ObjectiveOur aim was to evaluate associations of different risk factors with odds of diabetic retinopathy (DR) diagnosis and retinal neurodegeneration represented by macular ganglion cell-inner plexiform layer (mGCIPL).MethodsThis cross-sectional study analyzed data from individuals aged over 50 years examined between June 2020 and February 2022 in the community-based Beichen Eye Study on ocular diseases. Baseline characteristics included demographic data, cardiometabolic risk factors, laboratory findings, and medications at enrollment. Retinal thickness in both eyes of all participants was measured automaticallyviaoptical coherence tomography. Risk factors associated with DR status were investigated using multivariable logistic regression. Multivariable linear regression analysis was performed to explore associations of potential risk factors with mGCIPL thickness.ResultsAmong the 5037 included participants with a mean (standard deviation, SD) age of 62.6 (6.7) years (3258 women [64.6%]), 4018 (79.8%) were control individuals, 835 (16.6%) were diabetic individuals with no DR, and 184 (3.7%) were diabetic individuals with DR. The risk factors significantly associated with DR status were family history of diabetes (odds ratio [OR], 4.09 [95% CI, 2.44-6.85]), fasting plasma glucose (OR, 5.88 [95% CI, 4.66-7.43]), and statins (OR, 2.13 [95% CI, 1.03-4.43]) relative to the control individuals. Compared with the no DR, diabetes duration (OR, 1.17 [95% CI, 1.13-1.22]), hypertension (OR, 1.60 [95% CI, 1.26-2.45]), and glycated hemoglobin A1C (HbA1c) (OR, 1.27 [95% CI, 1.00-1.59]) were significantly correlated with DR status. Furthermore, age (adjusted β = -0.19 [95% CI, -0.25 to -0.13] μm;P< 0.001), cardiovascular events (adjusted β = -0.95 [95% CI, -1.78 to -0.12] μm;P= 0.03), and axial length (adjusted β = -0.82 [95% CI, -1.29 to -0.35] μm;P= 0.001) were associated with mGCIPL thinning in diabetic individuals with no DR.ConclusionMultiple risk factors were associated with higher odds of DR development and lower mGCIPL thickness in our study. Risk factors affecting DR status varied among the different study populations. Age, cardiovascular events, and axial length were identified as potential risk factors for consideration in relation to retinal neurodegeneration in diabetic patients.