Diabetic eye disease linked to neurodegenerative disorders

Diabetic retinopathy (DR) had a significant association with several types of neurodegenerative disorders, particularly cognitive disorders, a large meta-analysis showed.

DR more than doubled the risks of later development of systemic neurodegeneration and also increased the risks of a current neurodegenerative disorder. The severity of retinopathy did not influence the likelihood of systemic neurodegeneration, reported Frederik N. Pedersen, MD, of Odense University Hospital in Denmark, and colleagues.

Although far from definitive, the results argue for additional studies to examine the associations, they said in Ophthalmology Retina.

“It should be noted that studies [included in the meta-analysis] were equivocal in their findings and most available studies assessed cognitive function and impairment,” the authors acknowledged. “These circumstances require large, better-controlled observational studies. Furthermore, it is unknown whether DR enhancement influences cognitive function, and interventional clinical studies are warranted to assess the practical clinical importance of DR in relation to cognitive function.”

“Finally, diagnostic-specific studies were sparse, calling into question the clinical significance of these findings,” they said. “Nevertheless, statistically significant ORs [odds ratios] at 1.57 and 2.36 across cross-sectional and longitudinal studies, respectively, are consistent in suggesting effect sizes that merit further attention.”

The findings add to those of previous studies suggesting that patients with diabetic eye disease have an increased risk of several systemic diseases, including neurodegenerative disorders, said Sunir Garg, MD, of Wills Eye Hospital and Thomas Jefferson University in Philadelphia.

“We know that diabetes affects small blood vessels throughout the body,” said Garg, clinical spokesperson for the American Academy of Ophthalmology. MedPage today by email. “This includes the retina, kidneys, heart and brain. In addition, diabetes causes damage due to inflammation, scar tissue formation and nerve cell death. Some of these changes are also seen in neurodegenerative diseases.

The data analyzed by Pedersen and his colleagues seem to suggest that diabetic eye disease increases the risk of neurodegenerative disorders, regardless of the severity of diabetic retinopathy, he added. Nevertheless, “patients should not assume that just because they have diabetic eye disease, they will also develop a neurodegenerative disease. This highlights the importance of helping our diabetic patients control their blood sugar and blood pressure in order to reduce the likelihood of developing any complications of diabetes.”

Patients with diabetes should have an annual eye exam by an ophthalmologist as part of their routine care, Garg added.

The association between DR and neurodegenerative disorders has sparked interest, in part because the retina and optic nerve are brain-derived tissues and have similar pathogenic pathways, the authors noted. Previous research has shown an increased incidence of Parkinson’s disease and Alzheimer’s disease in diabetic patients. Brain MRI of patients with DR showed an increased prevalence of white matter lesions and reduced gray matter compared to people who did not have diabetic eye disease.

The collective evidence suggests “a future scenario, where retinal neurodegeneration may be an important factor in identifying those at risk for systemic neurodegenerative diseases,” the authors said. To investigate the question, Pedersen and colleagues performed a systematic review of the literature to identify studies on Alzheimer’s disease, Parkinson’s disease, and cognitive impairment associated with diabetic eye disease (retinopathy, angiopathy, or maculopathy).

They identified 27 studies for qualitative review, 14 of which provided data for the meta-analysis. Of the 27 studies, 13 were cross-sectional, 11 were cohort, and three were case-control studies. Three studies looked at Alzheimer’s disease, one at Parkinson’s disease and the others looked at the association between diabetic eye disease and cognitive impairment. Collectively, the studies included 1,398,041 patients with diabetes, and type 2 diabetes accounted for 1,379,544 of the total.

Analysis of cross-sectional studies showed that patients with DR had an OR of 1.57 for a current neurodegenerative disorder (95% CI 1.02-2.43, P= 0.043), and analysis of longitudinal surveys yielded an OR of 2.36 for incident neurodegeneration (95% CI 1.50-3.71, P=0.00021). The probability of systemic neurodegeneration was not affected by the severity of DR (OR 0.98, 95% CI 0.45-2.15).

Regarding studies of different types of neurodegeneration, eight of 13 cross-sectional surveys showed one or more associations between DR and cognitive impairment, as did the three case-control studies included in the analysis. Seven cohort studies produced one or more findings that implicated DR as a risk for future development of cognitive impairment. Two of the three cohort studies showed significant associations between DR and the future development of Alzheimer’s disease or dementia. The only study that analyzed DR and Parkinson’s disease showed a significant association with the future risk of neurodegenerative disorders in patients with DR.

  • Charles Bankhead is editor for oncology and also covers urology, dermatology and ophthalmology. He joined MedPage Today in 2007. To follow


Pedersen and his co-authors did not disclose any relationship with the industry.

Garg disclosed relationships with Merck Sharp & Dohme, Bausch & Lomb, Allergan, EyePoint Pharmaceuticals and Carl Zeiss Meditec AG.

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