Comparison of Antimetabolite Drugs as Corticosteroid-Sparing Therapy for Noninfectious Ocular Inflammation

To compare the relative effectiveness and side effect profiles of antimetabolite drugs in the treatment of noninfectious ocular inflammation. Retrospective cohort study. A total of 257 patients with inflammatory eye disease seen in a single-center, academic practice and treated with an antimetabolite as a first-line immunosuppressive agent from 1984 to 2006. Data recorded included demographics, antimetabolite and prednisone doses, use of other immunosuppressive drugs, response to therapy, and side effects associated with drug use. Ability to control ocular inflammation and to taper prednisone to ≤10 mg daily (“treatment success”); incidence of treatment-related side effects. Ninety patients with inflammatory eye disease were treated with methotrexate, 38 patients were treated with azathioprine, and 129 patients were treated with mycophenolate. Uveitis accounted for the majority of the diagnoses (67%, 66%, and 68% for methotrexate, azathioprine, and mycophenolate, respectively), followed by scleritis (23%, 18%, 17% for methotrexate, azathioprine, and mycophenolate, respectively). The median time to treatment success was 4.0, 4.8, and 6.5 months for the mycophenolate, azathioprine, and methotrexate treatment groups, respectively ( P = 0.02, log-rank test). The incidence of side effects was higher in the azathioprine group (0.29/person-year [PY]) compared with patients treated with methotrexate (0.14/PY) and mycophenolate (0.18/PY). More patients discontinued the drug because of side effects in the azathioprine group (0.24/PY vs 0.09/PY for the methotrexate group and 0.09/PY for the mycophenolate mofetil group). These data suggest that the time to control of ocular inflammation is faster with mycophenolate than with methotrexate. Azathioprine therapy has a higher rate of treatment-related side effects compared with the other 2 agents. The authors have no proprietary or commercial interest in any materials discussed in this article

Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study

PurposeTo describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial.DesignRandomized clinical trial with extended follow-up.MethodsReview of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically related.ResultsA total of 250 eyes (146 patients) had at least 1 implant placed. Median follow-up time after implant placement was 6 years (range 0.5-9.2 years). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval [CI]: 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. Thirty-nine implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%-48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, P < .001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or its treatment.ConclusionThere is an increasing risk of dissociation of Retisert implants during follow-up; the risk is greater with removal/exchange surgeries, but the risk of both spontaneous and surgically related events increases with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected

Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

PurposeTo identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.DesignCohort study using randomized controlled trial data.MethodsMulticenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.ResultsBaseline factors significantly associated with reduced BCVA included age ≥50 vs <50 years; posterior vs intermediate uveitis; uveitis duration >10 vs <6 years; anterior chamber (AC) flare >grade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P < .001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening.ConclusionsIntermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation