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Purpose of review Here, we provide an overview of Vogt-Koyanagi-Harada disease (VKH), including recent updates in our understanding of disease pathophysiology, classification and therapeutics. Recent findings Advancements in bioinformatics, metabolomics and genomics investigations continue to illuminate VKH pathogenesis, and may provide insight into future therapeutic options. Multimodal imaging is indispensable in the initial evaluation of VKH, and is becoming increasingly important in understanding disease pathogenesis, as well as monitoring therapeutic response. Enhanced VKH classification criteria, released in 2021, provide standardized guidelines and terminology for clinical and research purposes. Summary Modern research and imaging techniques continue to improve our understanding of VKH; more work is needed to further elucidate pathogenic mechanisms and establish optimal therapeutic recommendations.

To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.Secondary analysis of a randomized controlled trial.Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.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.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).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 (P0.01). 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; P0.05 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).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.

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 discontinued 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 of study drug.MAIN OUTCOME MEASURES: Main outcome measures were 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 corticosteroids.RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in 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, respectively, by week 150. Mean daily dose of 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 for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.

We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population.Retrospective data from 5,530 ...

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.

PURPOSE: To estimate the incidence of corneal endothelial transplantation and identify risk factors among patients with non-infectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with non-infectious 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 corneal endothelial transplantation (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 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.

Purpose To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases. Design Retrospective analysis of cohort study data. Methods Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days. Results The time to success was shorter (more favorable) for MMF than MTX (hazard ratio = 0.68, 95% confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8 months, then converges at 9 months. The onset of corticosteroid-sparing success took more than 3 months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups. Conclusions Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.

Purpose: This article investigates the optical coherence tomography (OCT) and fundus autofluorescence imaging findings in birdshot chorioretinopathy (BSCR) and their association with visual acuity (VA). Methods: In a retrospective, cross-sectional study, we evaluated OCT images for changes in retinal structure including cystoid macular edema (CME), epiretinal membrane, and outer retinal lesions. We assessed autofluorescence images for hypoautofluorescent and hyperautofluorescent changes and noted the distribution of the lesions. Demographic data and VA at the time of imaging were also collected. Associations between OCT and autofluorescence findings and logarithm of the minimum angle of resolution VA were tested using linear regression. Results: We conducted a chart review of 80 eyes from 40 patients with BSCR. Outer retinal lesions were found on OCT in 28 of 80 eyes (35%) and disruption of the outer segment ellipsoid zone (EZ) occurred in 23 eyes (28.7%). Macular hypoautofluorescent lesions were more common than hyperautofluorescent lesions, present in 58.8% and 13% of eyes, respectively. The presence of outer retinal lesions on OCT was significantly associated with reduced VA ( P = .006) as was EZ disruption ( P = .003). These associations remained significant after accounting for the presence of macular edema. There was a trend toward association of macular hypoautofluorescent lesions with decreased vision, although it was not statistically significant ( P = .17). Conclusions: The association of outer retinal lesions with decreased VA suggests a mechanism of central vision loss that is distinct from CME and may provide an additional objective finding to monitor disease activity in BSCR patients.

PURPOSE To develop an objective intraocular inflammation composite score. METHODS Cross-sectional study. Non-invasive image acquisition and processing were conducted from April 2017 to April 2019. Inflammation-grade stratified eyes from patients with active, inactive uveitis and healthy controls were recruited. After clinical assessment, four anterior and posterior segment image acquisition protocols per eye, using swept-source optical coherence tomography (SS-OCT), were performed at inclusion. Eight imaging biomarkers in three domains: anterior, intermediate and posterior were studied. They were ranked and selected by discriminatory power and correlation with clinical scores. A final SS-OCT-derived composite uveitis activity score (SS-UAS) was developed through multiple linear regression. RESULTS We studied 224 eyes with uveitis (165 active and 59 inactive) from 165 patients (mean age 46.6 SD 15.5 years; 55.3% women) and 38 eyes from 19 healthy controls (mean age 43.6 SD 17.1; 47% women). The selected SS-OCT-derived biomarkers to build the final score were anterior chamber hyper-reflective dots (anterior), high-definition relative vitreous intensity (intermediate) and the averaged thickened retinal index (posterior). Swept-source (SS)-UAS was highly discriminant between active and inactive, and between active and healthy eyes (means 2.06 SD 1.86, 0.93 SD 0.44, and 0.96 SD 0.38, respectively, both p -, Mann-Whitney U). Construct validity (Cronbach's alpha = 0.7), internal consistency, criterion validity and reliability (concordance correlation coefficient intra-rater = 0.99, 95% CI: 0.98-0.99; inter-rater = 0.98, 95% CI: 0.96-0.99) were favourable. CONCLUSIONS Global intraocular inflammation can potentially be staged and scored objectively, continuously, consistently and in a valid manner through the combined processing of SS-OCT scans.

