Detecting retinal neurodegeneration in people with diabetes: Findings from the UK Biobank

PLoS One. 2021 Sep 29;16(9):e0257836. doi: 10.1371/journal.pone.0257836. eCollection 2021.


Importance: Efforts are underway to incorporate retinal neurodegeneration in the diabetic retinopathy severity scale. However, there is no established measure to quantify diabetic retinal neurodegeneration (DRN).

Objective: We compared total retinal, macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness among participants with and without diabetes (DM) in a population-based cohort.

Design/setting/participants: Cross-sectional analysis, using the UK Biobank data resource. Separate general linear mixed models (GLMM) were created using DM and glycated hemoglobin as predictor variables for retinal thickness. Sub-analyses included comparing thickness measurements for patients with no/mild diabetic retinopathy (DR) and evaluating factors associated with retinal thickness in participants with and without diabetes. Factors found to be significantly associated with DM or thickness were included in a multiple GLMM.

Exposure: Diagnosis of DM was determined via self-report of diagnosis, medication use, DM-related complications or glycated hemoglobin level of ≥ 6.5%.

Main outcomes and measures: Total retinal, mRNFL and GC-IPL thickness.

Results: 74,422 participants (69,985 with no DM; 4,437 with DM) were included. Median age was 59 years, 46% were men and 92% were white. Participants with DM had lower total retinal thickness (-4.57 μm, 95% CI: -5.00, -4.14; p<0.001), GC-IPL thickness (-1.73 μm, 95% CI: -1.86, -1.59; p<0.001) and mRNFL thickness (-0.68 μm, 95% CI: -0.81, -0.54; p<0.001) compared to those without DM. After adjusting for co-variates, in the GLMM, total retinal thickness was 1.99 um lower (95% CI: -2.47, -1.50; p<0.001) and GC-IPL was 1.02 μm lower (95% CI: -1.18, -0.87; p<0.001) among those with DM compared to without. mRNFL was no longer significantly different (p = 0.369). GC-IPL remained significantly lower, after adjusting for co-variates, among those with DM compared to those without DM when including only participants with no/mild DR (-0.80 μm, 95% CI: -0.98, -0.62; p<0.001). Total retinal thickness decreased 0.40 μm (95% CI: -0.61, -0.20; p<0.001), mRNFL thickness increased 0.20 μm (95% CI: 0.14, 0.27; p<0.001) and GC-IPL decreased 0.26 μm (95% CI: -0.33, -0.20; p<0.001) per unit increase in A1c after adjusting for co-variates. Among participants with diabetes, age, DR grade, ethnicity, body mass index, glaucoma, spherical equivalent, and visual acuity were significantly associated with GC-IPL thickness.

Conclusion: GC-IPL was thinner among participants with DM, compared to without DM. This difference persisted after adjusting for confounding variables and when considering only those with no/mild DR. This confirms that GC-IPL thinning occurs early in DM and can serve as a useful marker of DRN.

Grant support

This collection of eye and vision data in UK Biobank was supported by UCL Institute of Ophthalmology and the UK National Institute for Health Research for a Biomedical Research Centre at Moorfields Eye Hospital in the form of a grant awarded to the center (BRC2) and to PF (BRC2_009). This study was also supported by a Moorfields Eye Charity Career Development Fellowship awarded to APK (R170005A), a UK Research and Innovation Future Leaders Fellowship awarded to APK (MR/T040912/1), the National Eye Institute in the form of a K23 Career Development Award to RC (1K23EY030911-01) and a grant awarded to MDA (P30EY025580). Research to Prevent Blindness, Inc. provided partial support in the form of an unrestricted grant awarded to the UW Madison Department of Ophthalmology and Visual Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.