Steroid Prevails Over Methotrexate, Ranibizumab for Uveitic Macular Edema

A dexamethasone implant significantly outperformed ranibizumab (Lucentis) and methotrexate for intravitreal treatment of persistent/recurrent uveitic macular edema, according to results of a randomized trial.

The implant reduced retinal thickness by 35% at 12 weeks as compared with 11% with methotrexate and 22% with ranibizumab. Additionally, the dexamethasone implant reduced macular edema significantly more than either of the comparators, and only patients randomized to dexamethasone had statistically significant improvement in visual acuity.

Spikes in intraocular pressure (IOP) occurred more often with dexamethasone, but increases ≥30 mm Hg were uncommon, reported Douglas A. Jabs, MD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and co-authors in Ophthalmology.

"Prior to this study, we didn't know the best treatment for persistent or recurrent macular edema, a major cause of vision loss in people with uveitis," Jabs said in a press release. "This trial strongly indicates that repeat intraocular corticosteroid injections are superior to either intravitreal injections of methotrexate or ranibizumab."

The results affirmed existing evidence of intravitreal corticosteroids as the standard of care for uveitic macular edema, said lead author Nisha R. Acharya, MD, of the University of California San Francisco.

"The vision gains in participants who received the corticosteroid treatment were very promising," she said.

Although intravitreal steroids are commonly used to treat uveitic macular edema, the condition may not resolve completely, and an estimated 40% of patients have relapses. Additionally, repeated intravitreal injections of corticosteroids pose a risk of elevated IOP and cataracts.

Several studies have generated promising preliminary data for the efficacy of intravitreal methotrexate and intravitreal ranibizumab, which are non-corticosteroid treatments for uveitic macular edema. At least one study suggested methotrexate can achieve sustained remission. Additionally, methotrexate and ranibizumab may have fewer ocular side effects as compared with corticosteroids, particularly elevated IOP and cataract, the authors noted.

To address the relative safety and efficacy of intravitreal therapy with corticosteroids, methotrexate, and ranibizumab, investigators in the randomized multicenter MERIT trial enrolled patients with uveitis associated with macular edema. They defined macular edema as a central subfield thickness (CST) exceeding the normal range by ±2 standard deviations. Eligible patients had received prior intravitreal corticosteroid therapy, and systemic corticosteroids or other immunosuppressives were allowed.

Patients were randomized 1:1:1 to the three intravitreal therapies in each eligible eye at randomization or as soon as possible thereafter. Patients assigned to dexamethasone received a second injection at 8 weeks if retreatment criteria were met, whereas those allocated to methotrexate received additional injections at 4 and 8 weeks if they met retreatment criteria, and the ranibizumab group received additional injections at 4 and 8 weeks irrespective of retreatment criteria.

Data analysis included 194 patients with 224 uveitic eyes. The primary endpoint was change in CST from baseline to 12 weeks.

All three treatments led to statistically significant reductions, led by dexamethasone (0.65 of baseline CST) and followed by 0.78 for ranibizumab and 0.89 for methotrexate. Intergroup comparison showed that dexamethasone achieved statistical significance versus methotrexate (P<0.001) and ranibizumab (P=0.018). CST decreased at weeks 4 and 8 with dexamethasone and ranibizumab, but not methotrexate. More patients randomized to dexamethasone had a ≥20% decrease in CST as compared with either of the comparator therapies.

Also at week 12, best corrected visual acuity improved significantly with dexamethasone but not with methotrexate or ranibizumab. The magnitude of improvement with the corticosteroid was 4.5 letters versus methotrexate (P<0.002) and 3.5 letters versus ranibizumab (P=0.02). Visual function score (NEI-VFQ-25) improved significantly with dexamethasone (P=0.002) and ranibizumab (P=0.27), but not methotrexate.

Significantly more patients in the dexamethasone group had IOP ≥24 mm Hg as compared with methotrexate (P=0.002) or ranibizumab (P=0.013). IOP ≥30 mm Hg occurred more often with dexamethasone, but differences versus the comparators did not reach statistical significance.

"These results suggest that intravitreal corticosteroid therapy, unless contraindicated, should be the preferred therapy for this indication," the authors concluded.

"Given the lower risks of IOP elevation with ranibizumab, the 24-week data may define a potential role for intravitreal ranibizumab in patients for whom concern exists about using intravitreal corticosteroids," they noted. "Ocular inflammation has been reported with anti-vascular endothelial growth factor treatments, but this adverse event was not seen in our study."

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