Filgotinib in Active Noninfectious Uveitis: The HUMBOLDT Randomized Clinical Trial.

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.

Incidence and Remission of Post-Surgical Cystoid Macular Edema Following Cataract Surgery in Eyes With Intraocular Inflammation.

PURPOSE: To evaluate the incidence, remission, and relapse of post-surgical cystoid macular edema (PCME) following cataract surgery in inflammatory eye disease. METHODS: A total of 1859 eyes that had no visually significant macular edema prior to cataract surgery while under tertiary uveitis management were included. Standardized retrospective chart review was used to gather clinical data. Univariable and multivariable logistic regression models with adjustment for inter-eye correlations were performed. RESULTS: PCME causing VA 20/50 or worse was reported in 286 eyes (15%) within 6 months of surgery. Adults age 18-64 years as compared to children (adjusted odds ratio [aOR] = 2.42, for ages 18 to 44 years and aOR = 1.93 for ages 45 to 64 years, overall P = .02); concurrent use of systemic immunosuppression (conventional aOR 1.53 and biologics aOR = 2.68, overall P = .0095); preoperative VA 20/50 or worse (overall P < .0001); cataract surgery performed before 2000 (overall P = .03) and PMCE in fellow eye (aOR = 3.04, P = .0004) were associated with development of PCME within 6 months of cataract surgery. PCME resolution was seen in 81% of eyes at 12 months and 91% of eyes at 24 months. CME relapse was seen in 12% eyes at 12 months and 19% eyes at 24 months. CONCLUSIONS: PCME occurs frequently in uveitic eyes undergoing cataract surgery; however, most resolve within a year. CME recurrences likely are due to the underlying disease process and not relapses of PCME.

Outcomes in Patients With Vogt-Koyanagi-Harada Disease From the First-Line Antimetabolites for Steroid-Sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX vs MMF) and disease stage (acute vs chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25 mg weekly oral MTX or 1.5 g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P = .12) or in BSCVA improvement (P = .78). MTX was superior to MMF in reducing CST (P = .003) and resolving SRD (P = .02). There was no significant difference in treatment success by disease stage (P = .25), but patients with acute VKH had greater improvement in BSCVA (P < .001) and reduction of CST (P = .02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. NOTE: Publication of this article is sponsored by the American Ophthalmological Society TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

Posterior capsular opacification and YAG laser capsulotomy in uveitis patients following cataract surgery.

OBJECTIVE: To evaluate the incidence of visually significant posterior capsule opacification (PCO with visual acuity ≤20/50) and the incidence of Nd:YAG laser capsulotomy in the year following cataract surgery for uveitic eyes. METHOD: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study using a standardized chart review process. RESULTS: Among 1,855 uveitic eyes of 1,370 patients who had undergone cataract surgery, visually significant PCO occurred in 297 eyes (16%), and YAG laser capsulotomy was done in 407 eyes (22%) within the first year following surgery. Higher odds of developing 20/50 visual acuity attributed to PCO were noted in children and young adults compared with adults older than 65 years of age (overall p = 0.03). Poorer preoperative visual acuity (overall p = 0.0069) and postoperative inflammation (odds ratio [OR] = 1.83; 95% CI, 1.37-2.45; p < 0.0001) were associated with PCO incidence. In multivariable analysis, risk factors for YAG laser capsulotomy were younger age groups compared with those older than 65 years of age at the time of surgery (adjusted OR [aOR] = 1.90-2.24; 95% CI, 1.90-2.24; overall p = 0.0007), female sex (aOR = 1.37; 95% CI, 1.03-1.82; p = 0.03), postoperative active inflammation (aOR = 165; 95% CI, 1.27-2.16; overall p < 0.0001), extracapsular cataract extraction compared with phacoemulsification (aOR = 1.70; 95% CI, 1.17-2.47; overall p < 0.0001), and insertion of an intraocular lens (aOR = 4.60; 95% CI, -2.29-9.25; p < 0.0001). Black race was associated with lower YAG laser capsulotomy incidence than Whites (aOR = 0.36; 95% CI, 0.24-0.52; overall p < 0.0001). CONCLUSIONS: Vision-reducing (≤20/50) PCO is common, occurring in about one sixth of uveitic eyes within 1 year of cataract surgery; a higher number (22%) of eyes underwent YAG laser capsulotomy within the first year. Age and postoperative inflammation following cataract surgery are the variables most associated with the incidence of visually significant PCO and YAG laser capsulotomy.

Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites.

PURPOSE: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites. METHODS: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint. RESULTS: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure. CONCLUSION: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment.Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference.

Characterization of autoimmune eye disease in association with Down's syndrome.

BACKGROUND: Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. RESULTS: We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. DISCUSSION: A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

Late diagnosis of Cutibacterium acnes (formerly Proprionibacterium acnes) endophthalmitis and the importance of dual testing with bacterial culture and polymerase chain reaction.

