Association Between Long-Lasting Intravitreous Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With Intermediate, Posterior, or Panuveitis.

IMPORTANCE: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. OBJECTIVE: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). INTERVENTIONS: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. MAIN OUTCOMES AND MEASURES: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. RESULTS: Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). CONCLUSIONS AND RELEVANCE: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00132691.

Treatment Options for Juvenile Idiopathic Arthritis (JIA) Associated Uveitis.

PURPOSE: To summarize the available published data regarding the treatment of JIA-associated chronic uveitis. METHODS: Available peer-reviewed publications regarding the treatments of JIA-associated uveitis were read by multiple authors (RMA, EM, JET, and DH) and the data from these reports were synthesized for this review. RESULTS: Juvenile idiopathic arthritis (JIA)-associated chronic uveitis is a significant cause of ocular morbidity and visual impairment in children, often resulting in more frequent complications and worse visual outcomes than other types of pediatric uveitis. Since not all patients respond to the first medication introduced, it is useful to have a wide range of available treatment modalities to address recalcitrant disease. Treatment options for JIA-associated uveitis have increased substantially over the past decade, particularly with the availability of newer biological agents in addition to established medication classes such as anti-inflammatories (including topical and systemic corticosteroids) and antimetabolites. CONCLUSIONS: Although data are increasing regarding biologic agents, definitive randomized prospective clinical trials would be helpful to determine their optimal dose, frequency, treatment duration, and long-term safety in children.

Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

OBJECTIVE: To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis). DESIGN: Randomized controlled parallel superiority trial. PARTICIPANTS: Patients with active or recently active uveitis. METHODS: Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis. MAIN OUTCOME MEASURES: Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked. RESULTS: On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more prescription-requiring infections than patients assigned to implant therapy (0.60 vs 0.36/person-year, P=0.034), without notable long-term consequences; systemic adverse outcomes otherwise were unusual in both groups, with minimal differences between groups. CONCLUSIONS: In each treatment group, mean visual acuity improved over 24 months, with neither approach superior to a degree detectable with the study's power. Therefore, the specific advantages and disadvantages identified should dictate selection between the alternative treatments in consideration of individual patients' particular circumstances. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression was well tolerated, suggesting that this approach is reasonably safe for local and systemic inflammatory disorders. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Complications of ganciclovir implant surgery in patients with cytomegalovirus retinitis: the Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial.

PURPOSE: To describe the complications of ganciclovir implant surgery in patients with cytomegalovirus retinitis. METHODS: Prospective data collection within the context of a randomized, controlled clinical trial, comparing a regimen of the ganciclovir implant plus oral ganciclovir to one of intravenous cidofovir for the treatment of cytomegalovirus retinitis in patients with AIDS. Adverse events were compared for patients undergoing implant surgery in the following groups: primary versus replacement implant surgery, inpatient versus outpatient surgery, and general versus local anesthesia. RESULTS: Fifty-six eyes of 42 patients underwent a total of 74 ganciclovir implant surgeries. Vitreous hemorrhage was the most common adverse event, occurring in 10% of eyes undergoing surgery with local anesthesia but in no eyes undergoing surgery with general anesthesia. All vitreous hemorrhages resolved within 60 days. Patients in the general anesthesia and inpatient surgery groups tended to have a lower risk of complications in the first 30 days than did patients in the local anesthesia and outpatient surgery groups, but no differences in the complication rate were found after 60 days. Visual acuity was similar among these different groups. There were no cases of endophthalmitis. CONCLUSION: Ganciclovir implant surgery in patients with AIDS and cytomegalovirus retinitis was associated with a low risk of serious complications in the first 60 days after surgery. Vitreous hemorrhage was the most commonly observed complication and resolved in all cases.