Which DRCR Retina Network protocol has affected the way you practice the most?
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Protocol T
The protocol that has affected the way I practice the most is Protocol T. Protocol T was a three-arm, head-to-head study comparing the efficacy of aflibercept, ranibizumab and bevacizumab for center-involving diabetic macular edema (CI-DME) and decreased best corrected visual acuity, with these anti-VEGF drugs delivered in an individualized as-needed fashion over a 2-year time frame. This was the first study that showed any clinically meaningful differences in efficacy between the available anti-VEGF drugs for any indication, and to date, such significant differences have only been demonstrated for DME.
Specifically, the Protocol T results indicated that for eyes with CI-DME that have moderate or greater degrees of decreased vision (BCVA Snellen equivalent of 20/50 or worse), aflibercept had better gains in mean BCVA and reduction in central subfield thickness by OCT at both 1 and 2 years of follow-up relative to the others, particularly bevacizumab, which was the least effective in terms of functional and anatomic outcomes. For milder degrees of DME with baseline BCVA better than 20/50, all three drugs performed comparably. As a result, there has since been a shift toward more aflibercept use for DME in practice, particularly for more severe cases.
The study also showed that these anti-VEGF drugs used in an as-needed fashion for DME yield good maintenance of visual gains with less treatment, on average, over time. This reinforces what was first demonstrated in the older Protocol I. Therefore, I favor this treatment approach in practice.
Lastly, Protocol T showed that the desired anatomic endpoint of DME resolution ultimately can be achieved in about three-quarters of eyes with the more effective on-label drugs (aflibercept and ranibizumab), although it may take frequent injections over 1 to 2 years to reach this goal. This raised the question related to the time sensitivity of DME treatment and, specifically, whether or not starting with a less effective anti-VEGF agent, such as bevacizumab, and then switching to a more effective one, such as aflibercept, at some point later in the course of therapy eventually yields visual results that are as good as starting with the latter. The good news is that this is currently being addressed in the Protocol AC study, and so the answer to this clinically important question in DME management is forthcoming.
Carl D. Regillo, MD, an OSN Retina/Vitreous Board Member, is the director of the Wills Eye Hospital Retina Service, professor of ophthalmology at Thomas Jefferson University and in practice at Mid-Atlantic Retina.
Protocols I, S, V
Thirty years ago, I treated diabetic macular edema with focal macular laser photocoagulation (MLP), and I treated proliferative diabetic retinopathy (PDR) with panretinal photocoagulation (PRP). I used to offer PRP to select patients with severe nonproliferative diabetic retinopathy (NPDR). The DRCR.net trial results have led me to change the way I practice.
Protocol I demonstrated that intravitreal anti-VEGF therapy (ranibizumab) was superior to MLP and intravitreal steroid (triamcinolone) therapy for DME. Now, I rarely treat DME with laser photocoagulation. Additional analyses demonstrated that anti-VEGF therapy induced regression of diabetic retinopathy as judged by the ETDRS Diabetic Retinopathy Severity Scale, a result that has been confirmed prospectively in several trials. I offer anti-VEGF therapy to patients with severe NPDR even if they do not have DME.
I used to offer PRP and MLP to patients with PDR and DME. Protocol S demonstrated that the best first treatment for most patients with PDR and 1) neovascularization that is not extensive, 2) a flat retina and 3) DME is anti-VEGF therapy and not PRP. Now, I offer anti-VEGF injections as initial therapy for such patients in lieu of PRP and MLP.
I used to obtain fluorescein angiography (FA) to help guide MLP for patients with DME involving the fovea and good vision. Protocol V demonstrated that one can defer treatment of patients with center-involving DME and good vision (20/20 to 20/25) and offer anti-VEGF therapy (aflibercept) once vision worsens without compromising visual outcome 2 years later. Now, even without FA, I can defer treatment for such patients with confidence, provided that they can follow up reliably.
Marco A. Zarbin, MD, PhD, FACS, is a professor and chair of the Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School.
- References:
- Baker CW, et al. JAMA. 2019;doi:10.1001/jama.2019.5790.
- Elman MJ, et al. Ophthalmology. 2010;doi:10.1016/j.ophtha.2010.02.031.
- Gross JG, et al. JAMA. 2015;doi:10.1001/jama.2015.15217.
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