AUG 29, 2011
Although six-month results from the BRAVO trial demonstrated significant visual gains and anatomic improvements in patients receiving monthly ranibizumab for macular edema following retinal vein occlusion, questions remain about long-term outcomes beyond six months. The August issue of Ophthalmology reports on the six to 12-month observation period during which the authors evaluated whether these impressive gains could be maintained after switching from monthly to as-needed therapy. On average, benefits were maintain, but the necessity for ongoing treatment after six months suggests that anti-VEGF therapy does not alter the underlying pathophysiology of an anatomic blockage in the retinal vein.
The BRAVO trial randomized 397 patients to six monthly injections of ranibizumab (0.3 mg or 0.5 mg) or sham. After six months, all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm received as-needed ranibizumab in the same dosage as the treatment period. Sham-treated patients received 0.5 mg. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met.
This as-needed treatment paradigm led to a mean of 2.8 (0.3 mg) and 2.7 (0.5 mg) additional injections during the six-month observation period. At month 12, the mean letter score gain experienced after the initial six monthly ranibizumab injections was maintained (16.4 in 0.3 mg group and 18.3 in 0.5 mg group). Patient-reported improvements in visual function mirrored improvements in BCVA, with increases in NEI VFQ-25 composite scores observed at month six maintained at month 12. Even patients
As-needed treatment in the sham/0.5 mg group resulted in rapid reduction in central foveal thickness (CFT) to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA. However, visual gains in the sham group were not as great at that in the two ranibizumab groups.
The authors note that because BRAVO excluded patients with a diagnosis of BRVO >12 months, these results do not address whether anti-VEGF therapy would benefit patients with chronic disease. However, the visual acuity gains in the sham group after month six are not likely to represent spontaneous improvement and more likely attributable to the institution of as-needed ranibizumab therapy, which implies a beneficial effect even in more chronic cases.
They conclude that future therapies that address the vein blockage primarily or reduce VEGF production in the affected retina may be necessary to reduce the need for ongoing injection therapy in many patients. Until that time, the mainstay of treatment for macular edema following BRVO is likely to involve frequent intraocular anti-VEGF injections with or without grid laser photocoagulation.