麻豆传媒

NEW ORLEANS -- Patients with persistent diabetic macular edema (DME) had no significant improvement in visual acuity when dexamethasone was added to ongoing treatment with ranibizumab (Lucentis), a randomized trial showed.

After 24 weeks of treatment, improvement in the electronic Early Treatment Diabetic Retinopathy study (E-ETDRS) score averaged 2.7 letters with dexamethasone and 3.0 letters with ranibizumab alone. The combination did lead to significantly less retinal thickening versus ranibizumab monotherapy.

A subgroup analysis suggested that pseudophakic eyes benefited more from the addition of dexamethasone, but the finding was based on relatively small numbers and small between-group differences, reported Raj K. Maturi, MD, of the Midwest Eye Institute in Indianapolis, and colleagues at the American Academy of Ophthalmology meeting. The data were published simultaneously in JAMA Ophthalmology.

"We had done a few small studies that showed there was a difference in [retinal thickening] but not as much in visual acuity, so I wasn't completely surprised by the results," Maturi told 麻豆传媒. "I did expect more of a difference in pseudophakes [with the addition of dexamethasone], and there was a difference that met statistical significance."

"Maybe the study wasn't long enough" he added. "It was just 6 months, and maybe we would have seen a different outcome with longer follow-up."

Multiple clinical trials demonstrated that intravitreous anti-VEGF therapy reduces retinal thickening and improves visual acuity in patients with DME. However, as many as two=thirds of treated patients have persistent edema that often is associated with reduced visual acuity.

In addition to their anti-inflammatory effects, corticosteroids reduce the breakdown of the blood-retinal barrier and have antiangiogenic properties, Maturi noted. Several studies showed that intravitreal corticosteroid therapy improved visual acuity in DME as compared with sham treatment, but was not as effective as laser photocoagulation or intravitreal anti-VEGF therapy.

Because corticosteroids consistently reduce retinal thickening, investigators hypothesized that the addition of a steroid might benefit patients with persistent DME and vision loss despite treatment with an anti-VEGF agent. Members of the Diabetic Retinopathy Clinical Research Network conducted a randomized phase II clinical trial to test the hypothesis.

The trial involved adults with diabetes and persistent DME despite treatment with ranibizumab (defined as unresponsive after a minimum of three intravitreal injections), associated with visual acuity of 20/32 to 20/320. Patients were randomized to receive dexamethasone in addition to ranibizumab or to continue intravitreal ranibizumab injections alone. Patients in both arms received three additional injections of ranibizumab (run-in phase) before initiating randomized treatment.

Data analysis included 116 patients and 129 treated eyes. The study population had a median age of 65 and even distribution of men and women. All but 5% of the patients had type 2 diabetes, and the median baseline hemoglobin A_1c was 7.4%. Maturi said 60% of eyes in the combination arm were phakic as were 50% in the ranibizumab group.

Mean improvement in visual acuity after the run-in phase was 3.0 letters in each treatment arm. Mean visual acuity letter scores at randomization were 63 in both groups.

The primary endpoint was the mean change in E-ETDRS from baseline to 24 weeks. The principal secondary endpoint was central subfield retinal thickness, as measured by optical coherence tomography.

The primary analysis showed that the mean improvement in visual acuity did not differ significantly between treatment groups. An adjusted analysis showed a between-group difference (combination minus monotherapy) of -0.5 letters (95% CI -3.6 to 2.5, P=0.73).

Comparison of the mean change in retinal thickness showed a significantly larger reduction in the combination arm (-110 µm vs -62 µm, P<0.001).

Subgroup analysis showed a greater adjusted mean difference in visual acuity in pseudophakic eyes in favor of the combination: 3.1 letters versus -3.0 letters for phakic eyes.

Maturi pointed out that the original trial design included only patients with pseudophakic eyes because of corticosteroids' known effect on cataract formation. However, because of slow patient accrual in the study, investigators modified the design to allow inclusion of phakic eyes. As a result, the findings in the subgroup analysis should be interpreted cautiously.

Combination treatment led to increased intraocular pressure or initiation of antihypertensive eyedrops in 19 (29%) eyes, as compared with none in the group that received ranibizumab injections alone (P<0.001). No patient in either treatment group developed endophthalmitis.