DRCR defines treatments, continues to grow, evolve

The NEI-funded network has greatly contributed to the understanding of diabetic eye disease, clinicians say.

Issue: December 2016

The Diabetic Retinopathy Clinical Research network was funded by the National Eye Institute in 2002 to facilitate multicenter clinical research of diabetic eye disease. More than 350 physicians participate at more than 140 clinical sites across the U.S.

“Optometrists are frequently the first eye doctors to see patients with diabetes and diabetic retinopathy,” Frederick L. Ferris III, MD, clinical director, National Eye Institute (NEI), and an active member of the network, told Primary Care Optometry News. “Screening for early signs of diabetic eye disease is crucial to preventing vision loss. It’s also very important to help patients understand the latest treatment options, many of which are new.”

In just 14 years, the network has completed more than 25 major studies, with five or six currently active, according to Lee M. Jampol, MD, network chair and Louis Feinberg Professor of Ophthalmology at Northwestern University Feinberg School of Medicine in Chicago. Carl W. Baker, MD, in a review from Current Opinion in Ophthalmology, wrote: “It has transformed the way we can perform clinical trials. The strength of the DRCR.net lies in its multicenter nature and the ability to recruit large numbers of patients across the country with a rigor that is required in clinical trials.”

Published findings

Michael Singer, MD, a network site investigator, said some of the most important protocols to come out of the network in the last 8 years are protocol B, protocol I and protocol T.

Protocol B compared the use of macular laser versus intravitreal triamcinolone for treating diabetic macular edema.

“It showed that although steroids initially increased vision, laser was better over time, with fewer side effects,” Singer told PCON.

Protocol I was the first large study to show that ranibizumab improved vision in patients with diabetic macular edema, and that deferring laser had a better response than prompt laser, according to Singer.

The results also showed that, in pseudophakic patients, triamcinolone was equivalent to ranibizumab for the treatment of diabetic macular edema (DME), he said.

In protocol T, the network compared the three anti-VEGFs – Lucentis (ranibizumab, Genentech), Eylea (aflibercept, Regeneron) and Avastin (bevacizumab, Genentech) – to treat diabetic macular edema.

Researchers separated 660 eyes into three groups, with each group receiving a separate anti-VEGF, for 2 years, Jampol explained. They included the ability to undergo focal laser after 6 months.

“There’s no way one drug company would have done a head-to-head of all three treatments,” he said.

The primary outcome showed that at 1 year, with visual acuity (VA) at or better than 20/50, all drugs performed similarly. If VA was 20/50 or worse, Eylea performed better than Lucentis and Avastin.

In the second year, they found, in terms of visual acuity, that the difference between Eylea and Lucentis was not significant, Singer said, but the difference between Eylea and Avastin was still significant.

The Diabetic Retinopathy Clinical Research (DRCR) network has been at the forefront of diabetic eye research, from focal laser treatment to anti-VEGFs. DRCR data and research is crucial for modern diabetic eye disease treatment and management, Singer said.

“The DRCR has helped prove the benefit of different treatment modalities in the care of diabetic patients,” he added.

Just a few years ago, appropriate treatment for DME was lacking; the only treatment available was panretinal photocoagulation, and now there are many options for treatment, Jampol said. The advances in treatment were made possible because of DRCR’s scope.

He hopes the network can lead to an increase in awareness for diabetic conditions of the eye.

“This is the leading cause of vision loss in working-age people,” he said. “It’s an epidemic because of the obesity problem and is present in every area of the world; it’s not just a problem in the U.S.”

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Future research

“There are several studies that I think are going to further our understanding of how best to treat patients,” Ferris said.

One of the future protocols that Jampol and his researchers are exploring is evaluating whether prompt vitrectomy is as useful as intravitreal anti-VEGF medication for vitreous hemorrhages.

He is excited to study whether eyes with good vision that have thickening of the macula should be treated at all or observed.

This is important for more than two-thirds of DME patients who still have good visual acuity, according to Ferris.

“Many patients with DME can spontaneously resolve, so you want to make sure that whoever you’re treating is going to get worse,” he said.

They are also studying new imaging and following diabetic eye changes with OCT angiography and widefield photography with fluorescence angiography. This will aid in evaluating the lesions outside of the area that has traditionally been observed, to assess the far peripheral retina, Ferris explained.

“This study demonstrates the importance of lesions outside the standard frame to see who is going to progress and who is not,” he said.

Another novel study will determine if it is possible to prevent progression, Jampol said.

“We are constantly evaluating new studies that we ought to be undertaking, one of which is the assessment of treatment with fenofibrate,” Ferris added.

A few months ago, the National Advisory Eye Council approved the network to expand into other retinal diseases.

“Potentially, we will have new studies looking at age-related macular degeneration and other retinal disease further down the road,” Ferris added.

Expanding the research footprint into AMD would be useful to optometrists.

The network is “a fantastic example of public-private collaboration,” PCON Editorial Board member Richard L. Lindstrom, MD, said recently in Ocular Surgery News. – by Abigail Sutton

References:
Baker CW, et al. Curr Opin Ophthalmol. May 2016;doi:10.97/ICU.0000000000000262.
Jampol, LM et al. JAMA. June 2011;doi:10.1001/jama.2014.2536.
Lindstrom RL. DRCR.net has great impact on understanding, treatment of diabetes-related eye disease. Ocular Surgery News. Aug. 10, 2016. http://www.healio.com/ophthalmology/retina-vitreous/news/print/ocular-surgery-news/%7B6cf9a6b9-cdd9-4c0a-9c8d-31120f06765d%7D/drcrnet-has-great-impact-on-understanding-treatment-of-diabetes-related-eye-disease.
Wells JA, et al. N Eng J Med. March 2015;doi:10.1056/NEJMoa141264.

For more information:
Frederick L. Ferris III, MD, clinical director of the NEI, is actively involved in the DRCR and in AREDS2 and has authored more than 200 research articles in peer-reviewed journals. Ferris can be reached at balintfyj@nei.nih.gov (via Joe Balintfy).
Lee M. Jampol, MD, is network chair of the DRCR and Louis Feinberg Professor of Ophthalmology at Northwestern University Feinberg School of Medicine, Chicago. Jampol can be reached at: (312) 908-8152 (via Stephanie Espino).
Michael Singer, MD, DRCR network site investigator, can be reached at msinger11@me.com.

Disclosures: Ferris reported no relevant disclosures. Jampol consults for Janssen on a study of a potential treatment for macular degeneration. Singer is a consultant, speaker and researcher for Genentech, Allergan, Regeneron and Optos.