Diabetic retinopathy affects millions of people, highlighting the urgent need for education, awareness and early intervention. Technological advancements, including artificial intelligence and home-based screening, are promising solutions—offering hope in managing this growing epidemic and reducing the burden on eye care professionals worldwide.
Striving for that ‘sweet life’ may be our goal, but not when it’s reflected in our HbA1c. Unfortunately, in many parts of the world, the number of people with diabetes, especially Type II, is increasing at staggering rates.
Nowadays, a Type II diabetes diagnosis is considered a normal part of aging, with many regard it as something that happens to their family members as they grow older. As of 2019, it was estimated that 463 million people, globally, are living with diabetes.1 If that isn’t frightening enough, within the four decades to follow, these estimates are expected to exceed 700 million.1
Diabetic eye care in a growing epidemic
Diabetes increases the risk of various health problems, including heart attack, stroke, kidney failure, and, of course, vision loss. Dr. Thomas W. Gardner—the scientific co-director of the Mary Tyler Moore Vision Initiative and a professor of ophthalmology and visual sciences, molecular and integrative physiology and internal medicine at the University of Michigan—is an expert in the physiology and management of the diabetic eye.
“Diabetic retinal disease remains a leading cause of blindness owing to the dramatic increase in the number of persons with diabetes worldwide,” Dr. Gardner said. “Recent evidence also shows that half of adolescents with Type I or Type II diabetes have diabetic retinal disease after 12 years.” This highlights the fact that vision loss as a consequence of diabetes is not only a concern for older people with diabetes.
“Diabetic retinal disease remains a leading cause of blindness owing to the dramatic increase in the number of persons with diabetes worldwide.”
– Dr. Thomas W. Gardner
With half a billion individuals diagnosed with diabetes, nearly a billion eyes need close monitoring for signs of diabetic retinopathy and macular edema, followed by prompt treatment. No small feat for an army of retina specialists and even a larger army of supporting eye care professionals.
This diabetes epidemic is straining eye care providers as they try to manage this increasing number of patients. It has been estimated that in the United States alone, 9.6 million people have been diagnosed with diabetic retinopathy, and more than 37 million have diabetes, requiring regular monitoring.2 In India, the demand for diabetic eye care is even greater.
Navigating the burden of diabetes in India
Dr. R. Rajalakshmi, a senior consultant ophthalmologist and the head of Medical Retina at Dr. Mohan’s Diabetes Specialities Centre in Chennai, India, and a clinical researcher at Madras Diabetes Research Foundation, shared how diabetes and diabetic retinopathy are impacting the people of India.
“One of the major challenges for India is the disproportionately large number of people with type 2 diabetes,” Dr. Rajalakshmi shared. “The ICMR-INDIAB study has shown that India is home to over 100 million people with diabetes. Approximately 12.5% of people with diabetes in India (i.e., over 12 million) have diabetic retinopathy, of which 4 million have severe sight-threatening diabetic retinopathy.”3-4
Dr. Rajalakshmi has an important role in the SMART India Study, a multicentric collaborative study done across 10 states and one union territory in India, which includes 42,146 study participants. “The SMART India study (translating research into clinical and community practice: a multi- centre Statistical and economical Modeling of risk-based strAtified and peRsonalized screening for complicaTions of diabetes in India) was conducted in people aged 40 years or above to estimate the burden of diabetes and its complications, and create risk prediction models.”
By assessing the population and its needs, SMART India can focus its efforts and initiatives where they are most needed and hopefully intervene earlier.
“The study has shown that glycemic control is suboptimal in about 75% of the participants with known diabetes.5 This is an important finding because the high prevalence of undiagnosed diabetes and suboptimally controlled diabetes can lead to an epidemic of diabetes complications. The study emphasizes the urgent need to identify and optimally treat people with diabetes to reduce the burden of the condition,” Dr. Rajalakshmi shared.
The burdens associated with diabetes may not always be well understood by non-medical professionals in the population; tiny changes are occurring within their bodies before they become even remotely aware of any symptoms. Once the changes become complications, these can be incredibly impactful, especially in working- age patients.
“These patients are at high risk of microvascular and macrovascular complications of diabetes and are therefore more economically challenged,” Dr. Rajalakshmi added, stressing the importance of education, awareness, early detection and management of the disease.
Advancements in screening and intervention
In the past, non-physician personnel would travel with portable fundus cameras, capturing photos to detect the early signs of diabetic eye disease within the community or in underserved areas. But we now understand that earlier detection is beneficial, and changes may be occurring long before the evidence becomes clear on a fundus photo.
