Dexamethasone surpasses ranibizumab and methotrexate for intravitreal treatment of AMD

Intravitreal drug delivery recently gained importance in past years and has become the gold standard for treatment of many retinal diseases, including neovascular age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion.

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

The MERIT Trial conducted by Dr. Nisha R. Acharya, MD, MS and team evaluated the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab.

The trial was Single-masked, randomized controlled clinical trial. Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes were included in the study. Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes.

The primary outcome was measured at 12 weeks, reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP).

The key findings of the study are

• A total of 194 partcipants (225 eligible eyes) were randomized to dexamethasone (n = 65 participants and 77 eyes), methotrexate (n = 65 participants and 79 eyes), or ranibizumab (n = 64 participants and 69 eyes).

• All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35%, 11%, and 22% for dexamethasone, methotrexate, and ranibizumab, respectively.

• Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P < 0.01) or ranibizumab (P = 0.018).

• Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001).

• Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups.

• Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME.

Researchers concluded that “At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent.”

Reference: Acharya NR, et al "Intravitreal therapy for uveitic macular edema -- Ranibizumab versus methotrexate versus the dexamethasone implant: the MERIT trial results" Ophthalmology 2023; DOI: 10.1016/j.ophtha.2023.04.011.