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 (SITE) Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at five participating United States 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 one year (95% CI=6.2–9.1%), increasing to 36.6% by ten years (95% CI=31.2–41.6%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (HR=2.68, 95% CI=2.00–3.59, p

Gordonia bronchialis is an aerobic actinomycetes that rarely causes infections in humans. Few reports describe Gordonia spp. causing eye-related infections. We report a case of chronic infectious endophthalmitis in Oregon, USA, associated with infection by G. bronchialis.

Purpose Chronic use of corticosteroids for the treatment of uveitis has been linked with drug-associated toxicity and adverse events (AEs). This study examines the association between corticosteroid dosage and incidence rates of corticosteroid-related AEs. Design A post hoc analysis of the VISUAL-1 and VISUAL-2 placebo-controlled clinical trials. Participants The clinical trials consisted of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate, posterior, and panuveitis. Patients were randomized to receive adalimumab or placebo and underwent a protocol-defined mandatory taper to discontinue their oral corticosteroids. Methods Adverse event data were collected at each visit and included an assessment of the corticosteroid relationship by the investigator. A longitudinal Poisson regression model was estimated controlling for time-dependent corticosteroid dose, age, sex, prior oral corticosteroid dose, prior topical corticosteroid use, and concomitant immunosuppressive drug use. Only patients randomized to placebo were considered. Main Outcome Measures The primary outcome measure was the frequency of AEs. Results The incidence rates of corticosteroid-related AEs among placebo patients during the prednisone treatment period in VISUAL-1 was statistically higher than after discontinuation (454.2 per 100 patient-years [PY] vs. 36.1 per 100 PY, incident rate ratio = 12.6, P P P P P P = 0.05) corticosteroid-related AEs per year compared with a patient taking 10 mg/day. Conclusions Evidence from VISUAL-1 and VISUAL-2 suggests that the incidence rates of corticosteroid-related AEs increase systematically with corticosteroid dose.

INTRODUCTION: We evaluated visual acuity (VA) over 5 years in a subspecialty non-infectious uveitis population. METHODS: Retrospective data from 5,530 non-infectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up. RESULTS: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P

Purpose: To determine the efficacy of pegylated interferon alfa-2A in the treatment of refractory inflammatory cystoid macular edema (CME)Methods: Retrospective chart reviewResults: Treatment with pegylated interferon alfa-2A led to an improvement in CME in all eyes of seven included patients, with a mean decrease in CMT from 478 µm to 310 µm (p < .05). The vision in one patient did not improve due to preexisting retinal atrophy. All other eyes showed improvement in vision, with a mean improvement in best LogMAR visual acuity from +0.59 to +0.28 (p < .05). The treatment effect was sustained with low-dose treatment every 2 weeks or less in the majority of patients. Two patients who stopped interferon treatment given flu-like symptoms and intolerable rash, respectively, showed rapid recurrence of CME.Conclusions: Weekly administration of pegylated interferon alfa-2A is an effective treatment for refractory inflammatory CME, though side effects may limit tolerability in some patients.

Purpose This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases. Design Retrospective cohort study. Methods Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4 US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors. Results A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR] = 109), undifferentiated choroiditis (OR = 9.18), sympathetic ophthalmia (OR = 8.43), primary or secondary panuveitis (OR = 7.09), multifocal choroiditis with panuveitis (OR = 4.51), and “other” forms of posterior uveitis (OR = 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate = 0.47% [0.40%-0.56%/eye-year]). VKH (HR = 13.2), sympathetic ophthalmia (HR = 5.82), undifferentiated choroiditis (HR = 6.03), primary or secondary panuveitis (HR = 4.21), and rheumatoid arthritis (HR = 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD. Conclusions Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.

