MUST Trial Confirms Advantages of Systemic Uveitis Tx

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A new analysis from the Multicenter Uveitis Steroid Treatment (MUST) Trial Follow-Up Study found that long-term risk and poor outcomes of glaucoma in uveitic eyes were significantly higher in patients receiving a fluocinolone acetonide implant (Retisert) compared to systemic therapy.¹

Although eyes in both treatment groups did well in terms of inflammation control, 79 of 196 implant-treated eyes (40%) developed glaucoma, compared to 17 of 209 eyes (8%) that received systemic treatment during follow-up (median, 6.9 years). Most cases of uveitic glaucoma were successfully managed with intraocular pressure (IOP)–lowering treatment, yet despite close monitor­ing, a minority experienced a worsening of visual field defects and/or cup-to-disc ratios.

“Because IOP-lowering treatment worked for avoiding further worsening of glaucoma in most cases, uveitic eyes should be monitored indefinitely for IOP elevation and glaucoma,” said John H. Kempen, MD, MPH, MHS, PhD, at Massachusetts Eye and Ear in Boston. “The risk of IOP elevation and glaucoma never goes away com­pletely, at least through seven to 10 years of follow-up.”

Elevated IOP. This prospective follow-up of 405 uveitic eyes (232 patients) found that implant therapy offered excellent inflammation control for the first few years. However, it was associated with IOPs of ≥30 mm Hg more often than systemic treatment, often leading to glaucoma.² At two years, the MUST Trial data showed no difference between the groups in best-corrected visual acuity outcomes. But at seven years, eyes randomized to systemic therapy fared better than the implant cohort by 1.4 lines on average.

Surprise finding. “We generally think that optic nerve injury from glaucoma is due to very high IOPs, so it was surprising that use of implant treatment was a slightly a stronger predictor of glaucoma than IOP measurements,” Dr. Kempen said. “That makes me won­der if there was more to glaucoma incidence than just IOP elevation. Could there be some structural effect of very long-lasting intraocular corticosteroids affecting glaucoma risk?”

Keep monitoring patients. Dr. Kempen monitors all uveitis patients for IOP elevation and glaucoma at least every three months. For implant patients, he prefers every six weeks for the first two years.

Also, the findings suggest value for early filtering surgery in implant eyes that appear to be developing substantially elevated IOP. In an earlier analysis from the MUST Trial, 45.3% of cases in the implant group required incisional surgery to lower IOP within seven years.³

Given these findings, and an economic analysis favoring systemic therapy, the researchers concluded that systemic therapy should be first line for average cases. “It is not yet known whether newer implants with lower doses of corticosteroid might compare to system­ic therapy more favorably,” Dr. Kempen said. “But initial systemic therapy did rather well in the MUST Trial, providing a high bar for new treatments to surpass to achieve first-line status for average cases. Implants are indicated when systemic therapy is not feasible or fails and for selected severe cases.”

—Miriam Karmel

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1 Kempen JH et al. Am J Ophthalmol. Published online July 3, 2020.

2 Friedman DS et al. Ophthalmology. 2013;120(8):1571-1579.

3 Kempen JH et al., for the Writing Committee for the MUST Tri­al and Follow-Up Study Group. JAMA. 2017;317(9):1993-2005.

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Relevant financial disclosures—Dr. Kempen: The MUST trial received a donation of fluocinolone acetonide intraocular im­plants from Bausch + Lomb for patients who would be unable to enroll in the trial without a donated implant.

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