PURPOSE: To describe two cases of C. acnes endophthalmitis that reinforce the importance of performing both bacterial culture and 16s polymerase chain reaction when the causative pathogen is unclear or difficult to culture, such as C. acnes. A case of C. acnes endophthalmitis complicated by sub-buckle scleral perforation is illustrated with intraoperative photography. METHODS: Two-case series. RESULTS: Case 1 describes a case of C. acnes endophthalmitis in a longstanding pseudophakic patient following multiple vitrectomies for recurrent retinal detachment, complicated by sub-buckle scleral perforation. Bacterial culture revealed C. acnes while 16s PCR was negative. Conversely, Case 2 demonstrates a case of chronic endophthalmitis diagnosed one year following cataract surgery. PCR (with repeat tap for confirmation) revealed C. acnes with a negative culture. CONCLUSION: When the causative pathogen of endophthalmitis is unclear, dual testing of microbial culture and C. acnes 16s PCR improves the diagnostic yield of investigations for fastidious pathogens. C. acnes can present as an indolent or virulent endophthalmitis.

Acanthamoeba-associated retinitis successfully treated with intravitreal and systemic antimicrobials.

Purpose: To describe a case of unilateral Acanthamoeba-associated retinitis in the absence of concomitant corneal infection in an immunocompetent host without risk factors. Observations: A 37-year-old woman presented with unilateral multifocal retinitis with minimal vitritis. Anterior segment was normal. Conventional diagnostics of bacterial, fungal, viral, Toxoplasma and Toxocara etiologies all returned negative. Empiric treatments were unsuccessful, including oral valacyclovir, oral fluconazole, as well as intravitreal injection of vancomycin and ceftazidime. Metagenomic deep sequencing (MDS) identified Acanthamoeba genomic fragments in the vitreous sample. Multiple intravitreal voriconazole injections were performed and achieved partial suppression of lesion growth. Subsequent dual therapy of oral voriconazole and trimethoprim-sulfamethoxazole led to resolution of the lesions and vision improvement without further injections. Conclusions and importance: This is an unusual case of unilateral Acanthamoeba-associated retinitis without concomitant corneal infection, diagnosed via unbiased DNA and RNA deep sequencing, with other etiologies ruled out by conventional approaches. Treatment with systemic and intravitreal therapy led to a successful resolution of retinitis and vision improvement. Our case demonstrates the potential of MDS as an unbiased diagnostic tool for rare ocular pathogens and the therapeutic effect of oral voriconazole with trimethoprim-sulfamethoxazole for Acanthamoeba intraocular infection.

Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality.

PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Incidence of and Risk Factors for Cataract in Anterior Uveitis.

PURPOSE: To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis. DESIGN: Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010). METHODS: Data were harvested by trained expert reviewers, using protocol-driven review of experts' charts. We studied cataract incidence-newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery-in 3923 eyes of 2567 patients with anterior uveitis. RESULTS: Cataract developed in 507 eyes (54/1000 eye-years, 95% CI 49-59). Time-updated risk factors associated with cataract included older age (≥65 vs <18 years: adjusted hazard ratio [aHR] 5.04, 95% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95% CI 1.10-3.14), band keratopathy (aHR 2.23, 95% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95% CI 2.83-4.87), and elevated intraocular pressure ≥30 vs 6-20 mm Hg (aHR 2.57, 95% CI 1.38-4.77). Primary acute (aHR 0.59, 95% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1%-equivalent use (≥2 drops/day) was associated with >2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher. CONCLUSIONS: Cataract complicates anterior uveitis in ∼5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence.

Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

Risk Factors Associated with Unexpected Refractive Outcomes in Uveitic Cataract Surgery.

OBJECTIVE: Assess refractive outcomes following uveitic cataract surgery and identify factors associated with deviations from the target refractive goal. METHODS: A multicenter retrospective chart review was performed for 216 subjects with uveitis undergoing cataract surgery. Prediction error was calculated and tested for association with demographic and clinical characteristics using single variable and multiple regression analysis. RESULTS: 39.8% of eyes deviated from the intended refractive target by at least 0.5 diopters (D). The mean prediction error was 0.56 ± 0.67 D. Younger age (p = 0.042), preoperative inflammatory corneal findings (keratic precipitates and/or band keratopathy) (p = 0.0004), and poorer postoperative visual acuity (p = 0.0054) were associated with a deviation from the intended refractive target by at least 1 D. CONCLUSIONS: A higher percentage of eyes undergoing uveitic cataract surgery deviated from the intended refractive target when compared to reported refractive outcomes in normal subjects. Younger age, preoperative inflammatory corneal sequelae, and poorer postoperative visual acuity were associated with this outcome.

Reduced Dose Methotrexate and Mycophenolate Mofetil in Noninfectious Uveitis: A Sub-Analysis from the First-Line Antimetabolites as Steroid Sparing Therapy (FAST) Trial.