To describe the finding of inferior corneal haze secondary to presumed inflammatory endothelio-10 pathy in a series of patients with pars planitis.Single-center retrospective observational consecutive case-series.Seven patients with an established diagnosis of pars planitis are described in this case series including four females and three males. The ages ranged from 5 to 31 years at presentation. Pars planitis was bilateral in six patients and unilateral in one patient. Fundus examinations revealed vitreous opacities and pars plana exudates in all seven patients, cystoid macular edema in four patients, and peripheral retinal vasculitis in two patients. Corneal examination revealed opacification of the posterior cornea in an inferior location in 10 of the 13 eyes with pars planitis. Only one of these eyes had keratic precipitates. For a given patient, corneal involvement was more commonly seen in the more inflamed eye. In one patient with active inflammation, microcystic corneal edema was noted to predate the formation of inferior corneal endothelial opacification, suggesting that physical proximity to the site of inflammation at the inferior pars plana is the cause of this notable physical finding.Inferior posterior corneal haze related to inflammatory endotheliopathy may occur in eyes with pars planitis. As patients with pars planitis may be otherwise asymptomatic, this corneal finding shouldprompt a detailed funduscopic examination to rule out this form of uveitis.

The development of the photoreceptors of human embryos and fetuses dating from 7 weeks to term were studied. The outer segments of rods and cones began to form at the seventh month. The arrangement of the newly formed discs were not regular, but at term they were arranged parallel to each other and perpendicular to the long axes of the outer segments. At the 9th month, no phagosome containing discs was seen in the pigment epithelial cells, but they were discerned in those of the term fetuses.

PurposeTo assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU).MethodsPatients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control).ResultsOver the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed.ConclusionApproximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.

Acute anterior uveitis is generally recognized as the most common form of uveitis. An association with HLA-B27 is seen in approximately half of cases of acute anterior uveitis. The prevalence of HLA-B27 varies widely between ethnic populations, with an approximate 8-10% prevalence in non-Hispanic whites and lower prevalence in Mexican- (4%) and African- (2-4%) Americans. A group of systemic inflammatory diseases, the spondyloarthropathies, similarly demonstrates a strong association with HLA-B27. The strength of association varies, depending on the specific spondyloarthropathy, with the strongest association found in patients with ankylosing spondylitis. The majority of patients with HLA-B27 associated uveitis will have an underlying spondyloarthropathy. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history to assess for features of a spondyloarthropathy as the characteristics of any associated uveitis may vary.

Purpose: To evaluate adalimumab as an immunomodulatory treatment for non-infectious ocular inflammatory diseases.Methods: Characteristics of patients treated with adalimumab were abstracted in a standardized chart review. Main outcomes measured were control of inflammation, corticosteroid-sparing effect, and visual acuity.Results: In total, 32 patients with ocular inflammation were treated with adalimumab. The most common ophthalmic diagnoses were anterior uveitis, occurring in 15 patients (47%), and scleritis, occurring in 9 patients (28%). At 6 months of therapy, among 15 eyes with active inflammation, 7 (47%) became completely inactive, and oral prednisone was reduced to ≤10 mg/day in 2 of 4 patients (50%). On average, visual acuity decreased by 0.13 lines during the first 6 months of treatment. Adalimumab was discontinued because of lack of effectiveness in four patients within 6 months.Conclusions: Adalimumab was moderately effective in controlling inflammation in a group of highly pre-treate...

To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis.Retrospective cohort study.Patients with uveitis at 4 US academic ocular inflammation subspecialty practices.Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate.Prevalence and incidence of NV.Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13,810 eyes had NV (prevalence = 0.77%, 95% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26,465 eye-years (incidence, 0.33%/eye-year; 95% CI, 0.27-0.41). Factors associated with incident NV include age35 years compared with35 years (adjusted hazard ratio [aHR], 2.4; 95% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed5 years ago, aHR, 2.4 [95% CI, 1.1-5.0] and aHR, 2.6 [95% CI, 1.2-6.0] for diagnosis within1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95% CI, 2.5-11), and panuveitis (aHR, 4.3; 95% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus.Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection.

