Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients

Yonatan Serlin, Tali Shafat, Jaime Levy, Aaron Winter, Marina Shneck, Boris Knyazer, Yisrael Parmet, Hadar Shalev, Ehud Ur, Alon Friedman

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
StatePublished - 1 May 2016


  • Angiography
  • Blood-brain barrier
  • Blood-retinal barrier
  • Diabetic retinopathy
  • Neuropsychiatry

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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