Abstract
BACKGROUND: Diabetic retinopathy (DR) is the leading cause of preventable blindness. Although hyperglycaemia is the primary driver, other modifiable risk factors may contribute to DR development. This study investigated the association between haemoglobin levels and DR risk in adults with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the TriNetX network (2010-2022). Adults aged ≥45 years with type 2 diabetes were divided into low haemoglobin (LHB, 8-12 g/dL) and control (≥12 g/dL) groups. Propensity score matching was used to address potential confounders. The primary outcome was new-onset DR occurring 6-36 months after the index date. The secondary outcomes included DR subtypes and diabetic ophthalmic complications. Subgroup analyses examined effect modifications by hypertension status, glycaemic control, and sex. RESULTS: After propensity score matching (28,882 patients per group), patients in the LHB group showed significantly higher risk of overall DR (HR: 1.33, 95% CI: 1.24-1.44), proliferative DR (HR: 1.95, 95% CI: 1.62-2.35), and non-proliferative DR (HR: 1.19, 95% CI: 1.06-1.33). Even mild haemoglobin reductions (10-12 g/dL) were associated with increased DR risk. The association was stronger in patients without hypertension (HR: 1.58 vs 1.21), remained consistent regardless of HbA1c levels, and was more pronounced in males than females. CONCLUSION: Low haemoglobin levels independently increased the risk of DR in adults with type 2 diabetes, with the strongest association for proliferative DR. Routine haemoglobin monitoring and maintenance of optimal levels may represent a modifiable risk factor for DR prevention along with glycaemic control and blood pressure management.