syndrome, the most serious of which are renal cell carcinoma and pheochromocytoma. For more information on VHL syndrome, see BCSC Section 6, Pediatric Ophthalmology and Strabismus, and Section 12, Retina and Vitreous. Chapter 11 in this volume discusses the histologic features of RCH.

When VHL syndrome is suspected, appropriate genetic consultation and ongoing screening are critical for early identification of the ocular and systemic manifestations of the disease. Patients with RCH can undergo genetic screening to determine whether they are at risk for developing systemic manifestations. More than 60% of patients with VHL syndrome have RCHs, which are often the first manifestation of the disease. Thus, by identifying the retinal lesions, the ophthalmologist is often the first medical specialist to diagnose VHL syndrome. Screening for systemic vascular anomalies (eg, cerebellar hemangioblastomas) and malignancies may reduce mortality, and aggressive screening for and early treatment of RCHs may reduce complications and improve long-term visual outcomes.

Treatment of RCH includes

• photocoagulation for small lesions, applied both to the lesion and the surrounding retina to create chorioretinal scarring and a blockade against expanding exudation

• cryotherapy for larger lesions located in the peripheral retina

• plaque brachytherapy or proton beam radiotherapy, or scleral buckling with cryotherapy for large lesions with more extensive retinal detachment

PDT has been used successfully to treat selected RCHs. The use of VEGF inhibitors in the treatment of RCH has been disappointing. Reports suggest that the principal efficacy of VEGF inhibitors is in reducing macular edema, but the impact on the size of the RCH has been variable. Although most optic nerve head lesions are rather resistant to treatment, some have responded to treatment with PDT, favored in this situation, or have been resected using vitrectomy-based techniques.

The visual prognosis remains guarded for patients with optic nerve head or large retinal lesions. The clinician should be aware that additional tumors may develop over time in patients with VHL syndrome, so careful serial examination of both eyes is required in order to identify and treat new tumors when they are small. Wide-field FA can be helpful in identifying small retinal hemangioblastomas in this setting.

• Singh AD, Shields CL, Shields JA. von Hippel-Lindau disease. Surv Ophthalmol. 2001;46(2):117–142.

Retinal vasoproliferative tumors

Retinal vasoproliferative tumors (VPTs) are uncommon acquired retinal lesions that may be primary and idiopathic (74% of cases) or may develop because of preexisting ocular disease (26% of cases), including inflammatory, traumatic, and degenerative ocular conditions (eg, retinitis pigmentosa). These lesions were initially called presumed acquiredretinal hemangiomas to differentiate them from RCH. Primary VPTs manifest in the third or fourth decade of life, and both sexes are equally affected. Most patients present with a single solitary lesion; however, in secondary cases, multiple tumors have been described.

Clinically, VPTs appear as an elevated pink and yellow vascular mass in the peripheral retina with associated subretinal exudation, which may be extensive. These lesions lack the prominent dilated feeder vessels typically seen in RCHs (Fig 18-6). Macular fibrosis, epiretinal membranes, cystoid macular edema, and subretinal fluid may lead to vision loss. Histologically, VPTs are composed of a mixture of glial cells and a network of fine capillaries with some larger dilated blood vessels.

Treatment of VPTs is notoriously difficult. Small peripheral VPTs that lack significant exudate or maculopathy may be managed with periodic observation. First-line treatment of symptomatic tumors generally involves triple freeze–thaw transconjunctival cryotherapy; repeated treatments are often required. Other treatment options include plaque brachytherapy, laser photocoagulation, and PDT. The use of anti-VEGF agents and intraocular steroids has been described. Chronic cases may require vitrectomy with membrane peel.

• Shields CL, Shields JA, Barrett J, De Potter P. Vasoproliferative tumors of the ocular fundus. Classification and clinical manifestations in 103 patients. Arch Ophthalmol. 1995;113(5):615–623.

Figure 18-6 Vasoproliferative tumor (VPT). A, Color fundus photograph shows a VPT in the temporal periphery of the right eye (arrow). The tumor appears as a pink and yellow elevated mass with tortuous internal vasculature and associated subretinal fibrosis and exudate (asterisks).B, B-scan ultrasonographic image demonstrates a heterogeneous, amorphous elevated mass (arrow). There is an associated retinal detachment (between arrowheads), which is not uncommon. C, Fluorescein angiogram highlights the internal vascular component of the tumor that demonstrates significant hyperfluorescent staining; late leakage is common. Loss of retinal vasculature is seen in the area of previous cryotherapy treatment (asterisk).D, OCT shows subretinal fluid tracking under the fovea, an epiretinal membrane, and significant foveal distortion.

(Courtesy of Jesse L. Berry, MD.)

Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.