Retinal Nerve Fiber Layer Thinning in Alzheimer’s Disease: A Histopathologic Validation of an Ocular Biomarker

Abstract

Purpose : The retinal nerve fiber layer (RNFL), as studied in vivo using optical coherence tomography (OCT), shows remarkable atrophy in Alzheimer’s Disease (AD), and has been proposed as a clinical biomarker for AD. This study aims to histopathologically confirm RNFL thinning in AD using postmortem tissue. We hypothesize that the RNFL 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. RNFL thickness was measured at 18 points along the horizontal meridian from the optic disc edge out to 4.5mm in both nasal and temporal directions. Welch’s t-test was used for statistical analysis.

Results : AD eyes exhibited significant RNFL thinning compared to controls. Temporally, AD mean total thickness was 716.03 ± 25.00μm compared to 1055.82.66 ± 38.81μm in controls (p< 0.05). AD RNFL was thinnest from the optic disc edge to the 1500μm mark temporally, having a mean total thickness of 608.33 ± 18.79μm in AD as compared to 913.01 ± 29.15μm in controls (p=0.008). However, distances beyond 1500μm revealed minimal RNFL thickness differences between AD and controls (143.49 ± 9.57μm and 182.82 ± 9.87μm, respectively; p=0.16). While RNFL thinning was also seen in the nasal region, these differences in thickness were not significant, having mean totals of 817.80 ± 29.91μm in AD and 1003.16 ± 30.28μm in controls (p=0.13). RNFL thinning was most severe and significant between 500μm and 2500μm nasally (323.28±11.96μm in AD and 473.20±12.67μm in controls; p=0.005).

Conclusions : These histopathological findings confirm the RNFL atrophy in AD as observed clinically using OCT. The predominant thinning of the RNFL temporally is suggestive of involvement of the papillomacular bundle. Such precise quantitative measurements may be useful in clinical practice as part of enhanced diagnostics and improved monitoring in patients affected with AD.

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