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Treatment of Diabetic Retinopathy

A Guest Column By Suveera Dang, MPH, Rajeev Ramchandran, MD, MBA, and Ajay E. Kuriyan, MD, MS

Diabetic eye disease is one of the leading causes of blindness and impaired vision. Almost 30 million Americans have diabetes and nearly 8 million have diabetic retinopathy. Diabetic retinopathy costs the country $6.2 billion each year.1,2 Diabetic retinopathy refers to damaged blood vessels in the innermost layer of the back of the eye called the retina. The retina is a key part of the eye that is responsible for turning the light that enters the eye into an electrochemical signal that is interpreted by the brain as the images one sees. Retinal vessels become damaged slowly over years once a person develops diabetes. A person with diabetes may not have vision changes or notice the early signs of diabetic retinopathy as vision loss is associated with later, more severe stages of the disease when more damage to the retina has occurred. When symptoms are noted with diabetic retinopathy, they typically include floaters, decreased visual acuity, blurred vision, and decreased color vision. However, diabetic retinopathy can be present without symptoms even in advanced stages. Therefore, it is important that Type 1 diabetic patients, usually diagnosed during childhood and who need insulin, initiate screening within five years of diagnosis, and that Type 2 diabetic patients, who are generally diagnosed as adults and start out not needing insulin, have their first eye exam at the time of diagnosis of diabetes to increase the odds of detecting diabetic retinopathy early prior to permanent retinal damage and vision loss. Thereafter annual dilated eye exams are recommended. Women with diabetes who become pregnant should have more frequent dilated eye exams starting in their first trimester as they can develop retinopathy and vision loss much more rapidly. Patients with diabetes should also carefully control their blood glucose levels and blood pressure to prevent or slow vision threatening diabetic retinopathy.

Diabetic retinopathy initially starts with microaneurysms, which are tiny swellings in the blood vessels of the retina. This stage is called mild nonproliferative diabetic retinopathy. Over time, damaged blood vessels can lead to decreased blood flow in the retina and as a result, decreased delivery of oxygen to the retina. In response to the lack of oxygen, the compound called VEGF (Vascular Endothelial Growth Factor), a growth factor that drives new blood vessel growth, is released by the retina to stimulate new blood vessels to grow on the retina in hopes of increasing the amount of oxygen delivered to retinal cells. This is known as proliferative diabetic retinopathy. These new vessels can easily bleed leading to bleeding into the vitreous gel that fills the eye. This is called a vitreous hemorrhage and may cause vision loss. The new blood vessels may also fibrose and pull on the retina, leading to a tractional retinal detachment and blindness. A vitreous hemorrhage or tractional retinal detachment requires vitrectomy surgery done in an operating room, which would remove the vitreous gel and any associated hemorrhage and relieve traction to reattach the retina.

VEGF also increases the permeability of blood vessels, which can lead to ‘leakage’ of fluid from capillaries causing edema or swelling of the retina at any level of retinopathy. This retinal swelling can lead to blindness if present in the central retina or macula, which is the most important region for vision. Thus, the presence of proliferative diabetic retinopathy and diabetic macular edema signify vision threatening disease that requires immediate treatment and close monitoring with frequent eye exams often every month over many months and at times over many years. Both can lead to permanent, irreversible blindness. To avoid diabetic retinopathy and related vision loss, patients must achieve tight control of both their blood glucose levels and blood pressure. Patients with proliferative diabetic retinopathy and/or diabetic macular edema should be referred to a retina specialist for management.

Proliferative diabetic retinopathy with and without macular edema can be treated with panretinal laser treatment and/or intravitreal anti-VEGF injections prior to needing vitrectomy surgery especially if discovered before vitreous hemorrhage or tractional retinal detachment occurs. These treatments are performed as outpatient office-based procedures in the US. Laser treatment for proliferative diabetic retinopathy cauterizes and destroys diseased retina to preserve healthy retina. In this way, side-effects of panretinal laser include permanent decrease in peripheral and color vision. Panretinal laser may also result in some tenderness or discomfort during or just after the procedure. Laser treatment may be given over multiple sessions until full treatment is achieved. However, once full treatment is completed, its effect is permanent and further treatments may not be needed as long as the patient has regular eye exams and good management of their diabetes.

Anti-VEGF antibodies can also be used to treat proliferative diabetic retinopathy. These anti-VEGF agents are injected through the white part of the eye called the sclera into the vitreous gel by an ophthalmologist after the eye is cleaned and anesthetized. Such a procedure is called an intravitreal injection. The patient usually feels some pressure, but often not pain when this is done. The injected medicine only last a few months in the eye and thus repeated injections and close follow-up with an ophthalmologist is often needed. Although there is a very small risk of developing a cataract, increased eye pressure, bleeding, infection, or a tear in the retina after having such an injection, there is not permanent destruction of the retina and thus not the loss of peripheral or color vision seen with panretinal laser. Intravitreal injections of anti-VEGF agents have also been shown to improve less severe levels of retinopathy than proliferative retinopathy and may be used to treat patients with such levels of diabetic eye disease in the future.

