Intravitreal Therapy for Uveitic Macular Edema – Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results

January 2024 

Jordan D. Deaner, MD
Uveitis and Vitreoretinal Surgery
Mid Atlantic Retina, Wills Eye Hospital
Assistant Professor, Thomas Jefferson University
Philadelphia, PA

 

Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group, Writing Committee:; Acharya NR, Vitale AT, Sugar EA, Holbrook JT, Burke AE, Thorne JE, Altaweel MM, Kempen JH, Jabs DA. 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. Epub 2023 Jun 13. PMID: 37318415

 

Uveitic macular edema (UME) is the most common complication of uveitis and is a common cause for decreased vision in uveitis despite treatment with systemic immunosuppressive therapy (IMT). Local intraocular and periocular corticosteroids often reduce the UME and improve vision, but recovery can be incomplete and require frequent retreatment. Local ocular corticosteroids have a well-known risk profile that includes elevation of intraocular pressure and cataract formation. The Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy (MERIT) Trial sought to compare the effectiveness of intravitreal corticosteroids versus intravitreal anti-VEGF versus intravitreal methotrexate for the treatment of persistent or recurrent UME in eyes with inactive or minimally active uveitis.

The MERIT trial was a multicenter, randomized, comparative clinical trial. Patients with minimally active or inactive, non-infectious, anterior, intermediate, posterior, or panuveitis and persistent or recurrent UME (defined as optical coherence tomography (OCT) central subfield thickness (CST) ≥ 2 standard deviations above the population mean with or without cystoid spaces) were randomized 1:1:1 to receive the 0.7 mg dexamethasone intravitreal implant (DEX) (Ozurdex, Allegan), 0.5mg/0.05ml of intravitreal ranibizumab (RAN) (Lucentis, Genentech), or 400ug/0.1ml of intravitreal methotrexate (MTX) at day 0. All patients had received a prior intravitreal corticosteroid injection, either triamcinolone >3 weeks prior or a DEX >11 weeks prior to enrollment. Patients with bilateral UME received the same treatment in both eyes. Criteria for retreatment included an OCT CST of >1.1 times the upper limit of normal or the presence of cystoid spaces in the central subfield. The retreatment schedules were individualized for each group. The dexamethasone treatment group required a second injection at 8 weeks if retreatment criteria were met, whereas the methotrexate treatment group required repeat injections at weeks 4 and 8 if retreatment criteria were met at those points. The ranibizumab treatment group required additional injections at 4 and 8 weeks regardless of retreatment criteria status. The primary outcome measured was change in CST from baseline at the 12-week visit. Secondary outcomes measured were mean change BCVA from baseline, the proportion of eyes with ≥20% reductiob or normalization of macular thickness, intraocular pressure (IOP) elevation, and need for glaucoma surgery.

194 patients (225 eyes) were randomized to DEX (65 patients, 77 eyes), methotrexate (65 patients, 79 eyes), or RAN (64 patients, 69 eyes). The median age of patients was 58 years and 43% of patients were on systemic IMT. Patients had a mean duration of uveitis of 4.3 years. Cystoid UME was present in ≥94% of eyes in all treatment groups. All eye received at least 1 injection of the assigned treatment. There was a significant reduction in OCT CST at 12 weeks in each treatment group: 35% reduction in DEX, 11% reduction in MTX, and 22% reduction in RAN. Reduction in OCT CST was significantly greater in the DEX group compared to the MTX (P<0.01) or RAN (P=0.018) groups. Eyes in the DEX group were also more likely to experience a ≥20% reduction in CST or normalization of CST.  The DEX group showed a significant improvement in BCVA from baseline compared to the MTX group (4.6 more letters, P<0.002) and the RAN group (3.5 more letters, P=0.02).  The incidence of IOP ≥24 mmHg or more was significantly higher in the DEX group compared to the MTX (HR 0.01, P=0.002) and RAN (HR 0.25, P=0.013) groups. However, the incidence of IOP elevations >30 mmHg was uncommon (≤10%) and was not statistically significant across the groups. Only 1 eye receiving DEX and 4 eyes receiving MTX required glaucoma surgery to control IOP.

Overall, intravitreal DEX was superior to intravitreal MTX and RAN in the treatment of minimally active or inactive, non-infectious, persistent or recurrent UME. The results of the MERIT trial suggest little role for MTX in the treat of minimally active or inactive UME. Risk of IOP elevation was greater in the DEX group, as expected, but IOP elevations ≥30 mmHg was infrequent in all groups.