We all know the typical algorithm for our patients having diabetes: Maintain healthy blood sugar and pressure control, get annual dilated eye examinations, and receive laser or anti-VEGF therapy if and when they develop vision-threatening diabetic retinopathy (DR).
We all know the typical algorithm for our patients having diabetes: Maintain healthy blood sugar and pressure control, get annual dilated eye examinations, and receive laser or anti-VEGF therapy if and when they develop vision-threatening diabetic retinopathy (DR). Although these treatments save vision, unfortunately, this “counsel, watch, and wait to treat” approach does not always result in optimal outcomes and without significant expenditure of resources.
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Evidence shows that as many as 20 percent of newly diagnosed patients with type 2 diabetes have some degree of DR already,1 and that early, tight control of blood glucose (as reflected by its three-month average, glycosylated hemoglobin or HbA1c) lowers both the incidence and progression of DR. Still, about 50 percent of patients have HbA1c levels above 7 percent,2 and while healthy metabolic control lowers the risk of diabetes complications, there are many patients who ultimately achieve good control and end up needing destructive photocoagulation or a series of injections into the eyes. This begs the question: Is there anything more we can do for our patients with diabetes?
Inspired by a 2011 paper published in IOVS (Kowluru, Beyond AREDS: is there a place for antioxidant therapy in the prevention/treatment of eye disease?),3 I became the principal investigator of a randomized, double-blinded placebo-controlled clinical trial called the Diabetes Visual Function Supplement Study (DiVFuSS) in an attempt to answer these questions. Results were recently published4 and presented at the ARVO Diabetic Retinopathy Meeting at the National Institutes of Health.
Previous work has linked diabetes and diabetic retinopathy to abnormalities of visual function (color vision,5 visual field,6 contrast sensitivity7) as well as to reduced macular pigment.8 Our goal in DiVFuSS was to see if visual function could be improved in patients with diabetes and DR while also assessing potential changes in serum lipids, markers of inflammation and mean glucose.
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Components of the test formula were selected based on previous studies showing some evidence of benefit in cell, animal and/or (limited) human models and consisted of lutein; zeaxanthin; vitamins D, C and E; alpha lipoic acid; coenzyme Q10; curcumin; fish oil; green tea and grape seed extracts, N-acetyl-cysteine; resveratrol; tocotrienols; benfotiamine; Pycnogenol (French maritime pine bark extract, Horphag Research); and low-dose zinc.
We assessed contrast sensitivity at five spatial frequencies, color vision, visual field mean deviation (5-2), macular pigment, diabetic retinopathy severity (comparative three-field fundus images), sdOCT central and subfield macular thickness, symptoms of diabetic peripheral neuropathy, and serum levels of high-sensitivity C-reactive protein (hsCRP), total cholesterol, LDL-C, HDL-C, triglycerides, as well as glycosylated hemoglobin in 67 adult subjects (27 with type 1 diabetes, and 40 with type 2 diabetes) at baseline and after six months of supplement vs. (identically appearing canola oil softgel) placebo.
No significant baseline differences were found between the placebo and supplement groups (between one-third to one-half of subjects in each group had mild to moderate non-proliferative DR (NPDR) by design, and there were no cases of macular edema). After six months, subjects receiving the supplement compared to placebo were found to have significantly better visual function on all measures, significantly higher macular pigment optical density (MPOD), significantly reduced neuropathy symptoms in those with symptoms at baseline, significantly reduced hsCRP, LDL-C and triglycerides, significantly (but modestly) increased HDL-C, and no appreciable change in A1c values (see Table 1). At unmasking, four subjects were found to have reduced DR severity on supplement (see Figure 1). There were no adverse events reported.
This is a relatively small study, and it remains to be seen if the test formula results in reduced incidence or progression of DR over time, or in patients with more advanced stages of DR and/or DME. This study does suggest, however, that clinically meaningful improvements can be achieved in visual function and biomarkers associated with diabetes and DR in patients who have no overt retinopathy as well as those with early retinopathy and, in particular, without affecting blood glucose control.
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In my view, DiVFuSS gives us another strategy for improving our patients’ vision and reducing their risk. This has great potential impact for patients with diabetes who develop DR despite good diabetes control, for those who are unable to achieve good control, and for those interested in prevention. In fact, we can do more for our patients than “counsel, watch, and wait to treat.”
Dr. Chous received funding for DiVFuSS from ZeaVision, for whom he is a consultant.
1. Owens DR, Volund A, Jones D, et al. Retinopathy in newly presenting non-insulin-dependent (type 2) diabetic patients. Diabetes Res. 1988 Oct;9:59–65.
2. Stark Casagrande S, Fradkin JE, Saydah SH, Rust KF, Cowie CC. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988−2010. Diabetes Care. 2013 Aug;36(8):2271-9. doi: 10.2337/dc12-2258.
3. Kowluru RA, Zhong Q. Beyond AREDS: is there a place for antioxidant therapy in the prevention/treatment of eye disease? Invest Ophthalmol Vis Sci. 2011 Nov; 7:52(12):8665−71.
4. Chous AP, Richer SP, Gerson JD, Kowluru RA. The Diabetes Visual Function Supplement Study (DiVFuSS). Br J Ophthalmol. 2016 Feb;100(2):227−34.
5. Utku D, Atmaca LS. Farnsworth-Munsell 100-hue test for patients with diabetes mellitus. Ann Ophthalmol. 1992 Jun;24(6):205−8.
6. Shrestha GS, Kaiti R. J Optom. Visual functions and disability in diabetic retinopathy patients. J Optom. 2014 Jan-Mar;7(1):37−43.
7. Stavrou EP, Wood JM. Letter contrast sensitivity changes in early diabetic retinopathy. Clin Exp Optom. 2003 May;86(3):152−6.
8. Scanlon G, Connell P, Ratzlaff M, Foerg B, McCartney D, Murphy A, OÊ¼Connor K, et al. Macular pigment optical density is lower in type 2 diabetes, compared with type 1 diabetes and normal controls. Retina. 2015 Sep;35(9):1808−16.