Added Benefits Seen With Early Initiation of Anti-VEGF Agents for Diabetic Retinopathy

Charles C. Wykoff, MD, PhD


May 26, 2016

In This Article

Additional Benefits of Anti-VEGF Therapy

Although the phase 3 trials leading to FDA approval of aflibercept (VISTA/VIVID[7,14]) and ranibizumab (RIDE/RISE[6,15]) for the treatment of center-involving DME causing VA loss demonstrated remarkable efficacy at improving retinal anatomy and function, they also revealed that these anti-VEGF agents can affect far more than just retinal edema.

First, anti-VEGF therapy can significantly blunt the progression from NPDR to PDR. At the 2-year primary endpoint in the RISE/RIDE study, PDR events were reduced from approximately 34% with sham treatment to 11% with monthly ranibizumab injections.[16,17] Similar slowing of DR worsening with VEGF blockade also was observed among eyes with less advanced forms of DR compared with macular laser treatment or sham.[14,16]

Second, beyond just slowing progression, anti-VEGF treatments actually improve DR severity in a substantial proportion of eyes,[14,17] a clinical finding not observed with laser therapy alone. At 2 years in the RISE/RIDE trials, 36%-37% of ranibizumab-treated eyes experienced DRSS improvement of two or more steps, compared with 5.4% of sham-treated eyes.[16] Similarly, at the 2-year point of the VISTA/VIVID study program, 29%-37% of aflibercept-treated eyes experienced DRSS improvement of two or more steps, compared with 8%-16% of sham-treated eyes.[14]

Of note, the impact of anti-VEGF treatments on DR severity appears to be most pronounced among eyes at highest risk for progression to PDR in the near future. In the RISE/RIDE study, over 75% of eyes with moderately severe and severe NPDR, corresponding to DRSS levels 47 and 53, experienced DRSS improvements of two or more steps with monthly ranibizumab through 1 to 3 years of treatment.[18]

Third, and perhaps most important, VEGF blockade appears to have a significant impact on the underlying retinal vasculature itself, slowing progressive capillary loss. In RISE/RIDE, fluorescein angiograms were read by masked graders for the presence and extent of retinal nonperfusion within the macula. Among eyes with no baseline retinal nonperfusion, the development of nonperfusion was significantly reduced at 2 years from approximately 30% with sham treatment to <10% with monthly ranibizumab treatment.[19] Similarly, sham-treated eyes demonstrated a faster rate of increasing nonperfusion compared with ranibizumab-treated eyes.[19]

Furthermore, analyses of small clinical series have suggested marked improvements in peripheral regions of retinal nonperfusion with VEGF blockade in some eyes with PDR.[20,21]


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