Purpose To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. Design Retrospective cohort study. Participants Patients diagnosed with anterior uveitis of longer than 3 months’ duration followed up at United States tertiary uveitis care facilities. Methods Estimation of remission incidence and identification of associated predictors used survival analysis. Main Outcome Measures Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or—for patients who did not return for follow-up after 90 days—remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied. Results Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% (95% confidence interval [CI], 30.4%–35.2%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95% CI, 0.44–0.83), bilateral uveitis (aHR, 0.75; 95% CI, 0.59–0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56–0.88), and glaucoma surgery (aHR, 0.63; 95% CI, 0.45–0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95% CI, 0.21–0.60) and synechiae (aHR, 0.62; 95% CI, 0.41–0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age ≥40 years vs. Conclusions Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course.

Purpose To assess how often non-infectious anterior scleritis remits and identify predictive factors. Methods Our retrospective cohort study at four ocular inflammation subspecialty centers collected data for each affected eye/patient at every visit from center inception (1978, 1978, 1984, 2005) until 2010. Remission was defined as inactivity of disease off all suppressive medications at all visits spanning at least three consecutive months or at all visits up to the last visit (to avoid censoring patients stopping follow-up after remission). Factors potentially predictive of remission were assessed using Cox regression models. Results During 1,906 years' aggregate follow-up of 832 affected eyes, remission occurred in 214 (170 of 584 patients). Median time-to-remission of scleritis = 7.8 years (95% confidence interval [CI]: 5.7, 9.5). More remissions occurred earlier than later during follow-up. Factors predictive of less scleritis remission included scleritis bilaterality (adjusted hazard ratio [aHR] = 0.46, 95% CI: 0.32-0.65); and diagnosis with any systemic inflammatory disease (aHR = 0.36, 95% CI: 0.23-0.58), or specifically with Rheumatoid Arthritis (aHR = 0.22), or Granulomatosis with Polyangiitis (aHR = 0.08). Statin treatment (aHR = 1.53, 95% CI: 1.03-2.26) within ≤90 days was associated with more remission incidence. Conclusions Our results suggest scleritis remission occurs more slowly in anterior scleritis than in newly diagnosed anterior uveitis or chronic anterior uveitis, suggesting that attempts at tapering suppressive medications is warranted after long intervals of suppression. Remission is less frequently achieved when systemic inflammatory diseases are present. Confirmatory studies of whether adjunctive statin treatment truly can enhance scleritis remission (as suggested here) are needed.

To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric noninfectious uveitis.Multicenter retrospective cohort study.Nine hundred sixteen children (1593 eyes) younger than 18 years at presentation with noninfectious uveitis followed up between January 1978 and December 2007 at 5 academic uveitis centers in the United States.Medical records review by trained, certified experts.Prevalence and incidence of IOP of 21 mmHg or more and 30 mmHg or more and incidence of a rise in IOP by 10 mmHg or more. To avoid underascertainment, outcomes were counted as present when IOP-lowering therapies were in use.Initially, 251 (15.8%) and 46 eyes (2.9%) had IOP ≥21 mmHg and ≥30 mmHg, respectively. Factors significantly associated with presenting IOP elevation included age of 6 to 12 years (versus other pediatric ages), prior cataract surgery, pars plana vitrectomy, duration of uveitis ≥6 months, contralateral IOP elevation, presenting visual acuity worse than 20/40, and topical corticosteroid use (in a dose-response relationship). The median follow-up was 1.25 years (interquartile range, 0.4-3.66). The estimated incidence of any observed IOP elevation to ≥21 mmHg, to ≥30 mmHg, and increase in IOP by ≥10 mmHg was 33.4%, 14.8%, and 24.4%, respectively, within 2 years. Factors associated with IOP elevation included pars plana vitrectomy, contralateral IOP elevation (adjusted hazard ratio [aHR], up to 9.54; P0.001), and the use of topical (aHR, up to 8.77 that followed a dose-response relationship; P0.001), periocular (aHR, up to 7.96; P0.001), and intraocular (aHR, up to 19.7; P0.001) corticosteroids.Intraocular pressure elevation affects a large minority of children with noninfectious uveitis. Statistically significant risk factors include IOP elevation or use of IOP-lowering treatment in the contralateral eye and local corticosteroid use that demonstrated a dose-and route of administration-dependent relationship. In contrast, use of immunosuppressive drug therapy did not increase such risk. Pediatric eyes with noninfectious uveitis should be followed up closely for IOP elevation, especially when strong risk factors such as the use of local corticosteroids and contralateral IOP elevation are present.

