Histological Evidence of Outer Retinal Atrophy Associated with Geographic Atrophy Secondary to Age-related Macular Degeneration

Abstract

 

Purpose

 

To examine the histologic findings of eyes with geographic atrophy (GA) associated with age-related macular degeneration for potential retinal abnormalities that may impact perifoveal visual function.

 

Methods

 

Macula-wide high-resolution sections were collected starting at the superior edge of an 8-mm diameter full-thickness punch, stained with toluidine blue, and examined by light microscopy. GA was defined as discrete areas of loss of retinal pigment epithelium (RPE) measuring at least 500 microns in diameter.

 

Results

 

There were 13 eyes of 13 donors with GA. Within the zone of confluent RPE loss there were thickened whorls of persistent basal laminar deposit (BlamD). Although the layer of confluent RPE cells usually ended co-terminously with the external limiting membrane border, isolated RPE cells were found in the atrophic area. Overlying neurosensory retina showed complete absence of photoreceptor inner and outer segments and nearly complete outer nuclear layer loss. Along the external border of confluent RPE BLamD was abundant, and rounded RPE cells lacked obvious apical processes. The superjacent retina at the ELM border showed a pronounced depopulation of the outer nuclear layer, absence of outer segments, and blunting or absence of inner segments. Surviving inner segments showed retraction of the ellipsoid portion toward or even internal to the internal limiting membrane. Extending radially away from the area of RPE loss the inner and outer segments were compromised. The number of nuclei in the outer nuclear layer returned to normal, yet isolated nuclei were scattered as far inward as the photoreceptor synaptic layer, signifying cellular stress. Subretinal drusenoid deposits were frequently present.

 

Conclusions

 

Taken in aggregate the retinal changes can be termed outer retinal atrophy and this abnormality extends well beyond the area of RPE loss in GA eyes. Outer retinal atrophy has potential negative impact on visual function of areas used for eccentric fixation in low vision rehabilitation. Strategies currently employed to try to halt the progression of GA need to consider the extent and severity of concurrent outer retinal atrophy.

 

 

Restoration in inner and outer segment lengths and increasing nuclei population in the outer nuclear layer progressing left to right away from an area of GA. (Artifactual detachment in right panel.)

 

Keywords: 412 age-related macular degeneration • 636 pathobiology