“Diabetic retinopathy has long been considered to be ‘microvascular’ disease, but accumulated evidence now reveals that diabetes also has profound effects on retinal nerve cells even though these changes are not revealed by fundus photographs or ophthalmoscopic examination,” Dr. Gardner explained. “However, tests of retinal function often show profound impairment of vision even when the retina appears nearly normal. We now understand that diabetes affects the entire neurovascular unit—the blood vessels, neurons, glial cells and microglial cells.”
“Diabetic retinopathy has long been considered to be ‘microvascular’ disease, but accumulated evidence now reveals that diabetes also has profound effects on retinal nerve cells even though these changes are not revealed by fundus photographs or ophthalmoscopic examination.”
– Dr. Thomas W. Gardner
The silver lining, or perhaps more appropriately, the candy coating to this current situation is that due to enhanced screening protocols, earlier intervention and improved treatment modalities, eye care professionals— particularly retina specialists—are better equipped than ever before to manage the eyes of millions.
Despite the continuing growth in the number of people with diabetes at staggering rates and the increasing prevalence of diabetic retinopathy, the severity of the disease has diminished. It can now be managed at earlier stages, reducing the devastating outcomes seen in past generations.
The management of diabetic retinopathy can be critical to both the individual and their family. The individuals affected are often of working age, raising children and caring for aging parents. If they lose their capacity to work, provide for their family or drive, the effects can spiral far beyond the individual’s quality of life.
That said, even when diabetic retinopathy or other complications have been detected and a treatment plan is in place, adhering to ongoing treatment and screening becomes a challenge in itself. Consider that in the era prior to anti-VEGF therapy for diabetic macular edema, diabetics would visit their ophthalmologist four times per year for monitoring, possibly involving laser treatment to stabilize vision.
Today, anti-VEGF treatment promises to deliver vision improvement. However, this also comes with a need for monthly monitoring or treatment appointments—posing a challenge for both patients and retinal specialists.
To address these needs, ongoing clinical research efforts are focused on extending the intervals between intravitreal anti-VEGF injections and exploring alternative therapeutic options, such as topical drops, implants or one-time gene therapy treatments. The recent FDA approval of high-dose aflibercept allows for intervals of 12 to 16 weeks between intravitreal injections, effectively reducing the frequency of visits by half.
Technology’s impact on patient care
Presentations of results from up-and-coming clinical trials at the recent American Academy of Ophthalmology (AAO) meeting did not disappoint. And while the retinal treatment pipeline does look a little like rush hour traffic, the future certainly looks bright.
There are numerous clinical trials underway across all phases of development. To address compliance issues and potential disparities in care and access to care, several emerging agents are offering home-based options, such as topical or oral treatments, long-term implantables, or the generation of anti-VEGF through gene therapy.
As we describe treatments and management strategies for diabetic retinopathy and macular edema, some of the most impactful influences may not come from drugs at all, but from growing technological applications.
Dr. R. Rajalakshmi and her team at SMART India acknowledge how advancements in technology will help shape how we care for this growing number of patients. “Innovative technologies like smartphones, teleophthalmology6 and the use of artificial intelligence (AI)7 are valuable strategies to improve screening for diabetic retinopathy and reduce the burden on the healthcare system in India,” Dr. Rajalakshmi said.
To gain a deeper understanding of the current technological advancements with direct applications to diabetic eye care, we turned to Dr. Rajiv Raman. He is a senior consultant in the Department of Vitreoretinal Services at Sankara Nethralaya and a professor at the Department of Medical Science and Technology at the Indian Institute of Technology in Madras.
“Over the past two decades, remarkable technological advancements have revolutionized diabetes management,” Dr. Raman shared. “The miniaturization of retinal cameras and the integration of AI for diabetic retinopathy detection have greatly improved DR screening accessibility.”
Dr. Raman emphasized the important role of technology in screening, allowing individuals to become their own retina imaging experts. “There is an ongoing need for even simpler hardware that allows patients to capture retinal images themselves, essentially creating a ‘retinal selfie’ for easy monitoring,” he said.
AI will also have an important role to play in managing diabetic eye care in the years to come. “Harnessing the power of big data, it is now essential to develop population- specific risk score algorithms,” Dr. Raman continued. “These algorithms would play a pivotal role in prioritizing DR screening for individuals at the highest risk. By tailoring risk assessments to specific populations, we can optimize the allocation of resources and target interventions where they are most needed.”
