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John D. Pitcher, III, Allan E. Kreiger, Ben J. Glasgow; Analysis of the Ophthalmic Vascular Features of Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4085.
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Hereditary vascular retinopathy (HVR), cerebroretinal vasculopathy (CRV), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) map to a single locus on chromosome 3p21.1-p21.3. These syndromes have recently been classified as autosomal dominant retinal vasculopathy with cerebral leukodystrophy (RVCL) and associated with mutations in TREX1, which encodes a 3’-5’ exonuclease that binds single stranded DNA and mispaired 3’ termini. Clinically, this manifests as visual loss from ischemic retinal vasculopathy. The purpose of this study is to describe and analyze the ocular histopathologic findings of RVCL, which have not been previously reported.
Eyes from a patient carrying the diagnosis of RVCL (n=2) and randomly selected control eyes (n=6) were obtained from autopsy and fixed in formalin. After bisection, each eye was examined in detail under the dissection microscope before being processed and sectioned for histopathologic evaluation. The retinal vasculature was highlighted by staining with hematoxylin and eosin (H&E), periodic acid schiff (PAS), and elastica Masson trichrome (EMT). Retinal (all those within 4 mm of the optic nerve), choroidal (three from each eye within 4 mm of the optic nerve), and iris vessel wall to lumen ratios and wall thicknesses were calculated and compared with controls using two-tailed t-tests. Areas of neovascularization were recorded. Fluorescein angiography (FA) images were reviewed for correlation.
Multilaminar basement membranes were noted in retinal capillaries only of RVCL eyes. The exteral wall to lumen ratio of these vessels was 6.0 (sd=1.9) and was significantly elevated with respect to controls (p<0.05). Maximum retinal vessel external wall thickness was 37.1 micrometers (sd=15.1) in RVCL eyes compared with 6.5 micrometers (sd=2.1) in controls. Extraretinal neovascularization was noted in all RVCL eyes and was adjacent to thickened capillaries and areas of ischemic nonperfusion on FA.
Eyes of patients with RVCL in this study demonstrated multilayered capillary basement membranes and walls that were significantly thickened. This histopathologic feature has been previously described in kidney and cerebral microvasculature of patients with this disease. Whether this finding is a primary or secondary result of the TREX1 mutation remains to be studied.
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