A weekly e-newsletter to help increase awareness and support patient education about diabetic macular edema. This week’s edition features Charles C. Wykoff, MD, PhD, discussing DME treatment options. Jorge A. Fortun, MD, discussing diagnostic tests and the importance of regular eye examinations. Anne Peters, MD, discussing the risk factors for diabetes and diabetic macular edema. Allen C. Ho, MD, discussing DME compliance tips and pearls.

PART 1
COMING SOON:

Anne Peters, MD

PART 2

Jorge A. Fortun, MD

PART 3

Charles C. Wykoff, MD, PhD

PART 4

Allen C. Ho, MD

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Diabetic Macular Edema: Treatment Options

Broadly, there are three categories of diabetic macular edema (DME). The first category is noncenter-involved DME (Figure 1), which can be clinically significant or not clinically significant. It is debated how best to treat these patients. I typically either observe these patients or consider treatment with focal macular laser.

The second category is center-involved DME eyes with visual acuity loss (Figure 2). These are the eyes for which we have the most phase 3 trial data. We have four FDA-approved medications: two are anti-VEGFs and two are steroid agents. I start with an anti-VEGF intravitreal agent in the majority of these eyes. I use that agent monthly, and if I do not see a robust anatomic response, then I either switch to a different anti-VEGF agent or incorporate a intravitreal steroid agent.

The third category is center-involved DME with preserved visual acuity (Figure 3). These are your 20/25 eyes with significant center-involved DME. We do not have much data analyzing these patients in the anti-VEGF era. The Diabetic Retinopathy Clinical Research Network’s V trial is an important phase 3 trial that is comparing observation to anti-VEGF therapy to macular laser in these patients.1 But we do not have any data yet so I usually let patients’ symptoms drive me in these cases. If patients are mostly asymptomatic, I will often observe them until there is documented worsening or if they notice that their vision is blurry or distorted. If they are symptomatic with good vision, then I will often start with an anti-VEGF agent and follow that with targeted focal laser after the central macula is dry.

Another way to consider DME patients is symptomatic versus asymptomatic. I am much more likely to observe an asymptomatic patient, at least initially, so that I can determine the trajectory of disease, because many eyes with DME progressively worsen but some do not. Some patients seem to fluctuate and stabilize, and if they control their systemic risk factors they may see improvement in their DME status.

The anti-VEGF agents work exceptionally well. We are fortunate to have access to three: two are FDA-approved agents (aflibercept and ranibizumab) and one is an off-label agent (bevacizumab). Unfortunately, these agents do not work maximally in all eyes. Therefore, I think it is worth considering incorporating alternative agents such as a steroid implant to the treatment regimen relatively early in a management course to maximize anatomic and visual benefits for our patients.

1. Clinicaltrials.gov. Treatment for CI-DME in eyes with very good VA study (Protocol V). https://clinicaltrials.gov/ct2/show/NCT01909791. Updated August 25, 2016. Accessed September 19, 2016.

Diabetic Macular Edema: Tests for Diagnosing DME

The gold standard for diagnosing and monitoring diabetic macular edema (DME), in my experience, is optical coherence tomography. There is, however, still a use for angiography to monitor the profusion status of the macula. Wide-field angiography plays a role as well, although the role of peripheral nonperfusion and peripheral vasculature within DME still remain to be determined. Going forward, optical coherence tomography angiography will allow physicians to see the structure of the macular vasculature in DME and perhaps also predict the earliest microvascular changes in diabetic retinopathy.

Diabetes is a global epidemic and is increasing both worldwide and here in the United States. In the next 20 years, it is estimated that the prevalence of diabetes will increase by 55% worldwide and 35% to 40% in North America.1 There are many patients with DME who are undiagnosed. The overall prevalence of DME in the United States is estimated at 2.3 million people, but only about 1.5 million receive a medical diagnosis of the disease, which means 800,000 remain undiagnosed and untreated. Within the 1.5 million who are diagnosed with diabetes, only 400,000 patients are treated.2,3

We are missing a lot of patients with DME. If you ask diabetic patients aged 40 and older why they do not seek annual eye examinations, the most common response (nearly 40%) is that they were unaware they needed regular examinations. Less common reasons included lack of insurance or the cost of the examination.4 I believe both primary care physicians and ophthalmologists/retina specialists play an important role in reminding patients they need regular eye examinations.

