Quantifying retinal putative gliosis in preclinical Alzheimer’s disease

Abstract

Purpose : Neuroinflammation plays a significant role in the amyloid pathological cascade of Alzheimer’s disease (AD). Mouse models of AD and post-mortem biopsy of AD patients reveal retinal glial activation comparable to CNS immunoreactivity. We hypothesized the surface area of retinal putative gliosis observed in vivo using en face Optical Coherence Tomography (OCT) imaging will be larger in preclinical AD (cognitively unimpaired; CU Aβ PET +ve) patients vs. controls (CU Aβ PET -ve).

Methods : The Spectralis II instrument was used to acquire macular centered 20×20 and 30x25-deg Spectral Domain OCT (SD-OCT) images of 76 participants (132 eyes). A cohort of 22 preclinical AD (40 eyes; mean age: 69 years; range: 60-80) and 20 control participants (32 eyes; mean age: 66 years; range: 58-82; p = 0.11) were included for the assessment of difference in surface area of retinal putative gliosis and retinal nerve fiber layer (RNFL) thickness. The surface area of retinal putative gliosis defined as hyperreflective structures was computed using a custom program in MATLAB analyzing three SD-OCT en face slabs. Vendor software was used to segment and compute RNFL thickness at the macular for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. Test-retest repeatability for the surface area of retinal putative gliosis was assessed in 39 participants (65 eyes) using intraclass correlation coefficient (ICC). Generalized linear mixed models were used to compare the difference in surface area of retinal putative gliosis and RNFL thickness at the nine ETDRS sectors between groups, accounting for correlation between eyes. A p-value < 0.05 was considered significant.

Results : Test-retest repeatability was good, ICC = 0.88 (95% CI = 0.81-0.93). The surface area of retinal putative gliosis was significantly greater in the preclinical group (0.97 ± 0.55 mm²) compared to controls (0.68 ± 0.40 mm²); F_(1,70) = 4.41, p = 0.039; Cohen’s d = 0.61. There was no significant difference between groups for RNFL thickness in the nine ETDRS sectors, p > 0.05.

Conclusions : Our analysis shows greater retinal putative gliosis in preclinical AD compared to controls. This demonstrates retinal putative gliosis as a potential biomarker for AD-related neuroinflammation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

En-face OCT (A, B), corresponding b-scans (C-F) and processed images (G,H) demonstrating increased retinal putative gliosis in preclinical AD vs. control.