Rx Perspectives

Ozurdex: A First for RVO Therapy

By Julia A. Haller, MD

Patients experiencing venous occlusive disease of the retina may be in need of swift intervention to bring about resolution of associated macular edema and subsequent improvement in vision. Although decades-old trials and newer, off-label studies have provided some guidance on options such as laser therapy, intravitreal steroids and more recently anti-VEGF agents, it was only recently that the first FDA-approved agent was made available — Ozurdex, a biodegradeable implant comprised of dexamethasone at a dose of 0.7 mg, manufactured by Allergan. The Ozurdex implant provides a bolus of dexamethasone five times as potent as triamcinolone.

The approval came on the strength of two prospective phase 3 trials of Ozurdex implantation in a total of 1267 patients experiencing either branch or central retinal vein occlusion (RVO), of which about two-thirds had BRVO and one-third had CRVO. Patients were randomized to one of three groups — the implant at a dose of dexa methasone 0.7 mg, an implant with half that dose (0.35 mg), or a sham injection — and followed for six months. At the sixmonth visit, patients could receive a second implant if visual acuity was below 20/20 or central retinal thickness was above 250 μm.

The primary endpoint was time to achieve a 15-letter gain in BCVA. Mean pretreatment visual acuity was 20/80. Mean central retinal thickness was over 500 μm in all three of the study groups.

Duration of macular edema at baseline may be significant when interpreting the data. About 85% of patients had disease longer three months, and fully one-third had disease for greater than six months.

Results and Analysis

At one month, results in both treated groups began to separate from the sham group. Mean change in visual acuity peaked at 60 days and tapered thereafter out to 180 days in all three groups (suggesting possible undertreatment), at which time a cumulative 41% of treated patients had gained three or more lines of vision, compared with 23% of sham patients.

Looking at the treatment's relative risk reduction, implantation of the 0.7 mg dexamethasone implant reduced the relative risk (RR) of visual acuity loss of three lines or more by about half, to 0.55 RR overall, with 0.45 RR in branch vein occlusion patients and 0.65 RR in CRVO patients. Including all patients who received an implant at the six-month visit and were followed to the 12-month mark (initially sham patients, too), there was a relative risk of 0.66 overall (0.67 for BRVO and 0.69 for CRVO).

About 20% of patients overall required only one treatment to maintain their favorable visual and central retinal thickness status out to the one-year endpoint. Patients receiving sham implant who went on to receive dexamethasone treatment at six months improved, but were unable to "catch up" to the outcomes achieved in those treated at baseline, suggesting that delay of treatment may have adversely impacted long term results.

IOP rise ≥ 25 mm Hg occurred in 1.2% of the 0.7 mg treatment group, 1.3% of the 0.35 mg group and 0.8% of the sham group. In all groups, the increase in pressure peaked at day 60 and returned to baseline by day 180. All were managed medically or with observation, except five eyes that required filtering surgery (two of which had neovascular glaucoma). Rates of cataract progression did not differ significantly between groups (7% in the 0.7 mg treatment group, 4% in the 0.35 mg group and 5% in the sham group).

The conclusion we can draw from this study is that Ozurdex is an effective treatment for macular edema due to RVO compared to sham. Earlier treatment may be associated with better visual outcomes, as was seen across all subgroups of patients. For instance, in the 0.7 mg treatment group, 48% of BRVO patients treated within three months gained three or more lines of vision and 56% achieved visual acuity of 20/40 or better.

Still, many questions remain. Many patients continue to have visual loss, and forthcoming research will address additional options for remedy, such as combination regimens. OM

Julia A. Haller MD, is Ophthalmologist-in-Chief at Wills Eye Institute in Philadelphia. She can be reached at jhaller@willseye.org.