The results of the MERIT trial
Aim
To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab.
Design
Single-masked, randomized controlled clinical trial.
Participants
Patients with minimally active or inactive uveitis and persistent or recurrent uveitic macular edema (ME) in one or both eyes.
Methods
Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral MS received the same treatment in both eyes.
The main measures
The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a ratio 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 MS, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP).
Results
One hundred ninety-four participants (225 eligible eyes) were randomly assigned 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.
The reduction in macular edema (ME) was significantly greater in the dexamethasone group than in the methotrexate (P < 0.01) or ranibizumab (P = 0.018) group. Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001).
IOP elevations of 10 mmHg, to 24 mmHg or higher, or both, were more common in the dexamethasone group; IOP spikes of 30 mmHg or greater were uncommon overall and were not significantly different between groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and were generally attributed to persistent MS.
Conclusions At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent macular edema (ME) than methotrexate or ranibizumab. The risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or greater were rare. |
Comments
Intraocular corticosteroids are best for treating complications of chronic inflammatory eye condition
Repeated treatment with corticosteroid injections improved vision in people with macular edema related to persistent or recurrent uveitis better than two other therapies, according to results from a clinical trial funded by the National Eye Institute (NEI). Compared with intravitreal (into the eye) injections of methotrexate or ranibizumab, corticosteroid treatment achieved greater reductions in retinal inflammation and was the only therapy in the study that improved vision. The report was published today in the journal Ophthalmology. NEI is part of the National Institutes of Health.
"Before this study, we did not know the best treatment for persistent or recurrent macular edema, a leading cause of vision loss in people with uveitis," said Douglas A. Jabs, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore. , president of the study. "This trial clearly indicates that repeated intraocular injections of corticosteroids are superior to intravitreal injections of methotrexate or ranibizumab."
Uveitis is a group of inflammatory conditions that affect the internal tissues of the eye. Uveitis can affect the front of the eye (anterior uveitis), the middle of the eye (intermediate uveitis), the back of the eye (posterior uveitis), or the front, middle, and back of the eye (panuveitis). Inflammation in the eye can cause fluid to build up in the central part of the light-sensitive retina of the eye, known as the macula, and decrease vision. This fluid buildup, called macular edema, is a complication of uveitis that often persists or recurs over time, despite uveitis treatment.
Initial treatment of uveitis-related macular edema seeks to control inflammation and reduce fluid under the retina. Although some patients achieve this goal with oral corticosteroids, most patients with macular edema also require intraocular corticosteroid injections. The dexamethasone intraocular implant is one such treatment. However, intraocular corticosteroids can increase the pressure inside the eye. High intraocular pressure is a key risk factor for glaucoma, which can damage the optic nerve and lead to vision loss. Intraocular corticosteroids can also cause cataracts, a clouding of the eye’s lens that decreases vision. Diagram showing areas of the eye affected by uveitis.
Uveitis is inflammation of the eye that originates in the uvea, which includes the iris, ciliary body, and choroid.
In this study, researchers compared three treatments for uveitis-related macular edema: an additional intraocular injection of corticosteroids, an injection of the anti-vascular endothelial growth factor (anti-VEGF) drug ranibizumab, or an injection of the anti-inflammatory drug methotrexate. . Anti-VEGF injections are used to treat age-related macular degeneration, as well as macular edema due to other causes, such as diabetic retinopathy. Previous small pilot studies suggested that ranibizumab injections and the anti-inflammatory effects of methotrexate could help reduce uveitis-related macular edema.
The clinical trial enrolled 194 participants (225 study eyes) with well-controlled uveitis but persistent or recurrent macular edema. Sixty-five participants received a dexamethasone corticosteroid, 65 participants received methotrexate, and 64 participants received ranibizumab. The study was conducted at 33 clinical sites, located in the United States, the United Kingdom, Australia, and India. All participants had previously received at least one intravitreal corticosteroid injection for uveitis-related macular edema.
Injection schedules for each group were based on how each treatment is generally used in clinical practice. Participants in the corticosteroid group received one dexamethasone implant injection at baseline and, if the macular edema had not resolved, another injection at eight weeks. The methotrexate group received one injection at baseline, then repeated injections at four and eight weeks if the macular edema did not resolve. The ranibizumab group received injections at baseline, four and eight weeks, even if macular edema resolved.
After 12 weeks , all three groups showed reductions in retinal inflammation. The reduction was greater in the dexamethasone group compared to the other two (35% reduction for corticosteroids; 20% for ranibizumab; 11% for methotrexate). Additionally, only the corticosteroid group showed an improvement in vision, almost five letters, about one row on an eye chart. The corticosteroid group had more occurrences of mild increases in intraocular pressure, but increases at high levels were infrequent (<10%) in all three groups.
"Intraocular corticosteroid treatment remains the most effective therapy for uveitis-related macular edema," said Nisha Acharya, MD, of the University of California, San Francisco, lead author of the study. "The improvements in vision in participants who received corticosteroid treatment were very promising."
Reference : The Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group. "Intravitreal therapy for uveitic macular edema – ranibizumab vs methotrexate vs the dexamethasone implant: The MERIT Trial Results." Ophthalmology, June 13, 2023. https://doi.org/10.1016/j.ophtha.2023.04.011
