American Diabetes Month: An Opportunity to Improve Awareness of Diabetic Retinopathy

Introduction

November is American Diabetes Month, and organizations like the National Institute of Diabetes and Digestive and Kidney Diseases are focusing efforts this year on highlighting the multitude of health complications associated with diabetes. Diabetes affects approximately 37 million Americans1 and more than half a billion people worldwide2, but despite the substantial (and ever-growing) patient population, there is still a general lack of awareness of the impact of this disease. For example, of the 37 million people living with diabetes in the U.S., it is estimated that as many as 8.5 million are undiagnosed and do not know they are living with the disease1.

While many people know that with diabetes, a person’s body doesn’t make enough insulin or use it as well as it can, few people recognize the wide range of health problems that can be associated with the disease. When diabetes is untreated, subsequent high blood sugar levels (hyperglycemia) can have adverse effects on almost every organ in the body, including the kidneys, nerves, heart, as well as the eyes. In this post, we are going to focus on the eyes.

There are a number of ophthalmic conditions under the umbrella of “diabetic eye disease,” including macular edema, cataracts, glaucoma and diabetic retinopathy (DR) – all of which can lead to vision loss if left untreated. In fact, DR is the leading cause of blindness in adults aged 20-743. With progressive diseases like DR, early diagnosis and treatment is essential, underscoring the need for greater awareness of eye complications, as well as the population as a whole.

How does diabetes cause eye disease?

Anyone with diabetes – Type 1, Type 2 or gestational – is at risk for DR, and the risk becomes greater the longer one has been living with the disease4. Hyperglycemia can induce inflammation which damages delicate tissues such as the endothelium of small blood vessels5, resulting in a steady loss of function. Prolonged hyperglycemia can cause disease in many organs: it can result in the accumulation of atherosclerotic plaques in larger arteries, leading to heart disease, and can impede the kidney’s blood filtration capabilities5. With DR, damage to the blood vessels that feed the retina can cause leakage, and the resulting buildup of fluid leads to swelling in parts of the retina (macular edema)6. In the early stages of DR, patients may not even be aware of a problem with their eyes, but the disease still can be detected during an eye exam (highlighting the importance of regular eye exams).

As DR progresses, damaged blood vessels are replaced with new ones, but because of the chronic inflammation caused by hyperglycemia, the new growth (angiogenesis) can be disorganized. This results in fragile vessels that may bleed into the clear gel-like fluid inside the eye7. This leakage associated with DR can lead to diabetic macular edema (DME), causing blurry vision6. At this stage, some people may notice dark spots (informally called “floaters”) or even patches of vision loss4.

Fortunately, DR is relatively easy to diagnose, and with regular exams DR can be detected in the early stages before any vision-threatening changes develop. Initial treatment is focused on managing diabetes through lifestyle and diet – regular exercise, managing blood glucose levels through monitoring and use of insulin, and following specific meal plans. This approach aims to positively impact multiple diabetes-related health problems, coupled with regular eye exams to monitor disease development – known as active surveillance, the so called “watch and wait” strategy8. However, the disease may gradually worsen over time even with management and more direct treatment may eventually be deemed necessary.

Current and future treatment options for DR

Previous OcuTerra Insights articles have discussed current treatment options: invasive procedures including laser photocoagulation and intravitreal injections, in which medication – usually anti-VEGF to inhibit the growth of new blood vessels – is injected directly to the back of the eye. While these therapies have been shown to be effective in improving the health of the retina by reducing the severity of DR, as well as arresting the further development of disease, they must be repeated on a regular basis to avoid progression9. Because these procedures are invasive and associated with certain side-effects and complications, physicians usually only employ these procedures in the later stages of disease once vision has deteriorated and other options have been exhausted.

Given the growing prevalence of diabetes and DR, and the lack of options for early-stage treatment, there is a pressing need for new early-stage and non-invasive therapies. This is why OcuTerra has developed OTT166, a novel selective integrin inhibitor designed to be delivered by eye drop. Through this novel delivery route, OTT166 is intended to be administered at home by patients, with the option for treatment to be initiated in the earliest stages of disease rather than waiting for a vision-threatening development to occur. If approved, OTT166 could improve retinal health while delaying or even preventing further disease development for millions of patients with DR.

American Diabetes Month presents the opportunity for more people to understand how diabetes is directly linked to serious diseases. The OcuTerra team is dedicated to improving treatment options for people with DR, and is currently studying OTT166 in the Phase 2 DR:EAM trial, evaluating its safety and efficacy in the treatment of DR. The study is scheduled to conclude at the end of 2023.

As the number of people living with diabetes grows both in the U.S. and worldwide, it will be essential to shift the paradigm of how we treat this disease and its complications. OcuTerra looks forward to concluding our clinical trials and potentially providing a much-needed new solution for this unmet need in diabetic eye disease.

References 

  1. Centers for Disease Control and Prevention. (2022, October 25). By the numbers: Diabetes in America. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/health-equity/diabetes-by-the-numbers.html

  2. Ong, K. L. et al. (2023). Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the global burden of disease study 2021. The Lancet, 402(10397), 203–234. https://doi.org/10.1016/s0140-6736(23)01301-6

  3. NIH. (2019). People with diabetes can prevent vision loss. National Eye Institute. https://www.nei.nih.gov/sites/default/files/2019-06/diabetes-prevent-vision-loss.pdf

  4. Centers for Disease Control and Prevention. (2022b, December 19). Diabetes and Vision Loss. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/managing/diabetes-vision-loss.html

  5. Li, Y. et al. (2023). Diabetic vascular diseases: Molecular mechanisms and therapeutic strategies. Signal Transduction and Targeted Therapy, 8(1). https://doi.org/10.1038/s41392-023-01400-z

  6. U.S. Department of Health and Human Services. (2023). Macular edema. National Eye Institute. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/macular-edema#

  7. Abcouwer, S. F. (2011). Angiogenic factors and cytokines in diabetic retinopathy. Journal of Clinical & Cellular Immunology, 1(11), 1–12. https://doi.org/10.4172/2155-9899.s1-011

  8. Bryl, A., Mrugacz, M., Falkowski, M., & Zorena, K. (2022). The effect of diet and lifestyle on the course of diabetic retinopathy—a review of the literature. Nutrients, 14(6). https://doi.org/10.3390/nu14061252

  9. Brown, D. M. et al. (2021). Evaluation of intravitreal AFLIBERCEPT for the treatment of severe nonproliferative diabetic retinopathy. JAMA Ophthalmology, 139(9), 946–955. https://doi.org/10.1001/jamaophthalmol.2021.2809

Brad Good