Interventions to treat and resolve diabetic macular edema include a less intense form of laser treatment called focal laser and the same intravitreal injections that are used to treat proliferative diabetic retinopathy. Such treatments often improve the edema, and in turn vision. Intravitreal injections have been shown to improve edema and vision better than focal laser if the center of the macula, called the fovea, is affected. Thus, these injections are often the first choice of treatment by ophthalmologists for these patients with focal laser reserved for those who do not improve initially with intravitreal anti-VEGF treatment. Multiple injections and frequent follow-up with the ophthalmologist over the course of months are often required. Intravitreal corticosteroid injections have also been used with some success to treat macular edema, but also are usually reserved for those who do not improve initially with anti-VEGF agents. In addition, when needed, focal laser can also be repeated in the future, but usually requires less treatment sessions than intravitreal injections

To highlight a real life example of treating diabetic retinopathy, we present a patient with proliferative diabetic retinopathy with macular edema who came to our clinic for care. He was treated with three intravitreal anti-VEGF injections as well as laser treatment in his right eye. However, his vision in his right eye worsened over time until he was only able to count fingers at two feet. His blood glucose levels had been high during this time with fasting levels in the 200’s. On exam, he was found to have a chronic vitreous hemorrhage. He underwent a vitrectomy surgery with removal of vitreous gel in the eye to clear the blood and relieve traction on the retina, He then received intravitreal anti-VEGF injections into the right eye to help prevent further bleeding and reduce the proliferative retinopathy. Over the course of monthly injections, his macular edema also reduced his vision improved to 20/100 in his right eye allowing him to read large print. Of note, he also was managing his diabetes better and his blood sugars were in the 120’s at all subsequent visits, which has helped improve his diabetic retinopathy.

In summary, current treatment options for diabetic retinopathy include tight control of glucose and blood pressure, followed by intravitreal anti-VEGF and steroid injections, focal and panretinal laser, and vitrectomy surgery. A personalized treatment plan for patients depends on disease severity including factors such as presence of macular edema, vitreous hemorrhage, vision loss, and ability to follow up to future appointments. For diabetic patients with retinopathy, consultation with a retina specialist to discuss treatment options and determine which course of treatment is best for the individual situation is encouraged. While diabetic retinopathy still remains the leading cause of blindness in the US working age population ages 20-74 years, new treatments derived from groundbreaking research can reverse retinal pathology from diabetes to ensure that permanent blindness and vision loss from diabetes is a thing of the past.

About the Authors

Dr. Rajeev S. Ramchandran

Dr.

Dr. Rajeev S. Ramchandran is Associate Professor of Ophthalmology in the University of Rochester Medical School’s Department of Ophthalmology. He is a practicing vitreoretinal surgeon and the Director of Population Eye Health at the Flaum Eye Institute. Dr. Ramchandran is part of the Diabetic Retinopathy Clinical Research Network. He also is on the board of directors of Prevent Blindness America where he serves as interim chair for the scientific committee. He uses the principles of population health surveillance research, implementation science, and program evaluation to develop, deploy, and assess strategies that promote eye and vision health. In these efforts, he actively works with a multidisciplinary team of experts in public health, primary care, photographic, imaging, and data science, as well as colleagues in industry and global health. In this way, Dr. Ramchandran seeks to prevent people from losing vision, improve sight, and end avoidable blindness at the population level in the US and abroad.

 

Ajay Kuriyan, M.D., M.S.

Ajay

Ajay Kuriyan, M.D., M.S., is an American Board of Ophthalmology Certified retinal specialist. He is a graduate of the University of Rochester School of Medicine and Dentistry and completed his ophthalmology residency and retinal fellowship of the University of Miami’s Bascom Palmer Eye Institute. Dr. Kuriyan’s clinical interests encompass the medical and surgical treatment of retinal disease. Some of these include retinal detachment surgery, drug therapy for macular degeneration and other diseases, the treatment of hereditary retinal diseases, and the treatment of diabetic eye disease.

As a researcher, Dr. Kuriyan has contributed to or authored more than 50 peer reviewed articles, textbook chapters, presentations and scientific posters. His specific research interests include the use and development of technology related to the earlier detection of retinal disease, the treatment of endophthalamitis and pediatric retinal disease. Dr. Kuriyan is a Heed Ophthalmic Fellow, a member of the American Retina Society, the American Academy of Ophthalmology, the Association for Research in Vision and Ophthalmology, and the Macula Society.

 

Suveera Dang

Suveera

Suveera Dang is a fourth-year medical student at the University of Rochester School of Medicine and Dentistry. She completed her Bachelor of Science degree in Human Development at Cornell University where she received the Urie Bronfenbrenner Award for Outstanding Performance in Research and the Henry Ricciuti Award. Prior to entering medical school, she completed her MPH at The Dartmouth Institute for Health Policy & Clinical Practice where she participated in various clinical research projects.

 

References:

1. Facts about diabetic eye disease. https://nei.nih.gov/health/diabetic/retinopathy. Accessed 7/7/18

2. PBA http://visionproblemsus.org/diabetic-retinopathy.html Accessed 7/7/18