Dr. Gottlieb et al reply.

We thank the author for their reply1 and appreciate the approach of having clear terminology and standard definitions within clinical practice guidelines or recommendations, that are applicable across specialist groups. A definition of controlled anterior uveitis or quiescent disease is important for treatment decisions, particularly when classifying a patient's disease as failing current therapy and making decisions for escalating therapy.

Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

OBJECTIVE: To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion. RESULTS: The survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo. CONCLUSION: Recommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access.

Efficacy of Adalimumab in Non-Infectious Uveitis Across Different Etiologies: A Post Hoc Analysis of the VISUAL I and VISUAL II Trials.

Purpose: To assess efficacy of adalimumab versus placebo in patients with active or inactive noninfectious intermediate, posterior, or panuveitis across different etiologies.Methods: VISUAL I (V-I) and VISUAL II (V-II) clinical trials included adults with active or inactive uveitis, respectively, randomized to receive adalimumab or placebo. In a post hoc subgroup analysis, time to treatment failure (TTF) starting at week 6 (V-I) or week 2 (V-II) was analyzed using the Kaplan-Meier method. Hazard ratios (HR) for TTF with 95% CI were calculated with Cox proportional hazards regression.Results: The analysis included 217 V-I patients and 226 V-II patients. Treatment failure occurred later and risk was significantly lower in patients with idiopathic uveitis receiving adalimumab versus those receiving placebo in V-I (HR = 0.50 [CI, 0.30-0.84]; P = .006) and V-II (HR = 0.43 [CI, 0.22-0.83]; P = .010).Conclusions: Treatment failure risk was lower in patients with idiopathic noninfectious uveitis receiving adalimumab versus those receiving placebo.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Long-term outcomes in a series of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome.

OBJECTIVE: Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare entity with a potentially poor visual prognosis. Our objective is to review the clinical presentation and long-term outcomes of patients with IRVAN syndrome. DESIGN: This is a retrospective case series. METHODS: We reviewed the charts of all the patients diagnosed with IRVAN syndrome at our tertiary care centre from 2002 to 2015. RESULTS: We included the long-term clinical outcomes of 7 eyes (5 patients) diagnosed with IRVAN syndrome. After a mean follow-up of 84.9 months, best-corrected visual acuity was 20/40 or better in the majority of eyes (70%). Four (57.1%) patients had systemic conditions, namely, multiple sclerosis, ischemic stroke, and positive antiphospholipid titres. All eyes were treated with laser photocoagulation. Four (40%) eyes received adjunctive intravitreal bevacizumab injections. CONCLUSION: IRVAN is an important diagnosis for clinicians to recognize. When treated in a timely manner, long-term visual outcomes can be favourable.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Trabeculotomy in the Treatment of Pediatric Uveitic Glaucoma.

PURPOSE: To evaluate the efficacy and safety of trabeculotomy in the treatment of pediatric uveitic glaucoma (UG). MATERIALS AND METHODS: We retrospectively reviewed all cases that underwent trabeculotomy for pediatric UG at our center between 2008 and 2014. Up to 2 trabeculotomies per eye were performed in patients with medically controlled uveitis. Surgical success was defined as final intraocular pressure <22 mm Hg and ≥6 mm Hg after 1 or 2 trabeculotomies, with or without medications. Kaplan-Meier survival analyses were done. RESULTS: A total of 33 trabeculotomies were performed in 28 eyes of 22 patients. Diagnoses included UG associated with juvenile idiopathic arthritis (68.2%), idiopathic uveitis (22.7%), and pars planitis (9.1%). The average age at surgery was 9.8±3.7 (5 to 17) years. With a mean follow-up of 33.6±18.3 (10 to 78) months, the overall surgical success was 81.8%. The cumulative survival probability after up to 2 trabeculotomies was 0.86 (95% confidence interval, 0.71-0.93) at 12 months and 0.77 (95% confidence interval, 0.60-0.87) at 24 months. Four (11.5%) eyes required a second trabeculotomy to achieve surgical success and 4 (7.7%) required filtrating procedures. Intraocular pressure improved from 31.4±7.6 (18 to 50) mm Hg preoperatively to 15.0±3.6 (8 to 23) mm Hg at final visits, whereas the number of glaucoma medications decreased from 4.2±1.1 (1 to 5) to 0.4±1.0 (0 to 4). Visual acuity and intraocular inflammation remained stable (P>0.05) and there were no major complications. CONCLUSIONS: Trabeculotomy is a safe and effective surgery for pediatric UG.

Rate of endophthalmitis after cataract surgery in quebec, Canada, 1996-2005.

OBJECTIVE: To estimate the annual incidence of endophthalmitis after cataract surgery from January 1, 1996, through December 31, 2005, in Quebec, Canada. METHODS: Deidentified data were obtained from an outpatient physician billing database (Quebec State Control for Health Insurance [RAMQ]) with regard to all cataract surgical procedures performed from January 1, 1996, through December 31, 2005, in Quebec. For this cohort, records of an International Classification of Diseases, Ninth Revision (ICD-9) code for endophthalmitis during the same years were requested from 2 sources: the RAMQ outpatient database and an inpatient hospital discharge database (Maintenance and Exploitation of Data for the Study of Hospitalized Patients [MED-ECHO]). Endophthalmitis after cataract surgery was assumed if it occurred within 90 days of the surgery. Risk factors were examined using chi(2) tests and logistic regression. RESULTS: After exclusions, 490 690 cataract surgical procedures were performed from January 1, 1996, through December 31, 2005. A total of 754 cases of endophthalmitis occurred within 90 days after surgery for an overall incidence rate of 1.5 per 1000 surgical procedures (95% confidence interval [CI], 1.4-1.7). Factors associated with endophthalmitis included age of 85 years or older (odds ratio [OR], 1.34; 95% CI, 1.06-1.70), male sex (1.44; 1.24-1.66), later year of surgery (0.94; 0.92-0.97), and region of cataract surgery, because regions 6 (2.21; 1.91-2.55) and 9 (4.00; 2.48-6.43) had higher rates compared with all other regions. CONCLUSION: Reasons that explain the apparent decrease in endophthalmitis, especially in 2005, should be explored and further research performed to understand why certain patients and regions have higher risks of endophthalmitis after cataract surgery.

Recurrent anterior uveitis after trabeculectomy with mitomycin C.

OBJECTIVE: To report 4 cases of recurrent anterior uveitis occurring 1-11 months after trabeculectomy with mitomycin C. DESIGN: Observational case series. PARTICIPANTS: Four patients in whom recurrent uveitis developed after trabeculectomy with mitomycin C, followed at Maisonneuve-Rosemont Hospital in Montreal, Quebec. METHODS: Retrospective review of the medical records. RESULTS: One to 11 months after trabeculectomy with mitomycin C, noninfectious, recurrent anterior uveitis developed in 4 patients with no prior history of uveitis. Topical and intravitreal corticosteroids were effective in reducing acute inflammation, yet 2 patients went on to have chronic anterior uveitis. CONCLUSIONS: Recurrent anterior uveitis presenting later than 3 weeks postoperatively may be associated with trabeculectomy with mitomycin C. It should be included in the differential diagnosis of a nonresolving blebitis.