Morphometric Analysis of the Retinal Ganglion Cell and Inner Plexiform Layers in Alzheimer’s Disease: Biomarkers in the Eye for degeneration in the Brain

Abstract

Purpose : The retinal ganglion cell layer (RGCL) and inner plexiform layer (IPL) undergo remarkable thinning in Alzheimer’s Disease (AD) as measured in vivo by optical coherence tomography (OCT). This study aims to histopathologically confirm the deterioration of these layers in AD postmortem tissue to validate their use as ocular biomarkers in clinical practice. We hypothesize that the RGCL and IPL will exhibit a significant reduction in thickness in AD.

Methods : 5 AD postmortem eyes (mean age: 86.2±15.10 years) were compared to 5 age-matched controls (mean age: 84.8±14.75 years). Tissues were fixed in phosphate-buffered formalin, dissected horizontally through the middle of the optic nerve, embedded into paraffin, sectioned and stained with hematoxylin and eosin. RGCL thickness was defined as the distance from the posterior RNFL to the anterior IPL. IPL thickness was defined as the distance from the posterior RGCL to the anterior margin of the outer plexiform layer. Thickness was measured at 18 points along the horizontal meridian in 100-500μm increment intervals starting from the optic disc edge out to 4.5mm temporally. Peripapillary and macular regions were both assessed. Pearson’s correlation and Welch’s t-test were used for analysis.

Results : RGCL and IPL were significantly thinner in AD relative to controls. RGCL mean total thickness was 412.35 ± 11.32μm in AD and 594.20 ± 15.03μm in controls (p=0.01). IPL mean total thickness was of 333.93 ± 3.68 μm in AD and 632.55 ± 5.93μm in controls (p=0.001). RGCL and IPL thinning was most severe in the peripapillary and parafoveal regions. Peripapillary RGCL measured 58.88 ± 4.69 μm in AD and 83.46 ± 1.57μm in controls (p=0.03). Peripapillary IPL measured 60.96 ±1.79μm in AD and in 76.34 ± 1.50μm controls (p=0.008). Parafoveal RGCL measured 122.64± 2.21μm in AD and 171.64 ±4.75 μm in controls (p=0.007). Parafoveal IPL measured 67.16±2.33μm in AD and 93.27±2.30μm in controls (p=0.005). RGCL and IPL thinning patterns were closely correlated (r=0.74).

Conclusions : We provide histopathological data confirming the loss of both the RGCL and IPL in AD. The degenerative changes in these layers, especially in the papillomacular bundle are of great importance as they not only enhance our understanding AD pathogenesis, but also potentiate the diagnostic value of OCT in clinical practice.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.