Corticosteroid implant for DME shows consistent, positive outcomes in real-life studies

Unlike with anti-VEGFs, real-life outcomes with Ozurdex are comparable to those of pivotal trials.

Issue: January 2017

Real-life studies in large cohorts of patients with diabetic macular edema showed highly encouraging results with the Ozurdex dexamethasone intravitreal implant.

“The real-life outcomes were comparable if not superior to those of pivotal trials, which is very reassuring for us clinicians,” Laurent Kodjikian, MD, PhD, said in an interview with Ocular Surgery News.

The disconnect between clinical trials and real-life outcomes is a major issue with anti-VEGF treatments, mainly due to noncompliance with the tight schedule of monitoring and injections that is mandatory to achieve best outcomes. While trials showed that at least eight injections are required in the first year, large real-life studies such as LUMINOUS showed that the average number is four to five, leading to a gain of about four letters. In an analysis published in OSLI Retina, Dugel and co-authors showed that 68% of patients stop anti-VEGF treatment at the end of the first year and 45% stop at 3 months.

“Anti-VEGFs are indeed effective but obviously need compliance — otherwise, results are not good. The advantage with Ozurdex is that we need fewer injections and fewer follow-up visits. It’s much less burden for the patients, caregivers and doctors, too, less financial burden for the health care system, and results are good,” Kodjikian said.

Good outcomes

Kodjikian published his large experience with more than 1,000 Ozurdex (Allergan) injections in two studies. The first study, RELDEX, was published in Retina and was the largest real-life study on Ozurdex in DME, retrospectively reviewing 128 eyes of 89 patients followed over a period of 3 years.

“A progressive improvement in mean BCVA, up to 9.5 letters at 3 years, was observed, together with reduction of the edema. This was achieved with a mean number of 3.7 injections. With time, the mean number of injections per year decreased and the intervals between re-treatments increased,” Kodjikian said.

The second study, SAFODEX, also published in Retina, focused on safety, particularly with regard to IOP elevation. It included 421 consecutive eyes of 361 patients treated with one or more Ozurdex implants between 2010 and 2015.

“We were able to demonstrate that the risk of hypertension is small. IOP increased in 28.5% of the eyes and in 97% of them was easily managed with topical medications. Only 11% of the DME eyes had IOP more than 25 mm Hg,” Kodjikian said.

Cataract concerns

Cataract commonly occurs as an effect of corticosteroid treatment, in most cases after three injections of Ozurdex. For this reason, Kodjikian recommends using anti-VEGFs in younger patients with a clear lens, while patients around the age of 60 to 65 years, who are the majority of DME patients, are good candidates for Ozurdex, and also because diabetes itself increases the risk of cataract, which develops more frequently and at an earlier age in these patients.

The RELDEX study also demonstrated that by injecting Ozurdex 1 month before cataract surgery, there is no postoperative decrease in visual acuity. In the MEAD study, the pivotal study on Ozurdex, cataract surgery was found to be a risk for vision loss in DME patients.

“The MEAD study protocol established that Ozurdex should be injected at 6-month intervals, and cataract surgery was consequently performed in many cases when the drug was no longer effective in the eye. In our study we could choose when to inject Ozurdex and when to schedule cataract surgery, and so the high majority of my patients were injected 1 month before cataract surgery. The protective effect of the corticosteroid made the eyes develop less postoperative inflammation and for the following 3 months prevented the increase of the macular edema. Increased macular edema was the cause of decreased VA in the MEAD study during the first 6 to 9 months after cataract surgery,” Kodjikian said.

In real life, the 6-month interval in between injections was shown to be too long for sustained efficacy of the drug.

“Ozurdex is effective for 4 to 5 months, and then you have to reinject. However, from my experience I have the impression that over time fewer and fewer injections might be needed, something we’ll need to prove in future studies,” Kodjikian said. – by Michela Cimberle

References:
Dugel PU, et al. Ophthalmic Surg Lasers Imaging Retina. 2016;doi:10.3928/23258160-20160229-09.
Malclès A, et al. Retina. 2016;doi:10.1097/IAE.0000000000001234.
Malclès A, et al. Retina. 2016;doi:10.1097/IAE.0000000000001369.

For more information:
Laurent Kodjikian, MD, PhD, is a professor of ophthalmology and chair of the University of Lyon and associate chair of the Department of Ophthalmology, Croix-Rousse Teaching Hospital, Lyon, France. He can be reached at email: kodjikian@gmail.com.

Disclosure: Kodjikian reports he is a consultant to Allergan, Alcon, Bayer, Novartis and Théa.