PurposeTo test whether quantitative functional tests and optical coherence tomography (OCT)-defined structure can serve as effective tools to diagnose and monitor early diabetic neuroretinal disease.MethodsFifty-seven subjects with diabetes (23 without diabetic retinopathy [no DR], 19 with mild nonproliferative diabetic retinopathy [mild NPDR], 15 with moderate to severe [moderate NPDR]), and 18 controls underwent full ophthalmic examination, fundus photography, spectral-domain optical coherence tomography (SD-OCT), e-ETDRS (Early Treatment Diabetic Retinopathy Study) acuity, and the quick contrast sensitivity function (qCSF) method. Perimetry testing included short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), frequency doubling perimetry (FDP), and rarebit perimetry (RBP).ResultsETDRS acuity and RBP were not sensitive for functional differences among subjects with diabetes. AULCSF, a metric of qCSF, was reduced in diabetics with moderate compared to mild NPDR (P = 0.03), and in subjects with no DR compared to controls (P = 0.04). SWAP and SAP mean deviation (MD) and foveal threshold (FT) were reduced in moderate compared to mild NPDR (SWAP, MD P = 0.002, FT P = 0.0006; SAP, MD P = 0.02, FT P = 0.007). FDP 10-2 showed reduced MD in moderate compared to mild NPDR (P = 0.02), and FDP 24-2 revealed reduced pattern standard deviation (PSD) in mild NPDR compared to no DR (P = 0.02). Structural analysis revealed thinning of the ganglion cell layer and inner plexiform layer (GCL+IPL) of moderate NPDR subjects compared to controls. The thinner GCL+IPL correlated with impaired retinal function.ConclusionsThis multimodal testing analysis reveals insights into disruption of the neuroretina in diabetes and may accelerate the testing of novel therapies.

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PurposeTo elucidate the relationship between disorganization of retinal inner layers (DRILs) and retinal function in diabetic patients without diabetic retinopathy (DR) and with nonproliferative DR, but without diabetic macular edema (DME).MethodsFifty-seven participants with diabetes mellitus (DM) and 18 healthy controls underwent comprehensive ophthalmic examination, fundus photography, and spectral-domain optical coherence tomography. Scans of the fovea were evaluated for the presence of DRIL. Retinal function was evaluated using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, the quick contrast sensitivity function (qCSF) on the AST Sentio Platform, short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), and frequency doubling perimetry (FDP). ANOVA and Kruskal-Wallis were used to compare retinal function in subjects with and without DRIL. Tukey-Kramer test and Wilcoxon were used for post hoc analysis.ResultsDRIL was identified in 9 of 57 diabetic subjects. DRIL subjects had higher body mass index and longer diabetes duration compared to diabetic subjects without DRIL (P = 0.03 and P = 0.009, respectively). Subjects with DRIL had reduced ETDRS visual acuity (P = 0.003), contrast sensitivity function (P = 0.0003), and SAP performance (PSD, P < 0.0001) compared to controls and diabetic subjects without DRIL. Structural analysis revealed inner retinal thinning, and some outer retinal thinning, associated with DRIL.ConclusionsDiabetic subjects with DRIL have reduced retinal function compared to those without DRIL, and defective retinal lamination may be an early cellular consequence of diabetes responsible for this in some patients. Following further longitudinal studies, DRIL may be a readily available and reliable structural biomarker for reduced retinal function in early diabetic neuroretinal disease.