Dexamethasone implant treats persistent macular edema

October 15, 2005

Baltimore—The intravitreal bioerodable dexamethasone implant, evaluated in the Posurdex (Oculex Pharmaceuticals Inc./ Allergan) for Persistent Macular Edema Study, is a drug-delivery system that achieved the primary efficacy outcome, i.e., 2 lines or more improvement in vision 90 days after treatment, with the 700-mg dose.

Baltimore-The intravitreal bioerodable dexamethasone implant, evaluated in the Posurdex (Oculex Pharmaceuticals Inc./ Allergan) for Persistent Macular Edema Study, is a drug-delivery system that achieved the primary efficacy outcome, i.e., 2 lines or more improvement in vision 90 days after treatment, with the 700-mg dose.

A significant visual improvement of three or more lines of vision at 180 days after treatment was seen compared with the untreated patients, according to Julia A. Haller, MD.

The implant is available as a tablet containing 350- or 700-mg doses of drug and an extruded form that can be placed in an applicator for insertion in an office setting. The dexamethasone is placed in a biodegradable polylactic glycolic acid implant that biodegrades in the eye to water and carbon dioxide.

Eligible patients were assigned either to observation or to one of the doses of dexamethasone delivered in tablet form, which required surgical implantation. The primary efficacy outcome was a two-line or greater increase in best-corrected visual acuity 90 days after implantation; the secondary endpoints correlated with the primary endpoint and included improved contrast sensitivity, decreased leakage on fluorescein angiography, and decreased retinal thickening measured by optical coherence tomography (OCT), Dr. Haller explained. She is the Katharine Graham professor of ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore.

To implant the device, a small conjunctival cutdown was performed followed by a sclerotomy. The tablet was tucked through the sclerotomy into the vitreous base and the incision was then sutured, Dr. Haller explained.

A total of 306 patients were included in the study, most of whom had diabetic retinopathy (n = 165); 102 patients had central or branch retinal vein occlusion, 25 had Irvine-Gass syndrome, and 14 had uveitic macular edema, according to Dr. Haller. One hundred patients received the 350-mg dose, 101 the 700-mg dose, and 105 patients were observed.

"Considering the primary endpoint at 90 days, the group that received the 700-mg dose was statistically significantly better compared with the observation group at the same time point. By day 180, the treatment effect persisted with a significant difference between the two groups. When we looked at three lines or more of visual acuity improvement, there was a difference at day 90 that had not reached statistical significance but did so by day 180 with an apparent dose response in both cases," Dr. Haller reported.

The secondary endpoint response was correlated with the visual acuity improvement in the treated patients. She explained that when the reading center evaluated leakage on fluorescein angiography, there were three levels or more of improvement in 25.3% of eyes in the 700-mg group at 90 days compared with only 1.1% in the observation group. When the investigators looked at changes in the retinal thickness measured by OCT, there was an average increase of 11 µm of retinal thickness in the observation group compared with the 700-mg group, in which there was an average decrease of 142 µm in retinal thickness.

Sixteen percent of patients in the 700-mg group had IOP increases greater than 10 mm Hg compared with 3% of patients in the observation group at any time during the study. All increases in IOP were controlled by topical antiglaucoma medications. Following the perioperative period, the percentage of patients with increases in IOP decreased to 11% in the 700-mg group, 7% in the 350-mg group, and remained at 3% in the observation group, Dr. Haller explained.

Up to 6 months after treatment, there was no increase in the progression of cataract in the treated patients.

"There was also a significant visual improvement of three or more lines 180 days after treatment compared with the patients who were observed. All the secondary efficacy outcomes were consistent with the best-corrected visual acuity improvement, specifically fluorescein angiographic leakage, OCT thickness, and contrast sensitivity. There was a clear dose response between the two treatment doses. No major safety issues were identified," Dr. Haller stated.

A phase III study is currently ongoing; in this trial the extruded form of the drug (350- or 700-mg doses) is injected into the vitreous base and its effect evaluated.