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44 R E T I N A L P H Y S I C I A N | J A N U A R Y / F E B R U A R Y 2 0 1 7 Diabetic Retinopathy: Halting and Reversing Progression The second of three parts STEPHEN J. SMITH, MD • MARGARET A. GREVEN, MD • PRITHVI MRUTHYUNJAYA, MD, MH H alting and reversing diabetic retinopathy plays an important role in vision preserva- tion in our patients with diabetes. Part 1 of this series focused on systemic disease con- trol, laser photocoagulation, and surgical and pharmacologic vitreolysis in the treatment of DR. Part 2 of this series will look at the evidence presented over the last decade, showing the markedly positive effects of intravit- real anti-VEGF and steroids on DR progression. As mentioned in part 1 of this three-part series, various methods to assess DR progression and treatment response have been utilized in major clinical trials. A number of the methods utilized in several key anti-VEGF and steroid treatment trials are summarized in the Table. It is worth noting that some measures focus on the structural assessment of progression, including the DR severity score (DRSS), while others consider the sever- ity of DR (nonproliferative DR [NPDR] vs proliferative DR [PDR]), and still others assess indirect measures that may be surrogates for DR progression, including changes in best-corrected visual acuity and structural changes, as assessed by optical coherence tomography. Framing the results of these studies in light of the met- rics presented can help clinicians to interpret the value of DR progression as a treatment outcome. Determining the clinical value of changes in DRSS will be the focus of part 3 of this series. ANTI-VEGF THERAPY e introduction of intravitreal anti-VEGF therapy has been perhaps the single greatest therapeutic advancement in medical retina in the last 50 years. Several multicenter, randomized, controlled trials have conclusively demon- strated the superiority of anti-VEGF injections for diabetic macular edema, compared to sham, laser, and intravitreal triamcinolone acetonide injections. Ranibizumab RIDE and RISE were pivotal studies investigating the role of ranibizumab (Lucentis, Genentech, South San Francisco, CA) for DME. 1 A secondary analysis of these studies was DR progression utilizing the DRSS. Ip and colleagues 9 reported that a ≥3-step DR improvement in patients with NPDR or PDR was achieved at 36 months in 15.0% and 13.2% of patients receiving 0.3 mg or 0.5 mg of ranibizumab monthly, respectively. In contrast, only 3.3% of patients in the sham/0.5-mg ranibizumab cross- over group achieved the same degree of DR improvement. e cumulative probability of DR progression to PDR by month 36 was 39.1% of eyes in the sham/crossover group vs 18.3% and 17.1% of eyes treated with 0.3 mg or 0.5 mg of ranibizumab monthly, respectively. After switching to monthly ranibizumab, the patients in the sham group had an attenuated rate of PDR development more comparable to the arms receiving intensive anti-VEGF. To further explore the possibility of an extended treatment benefit following initial intensive anti-VEGF therapy, the open-label extension of RIDE and RISE enrolled 500 patients who had previously completed the 36-month randomized core studies. For these patients, retreatment with 0.5 mg of ranibizumab was offered Stephen J. Smith, MD, Margaret A. Greven, MD, and Prithvi Mruthyun- jaya, MD, MHS, serve on the faculty of the Byers Eye Institute of the Stanford University School of Medicine in Palo Alto, CA. None of the authors reports any financial interests in products mentioned here. Dr. Mruthyunjaya can be reached via e-mail at firstname.lastname@example.org.