Histopathologic observations in choroideremia with emphasis on vascular changes of the uveal tract

Abstract

The patient presented is a member of a four-generation kindred that has exhibited progressive retinal degenerative changes of choroideremia in an X-linked pattern. The patient was seen initially at age 44 with clinical retinal findings consistent with choroidal sclerosis. Over a 20-year interval of observation, the findings evolved into a clinical picture consistent with choroideremia. The patient died at age 66. Both eyes were obtained at autopsy. The histologic findings included extensive chorioretinal atrophy and epiretinal membrane formation. Additionally, Bruch's membrane was calcified and disrupted. Retinal (glial) cells had migrated through the ruptures in Bruch's membrane. There was production of thin and thicker basement membranes by glial (Müller) cells on the choroidal (collagenous) side of Bruch's membrane. There was hypoproduction of basement membrane by vascular endothelial cells and their pericytes both in the posterior uveal tract associated with loss of retinal pigment epithelial (RPE) cells and overlying retina and in the anterior uveal tract associated with loss of dilator muscle and flattening of the iris pigment epithelium. The finding of vascular endothelial cell abnormalities throughout the uveal tract strongly supports the concept that the primary defect in choroideremia lies with the uveal vessels rather than the RPE.