Retinal Thickness and Morphology Changes on OCT in Youth with Type 2 Diabetes: Findings from the TODAY Study

Abstract

Objective: To evaluate changes in retinal thickness and morphology using OCT in youth with type 2 diabetes (T2D) and to identify systemic biomarkers correlating with these changes.

Design: Retrospective subgroup analysis of a prospective study.

Participants: Participants who underwent OCT imaging in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial and its follow-up study TODAY2.

Methods: In 2010-2011 (TODAY) and 2017-2018 (TODAY2), 6 × 6-mm macular volume OCT scans were acquired, segmented, and analyzed to generate total retinal thickness, inner retinal thickness, and outer retinal thickness. The main retinal morphologies graded were intraretinal cystoid spaces, subretinal fluid, and posterior vitreous detachment (PVD).

Main outcome measures: Changes in total and individual retinal layer thickness and development of abnormal vitreomacular morphology between TODAY and TODAY2.

Results: Participants had a mean age of 17.9 ± 2.4 years and glycated hemoglobin (HbA1c) of 8.2 ± 2.8% in TODAY and a mean age of 25.0 ± 2.4 years and mean HbA1c of 9.5 ± 2.8% in TODAY2. Longitudinally between assessments, there were overall decreases in outer retinal thickness from 167.2 ± 11.5 microns to 158.4 ± 12.8 microns (P < 0.001) and in photoreceptor thickness from 30.3 ± 2.9 microns to 29.8 ± 4.1 microns (P = 0.04) in the central subfield, while in the inner subfield, we noted a decrease in outer retinal thickness from 150.5 ± 10.1 microns to 144.9 ± 10.5 microns (P < 0.001) and an increase in inner retinal thickness from 136.9 ± 11.5 microns to 137.4 ± 12.6 microns (P = 0.01). Multivariate analysis showed that in the center subfield, HbA1c increases were associated with increases in total retinal thickness (r: 0.67, P = 0.001), whereas fasting glucose was positively correlated with inner retinal thickness (r: 0.02, P = 0.02). In the inner subfield, both systolic (r: -0.22, P < 0.001) and diastolic (r: -0.22, P = 0.003) blood pressures were negatively correlated with total retinal thickness. There was an increase in PVD (18.9%) and cystoid spaces (4.2%).

Conclusions: Youth with T2D develop retinal thickness changes on OCT, including increases in total retinal and inner retinal thickness in the center subfield that correlate with HbA1c and fasting glucose, respectively. Taken together with the increased prevalence of abnormal vitreomacular morphology in this cohort at risk, these findings emphasize the importance of controlling risk factors to prevent the development of sight-threatening retinal complications.

Keywords: DR, diabetic retinopathy; EZ, ellipsoid zone; Glycemic control; HbA1c, glycated hemoglobin; ILM, internal limiting membrane; INL, inner nuclear layer; Macular morphology; NPDR, nonproliferative DR; OPL, outer plexiform layer; PVD, posterior vitreous detachment; Posterior vitreous detachment; RPE, retinal pigment epithelium; Retinal thickening; SD-OCT, spectral-domain OCT; T2D, type 2 diabetes; TD-OCT, time-domain OCT; TODAY, Treatment Options for Type 2 Diabetes in Adolescents and Youth; Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

Figure 1

Retinal thickness measurement for the central subfield and inner subfield of the OCT grid based on segmentation of the retina. EZ = ellipsoid zone; ILM = internal limiting membrane; OPL = outer plexiform layer; RPE = retinal pigment epithelium.

Figure 2

Representative OCTs showing thickness and morphological changes from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study baseline to TODAY2 follow-up. Case A (top) showed presence of cysts (arrow) in the TODAY2 visit, while the baseline in TODAY showed normal OCT. The diabetic retinopathy severity score (DRSS) level from the fundus photograph corresponding to the TODAY2 visit of case A was mild proliferative diabetic retinopathy (PDR) (61B). Case B (bottom) showed retinal thickening, posterior vitreous detachment (PVD) and epiretinal membrane (ERM) with retinal traction and distortion (RTD) (arrows), as well as photocoagulation scars (arrowheads) temporally while the baseline OCT was normal. The DRSS level from the fundus photograph corresponding to the TODAY2 visit of Case B was high-risk PDR (71C).