Association Between Macular Ganglion Cell-Inner Plexiform Layer and Non-Proliferative Retinopathy Without Macular Edema in Type 2 Diabetes via Diabetes Duration and HbA1c Link

<b>Background/Objectives:</b> This study aimed to evaluate the association between the thickness of the macular ganglion cell-inner plexiform layer (GC-IPL), a marker of retinal neurodegeneration, and diabetic retinopathy (DR), a microvasculopathy, in type 2 diabetic patients (T2DM), and to determine the related risk factors. <b>Methods:</b> This cross-sectional study included 50 eyes of 25 T2DM with a median age of 64 and a median diabetes duration of 13 years. Complete diabetological, nephrological, and ophthalmological examination was performed, including color fundus photography according to the EURODIAB methodology and optical coherence tomography (OCT) of the macula. Patients with proliferative DR and diabetic macular edema were not included in the study. Data were analyzed using the software package Statistica™ 14.0.1.25 (TIBCO Inc., USA). <b>Results:</b> Fifty eyes were divided into two groups: no DR (<i>n</i> = 34) and non-proliferative DR (NPDR) (<i>n</i> = 16). The NPDR group had longer diabetes duration (<i>p</i> = 0.042), higher HbA₁c (<i>p</i> = 0.002), lower HDL cholesterol (<i>p</i> = 0.036), and also lower macular GC-IPL thickness (<i>p</i> = 0.027) than those without DR. The correlation between DR and GC-IPL was significantly negative (R = -0.319, <i>p</i> = 0.024). DR was positively related to diabetes duration (<i>p</i> = 0.047) and HbA₁c (<i>p</i> = 0.003), while the relation between GC-IPL and diabetes duration (<i>p</i> = 0.042) and HbA₁c (<i>p</i> = 0.043) was negative. Binary logistic regression analysis showed that HbA₁c (OR = 2.77, <i>p</i> = 0.007) and HDL cholesterol (OR = 0.08, <i>p</i> = 0.031) were the main predictors for DR, whereas the best model for predicting the GC-IPL thickness (R² = 0.223) obtained from stepwise regression analysis included HDL cholesterol, triglycerides, estimated glomerular filtration rate, and albumin/creatinine ratio. <b>Conclusions:</b> The negative correlation between macular GC-IPL and DR in T2DM indicates the coexistence of two parts, neurodegenerative and microvascular, in one diabetic eye complication, linked by the same well-known risk factors: diabetes duration and HbA₁c.