Diabetes is not a homogenous disease so we cannot use clinical trials exclusively to help guide our treatment. We can adhere to the clinical trial data but not strictly, because each patient is different. We are fortunate to have many pharmacological tools as well as laser in our armamentarium. These treatments need to be applied to each patient in an individual manner.

1. Mediterranean Group for the Study of Diabetes. mgsd.org. About diabetes: epidemiology of diabetes in Mediterranean. http://www.mgsd.org/informations-2/about-diabetes/. Accessed October 5, 2016.

2. BioTrends Research Group. TreatmentTrends: Diabetic Retinopathy/Diabetic Macular Edema (US) 2013.

3. Proprietary Quantitative Market Research (n=103 retina specialists, n=23,994 DME eyes with central involvement); fielded November 2013.

4. Chou CF, Sherrod CE, Zhang X, et al. Barriers to eye care among people aged 40 years and older with diagnosed diabetes, 2006-2010. Diabetes Care. 2014;37(1):180-188.

Diabetes and DME: Common Risk Factors

The most common risk factors for type 2 diabetes include being older than 30 years of age, having a sedentary lifestyle, and having a body mass index of 25 to 29.9. In addition, having a family history of diabetes, having given birth to a baby who weighed more than 9 lbs, the presence of cardiac risk factors, including a history of hypertension and abnormal cholesterol levels, also increases a person’s risk for diabetes.1 While the risk for diabetes increases with age, younger patients who are obese and have a strong family history of diabetes are at increased risk of type 2 diabetes as well. Ethnicity can also play a role. Certain ethnic groups are at higher risk, including Native Americans, African-Americans, Latinos, Pacific Islanders, and Asians.

Anyone older than 45 years should have a screening test for diabetes, with repeat screening every 3 years. Those with risk factors, specifically those who are overweight and have a positive family history of diabetes, should be screened at a younger age. There is no standard for how young screening should begin, but in my practice, I have seen 10-year-olds with type 2 diabetes. A fasting blood test will determine your fasting blood sugar. According to the American Diabetes Association, results higher than 100 mg/dL indicate prediabetes and higher than 125 mg/dL is diabetes.2

Once a patient is diagnosed with prediabetes, it is important for he or she to increase moderate intensity physical activity (such as brisk walking) to at least 150 minutes a week and to lose weight. The weight loss does not need to be dramatic, because losing 7% of your body weight, which is about 10 to 15 pounds for most people, can decrease the risk of developing diabetes.1 Advise patients that the goal of exercise and weight loss is not about looking thin, it is about losing enough weight to improve their body's ability to use insulin and process glucose and help the body’s insulin-producing cells, the beta cells, function better. The research shows that it can be very helpful.2

If diet and exercise are not effective, a medication called metformin, which is indicated for type 2 diabetes, can halt the progression from prediabetes to diabetes.3 It is an off-label use, but many physicians are prescribing metformin to prevent the development of diabetes.3 It is really important that patients know if they have prediabetes, because it is better to prevent it than to treat it.4 Patients can utilize in-person and online Diabetes Prevention Programs offered by the CDC.

For those who have diabetes, the risk for developing diabetic retinopathy and diabetic macular edema depends on two factors: duration of diabetes and the level of glucose control. If a person has had diabetes since childhood, he or she is likely going to have some form of diabetic retinopathy by age 80 years. However, having mild retinopathy may not impact visual acuity and effective treatments are available for more serious forms of eye disease. This is why regular eye examinations are so important—it is possible to have 20/20 visual acuity but still have damage in the back of the eye. Ophthalmologists have the tools to detect and treat, if needed, the ocular complications of diabetes to help maintain vision.

1. American Diabetes Association. Diagnosing Diabetes and Learning About Prediabetes. diabetes.org. www.diabetes.org/are-you-at-risk/prediabetes/?loc=atrisk-slabnav. Last Edited June 9, 2015. Accessed October 5, 2016.

