Dexamethasone superior to ranibizumab, methotrexate for recurrent uveitic ME

Treatment with dexamethasone implant results in better outcomes for patients with persistent or recurrent uveitic macular edema (ME) at 12 weeks when compared with methotrexate or ranibizumab, a study has shown. The risk of intraocular pressure (IOP), however, is higher with dexamethasone, but elevations to levels of 30 mm Hg or more are rare.

“These results suggest that intravitreal corticosteroid therapy, unless contraindicated, should be the preferred therapy for this indication,” the investigators said.

This single-masked, randomized controlled trial was conducted to assess the effectiveness of three different intravitreal therapies in patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes at 33 centres. Those with bilateral ME received the same treatment in both eyes.

A total of 194 participants (225 eyes) met the eligibility criteria. Of these, 65 (77 eyes) were randomized to dexamethasone, 65 (79 eyes) to methotrexate, and 64 (69 eyes) to ranibizumab. All eyes were treated with at least one injection of the assigned treatment. [Ophthalmology 2023;130:914-923]

Central subfield thickness (CST) significantly decreased at week 12 relative to baseline in each treatment group: 35 percent for dexamethasone, 11 percent for methotrexate, and 22 percent for ranibizumab. ME reduction was significantly greater with dexamethasone than with either methotrexate (p<0.01) or ranibizumab (p=0.018).

Notably, only patients treated with dexamethasone demonstrated a statistically significant improvement in best-corrected visual acuity (BCVA) during follow-up (4.86 letters; p<0.001).

However, the dexamethasone group was more likely to have IOP elevations of “10 mm Hg, to 24 mm Hg or more,” but IOP spikes to 30 mm Hg or higher were infrequent overall and did not differ significantly among groups.

In addition, patients treated with methotrexate were more likely to have reductions in BCVA of 15 letters or more, which were attributable to persistent ME.

“In summary, dexamethasone was superior to methotrexate and ranibizumab for the treatment of persistent or recurrent ME in patients with inactive or minimally active uveitis at 12 weeks,” the researchers said.

“The risk of moderate IOP elevation was greater with dexamethasone, but the occurrence of IOP elevation to the 30-mm Hg or more threshold, occurrence of glaucoma, and the need for glaucoma surgery were minimal,” they added.

Standard vs alternative treatments

Earlier studies suggested the efficacy of intravitreal methotrexate and ranibizumab for uveitic ME. [Retina 2013;33:2149-2154; Ophthalmology 2009;116:797-801; Am J Ophthalmol 2009;148:303-309.e2; Retina 2014;34:2431-2438]

In the MERIT Trial, researchers directly compared these alternative treatments with dexamethasone intravitreal implant. Results for retinal thickness and BCVA showed the superiority of dexamethasone. [Clin Ophthalmol Auckl N Z 2011;5:139-146; Expert Opin Pharmacother 2011;12:1127-1131; Arch Ophthalmol 2011;129:545-553; Ophthalmologica 2012;228:229-233; Retina 2017;37:1692-1699]

Furthermore, in the POINT Trial, dexamethasone implant and intravitreal triamcinolone were each superior to periocular triamcinolone injections at 8 weeks. [Ophthalmology 2019;126:283-295]

“Persistent or recurrent uveitic ME is a common occurrence, with 40 percent of eyes showing persistent ME 2 years after initiating therapy and 40 percent of eyes with resolved ME relapsing after resolution,” the researchers said. [Ophthalmology 2015;122:2351-2359]

“Patients often require ongoing therapy, including repeated local injections, so determining if a benefit exists to switching to another type of therapy versus continuing treatment with corticosteroid injections is clinically important,” they added.