Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients

Introduction: Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome.

Methods: A retrospective cohort study was conducted among subjects with diabetes (N=2982) with FA-confirmed NPDR (N=2606) or PDR (N=376). Incidence and probability to develop brain pathologies and mortality were investigated in a 10-year follow-up study. We used Kaplan-Meier, Cox and logistic regression analyses to examine association between DR severity and neuropsychiatric morbidity adjusting for confounders.

Results: Patients with PDR had significantly higher rates of all-cause brain pathologies (P<0.001), specifically stroke (P=0.005), epilepsy (P=0.006) and psychosis (P=0.024), and a shorter time to develop any neuropsychiatric event (P<0.001) or death (P=0.014) compared to NPDR. Cox adjusted hazard ratio for developing all-cause brain impairments was higher for PDR (HR=1.37, 95% CI 1.16-1.61, P<0.001) which was an independent predictor for all-cause brain impairments (OR 1.30, 95% CI 1.04-1.64, P=0.022), epilepsy (OR 2.16, 95% CI 1.05-4.41, P=0.035) and mortality (HR=1.35, 95% CI 1.06-1.70, P=0.014).

Conclusions: This is the first study to confirm that angiography-proven microvasculopathy identifies patients at high risk for neuropsychiatric morbidity and mortality.