The differential diagnosis of a patient presenting with anterior uveitis is broad and can present a diagnostic challenge. In this study, we evaluate the characteristic findings of inflammatory cells on optical coherence tomography (OCT) both in vitro and in vivo.Blood from two healthy volunteers was prepared using standardized methods for cell sorting with a flow cytometer (FASCAria). Neutrophils, lymphocytes, monocytes, and red blood cells were placed in suspension and scanned with a 26-kHz Fourier-domain OCT system (RTVue) with 5-μm axial resolution. Custom software algorithms were used to identify cells based on their reflectance distribution. These algorithms were then applied to OCT images obtained from uveitis patients with active anterior chamber inflammation.On OCT images the cells appeared as hyperreflective spots. In vitro, cell reflectance was statistically significantly different between all of the cell types (neutrophils, monocytes, lymphocytes, and red blood cells, P0.001, Mann-Whitney test). In vivo, the relationship between underlying disease and cell type imaged on OCT was highly statistically significant, with human leukocyte antigen (HLA)-B27-associated uveitis patients having a predominantly polymorphonuclear pattern on OCT and sarcoidosis and inflammatory bowel disease patients having a predominantly mononuclear pattern on OCT (P0.001, Fisher's exact test).These in vitro and in vivo data demonstrate the potential of OCT to evaluate cells in the anterior chamber of patients noninvasively. Optical coherence tomography may be a useful adjunct to guide the diagnosis and treatment of ocular inflammatory conditions.

Purpose: To examine RTVue (Optovue, Inc) optical coherence tomography (OCT) as a method for measuring scleral thickness. Methods: A prospective, single-center study of eyes with a variety of ocular diseases (no scleral diseases) was performed to image scleral thickness utilizing the RTVue OCT. Repeated measurements of scleral thickness were performed using a line scan 3 mm from the limbus in the inferior nasal and inferior temporal quadrants of each eye. Obtained values were analyzed statistically. Results: A total of 25 eyes in 14 subjects were measured. An average of 3 measurements per location per eye were taken. The mean scleral thickness 3 mm from the limbus was 654.22 μm. The average standard deviation of the measurements from each location was 30.88 μm. The Original Research Article Cramer et al.; OR, 3(4): 95-99, 2015; Article no.OR.2015.016 96 boundary of the conjunctiva and sclera was easily distinguishable. Conclusion: The results of this study suggest that RTVue high-resolution OCT is a user-friendly modality for measuring scleral thickness.

Currently available treatment options for non-infectious scleritis, including non-steroidal anti-inflammatory drugs, systemic corticosteroids and immunosuppressive therapies, have both efficacy and side effect limitations. Iontophoretic delivery of corticosteroids has been demonstrated to be effective for anterior uveitis and represents a potential new approach to scleritis therapy. We hypothesised that iontophoretic delivery would provide effective and precise medication delivery to the sclera, while limiting systemic exposure and side effects. This first-in-human randomised, double-masked, dose-escalating study of iontophoretic administration of dexamethasone phosphate for scleritis suggests the treatment to be well tolerated and safe (within the limitations of the 18 patients sample size). There was a suggestion of efficacy in the lowest (1.2 mA/min at 0.4 mA) dose group (corresponding to the superficial location of scleritis compared with anterior uveitis), with 5/7 eyes meeting the primary efficacy outcome within 28 days. Our results suggest iontophoretic delivery of corticosteroids is a promising potential treatment for scleritis, with favourable safety and preliminary efficacy results in this phase 1 trial.Trial registration numberNCT01059955.

