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MEAD study: Corticosteroid implant improves BCVA at 3 years in eyes with DME
Some phakic eyes developed cataracts and lost vision after 1 year but then continued to make gains after cataract surgery.
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A steroid-eluting implant modestly increased IOP and cataract development but improved long-term best corrected visual acuity in patients with diabetic macular edema, according to the MEAD study.
The study authors described 3-year results achieved with 0.7-mg and 0.35-mg implants of Ozurdex (dexamethasone intravitreal implant, Allergan) vs. sham treatment.
Pravin U. Dugel
“The most significant finding was that it met its primary endpoints,” Pravin U. Dugel, MD, lead investigator and OSN Retina/Vitreous Board Member, said. “I think it’s important to understand this study in the context of what we have right now. We need more than laser photocoagulation and anti-VEGF drugs to treat diabetic macular edema.”
In June, the U.S. Food and Drug Administration approved Ozurdex 0.7 mg for adults with DME who are pseudophakic or phakic and scheduled for cataract surgery.
Study results were published online ahead of print in Ophthalmology.
Study design and methods
The MEAD study comprised two multicenter phase 3 clinical trials that included 1,048 patients randomized to receive a 0.7-mg implant (351 patients), a 0.35-mg implant (347 patients) or sham treatment (350 patients).
The mean duration of DME before the study was 24.9 months.
The primary efficacy endpoint was a gain of at least 15 letters of best corrected visual acuity from baseline. Central retinal thickness, IOP and adverse events were also evaluated.
The mean number of treatments was 4.1 with the 0.7-mg implant, 4.4 with the 0.35-mg implant and 3.3 with sham treatment. Patients were followed for 3 years.
Visual acuity and cataract
BCVA improved 15 letters or more in 22.2% of patients with the 0.7-mg implant, 18.4% of patients with the 0.35-mg implant and 12% of patients with sham treatment (P ≤ .018).
Patients in both dexamethasone groups gained 15 letters significantly earlier than those in the sham treatment group (P < .001 and P =.005, respectively).
Mean average change in BCVA was 3.5 letters with the 0.7-mg implant, 3.6 letters with the 0.35-mg implant and 2 letters with sham treatment. Average change was significantly greater in the 0.7-mg group (P = .023) and 0.35-mg group (P = .019) than in the sham treatment group.
Rates of cataract-related adverse events in phakic eyes were 67.9% in the 0.7-mg group, 64.1% in the 0.35-mg group and 20.4% in the sham treatment group.
Some phakic eyes lost vision after 1 year because of cataract development or progression, but visual improvement was restored after cataract surgery. At 3 years, dexamethasone yielded significant improvement in BCVA, regardless of lens status at baseline.
“Cataract formation confounded the visual acuity measurement and caused the decline in vision,” Dugel said. “But the fact that there is a dramatic improvement in the end also tells me, as has been in my clinical experience, that if cataract surgery is required, it’s probably a lot better to have the device onboard because these patients do exceptionally well.”
Anatomic outcomes, adverse events
The mean average reduction in central retinal thickness from baseline was 111.6 µm in the 0.7-mg group, 107.9 µm in the 0.35-mg group and 41.9 µm in the sham group; the reduction was significantly greater in both implant groups than in the sham group (P < .001).
Central retinal thickness increased after cataract surgery in the sham treatment group but not in the dexamethasone groups. This suggested that dexamethasone may have a protective effect after cataract surgery, according to the study authors.
IOP increased by at least 10 mm Hg in 27.7% of patients in the 0.7-mg group, 24.8% of patients in the 0.35-mg group and 3.7% of patients in the sham treatment group. Two patients in the 0.7-mg group and one patient in the 0.35-mg group required trabeculectomy.
“There were very few people, about 0.1%, that actually required incisional surgery. Most of them had increased intraocular pressure that was quite well and easily and predictably managed,” Dugel said.
Vitreous hemorrhage was identified in 6.9% of eyes in the 0.7-mg group, 13.1% of eyes in the 0.35-mg group and 7.1% of patients in the sham group; no cases of vitreous hemorrhage required vitrectomy and most resolved quickly. – by Matt Hasson
Reference:
Boyer DS, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.04.024.
For more information:
Pravin U. Dugel, MD, can be reached at Retinal Consultants of Arizona, 1101 E. Missouri Ave., Phoenix, AZ 85014; 602-222-2221; email: pdugel@gmail.com.
Disclosure: Dugel is a consultant for Allergan.
Perspective
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Carl D. Regillo, MD, FACS
For nearly 14 years, we have known that intraocular steroids can reduce excessive macular thickness and improve visual acuity in eyes with center-involving DME. In practice, there has been off-label use of triamcinolone injected intravitreally for DME, and the risks and benefits of this type of steroid administration have been studied in large-scale, comparative clinical trials.
The MEAD study published by Boyer et al is a phase 3 sham-controlled clinical trial that tested the commercially available 0.7 mg dexamethasone slow-release intravitreal implant to treat center-involving DME and showed a good efficacy and safety profile with an average of approximately four intravitreal administrations over the course of the 3-year study. Rates of elevated IOP and cataract formation were comparable to prior experience with this or other steroid products.
Visual acuity improvement rates were good early on but later were compromised by cataract development. In pseudophakic eyes, the visual acuity gains remained good over the length of the study. By design, re-administration of the dexamethasone implant was restricted to every 6 or more months as needed. In practice, it is known from experience with retinal vein occlusion-related macular edema treatment that the device may not have its full effect for an entire 6-month time frame. Therefore, as in the RVO setting, more frequent administration may be needed with this device in a given patient for optimal control of DME.
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