2. Knowler WC, Fowler SE, Hamman RF, et al; Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677–1686.

3. Bray GA, Edelstein SL, Crandall JP, et al; Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012;35(4):731–737

4. Overview of the Diabetes Prevention Program (DPP), National Institute of Diabetes and Digestive and Kidney Disease. niddk.nih.gov. www.niddk.nih.gov/about-niddk/research-areas/diabetes/diabetes-prevention-program-dpp/Pages/default.aspx. Accessed on September 27, 2016.

Diabetic Macular Edema: Compliance Tips and Pearl

I encourage patients with diabetes to comply with therapy by emphasizing the positive points and educating them about the negative. That is, they can lose vision unless they have regular examinations and follow the recommended protocol for disease management. I believe that showing patients their optical coherence tomography images so they can track the reduction of their diabetic macular edema helps patients to understand why treatment is important. It encourages them to be more engaged in how the therapy is affecting their potential for best vision and, therefore, helps them comply with the therapy.

Regular eye examinations are important because diabetic retinopathy is still the No. 1 cause of blindness among working-age Americans.1 Patients with diabetes mellitus may be unaware that they have vision-threatening disease, because it does not always cause pain and/or redness in the eyes. It is the responsibility of the physician to emphasize the importance of visual screenings to their patients. Family practitioners are graded on whether their diabetic patients are having regular eye screenings. Public education campaigns are very important as well. They are designed to work in conjunction with physicians to inform patients about their risk of vision loss as a complication of diabetes.

As a retina specialist, I focus on vision and the anatomy that we see with optical coherence tomography. However, to provide the best possible care for a patient with diabetic macular edema, I think it is important to step into the shoes of the patient who is experiencing vision loss. These are patients who often are being affected in a variety of ways. Perhaps their hands and feet are starting to go numb. Maybe the doctor is telling them that their kidneys are not working properly. They may not be getting regular exercise that is beneficial to control their blood sugar and blood pressure and help them have a sense of well-being.

These patients need encouragement. Encourage them to monitor their A1C levels and to walk 30 minutes a day. If they cannot walk 30 minutes a day, then tell them to start with 10 minutes a day. They should be mindful about what they are eating and drinking, because their diet affects how they feel, their blood sugar, and their vision. If they comply, they not only regain a sense of control, but they may also improve their vision.

1. Sieving PA. Sharp rise in diabetic eye disease makes american diabetes month ever more important. Nie.nih.gov. https://nei.nih.gov/news/statements/diabetesmonth2012. Accessed October 5, 2016.

Charles C. Wykoff, MD, PhD, is co-director of research at Retina Consultants of Houston and deputy chair of ophthalmology at the Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas. He is also a member of the Retina Today editorial board. Dr. Wykoff may be reached at ccwmd@houstonretina.com. He disclosed a financial relationship with Alimera, Allergan, Bayer, Clearside, Genentech, and Regeneron.

Jorge A. Fortun, MD, assistant professor of ophthalmology at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine; and cosection editor of the VBS page in Retina Today and on eyetube.net. He may be reached at jfortun@med.miami.edu. Dr. Fortun reported financial disclosure to Regeneron.

Anne Peters, MD, is a professor of medicine at the Keck School of Medicine of University of Southern California; director of the University of Southern California Westside Center for Diabetes; and director of the Comprehensive Diabetes Center at Roybal Community Medical Cente. Dr. Peters may be reached at momofmax@mac.com. Financial disclosure: consultant/advisory board/speaker for Abbott Diabetes Care, Becton Dickinson, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly and Company, Intarcia, Janssen, Lexicon, Medtronic-Minimed, Merck, Novo Nordisk, Omada Health, OptumRx, Sanofi, and United Healthcare; research support from Dexcom; editorial fees from Medscape.

Allen C. Ho, MD, is director of retina research at Wills Eye Hospital and professor of ophthalmology at Thomas Jefferson University, both in Philadelphia, Pennsylvania; and chief medical editor of Retina Today. Dr. Ho can be reached at achomd@gmail.com. Financial disclosure: consultant to Genentech and Regeneron.

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About Retina Today

Retina Today is a publication that delivers the latest research and clinical developments from areas such as medical retina, retinal surgery, vitreous, diabetes, retinal imaging, posterior segment oncology and ocular trauma. Each issue provides insight from well-respected specialists on cutting-edge therapies and surgical techniques that are currently in use and on the horizon.