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To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil. Subanalysis of a block-randomized, observer-masked, multicenter clinical trial. Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017. Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group. Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity. Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 μm and 342 μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 μm (interquartile range [IQR], −132.3 to 4.0) and 54 μm (IQR, −95.5 to −4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, −32.3 to −0.5) and 50 μm (IQR, −181.0 to −10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92). Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema. [ABSTRACT FROM AUTHOR]

Purpose: To describe the epidemiologic, clinical, and histopathologic features of a presumed trematode granulomatous anterior uveitis, primarily in children from south India.Design: Prospective, noncomparative, case series.Methods: Children with clinical evidence of granulomatous anterior uveitis were selected for the study. Those who presented with distinct anterior chamber nodules were evaluated. Demographic details, such as clinical findings and course of illness, were noted. Patients underwent either medical treatment or surgical aspiration of the lesion based on the size of the lesion. Aspirated materials were subjected to histopathologic analysis and cultures for bacteria and fungi. Response to treatment and final visual status were evaluated.Results: One hundred thirteen patients with anterior chamber nodules were seen between 1998 and 2000. Ninety-three (82.4%) were males and 20 (17.7%) were females. The median age was 11.0 years. All patients were from south India and all gave a history of bathing or swimming in the local pond or river. All had normal systemic work ups. Of the 113 patients, 110 had anterior chamber nodules and three had both anterior chamber and subconjunctival nodules. Aspirates of the anterior chamber lesions revealed lymphocytes, intact and necrotic neutrophils, and eosinophils admixed with histiocytes. One subconjunctival nodule showed necrotizing granuloma, displaying the tegument of a trematode. Those patients who were followed had good visual recovery after medical or surgical intervention or both.Conclusion: The present study shows a newly recognized granulomatous anterior uveitis caused by a presumed water-borne trematode infection. This infection appears to be a common cause of pediatric granulomatous anterior uveitis in south India. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale). Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 μg (n = 208), 440 μg (n = 208), or 880 μg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg dose. The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 μg compared with 44 μg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. Intravitreal sirolimus 440 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reliability of clinical grading of vitreous haze using a new 9-step ordinal scale versus the existing 6-step ordinal scale. Design: Evaluation of diagnostic test (interobserver agreement study). Participants: A total of 119 consecutive patients (204 uveitic eyes) presenting for uveitis subspecialty care on the study day at 1 of 3 large uveitis centers. Methods: Five pairs of uveitis specialists clinically graded vitreous haze in the same eyes, one after the other using the same equipment, using the 6- and 9-step scales. Main Outcome Measures: Agreement in vitreous haze grade between each pair of specialists was evaluated by the κ statistic (exact agreement and agreement within 1 or 2 grades). Results: The scales correlated well (Spearman's ρ = 0.84). Exact agreement was modest using both the 6-step and 9-step scales: average κ = 0.46 (range, 0.28-0.81) and κ = 0.40 (range, 0.15-0.63), respectively. Within 1-grade agreement was slightly more favorable for the scale with fewer steps, but values were excellent for both scales: κ = 0.75 (range, 0.66-0.96) and κ = 0.62 (range, 0.38-0.87), respectively. Within 2-grade agreement for the 9-step scale also was excellent (κ = 0.85; range, 0.79-0.92). Two-fold more cases were potentially clinical trial eligible on the basis of the 9-step than the 6-step scale (P<0.001). Conclusions: Both scales are sufficiently reproducible using clinical grading for clinical and research use with the appropriate threshold (≥2- and ≥3-step differences for the 6- and 9-step scales, respectively). The results suggest that more eyes are likely to meet eligibility criteria for trials using the 9-step scale. The 9-step scale appears to have higher reproducibility with Reading Center grading than clinical grading, suggesting that Reading Center grading may be preferable for clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reproducibility of new criteria for grading the site and activity of intraocular inflammation. Design: Cross-sectional agreement study. Methods: Grading of 202 eyes of 101 patients with uveitis was conducted by pairs of uveitis subspecialists at three uveitis subspecialty clinics. Agreement in grading location of inflammation, anterior chamber (AC) cells, AC flare, vitreous cells (present or absent), and vitreous haze was calculated. Results: Proposed criteria for grading the location of intraocular inflammation had moderate reproducibility (κ range, 0.49 to 0.61). Reproducibility improved (κ range, 0.61 to 0.73) when the newly proposed category of anterior and intermediate uveitis was excluded. The ranges of κ statistics for exact agreement on gradings of AC cells (range, 0.34 to 0.43) demonstrated low to moderate levels of agreement, and gradings of AC flare (range, 0.50 to 0.64), vitreous cells (range, 0.48 to 0.51), and vitreous haze (0.53) were in the moderate agreement range. However, agreement within 1 grade was outstanding for AC cells (κ range, 0.81 to 1.00) and vitreous haze (κ, 0.75). For AC flare, a distribution skewed toward low grades within 1 grade made κ statistics unstable. Conclusions: Proposed methods for grading inflammatory activity have moderate reproducibility for exact agreement in most instances. However, agreement within 1 grade is excellent for grading of AC cells and vitreous haze. The method for grading the site of intraocular inflammation also produces moderate levels of agreement, and in our hands was improved by excluding both anterior and intermediate uveitis. Improved methods for grading AC flare and vitreous cells are needed. [Copyright &y& Elsevier]