Concentric Retinitis Pigmentosa: Clinicopathologic Correlations

Abstract

Progressive concentric (centripetal) loss of vision is one pattern of visual ®eld loss in retinitis pigmentosa. This study provides the ®rst clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell speci®c antibodies. Unrelated simplex/ multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric ®eld loss, normal or near normal rod and cone sensitivity within the preserved visual ®eld, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective or modify photoreceptor degeneration in concentric retinitis pigmentosa.

Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model

“…Moreover, we could demonstrate for the first time that this direct contact seems to cause RPE cells to detach from Bruch′s membrane and to migrate along the contacting vessels towards the inner retina. Our murine whole-mount data illustrate the arrangement of pigmented cell clusters outlining retinal capillaries that correlate well with BSPs in humans [3,[8][9][10][11][12]. Moreover, using OCT investigation in an RP patient we could demonstrate perivascular pigmentation in vivo, thereby proving that BSPs are located at different retinal layers ranging from the RPE to the GCL comparable to our findings in the mouse model.…”

“…In a number of histological studies on human donor eyes, BSPs were found only in areas devoid of photoreceptors, and were formed by RPE cells migrating along retinal vessels [3,[8][9][10][11][12]. However, the trigger for detachment of RPE cells from Bruch′s membrane and successive migration has still remained unclear.…”

“…The affinity of RPE cells to vascular basal lamina or ECM around retinal blood vessels might play a role [3,8,10]. Alternatively, the release of cytokines from vascular endothelium has been suggested as a factor that might trigger RPE migration [3,10].…”

“…A hallmark of typical RP is the presence of intraretinal melanin deposits that can be identified as bone spicule pigments (BSP) on ophthalmoscopy [1][2][3]. Despite many details of such pigmentation that have been described in the past [3,[5][6][7][8][9][10][11][12] there has been no comprehensive study on the nature of BSPs and especially the conditions for their development. One reason may be that the access to donor eyes is limited, and histomorphological studies on human patients concerned small numbers of advanced cases of RP [5,[7][8][9]11], which restrict characterization of the dynamic process of the disease.…”

“…Despite many details of such pigmentation that have been described in the past [3,[5][6][7][8][9][10][11][12] there has been no comprehensive study on the nature of BSPs and especially the conditions for their development. One reason may be that the access to donor eyes is limited, and histomorphological studies on human patients concerned small numbers of advanced cases of RP [5,[7][8][9]11], which restrict characterization of the dynamic process of the disease. Hence, we based our work on a murine homologue of an autosomal-recessive form of human RP, the rhodopsin knockout (rho -/-) mouse in which the rhodopsin gene is disrupted [13].…”