With diabetes, we tend to concentrate on the stabilization of the disease as a whole. This is a good thing. However, there is not enough attention spent on microvascular (small vessel disease) complications of diabetes, specifically diabetic retinopathy, which is an umbrella term. There are at least three different disorders that make up diabetic retinopathy. These are dot and blot hemorrhages, proliferative diabetic retinopathy and diabetic macular edema. The latter two are the most likely disorders to cause vision loss. Our focus for this article will be on diabetic retinopathy as a whole and diabetic macular edema.
Diabetic retinopathy is the No. 1 cause of vision loss in those who are of working age, 25 to 74 years old (1). Risk factors include duration of diabetes, not well-controlled glucose (sugars), type 1 more than type 2, smoking, high blood pressure, kidney disease, pregnancy and high cholesterol (2).
What is diabetic macula edema, also referred to as DME? This disorder is edema, or swelling, due to extracellular fluid accumulating in the macula (3). The macula is a yellowish oval spot in the central portion of the retina — in the inner segment of the back of the eye — and it is sensitive to light. The macula is the region with greatest visual acuity. Hence, when fluid builds up, there is potential loss of vision.
Whew! Did you get all that? If not, to summarize: diabetic macula edema is fluid in the back of the eye that may cause vision loss. DME affects approximately 1 in 25 patients with diabetes according to a recent study (4). However, the results also showed that this number is significantly greater (2.6 times) in blacks compared to non-Hispanic whites. And the highest risk factor for DME was for those with the longest duration of diabetes. Ironically, an oral class of drugs, thiazolidinediones, which includes rosiglitazone (Avandia) and pioglitazone (Actos), used to treat type 2 diabetes may actually increase the risk of DME. However, the results on this are conflicting.
DME is traditionally treated with lasers. But intravitreal (intraocular — within the eye) injections of a medication known as ranibizumab (Lucentis) may be a route that is as effective as laser. Studies suggest that injections alone may be as effective as injections plus laser treatments, though the studies are in no way definitive. Unfortunately, many patients are diagnosed with DME after it has already caused vision loss. If not treated after having DME for a year or more, patients can experience permanent loss of vision (5).
In a cross-sectional study (a type of observational study) using NHANES data from 2005-08, among patients with DME, only 45 percent were told by a physician that the diabetes had affected their eyes (6). Approximately 46 percent of patients reported that they had not been to a diabetic nurse educator, nutritionist or dietician in more than a year — or never. The problem is that the symptoms of vision loss don’t necessarily occur until the latter stages of the disorder. According to the authors, there needs to be an awareness campaign about the importance of getting your eyes examined on an annual basis if you have diabetes. Many patients are unaware of the association between vision loss and diabetes.
According to a study, there is good news in that the percentage of patients reporting visual impairment from 1997 to 2010 decreased (7). However, the absolute number of patients with vision loss has actually continued to grow, but at a lesser rate than diabetes as a disease has grown.
Treatment laser and injection
There seems to be a potential paradigm shift in the making for the treatment of DME. Traditionally, patients had been treated with lasers. The results from a recent randomized controlled trial, the gold standard of studies, showed that intravitreal (delivery directly into the eye) injections with ranibizumab (Lucentis), whether given prompt laser treatments or treatments delayed for at least 24 weeks were equally effective in treating DME (8).
In fact, some in the delayed group, 56 patients or about half, never even required laser treatments at all. Unfortunately, intravitreal injections may be used as frequently as every four weeks. Though in practice, ophthalmologists generally are able to inject patients with the drug less frequently. However, the advantage of receiving prompt laser treatments along with the injections was a reduction in the median number of injections by four over a five-year period.
Increased risk with diabetes drugs
You would think that drugs to treat type 2 diabetes would prevent DME from occurring as well. However, in the THIN trial, a retrospective (backward-looking) study, a class of diabetes drugs, thiazolidinediones, including Avandia and Actos, actually increased the occurrence of DME compared to those who did not use these oral medications (9). Those receiving these drugs had a 1.3 percent incidence of DME at year one, whereas those who did not had a 0.2 percent incidence. This incidence was persistent through the 10 years of follow-up. To make matters worse, those who received both thiazolidinediones and insulin had an even greater incidence of DME. There were 103,000 diabetes patients reviewed in this trial. It was unclear whether the drugs, because they were second line treatments, or the severity of the diabetes itself may have caused these findings.
This is in contrast to a previous
ACCORD eye substudy, a cross-sectional analysis, which did not show an association between thiazolidinediones and DME (10). This study involved review of 3,473 participants who had photographs taken of the fundus (the back of the eye).
What does this ultimately mean? Both of these studies were not without weaknesses. It was not clear how long the patients had been using the thiazolidinediones in either study or whether their sugars were controlled and to what degree. The researchers were also unable to control for all other possible confounding factors (11). Thus, there needs to be a prospective trial done to sort out these results.
The risk of progression of diabetic retinopathy was significantly lower with intensive blood sugar controls using medications, one of the few highlights of the ACCORD trial (12). Medication-induced intensive blood sugar control also resulted in more increased mortality and no significant change in cardiovascular events. But an inference can be made: a nutrient-dense, plant-based diet that intensively controls blood sugar is likely to decrease the risk of diabetic retinopathy complications (13) (14).
The best way to avoid diabetic retinopathy is obviously to prevent diabetes. Barring that, it’s to have sugars well controlled. If you or someone you know has diabetes, it is imperative that they get a yearly eye exam from an ophthalmologist so that DME and diabetic retinopathy, in general, is detected as early as possible, before permanent vision loss can occur. It is especially important for those diabetes patients who are taking the oral diabetes class thiazolidinediones, which include rosiglitazone (Avandia) and pioglitazone (Actos).
(1) Diabetes Care. 2014;37 (Supplement 1):S14-S80. (2) JAMA. 2010;304:649-656. (3) www.uptodate.com. (4) JAMA Ophthalmol online. 2014 Aug. 14. (5) www.aao.org/ppp. (6) JAMA Ophthalmol. 2014;132:168-173. (7) Morb Mortal Wkly Rep. 2011;60:1549-1553. (8) ASRS. Presented 2014 Aug. 11. (9) Arch Intern Med. 2012;172:1005-1011. (10) Arch Ophthalmol. 2010 March;128:312-318. (11) Arch Intern Med. 2012;172:1011-1013. (12) www.nei.nih.gov. (13) OJPM. 2012;2:364-371. (14) Am J Clin Nutr. 2009;89:1588S-1596S.
Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to medicalcompassmd.com.