Abstract
Purpose: :
To assess the clinical features of retinal hemangioblastomas (RHs) in VHL disease and to establish clinical correlations with the genotype of the VHL mutation.
Methods: :
A cross–sectional study of 335 patients from 220 families with VHL–related RHs was performed. Germ–line mutations in the VHL gene were found in 98% of patients.
Results: :
The mean age of VHL patients screened with RHs was 36.9 years. 55% were female, 91% were white, and 57% had bilateral RHs. Of all 670 eyes studied, 40 (6.0%) eyes had been enucleated; 38 (11%) patients had unilateral enucleations, while 1 patient had both eyes enucleated. 29 eyes (4.3%) were phthsical or pre–phthsical. Of the remaining 601 eyes, RHs were located at the optic nerve only in 37 (6.2%) eyes, in the peripheral retina only in 387 (64%) eyes, at both locations in 33 (5.5%) eyes, and absent in 144 (24%) eyes. Of the 420 eyes that had peripheral RHs, 262 (62%) had a total of 1–2 RHs, 84 (20%) have 3–4, and 74(18%) have ≥ 5. 105 (25%) of these eyes have greater than 1 quadrant of peripheral retinal involvement. Of all 335 patients studied, 18 (5.4%) had < 20/160 in the better–seeing eye, and 106 (32%) had < 20/160 in the worse–seeing eye. Optic nerve RHs, larger peripheral RH number, and involvement of greater than 1 quadrant were all statistically associated with worse visual acuity. 327 (98%) patients were grouped by genotype according to their mutant protein structure into 5 categories: amino–acid substitutions (49%), truncations (43%), complete deletions (2.8%), small deletions (1.8%), and splice mutations (3.4%). Complete deletions were associated with better visual acuity (eyes with vision > 20/40), compared to amino–acid substitutions and truncations which have similar phenotypes in terms of RH number and visual acuity.
Conclusions: :
Ocular involvement in VHL disease is frequently bilateral and is associated with significant visual morbidity depending on tumor extent and location. Complete deletion of the VHL gene is associated with a better visual outcome compared with amino–acid substitutions and protein truncations.
Keywords: tumors • clinical (human) or epidemiologic studies: natural history • genetics