Experts agree that the best management strategy for the complications of diabetic eye disease is to prevent diabetes in the first place—meaning managing the actionable risk factors associated with the development of Type II diabetes.
While we can’t change our age or gender, we do have some control over modifiable lifestyle-related risk factors, such as our blood sugar level, blood pressure and cholesterol level. These factors play a significant role in diabetes and its associated cellular and microvascular morbidities.
These risk factor profiles are being refined by incorporating key measures to enhance our understanding of individuals who are likely to experience adverse outcomes, and who will need to be monitored more carefully and counseled accordingly.
“In recent years, there has been a promising shift towards identifying blood-based biomarkers, such as serum cystatin, which can be integrated into risk factor score algorithms,” Dr. Raman shared. “This innovative approach offers the potential for effective ‘prescreening’ of diabetic retinopathy. Combining these blood-based biomarkers with risk assessment algorithms could provide a non- invasive and efficient means of identifying individuals at risk of DR, allowing for timely intervention and ultimately preventing vision loss.”
“In recent years, there has been a promising shift towards identifying blood-based biomarkers, such as serum cystatin, which can be integrated into risk factor score algorithms.”
– Dr. Rajiv Raman
Global initiatives for diabetic retinopathy
With the surge of diabetes globally, screening for and managing diabetic retinopathy will need to remain a health priority for the foreseeable future. In response to this need, important initiatives are taking the lead to ensure that research continues and that patients and the public have access to validated sources of information and programs for education and awareness.
Dr. Gardner shared his involvement with such a program, a legacy established by the icon and actress Mary Tyler Moore, in support of diabetes research. “The Mary Tyler Moore Vision Initiative* is working to eliminate blindness caused by diabetes by promoting a modern understanding of diabetic retinal disease. This initiative focuses on how the disease can be more effectively and quantitatively assessed, and how new endpoints for diagnosis and treatment can lead to earlier detection and vision restoration,” he said.
A landmark workshop was held in October 2022, featuring 90 attendees with a diverse representation from around the world. Patients and representatives from leading biopharmaceutical, bio-tech, and medical device companies, as well as JDRF, the National Institutes of Health, the American Diabetes Association, the US Food and Drug Administration and others, met with researchers and clinicians from the United States, Europe, Japan, Singapore and Australia.
The goal of the meeting was to discuss various methods for improved diagnosis of diabetic retinal disease, with an emphasis on visual function and ensuring that the voices of patients are heard. The next workshop was held in November 2023.
* marytylermoore.org
References
1. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.
2. Lundeen EA, Burke-Conte Z, Rein DB, et al. Prevalence of Diabetic Retinopathy in the US in 2021. JAMA Ophthalmol. 2023;141(8):747-754.
3. Anjana RM, Unnikrishnan R, Deepa M, Pradeepa R, Tandon N, Das AK, et al. ICMR- INDIAB Collaborative Study Group. Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross- sectional study (ICMR-INDIAB-17). Lancet Diabetes Endocrinol. 2023;11(7):474-489.
4. Rajalakshmi R, Vasconcelos JC, Prevost AT, Sivaprasad S, Deepa M, Raman R, Ramasamy K, Anjana RM, Conroy D, Das T, Hanif W, Mohan V. SMART India Study Collaborators. Burden of undiagnosed and suboptimally controlled diabetes in selected regions of India: Results from the SMART India population-level diabetes screening study. Diabet Med. 2023;40(10):e15165.
5. Raman R, Vasconcelos JC, Rajalakshmi R, Prevost AT, Ramasamy K, Mohan V, et al. SMART India Study Collaborators. Prevalence of diabetic retinopathy in India stratified by known and undiagnosed diabetes, urban-rural locations, and socioeconomic indices: results from the SMART India population-based cross- sectional screening study. Lancet Glob Health. 2022;10(12):e1764-e1773.
6. Rajalakshmi R, UmaSankari G, Prathiba V, Anjana RM, Unnikrishnan R, Venkatesan U, JebaRani S, Shanthirani CS, Sivaprasad S, Mohan V. Tele-Ophthalmology Versus Face-to- Face Retinal Consultation for Assessment of Diabetic Retinopathy in Diabetes Care Centers in India: A Multicenter Cross-Sectional Study. Diabetes Technol Ther. 2022;24(8):556-563.
7. Rajalakshmi R, Subashini R, Anjana RM, Mohan V. Automated diabetic retinopathy detection in smartphone-based fundus photography using artificial intelligence. Eye (Lond). 2018;32(6):1138-1144.
Editor’s Note: A version of this article was first published in PIE Magazine Issue 28.
