The association of vitreous biomarker levels and optical coherence tomography markers to cognitive status

Abstract

Purpose : Finding a method towards early diagnosis of Alzheimer's disease (AD) remains a significant challenge. Since the eye is an extension of the central nervous system and provides the possibility for non-invasive and multi-modal examination for early biomarkers of AD, we performed a retrospective clinical study to evaluate the association between vitreous biomarkers and cognitive function with optical coherence tomography (OCT) quantitative markers.

Methods : This is a secondary retrospective analysis of a prospective study of 95 patients that underwent vitrectomy surgery and vitreous biopsy for biomarker analysis. In the original study, vitreous Aβ40, Aβ42 and tTau were significantly associated with cognitive status by Mini-mental state examination (MMSE). In this study, quantitative measurements were obtained retrospectively on a subset of patients who underwent OCT during the course of clinical care (choroidal thickness, total macular volume, average retinal thickness). A linear regression model was used to examine the association between vitreous biomarkers, MMSE and OCT markers. All analyses were performed using Stata/IC 12.1 (College Station, TX).

Results : Sixty patients (68% male with mean age of 54.4 ± 15.4 years old) met the inclusion criteria. A lower choroidal thickness was associated with higher vitreous biomarker levels in multivariate analysis after adjusting for age, gender, race, macular disease, anti-VEGF injection, diabetic retinopathy, glaucoma and AMD (IL10 (p= 0.02), IL6 (p= 0.03), IL15 (p= 0.02), VEGF-D (p= 0.04), VCAM1(p= 0.01), Eotaxin-3 (p= 0.04), IL17a (p= 0.01), IP10 (p= 0.02), MIP1a (p= 0.03), Aβ42 (p= 0.01)). There was a significant positive association between higher MMSE Score and macular volume in univariate (p= 0.003) and multivariate analyses (p= 0.05). Also, higher IL4, IL6 were associated with lower MMSE score in univariate (p= 0.003,0.009) and multivariate linear regression (p= 0.008,0.01).

Conclusions : Choroidal thickness is significantly associated with vitreous inflammatory cytokines and Aβ42. We additionally found that higher cognitive status is associated with higher macular volume, while lower cognitive status was associated with upregulation of IL4 and IL6. These findings confirm an association between retinal/choroidal cell layer thickness, vitreous neuro-inflammatory cytokines, and cognitive status measured by MMSE.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.