Ophthalmology has a long history of performing large-scale clinical trials to guide our management of eye diseases — one of many reasons to take pride in your chosen field. The older landmark trials provide the framework for newer studies. Being familiar with both lets you speak the same language as your attendings and build your patient care around a core of evidence-based medicine.
The Diabetic Retinopathy Clinical Research Network (DRCR.net) is a broad research effort across multiple centers. Funded by the National Eye Institute, the DRCR.net develops a series of clinical trials to answer specific questions about diabetic retinopathy.
Two of these trials have risen to prominence in the last year or so. Familiarizing yourself with them will give you a head start with your patients and attendings.
Injections vs. laser treatment
The DRCR.net Protocol S results published in November 2015 compared intravitreal anti–vascular endothelial growth factor (anti-VEGF) injections to the long-time standard of care, panretinal photocoagulation (PRP) laser. Specifically, the study looked at whether monthly ranibizumab (Lucentis) injections could treat proliferative diabetic retinopathy (PDR) as effectively as PRP.
Laser is generally quite effective at causing neovascularization in PDR to regress, but it damages the peripheral retina and can cause peripheral visual field loss. Anti-VEGF agents have also been observed to regress neovascularization, but we didn’t know how long that effect lasted.
The randomized trial compared the eyes of patients who received either PRP at the outset or monthly ranibizumab. Both arms followed a well-defined protocol that allowed for secondary ranibizumab or vitrectomy surgery if needed.
At two years, the ranibizumab group had more visual acuity gain (2.8 vs. 0.2 letters), less visual-field loss, less need for vitrectomy and less diabetic macular edema (DME). The bottom line was that monthly ranibizumab was noninferior to PRP laser for PDR at two years.
Of course the caveat — and one to keep in mind with the typical resident clinic — is that monthly injections present a treatment burden and require a good deal of patient compliance. Both options — injections and laser — remain important tools in treating PDR.
The best anti-VEGF regimen for DME?
The next study, DRCR.net Protocol T, released one-year results in March 2015 and two-year results in June 2016. This protocol compared three anti-VEGF agents in the treatment of DME: aflibercept (Eylea), ranibizumab and bevacizumab (Avastin). DME is the most common cause of vision loss in diabetic retinopathy. Ophthalmologists already use all three agents to treat DME. This study compared the three medicines when used first monthly and then according to a specific algorithm.
The year 1 data showed that, across all eyes, there was no statistical difference between the medicines. However, in eyes that were 20/50 or worse, aflibercept was slightly better at improving vision.
The year 2 data, interestingly, detailed that, in worse-seeing eyes, aflibercept remained statistically better than bevacizumab, but no difference emerged when either was compared to ranibizumab. All three drugs improved vision from baseline, and the patients required fewer injections in year 2 than in year 1.
If we’re to draw one conclusion from this trial, it would be that all three anti-VEGF agents work well for DME but should be used consistently and might be needed for more than a year.
These studies have many more facets to them than mentioned here, and aspects of big clinical trials can be quite complex, but it’s never too early to start diving into the literature. Start dropping DRCR.net data right away and impress those retina attendings!
* * *
About the author: D. Wilkin Parke III, MD, is a vitreoretinal specialist with VitreoRetinal Surgery, PA in Minneapolis and has been a member of YO Info’s editorial board since 2015.