Objective: To evaluate the association between serum vitamin D3 levels in patients with type two diabetes mellitus (T2DM) and diabetic macular edema (DME) taking into consideration other factors such as demographic, metabolic, and clinical confounders. Methods: This retrospective case–control study included patients with T2DM attending a tertiary ophthalmology clinic. Cases were patients with clinical and OCT-confirmed DME. Controls had no DME. Patients with severe NPDR or higher stage were excluded. The study involved collecting several variables including age, sex, diabetes duration, HbA1c, BMI, smoking status, vitamin D3 levels, comorbidities, and vitamin D supplementation. Vitamin D3 was categorized into three groups: 30 ng/mL. Logistic regression was used to identify independent predictors of DME. Results: A total of 332 participants were analyzed. A total of 184 control patients were compared to 148 DME patients. DME patients had significantly longer diabetes duration (12.91 y vs 17.21 y, p 30 ng/mL) was protective. Cigarette smoking, paradoxically, was found to be associated with lower odds for DME. Conclusion: Vitamin D3 deficiency is associated with increased odds of DME. Interpretation should be cautious due to methodological limitations, including potential selection bias, unmeasured confounding, and lack of adjustment for diabetic retinopathy severity. Further research is required to explore further cause-effect relationship and effect of supplementation on the disease itself and response to treatment. Keywords: type 2 diabetes mellitus, diabetic retinopathy, diabetic macular edema, Vitamin D3, smoking, risk factors, anti-VEGF
Al-Latayfeh et al. (2026) studied this question.