Recent Evaluations of Combination Therapy
Studies suggest that combining anti-VEGF and sustained-release steroid therapy may be beneficial in treating retinal vascular disease.
BY DESIREE IFFT, CONTRIBUTING EDITOR
The results of two recent prospective studies1,2 support the idea that combining anti-VEGF and sustained-release steroid therapy can be beneficial for patients with retinal vascular disease.
According to Michael A. Singer, MD, “In our study,1 we looked at the effectiveness of the combination of Avastin and Ozurdex in patients with retinal vein occlusion, primarily in terms of duration. We wanted to see whether the combination could add predictability to the equation, which it did.” The therapeutic effect of combination therapy, i.e., an edema-free macula on OCT, lasted for an average of 4 months in the study patients.The study also demonstrated the anatomic benefits of combined therapy. For example, at the second study visit, 38% of the patients treated with Avastin had central field thickness less than 300 µm. When Ozurdex was added, the percentage increased to 68%. “We expect these types of results to translate to patients with DME as well,” Dr. Singer says. “A number of studies are looking at this now, including REINFORCE.”
In another recent study,2 Raj Maturi, MD, and colleagues examined whether it’s beneficial to add Ozurdex to the treatment regimen of patients whose DME had been only partially responsive to multiple Avastin injections. Patients in the study were randomized to receive Avastin plus Ozurdex or Avastin monotherapy. Monotherapy eyes received Avastin monthly if indicated. Combination therapy eyes received monthly Avastin if indicated plus Ozurdex at month 1, month 5 and month 9. An Avastin injection was indicated at every monthly visit if central subfield thickness (CST) on OCT was greater than 250 µm and visual acuity was worse than 20/25.
At 12 months, visual acuity gains were similar in both groups, but improvement in CST and retinal volume were superior in the combination therapy group. The combination therapy group received three fewer supplemental Avastin injections than the monotherapy group, but also required an average of 2.1 Ozurdex implants, somewhat of a counterbalance from a treatment burden standpoint. “Interestingly, it appears that once a patient receives multiple anti-VEGF injections, additional anti-VEGF injections don’t bring about any further reduction in edema,” Dr. Maturi says (Figure 1). “On the other hand, edema decreased markedly in the group that also received Ozurdex, leaving us to wonder if perhaps the best course might be to use sustained-release steroids alone in patients who are only partially responsive to a trial of anti-VEGF therapy.”
![](https://res.cloudinary.com/broadcastmed/image/fetch/q_auto,f_auto/dpr_auto/https://retinalphysician.com/media/j3vorxko/rp_may_s2_1401.jpg)
Figure 1. In Maturi et al., continued repeated Avastin injections did not provide a visual benefit in the Avastin alone group of DME patients. However, patients in the combination therapy group who had received the most Avastin injections prior to study enrollment gained the most vision with the addition of Ozurdex.
The study also demonstrated that the therapeutic effects of Ozurdex in the DME patient population last approximately 3 months. Based on that finding and others from this study, Dr. Maturi is conducting an additional study involving patients with anti-VEGF-resistant DME in which Ozurdex will be given every 3 months while supplemental Avastin is discontinued. He expects to have results from the follow-up study by summer 2015. ■
References
1. Singer MA, Bell DJ, Woods P, et al. Effect of combination therapy with bevacizumab and dexamethasone intravitreal implant in patients with retinal vein occlusion. Retina. 2012;32(7):1289-1294.
2. Maturi RK, Bleau L, Saunders J, et al. A 12-month, single-masked, randomized controlled study of eyes with persistent diabetic macular edema after multiple anti-VEGF injections to assess the efficacy of the dexamethasone-delayed delivery system as an adjunct to bevacizumab compared with continued bevacizumab monotherapy. Retina. E-pub ahead of print: March 30, 2015. doi: 10.1097/IAE.0000000000000533.