Retinal Histopathology in Eyes from Patients with Stargardt Disease.

Abstract

Purpose : Stargardt disease (STGD) is an early onset form of macular degeneration with an estimated frequency between 1 in 8,000 to 10,000. We present the histopathologic findings in eyes from two donors with Stargardt Disease.

Methods : Eyes were obtained through the FFB eye donor program from a 69 year-old male who died from myocardial infarction. The donor was clinically diagnosed with Stargardt disease with an unknown mutation. The eyes were fixed within 15 hours of death and examined with macroscopic fundus photography (MF), confocal scanning laser ophthalmoscope (cSLO) and spectral-domain optical coherence tomography (SD-OCT). Small areas from the fundus macula and periphery were processed for electron microscopy and indirect immunofluorescence, using specific antibodies to retinal proteins. These donor eyes were compared to a matched normal eye (84 y.o.) and to eyes from a 66 y.o. female STGD donor previously characterized and known to carry compound mutations in the ABCA4 gene.

Results : MF images of both STGD donor eyes showed a normal-appearing optic disc, prominent choroidal vessels, and areas of retinal degeneration in the perifoveal region. cSLO autofluorescence (AF) of the 69 year-old STGD donor identified the optic disk and hypofluorescent macula region. cSLO-AF of donor carrying the ABC4 mutations displayed a large well-defined area with weak AF signal when compared to the control. SD-OCT identified retinal changes including disorganization of retinal lamina and absence of the photoreceptor layer in both STGD eyes as compared to the control eyes. Histology analysis showed a severely degenerated fovea with little evidence of any retinal layering or remaining RPE in the STGD donor carrying the ABC4 mutations. The other STGD donor displayed inner nuclear layer disorganization in the perifovea with preservation of some of the RPE. In contrast, retinal nuclear layers were present in the periphery of both STGD donors. The perifoveal region contained few cones labeled with cone specific antibodies; some rhodopsin-labeled cells in the STGD donor carrying the ABC4 mutations. However, the perifovea of the other STGD donor displayed several stubby cones and very few rhodopsin-labeled cells. Cone synapses were not observed in either STGD donor eyes.

Conclusions : Postmortem analysis of eyes with STGD disease revealed a highly degenerated perifoveal region with preservation of the peripheral retina.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.