Intravitreal implant with laser outperforms laser alone in diffuse DME

Combination treatment improved visual acuity, but IOP spikes and worsening cataracts underscored a need for further study, speaker says.

A dexamethasone intravitreal implant combined with laser photocoagulation yielded better visual results than laser monotherapy in treating diffuse diabetic macular edema, according to a speaker.

David Callanan, MD, reported on 12-month results achieved with Ozurdex (dexamethasone intravitreal implant, Allergan).

“There was a greater improvement in best corrected visual acuity in patients treated with combination therapy vs. laser alone. Over 12 months, the retinal thickness and leakage area decreased more,” Dr. Callanan said at the Association for Research in Vision and Ophthalmology meeting in Fort Lauderdale, Fla.

The pathogenesis of diabetic macular edema is multifactorial, but disruption of the blood-retinal barrier plays a significant role, Dr. Callanan said.

“Laser photocoagulation is the standard of care,” he said. “It can reduce the risk of moderate vision loss, but it generally produces only a small improvement in visual acuity. Corticosteroid therapy can affect a lot of these processes involved in blood-retinal barrier breakdown, including enhancing the barrier function of the vascular-type junctions, preventing leukocyte migration and inhibiting prostaglandin, inflammatory cytokines and VEGF expression.”

Dr. Callanan and colleagues set out to gauge the safety and efficacy of steroid therapy in improving vision in patients with diffuse DME.

“One of the rationales for this study was that the addition of steroid therapy to laser photocoagulation might actually reduce the risk of clinically significant visual loss and improve the likelihood of visual improvement, particularly in patients with diffuse diabetic macular edema,” he said.

Patients and measurements

The randomized double-masked study included 126 patients with DME who received the dexamethasone intravitreal implant followed by laser at 1 month and 127 patients with DME who received sham injections and laser monotherapy at 1 month.

All patients had central retinal thickness of at least 275 µm and best corrected visual acuity between 34 and 70 letters. Retinal thickening had to result from diffuse DME based on analysis of optical coherence tomography and angiography, Dr. Callanan said.

A reading center evaluated OCT scans and angiograms for the presence of diffuse DME, but patients were allowed to be enrolled based on the investigator’s opinion, without pre-certification by the reading center.

Patients were randomized 1:1 to undergo combination therapy or sham injection and laser at 1 month. As needed, patients underwent re-treatment with the dexamethasone implant at a minimum of 6 months. Patients were also eligible to be re-treated with laser every 3 months, to simulate the treatment protocol in a clinical setting, Dr. Callanan said.

The primary outcome measure was the proportion of patients who gained at least 10 letters in best corrected visual acuity at 12 months. A secondary measure was change from baseline BCVA, central retinal thickness and safety.

The combined therapy and laser monotherapy groups were compatible in terms of age, gender, duration of DME, baseline central retinal thickness, visual acuity and percentage of patients who had previously undergone laser treatment, Dr. Callanan said.

Outcomes and adverse events

After 12 months, 28% of patients in the combination therapy group and 24% of patients in the laser group had at least a 10-letter improvement in BCVA, Dr. Callanan said.

Among patients with diffuse edema documented by the reading center, the combination therapy group had significantly higher increases in BCVA at 1, 4, 6, 7 and 9 months (P < .05). They also showed significantly greater mean reductions in diffuse leakage area at 4, 6, 9 and 12 months (P < .05).

“If you look at the mean change from baseline in diffuse leakage in angiography in this same group, you see that there was a significant difference,” Dr. Callanan said. “In the group that received the dexamethasone implant, [there was] a significant decrease in diffuse leakage on angiography.”

OCT data showed that swelling decreased rapidly in patients treated with the dexamethasone implant. Swelling decreased gradually in the laser monotherapy group, Dr. Callanan said.

Increased IOP was the only adverse event, and it occurred more frequently in the combination therapy group (20%) than in the monotherapy group (2%; P < .001). However, most patients did not require medication, and no patient required surgery to reduce IOP.

The combination therapy and laser monotherapy groups had similar rates of vitreous hemorrhage, vitreous detachment, retinal hemorrhage, subcapsular cataract and retinal detachment, Dr. Callanan said.

Researchers found that cataracts may have worsened in the combination therapy group, Dr. Callanan said.

Further study is needed with earlier re-treatment to determine the best course of combination therapy for DME patients. – by Matt Hasson and Courtney Preston

• David Callanan, MD, can be reached at Texas Retina Associates, 801 W. Randol Mill Rd., Suite 101, Arlington, TX 76012; 817-261-9625: email: dcallanan@texasretina.com.
• Disclosure: Dr. Callanan receives financial support from Allergan and is a consultant to Bausch + Lomb.