PURPOSE: Some patients taking methotrexate (MTX) or mycophenolate mofetil (MMF) experience intolerable side effects at full doses. We evaluated whether dose reduction affected treatment outcomes in uveitis patients. METHODS: Subanalysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. Patients were randomized to receive MTX (25 mg weekly) or MMF (3 g daily). A pre-specified dose reduction protocol could be employed for intolerable side effects. Primary analysis was performed at 6 months. RESULTS: 43/194 patients (22%) required dose reduction. 88/151 patients (58%) on maximum doses and 32/43 patients (74%) on reduced doses were deemed treatment successes at 6 months. The odds ratio point estimate (1.60, 95% CI 0.72-3.74) favored dose-reduction but this was not significant. Following reduction, adverse events improved at the subsequent study visit (79 events reduced to 63 events). CONCLUSION: Dose reduction of antimetabolites was not associated with worse outcomes in this subanalysis of a uveitis trial.

Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as Steroid-Sparing Treatment Uveitis Trial.

PURPOSE: To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil. DESIGN: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial. PARTICIPANTS: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017. METHODS: 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. MAIN OUTCOME MEASURES: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity. RESULTS: 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). CONCLUSIONS: 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.

Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors.

PURPOSE: To estimate the incidence of corneal endothelial transplantation (CET) and identify risk factors among patients with noninfectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with noninfectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of CET, including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet membrane endothelial keratoplasty procedures. The incidence of CET was calculated. Potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis, with a median follow-up of 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%-1.53%). Risk factors for CET included age >60 years vs <40 years (adjusted hazard ratio [aHR], 16.5; 95% CI, 4.70-57.9), anterior uveitis and scleritis vs other types (aHR, 2.97; 95% CI, 1.46-6.05; and aHR, 4.14; 95% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR, 2.84; 95% CI, 1.32-6.13), cataract surgery (aHR, 4.44; 95% CI, 1.73-11.4), tube shunt surgery (aHR, 11.9; 95% CI, 5.30-26.8), band keratopathy (aHR, 5.12; 95% CI, 2.34-11.2), and hypotony (aHR, 7.38; 95% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, peripheral anterior synechia, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing CET; these factors likely are associated with endothelial cell damage.

Risk of Cataract in Intermediate Uveitis.

PURPOSE: To determine the incidence of and predictive factors for cataract in intermediate uveitis. DESIGN: Retrospective cohort study. METHODS: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at 5 participating US tertiary care uveitis centers. The primary outcome was development of vision-compromising cataract as defined by a decrease in visual acuity to 20/40 or less, or requiring cataract surgery. Survival analysis assessed visually defined cataract to avoid bias due to timing of surgery vis-à-vis inflammatory status. RESULTS: Among 2,190 eyes of 1,302 patients with intermediate uveitis, the cumulative incidence of cataract formation was 7.6% by 1 year (95% confidence interval [CI] = 6.2%-9.1%), increasing to 36.6% by 10 years (95% CI = 31.2%-41.6%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (hazard ratio = 2.68, 95% CI = 2.00-3.59, P < .001), and in eyes with epiretinal membrane formation (hazard ratio = 1.54, 95% CI = 1.15-2.07, P = .004). Higher dose corticosteroid therapy was associated with significantly higher incidence of cataract, especially time-updated use of topical corticosteroids ≥2 times/d or ≥4 periocular corticosteroid injections. Low-dose corticosteroid medications (oral prednisone 7.5 mg daily or less, or topical corticosteroid drops <2 times/d) were not associated with increased cataract risk. CONCLUSIONS: Our study found that the incidence of clinically important cataract in intermediate uveitis is moderate. The risk is higher with markers of severity and with higher doses of corticosteroid medications, the latter being potentially modifiable.

Health- and Vision-Related Quality of Life in a Randomized Controlled Trial Comparing Methotrexate and Mycophenolate Mofetil for Uveitis.

PURPOSE: To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites. DESIGN: Secondary analysis of a randomized controlled trial. PARTICIPANTS: Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico. METHODS: From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests. MAIN OUTCOME MEASURES: Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months). RESULTS: Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively). CONCLUSIONS: Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

Contemporaneous Risk Factors for Visual Acuity in Non-Infectious Uveitis.

INTRODUCTION: We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population. METHODS: Retrospective data from 5,530 noninfectious uveitis patients were abstracted by expert reviewers, and contemporaneous associations of VA with demographic and clinical factors were modeled. RESULTS: Patients were a median of 41 years old, 65% female, and 73% white. Eyes diagnosed ≥5 years prior to cohort entry had worse VA (-1.2 lines) than those diagnosed <6 months prior, and eyes with cataract surgery performed prior to entry had worse VA (-5.9 lines) than those performed during follow-up. Vitreous haze (-4.2 lines for 3+ vs quiet), hypotony (-2.5 lines for ≤5 mm Hg vs 6-23 mm Hg), and CNV (-1.8 lines) all were strongly associated with reduced VA. CONCLUSION: Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery.