Ophthalmologist and Physician-Scientist
New Compounds to Treat Proliferative Diabetic Retinopathy

New Compounds to Treat Proliferative Diabetic Retinopathy

One retinal disease that may lead to blindness is diabetic retinopathy. Poorly controlled diabetes mellitus can raise blood glucose levels and cause damage in several different organ systems. Within the eye, diabetes can damage the retina, a membrane on the inner surface of the back of the eye. The cornea and lens focus light rays onto the retina, which converts the light into electrical signals and sends them to the brain. Not all people with diabetes will develop diabetic retinopathy, although individuals who have had the disease for long periods of time or who have poor glycemic control are at greater risk. People with certain comorbidities, including hypercholesterolemia, hypertension and renal disease, also have a greater risk of developing diabetic retinopathy.

Usual Progression of Diabetic Retinopathy

In the early stages of diabetic retinopathy, called the nonproliferative period, capillaries throughout the retina become damaged by high blood sugar levels and develop areas of weakness known as microaneurysms. Red blood cells are able to escape through the weakened areas, which leads to small areas of hemorrhage that are visible via an ophthalmoscope. Fluid from the blood can also escape from the weakened vessels and can cause exudates. Exudates generally do not interfere with vision unless they affect the macula, which is responsible for central vision. To halt the blood leakage, treatment consists of photocoagulation, the use of a small laser to seal the blood vessels.

If diabetic retinopathy continues to progress, it enters the proliferative phase where new blood vessels begin to grow to supply the damaged areas of the retina. While this may sound like a helpful process, the new blood vessels are fragile and can bleed into the vitreous gel in front of the retina and eventually cause scars to form. These scars may cause the retina to detach from the wall of the eye, which leads to vision loss. At this stage, ophthalmologists use a more aggressive laser approach to treat the condition. Generalized photocoagulation minimizes the ability of new, fragile blood vessels to grow. Furthermore, patients may receive a drug such as ranibizumab, which blocks the action of vascular endothelial growth factor (VEGF), which drives the growth of the new blood vessels. In severe cases involving retinal detachment, ophthalmologists typically use surgical techniques, which are more invasive and carry more risks than laser treatments. 

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Potential New Options to Treat Diabetic Retinopathy

Recently, researchers from the University of Surrey in the United Kingdom, and the Eugene and Marilyn Glick Eye Institute at Indiana University School of Medicine, uncovered a potential new treatment for patients with advanced diabetic retinopathy. The results of their research were published in April 2019, Journal of Natural Products. The scientists studied natural compounds that may stop the abnormal growth of blood vessels in diabetic retinopathy. They tested homoisoflavonoids from the Hyacinthaceae plant family, as well as some synthetic derivatives. Their paper reports on the ability of these compounds to stop vascular proliferation, and they found one synthetic derivative with significant potential for future therapeutic application.

The researchers carefully documented the effect of a variety of different natural products from Hyacinthaceae plants on enzyme activity within the eye. These results suggest many new avenues of exploration for the treatment of blinding eye diseases that involve neovascularization. Importantly, these compounds could be used to treat a variety of ophthalmologic diseases affecting the retina, such as retinopathy of prematurity, which can affect up to 20 percent of infants born before 32 weeks. The therapy could also provide a new option for patients with wet age-related macular degeneration, which has emerged as one of the world’s leading causes of blindness.

Why New Treatments Hold Promise

There is the question of why new potential avenues for treatment of retinal neovascularization have caused excitement, considering anti-VEGF treatments such as ranibizumab already exist. In reality, while monoclonal antibody treatments such as ranibizumab have helped many people, they are not effective in all patients. Furthermore, the production of monoclonal antibodies is costly, so patients may have difficulty accessing these treatment options. In addition, the drugs are administered to the eye via an injection; not all patients can tolerate this means of drug delivery. A natural solution would address these challenges by offering a less expensive treatment that more patients can tolerate.

The findings from the new study have opened several paths for research. At the same time, however, much work remains to be done before these treatments become commercially available for patients. The two institutions involved in the research are already working together to spearhead more research that could lead to new drug approvals in the future, while also investigating other potential applications of homoisoflavonoid compounds. Blindness is a major health issue with dramatic impacts on patients, caregivers, family members, and larger communities, so any drug with the potential to save eyesight is a welcome development.