# Functional and structural biomarkers linked to diabetic retinal neurodegeneration in pre-clinical and early diabetic retinopathy

## TL;DR

This study identifies functional and structural biomarkers for early diabetic retinal neurodegeneration, showing that visual function and retinal thickness changes can help detect and track the condition.

## Contribution

The study introduces hRSD and OCT-derived retinal thicknesses as potential standardized biomarkers for early diabetic retinal neurodegeneration.

## Key findings

- Functional measures like hRSD and VA were significantly worse in diabetic participants compared to healthy controls.
- Structural changes, including retinal thinning in multiple layers, were observed in diabetic participants with no or early retinopathy.
- Longitudinal data showed progressive thinning of retinal layers in diabetic participants over time.

## Abstract

Diabetic retinal neurodegeneration (DRN) is increasingly recognised as an early and progressive neuronal dysfunction. Despite emerging therapeutic approaches, there are no standardised biomarkers. We aim to investigate functional and structural biomarkers of DRN in people with diabetes (PWD) with no or early diabetic retinopathy (DR).

Functional measures included handheld radial shape discrimination (hRSD), near and distant visual acuity (VA). Structural changes were evaluated using optical coherence tomography (OCT)-derived retinal thicknesses (Early Treatment Diabetic Retinopathy Study (ETDRS) subfields). Mean thicknesses of the inner and outer ETDRS subfields were averaged to derive inner and outer ring estimates. Pearson’s correlation assessed associations between normally distributed variables. Group differences were analysed using Student’s t-test for continuous data, Chi-squared or Fisher’s exact tests for categorical variables, and one-way ANOVA with Bonferroni-adjusted post hoc tests for multiple groups.

The study included a single eye from 50 healthy participants (HP; Group 1, 55 ± 14y), 26 PWD with no DR (Group 2, 55 ± 14y), and 46 with early DR (Group 3, 57 ± 17y). hRSD and VA were worse in Groups 1 to 3 (all p < 0.001). Worse function (measured via hRSD) was associated with inner retinal thinning (p < 0.05). Compared to HP, PWD (Groups 2 and 3) showed thinning of the total retina (most subfields), retinal nerve fibre layer (RNFL; outer ETDRS ring), ganglion cell layer (GCL) and inner plexiform layer (IPL) in the inner ring, and outer nuclear layer (ONL) in the central subfield (CSF) (p < 0.05). Group 3 also showed GCL and IPL thinning (outer ring) (p < 0.05). In 23 PWD followed over 205 ± 109 days, GCL, IPL, and inner nuclear layer (INL) thicknesses decreased (p < 0.05).

Functional and structural changes occur early in DR. hRSD and retinal thicknesses are promising biomarkers for DRN. Longitudinal data suggest DRN to be progressive.

Not applicable.