Virtual model aids understanding of diabetic retinopathy progression

Informatics meets optometry in novel research that uses advanced computational methods to map the progressive deterioration of diabetic retinopathy, providing clinicians better insight into the disease's course.

Published in the journal PLOS Computational Biology in June, the study presents a computer-generated retinal tissue model that illustrates the variable domino effect leading to diabetic retinopathy—from initial elevated blood sugar levels to the resulting vascular damage in the retina—in a way often only observed using multiple, invasive procedures.

"This paper establishes a step-by-step pathway from a diabetic's elevated blood sugars to the vascular complications in the eye," said Thomas Gast, M.D., senior scientist at the Indiana University (IU) School of Optometry and study lead author, in a news release. "Therapeutically, understanding a disease can lead to improved treatments."

Conducted by scientists at IU School of Optometry and the Biocomplexity Institute in the IU School of Informatics and Computing, the research "provides the first strong evidence for why this pattern of disease progression is so variable, and it predicts where damage will occur next." The virtual model shows how loss of blood flow triggers production of vascular endothelial growth factor (VEGF), and how the cascading damage spreads into new blood vessels.

Influencing 'individualized therapy'

Based on the patient's specific vascular structure, the model can estimate the specific rate and pattern of vascular damage resulting from blood vessel blockage. The data could help influence therapy, such as laser photocoagulation, allowing for the strategic placement of 'firebreaks' around areas where the model predicts vascular damage will spread.

This is perhaps the most "tantalizing" promise of the study, notes A. Paul Chous, O.D., AOA representative to the National Diabetes Education Program of the National Institutes of Health.

"This model suggests the potential to customize photocoagulation therapy to achieve maximal effect against eye disease with minimal damage to healthy, adjacent areas—what the authors describe as an 'intelligent firewall' against paracrine-mediated geographic enlargement of retinal disease," Dr. Chous writes in review of the study.

The study demonstrates "paracrine signaling" in the retinas of patients with diabetes; that is, biochemical mediators released by one damaged cell induce changes in nearby cells, altering the behavior or differentiation of those cells, Dr. Chous states.

"Secondly, this work again demonstrates that VEGF not only induces neovascularization, but also injures adjacent capillary cells to promote a cascading effect of leakage, closure and hypoxia," he says. "Thirdly, the model developed by these investigators suggests that individual variability in patients' retinal capillary geography and oxygen demand predicts the 'spread' of VEGF to adjacent cells and the progression of diabetic retinopathy and/or macular edema."

However, Dr. Chous notes there are limitations. "Mapping every patient's unique capillary configuration is expensive and time-consuming at the moment, so it will be interesting to see if these barriers can be reduced enough to make this customizable strategy a viable option for our patients."

Study authors plan to begin animal studies and suggest this model could eventually lead to better treatment for the leading cause of blindness in American adults.

The toll of diabetic retinopathy

Diabetic retinopathy, a condition that causes progressive damage to the retina resulting in serious, sight-threatening complications, is also the leading cause of new blindness in adults ages 20-74 years old and affects up to 80% of patients who have had diabetes for 20 years or more. Essentially derived from the swelling of retinal tissue, diabetic retinopathy can be caught early with a comprehensive, dilated eye examination, helping limit the potential for significant vision loss.

Access the AOA's Evidence-based Clinical Practice Guideline, Care of the Patient with Diabetes Mellitus—Second Edition.