Clinical characterization of retinal capillary hemangioblastomas in a large population of patients with von Hippel-Lindau disease

Abstract

Objective: To report the epidemiology and ocular phenotype of retinal capillary hemangioblastomas associated with von Hippel-Lindau (VHL) disease in a large cohort of patients and to correlate patient and ocular characteristics to visual morbidity in this population.

Design: Cross-sectional study.

Participants: In 220 unrelated pedigrees, 335 patients affected with VHL disease and retinal capillary hemangioblastomas (RCHs) in at least 1 eye.

Methods: Demographics of the patient population were recorded and the ocular phenotype of each patient was obtained with a comprehensive ocular examination.

Main outcome measures: The patient population was characterized and the ocular phenotype described in relationship to tumor location, number, and extent of retinal involvement. Correlations between patient demographics, ocular phenotype, and visual function were analyzed.

Results: We detected RCHs unilaterally in 42.1% and bilaterally in 57.9% of patients. No correlation was detected between the age, gender, or laterality of involvement. Of involved eyes, 86.6% had tumors that could be individually visualized; of these, tumors were commonly found in the peripheral retina (84.7%) only, and less commonly in the juxtapapillary area (15.3%). The tumor count in the periphery averaged 2.5+/-1.8 per eye, with 25.2% of eyes having >1 quadrant of retinal involvement. Of involved eyes, 13.4% were enucleated or prephthsical; approximately 1 in 5 patients had > or =1 eyes so affected. Severe visual impairment (visual acuity < or =20/160) in affected eyes were more likely to be associated with increasing age, the presence of juxtapapillary lesions, and an increasing number and extent of peripheral lesions.

Conclusions: This large cohort of VHL patients with RCHs has enabled a systematic and quantitative characterization of the demographics, ocular features, and visual function in VHL disease. Clinical correlations between the visual morbidity and ocular features of the disease were also performed, producing measures that can help clinicians to estimate visual prognoses better based on the ocular phenotype of the disease.

Figure 1

Age distribution of 335 patients with retinal capillary hemangioblastomas (RCHs) related to von Hippel-Lindau disease.

Figure 2

Schematic diagram showing the subcategorization of 670 eyes of 335 patients with retinal capillary hemangioblastomas (RCHs) related to von Hippel-Lindau disease according to ocular phenotype.

Figure 3

Distribution of peripherally-located retinal capillary hemangioblastomas (RCHs) found in 421 eyes depicted as number of RCHs per eye.

Figure 4

Visual acuities in all 335 patients with retinal capillary hemangioblastomas(RCHs) related to von Hippel-Lindau disease. A. Distribution of visual acuities of 335 patients in their better-seeing eye (top panel) and worse-seeing eye (bottom panel). B. Distribution of visual acuities of all 670 eyes in 335 patients according to eyes without angiomatous involvement (dark bars, left, n = 141) and eyes with angiomatous involvement (white bars, right, n = 529).

Figure 5

Visual acuities of eyes with retinal capillary hemangioblastomas (RCHs) related to von Hippel-Lindau disease. according to phenotype subcategories. A, Distribution of visual acuities of affected eyes according to the location of documented RCHs. Location categories were: RCH in the peripheral location only (n = 388 eyes), in the juxtapapillary location only (n = 37 eyes), and in both juxtapapillary and peripheral locations (n = 33). B, Distribution of visual acuities according to number of peripheral RCHs in eyes with documented RCHs (n = 421 eyes). Categories were: 1-2 RCHs/per eye (n = 262 eyes), 3-4 RCHs/per eye (n = 84 eyes), >5 RCHs/per eye (n = 75). C, Distribution of visual acuities according to whether RCHs extended to less (n = 316) or greater (n = 105) than one quadrant of peripheral retinal involvement.