This article was originally published in a sponsored newsletter.

Uveitis comes with its own unique set of challenges and visually devastating complications, especially macular edema.¹ Frustratingly, uveitic macular edema may persist despite control of ocular inflammation. Typically, uveitic macular edema without overlying inflammation has been treated locally with topical, periocular, or intraocular steroids. Of the intravitreal options, dexamethasone implants are a popular choice.² However, steroid treatments are not without side effects. Other treatments have been raised as potential alternatives for uveitic macular edema, including anti-vascular endothelial growth factor (anti-VEGF) injections (i.e., ranibizumab [Lucentis, Genentech]) and intravitreal methotrexate, with varied results. Given the variety of options, the Macular Edema Ranibizumab versus Intravitreal Anti-Inflammatory Therapy (MERIT) trial was developed to compare the intravitreal dexamethasone implant vs non-steroidal options, including intravitreal ranibizumab and intravitreal methotrexate.³

The MERIT trial was a multi-center, randomized, parallel treatment trial. Patients with anterior, intermediate, posterior and panuveitis were allocated on a 1:1:1 ratio for the treatments listed above. This study enrolled patients from the United States, United Kingdom, India, Australia, and Canada. Inclusion criteria required patients to be older than the age of 18, and to have inactive or minimally inactive uveitis with macular edema. Patients were treated with intravitreal dexamethasone (0.7 mg implant), ranibizumab (0.5 mg in 0.05 mL), or methotrexate (400 g in 0.1 mL). Retreatment was required if patients presented with a central subfield thickness (CST) of more than 1.1 times the upper limit of normal, or if cystoid spaces were present in the 1mm central subfield despite a normal CST. If either of these characteristics were present, the dexamethasone implant group was retreated at week 8 and the methotrexate group was retreated at week 4 and week 8. In the ranibizumab group, retreatment was done at week 4 and week 8, regardless of fluid status, given the common practice of treating with anti-VEGF for three monthly injections. If patients’ intraocular pressure measured more than 35 mmHg, or patients required more than three IOP-lowering medications, retreatment was held.

The results of the trial were measured at the 12-week mark. After this point, the investigators were encouraged to treat with the original randomized medication, but treatment was ultimately left to the discretion of the treating physician.³ At 12 weeks, all three groups showed a statistically significant decrease in CST compared to their baseline measurement, with dexamethasone showing the most reduction (35%) compared to ranibizumab (22%) and methotrexate (11%). BCVA significantly improved with dexamethasone treatment, while it did not improve with the ranibizumab or methotrexate groups. There were significantly more increases in intraocular pressure to 24 mmHg or more in the dexamethasone group as well.

Overall, the authors concluded that dexamethasone outperformed ranibizumab and methotrexate for the treatment of uveitic macular edema, with a statistically significantly higher reduction in CST compared to the other treatments. The dexamethasone group was also the only group to show a statistically significant improvement in BCVA. Interestingly, the authors noted that the greatest improvement with dexamethasone occurred at 8 weeks, which led them to speculate that the duration of dexamethasone may be shorter than 12 weeks (a timeline established in a prior trial).^2,3 Finally, the authors noted that a limitation of this study was the follow-up period of 12 weeks, and they plan to analyze the results of the 24-week results in a later publication.

  References:

1. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996 Apr;80(4):332-336. doi:10.1136/bjo.80.4.332
2. The Multicenter Uveitis Steroid Treatment Trial (MUST) Reasearch Group, Thorne JE, Sugar EA, et al. Periocular triamcinolone versus intravitreal triamcinolone versus intravitreal dexamethasone implant for the treatment of uveitic macular edema: the PeriOcular versus INTravitreal corticosteroids for uveitic macular edema (POINT) trial. Ophthalmology. 2019 Feb;126(2):283-295. doi:10.1016/j.ophtha.2018.08.021
3. The Multicenter Uveitis Steroid Treatment Trial (MUST) Reasearch Group, Writing Committee, Acharya NR, Vitale AT, et al. Intravitreal therapy for uveitic macular edema-ranibizumab versus methotrexate versus the dexamethasone implant: the MERIT trial results. Ophthalmology. 2023 Sep;130(9):914-923. doi:10.1016/j.ophtha.2023.04.011

Sruthi Arepalli, MD is Assistant Professor of Vitreoretinal Surgery and Uveitis at Emory University.