Findings of a 12-week preliminary trial comparing intravitreal treatment options for persistent uveitic macular edema suggest that the dexamethasone implant, the current established treatment, remains the superior choice when compared to repeated ranibizumab or methotrexate injections.
Study design
The Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy (MERIT) trial is a single-masked, randomized clinical trial that evaluated the effectiveness of intravitreal ranibizumab vs methotrexate vs the dexamethasone implant for the treatment of persistent or recurrent uveitic macular edema. A total of 225 eyes (194 patients) with macular edema and minimally active or inactive uveitis (i.e., ≤0.5+ anterior chamber cells, ≤0.5+ vitreous haze grade, and ≥4 weeks without active retinal or choroidal lesions) were enrolled and randomized 1:1:1 among the 3 treatment arms. Patients with bilateral macular edema were treated with the same medication in both eyes.
Outcomes
Although all eyes showed improvement at the 12-week primary endpoint, eyes treated with the dexamethasone implant had a significantly greater reduction in macular edema (as measured by central subfield thickness on OCT) compared to those treated with methotrexate (p < 0.001) or ranibizumab (p = 0.018). Eyes in the dexamethasone arm also showed statistically significant improvement in best corrected visual acuity (4.86 letter gain, p < 0.001), whereas eyes treated with ranibizumab or methotrexate did not. Intraocular pressure increases to 24 mm Hg or more were statistically more common in eyes treated with dexamethasone; moreover, 10% of eyes treated with dexamethasone experienced a rise in IOP to 30 mm Hg or more, as compared to only 1% of eyes treated with ranibizumab or methotrexate.
Limitations
The primary endpoint was at 12 weeks and, thus, longer-term outcomes cannot be assessed. This may be relevant for IOP- and cataract-related adverse events, which may be more common with steroid-related treatment than with ranibizumab or methotrexate but take time to develop. Longer outcome timepoints would help better assess durability of effect and treatment burden. Moreover, treating physicians in this study were able to change treatment after 12 weeks, which may limit future intention-to-treat analyses in eyes with treatment crossovers.
Clinical significance
At 12 weeks, the dexamethasone implant resulted in significantly better anatomic and visual outcomes for the treatment of uveitic macular edema in eyes with minimally active or inactive uveitis compared to ranibizumab or methotrexate, suggesting it should still be the treatment of choice for these cases.
Financial disclosures: Dr. M. Ali Khan discloses financial relationships with Allergan, Apellis Pharmaceuticals, Genentech (Consultant/Advisor); Regeneron Pharmaceuticals (Grant Support).