Study: No long-term benefit for steroids in treating diabetic macular edema

Findings from a DRCR.net study indicate that steroids offer short-term results, but laser was more beneficial overall.

Long duration of steroid therapy does not appear to have benefit over focal/grid photocoagulation for patients with diabetic macular edema.

In an examination of 3-year results of patients undergoing treatment for diabetic macular edema with either steroid or photocoagulation, an early benefit was seen for high-dose steroids. But over time, photocoagulation proved more beneficial in restoring vision and normal retinal architecture with fewer side effects.

Patients in the multicenter DRCR.net trial were initially followed for 2 years for change in visual acuity and retinal thickness after discretionary therapy with either focal/grid photocoagulation or 1-mg or 4-mg triamcinolone. A 3-year follow-up of patients, presented by Mary Elizabeth Hartnett, MD, at Retina Congress 2009 and published in Archives of Ophthalmology, discussed the initial findings of the study. Dr. Hartnett recounted her views of the study as a practicing vitreoretinal specialist.

“There are more people who had improvement of five to nine letters in the laser group starting at 16 months and continuing to 20 months and 24 months,” Dr. Hartnett said.

There was a higher incidence of cataract in the steroid groups, especially at higher doses. However, visual impairment due to lens opacity likely did not skew final visual acuity data, according to Dr. Hartnett.

“Even when they did look at patients who were pseudophakic at baseline, they still found a benefit for the laser,” she said.

DRCR.net is conducting an ongoing clinical trial to investigate whether steroids or anti-VEGF agents may be beneficial in combination with laser compared to laser alone when treating diabetic macular edema.

Efficacy outcomes

At the 2-year endpoint of the trial, the 330 eyes treated with laser had a mean gain of one letter compared with two-line and three-line losses in the 1-mg (256 eyes) and 4-mg (254 eyes) triamcinolone groups, respectively. The percentage of eyes gaining 15 or more letters was similar (18% laser, 14% 1-mg and 17% 4-mg), but more eyes at least maintained and fewer lost vision with laser therapy compared with either steroid group.

The only time point at which steroid showed statistically significantly improved vision compared with laser was at the 4-month follow-up, with a greater difference seen with the higher dose. However, there was no difference by 1 year, and at 16 months, laser overtook steroid for the duration of the study.

At 3 years, the 115 eyes in the laser group had a mean five-letter gain in visual acuity compared with baseline, while there was no difference among the 93 eyes in the 1-mg group and the 98 eyes in the 4-mg triamcinolone group.

Laser also proved more beneficial in reduction of central retinal thickness. There was a loss of 175 µm in the laser group compared with losses of 124 µm in the 1-mg and 126 µm in the 4-mg triamcinolone groups. A greater percentage of eyes had a final central retinal thickness less than 250 µm in the laser group compared with either steroid group.

“It has to be recognized that not all patients enrolled in this study were analyzed in this 3-year report, and patients were allowed to have other treatments than what they were initially randomized to have,” Dr. Hartnett said. “At least 80% of patients in each group, triamcinolone vs. laser, with the potential to complete the study actually did.”

Visual acuity and macular thickness measured on optical coherence tomography for the 4-mg triamcinolone group were consistent with the case series at 4 months, but were no different from laser at 1 year and worse than laser at 2 years. Between years 2 and 3, visual acuity improved more often than it worsened in both groups, and residual diabetic macular edema tended to lessen in all groups.

“Treatment groups were in the same direction in year 3 as in year 2 and slightly favored the laser group,” Dr. Hartnett said. Eyes with 4-mg triamcinolone were more likely to require cataract surgery, though few needed surgery for glaucoma. No long-term benefit of triamcinolone was appreciated at 3 years.

“Therefore, focal/grid laser treatment is the most effective treatment for patients with diabetic macular edema and is currently the benchmark for clinical trials for diabetic macular edema,” Dr. Hartnett said.

Safety data

Adverse effects of treatment were more prominent in the two triamcinolone groups than in the laser therapy group. During the 3 years of follow-up, 3% of laser eyes and 17% and 31% of 1-mg and 4-mg triamcinolone eyes, respectively, had an increase in IOP of 10 mm Hg or higher at any point. The 3-year cumulative incidences of cataract extraction were 31%, 46% and 83% for the three groups.

Despite the safety risks of long-duration triamcinolone therapy seen in the study, there still may be a role for steroid therapy in managing diabetic macular edema. For instance, Dr. Hartnett said, quickly stamping down a swollen macula with steroids may aid in more focused delivery of photocoagulation to a microaneurysm. In turn, more focused photocoagulation therapy may reduce energy leakage, burn and scarring on adjacent retinal structures. This question will be addressed in the trial testing laser alone vs. laser plus triamcinolone or laser plus anti-VEGF agent.

Another reason for ongoing trials with triamcinolone is that results from the DRCR.net study, although large-scale in design, may not be relevant for all patients in all situations.

“There are still questions that haven’t been answered,” Dr. Hartnett said. “One of the difficult things with clinical trials is that to really answer a question you’ve got to enroll people that are pretty close or similar as to whatever it is that you’re addressing. But then there are people who fall outside of that that you have to use clinical judgment to determine whether or not they’d benefit.” – by Bryan Bechtel

References:

• Diabetic Retinopathy Clinical Research Network (DRCR.net), Beck RW, Edwards AR, et al. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009;127(3):245-251.
• Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115(9):1447-1449.

• Mary Elizabeth Hartnett, MD, can be reached at 5109D Bioinformatics Building, CB #7040, 130 Mason Farm Road, Chapel Hill, NC 27599; 504-412-1200; fax: 504-412-1315; e-mail: hartnet@med.unc.edu.