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Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.

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PURPOSE: To examine postoperative outcomes of internal limiting membrane peeling (ILMP) versus flap (ILMF) in the closure of full-thickness macular holes. METHODS: Retrospective chart review of patients who underwent pars plana vitrectomy and gas tamponade with ILMP or ILMF to close full-thickness macular hole at the Atrium Health Wake Forest Baptist from January 2012 to October 2022 with at least 3 months follow-up. Main outcome measures were type 1 primary full-thickness macular hole closure and postoperative best-corrected visual acuity in mean logMAR. RESULTS: One hundred thirty and 30 eyes underwent ILMP and ILMF, respectively. There were no significant differences in baseline characteristics between the groups. Ninety-six percent of ILMP eyes and 90% of ILMF eyes achieved primary hole closure ( P = 0.29). Among all eyes with primary hole closure, best-corrected visual acuity at 1 year was not different between the groups, but when stratified by lens status, it was superior in the ILMP versus ILMF group in pseudophakic eyes: the estimated least-squares mean best-corrected visual acuity (Snellen equivalent) (95% confidence interval) was 0.42 (20/50) (0.34, 0.49) in the ILMP group and 0.71 (20/100) (0.50, 0.92) in the ILMF group. CONCLUSION: Internal limiting membrane peeling and ILMF techniques yielded similarly high full-thickness macular hole closure rates. In pseudophakic eyes with primary hole closure, ILMF eyes had worse best-corrected visual acuity at 1 year.

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PURPOSE OF REVIEW: The transition from 20-gauge vitrectomy surgery to 23-gauge and 25-gauge instrumentation was not without its complications. Early instrumentation provided limitations in surgical technique, including limited illumination, instrument flex, and efficiency of vitreous removal. The most concerning finding arose from two separate retrospective studies which reported increased rates of postoperative endophthalmitis following small-gauge vitrectomy. This situation raised questions as to whether this shift in technique was appropriate. RECENT FINDINGS: Following these concerning reports of complication, a Microsurgery Safety Task Force was convened to evaluate the scientific evidence and create guidelines with the intent to minimize the rates of postoperative infection with small-gauge vitrectomy surgery. Further studies of wound architecture and advances in instrumentation and surgical technique have improved outcomes. More recent studies demonstrate equivalent rates of postoperative endophthalmitis between 20-gauge and smaller gauge instrumentation. SUMMARY: The guidelines of the Microsurgery Safety Task Force, evolutions in instrumentation and surgical technique, and improved understanding of small-gauge vitrectomy wound construction have yielded comparable results in endophthalmitis rates for small-gauge vitrectomy versus traditional 20-gauge approaches.

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