Systemic Lactate Dehydrogenase Levels as a Predictor of Progression from Non-Proliferative to Proliferative Diabetic Retinopathy

<b>Objective:</b> Diabetic retinopathy (DR) is a leading cause of blindness, and understanding its progression from non-proliferative (NPDR) to sight-threatening proliferative diabetic retinopathy (PDR) is crucial. Systemic lactate dehydrogenase (LDH) has been implicated in various disease processes. We investigated the association between systemic LDH levels at the time of NPDR diagnosis and the 1-year risk of progression to PDR and its complications. <b>Methods:</b> We conducted a retrospective, propensity-matched cohort study using the TriNetX US Collaborative Network. Patients with type 2 diabetes and a new diagnosis of NPDR were stratified into three groups based on a single LDH measurement taken within 6 months of the index date: low (<200 U/L), moderate (201-280 U/L), and high (≥281 U/L). Two separate analyses were performed: one comparing the low-LDH group to the moderate-LDH group, and another comparing the low-LDH group to the high-LDH group. The primary outcomes were the 1-year absolute risks and risk ratios (relative risk, RR) for PDR, tractional retinal detachment (TRD), and vitreous hemorrhage (VH). <b>Results:</b> Comparing the low-LDH cohort to the moderate-LDH cohort, the moderate-LDH group had a higher 1-year absolute risk of PDR (3.93% vs. 2.96%), TRD (1.35% vs. 0.99%), and VH (4.38% vs. 3.51%). Comparing the low-LDH group to the high-LDH group, the high-LDH cohort showed an increased risk for PDR (3.66% vs. 3.00%), TRD (1.27% vs. 0.96%), and VH (1.27% vs. 0.96%). <b>Conclusions:</b> Our findings demonstrate a consistent, dose-dependent relationship between higher systemic LDH levels and an increased risk of progression to PDR and its complications.