Purchase this article with an account.
W.T. Wong, E. Agron, H.R. Coleman, G. Reed, K. Csaky, G. Glenn, W.M. Linehan, P. Albert, E.Y. Chew; Clinical and Molecular Characterization of Ocular Involvement in Von–Hippel–Lindau (VHL) Disease . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4693.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To assess the clinical features of retinal hemangioblastomas (RHs) in VHL disease and to establish clinical correlations with the genotype of the VHL mutation.
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.
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.
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.
This PDF is available to Subscribers Only