Retinal hemangioblastoma (also called angioma) is the most common presentation of von Hippel–Lindau (VHL) disease (Maher et al. 1990). The exact proportion of patients with retinal hemangioblastoma who have this disease is unclear. The most frequent estimate is 40 %, but Neumann and Wiestler (1991) detected evidence of the disease in 86 % of their patients with retinal angiomatosis. All patients with retinal angioma should be investigated for subclinical manifestations of VHL disease. All patients with multiple retinal angiomas satisfy clinical diagnostic criteria for VHL disease, but in atypical cases, an expert ophthalmological review is helpful to confirm that the lesions are hemangioblastomas and not other types of the vascular lesion (e.g., Coat disease). Webster et al. (1998) investigated 17 cases with VHL-like solitary ocular angioma and found no evidence of other complications of this disease in themselves or in family members. They concluded that sporadic ocular angioma can occur in the absence of VHL disease. The Tumours are similar in anatomical location, and cases are similar in the age of presentation and degree of visual morbidity compared to those with the disease. Overall the risk of underlying VHL disease in a patient with a solitary ocular angioma was 30 %; this risk decreased with negative DNA and clinical screening and also with increasing age (Table 1) (Webster et al. 1999).
Table (1) Estimated the probability of underlying VHL disease in a patient with a solitary ocular angioma after a careful ophthalmic screening
|Probability by age group (years)|
|Other negative information||<20||21–40||41–60||>60|
|Parent history + systemic screening||0.17||0.05||0.02||0.01|
|DNA + parent history||0.06||0.04||0.03||0.03|
|DNA + systemic screening||0.10||0.04||0.02||0.01|
|DNA + systemic screening + parent history||0.06||0.01||0.00||0.00|
Source: From Webster et al. (2000) – J Med Genet. 37:62–3
Histologically VHL-associated retinal hemangioblastomas resemble cerebellar hemangioblastomas with stromal cells surrounding capillary endothelial cells and glial cell admixed. Molecular studies demonstrate that loss of the wild-type VHL allele occurs in the stromal cells, and this leads to activation of HIF transcription factors and expression of vascular endothelial growth factor and other angiogenic factors (Chan et al. 2007).