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. ispartof: OPHTHALMOLOGY vol:125 issue:7 pages:1075-1087 ispartof: location:United States status: published

Purpose: Keratic precipitates (KP) are a common feature of uveitis. We prospectively examined KP with the Heidelberg Retinal Tomograph II confocal laser scanning microscope and Rostock Corneal Module (HRT-RCM) to explore their diagnostic implications.Methods: Prospective, observational, multicenter study. HRT-RCM images were classified by two masked observers.Results: 120 scans on 120 eyes from 110 subjects were included. The majority (N = 93) had non-infectious uveitis. Sixty eyes had active disease at scanning. Eight KP morphologies were defined. Agreement between the two masked graders was high (Kappa value across all categories = 0.81). Cluster and nodular KP were associated with active infectious uveitis (p < 0.01): patients with cluster KP (odds ratio [OR] = 3.03, 95% confidence interval [CI]: 1.43, 6.45) and nodular KP (OR = 3.89, 95% CI: 1.42, 10.65) were more likely to have infectious uveitis than those without.Conclusions: Laser confocal microscopy of KP may have a role in determining be...

Purpose To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis. Design Retrospective, multicenter, cohort study. Participants Patients aged ≥18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. Methods Demographic, ocular, and treatment data were extracted from medical records of uveitis cases. Main Outcome Measures Prevalent and incident OHT with intraocular pressures (IOPs) of ≥21 mmHg, ≥30 mmHg, and increase of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT). Results Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21 mmHg and OHT ≥30 mmHg are 14.4% (95% confidence interval [CI], 13.4–15.5) and 5.1% (95% CI, 4.7–5.6) per year, respectively. Statistically significant risk factors for incident OHT ≥30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [≥8×/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT. Conclusions Ocular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.

Chronic use of corticosteroids for the treatment of uveitis has been linked with drug-associated toxicity and adverse events (AEs). This study examines the association between corticosteroid dosage and incidence rates of corticosteroid-related AEs.A post hoc analysis of the VISUAL-1 and VISUAL-2 placebo-controlled clinical trials.The clinical trials consisted of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate, posterior, and panuveitis. Patients were randomized to receive adalimumab or placebo and underwent a protocol-defined mandatory taper to discontinue their oral corticosteroids.Adverse event data were collected at each visit and included an assessment of the corticosteroid relationship by the investigator. A longitudinal Poisson regression model was estimated controlling for time-dependent corticosteroid dose, age, sex, prior oral corticosteroid dose, prior topical corticosteroid use, and concomitant immunosuppressive drug use. Only patients randomized to placebo were considered.The primary outcome measure was the frequency of AEs.The incidence rates of corticosteroid-related AEs among placebo patients during the prednisone treatment period in VISUAL-1 was statistically higher than after discontinuation (454.2 per 100 patient-years [PY] vs. 36.1 per 100 PY, incident rate ratio = 12.6, P0.001). Incidence rate ratios among VISUAL-2 patients were similarly high (317.5 per 100 PY vs. 41.1 per 100 PY, incident rate ratio = 7.7, P0.001). Based on the Poisson multivariate longitudinal Generalized Estimating Equation (GEE) model, each 10 mg increase in prednisone dose is associated with a 1.5- and 2.6-fold increase (P0.001 and P0.001) in the rate of corticosteroid-related AEs in VISUAL-1 and VISUAL-2, respectively. This implies in turn that a patient with active uveitis taking 60 mg/day of prednisone will experience, on average, an additional 10.1 (95% confidence interval (CI), 6.3-14.5; P0.001) corticosteroid-related AEs per year compared with a patient taking 10 mg/day, whereas a patient with inactive uveitis taking 35 mg/day of prednisone will experience, on average, an additional 23.5 (95% CI, 7.6-52.7; P = 0.05) corticosteroid-related AEs per year compared with a patient taking 10 mg/day.Evidence from VISUAL-1 and VISUAL-2 suggests that the incidence rates of corticosteroid-related AEs increase systematically with corticosteroid dose.

Purpose To evaluate the benefits and complications of periocular depot corticosteroid injections in patients with ocular inflammatory disorders. Design Multicenter, retrospective cohort study. Participants A total of 914 patients (1192 eyes) who had received ≥1 periocular corticosteroid injection at 5 tertiary uveitis clinics in the United States. Methods Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained at every visit via medical record review by trained reviewers. Main Outcome Measures Control of inflammation, improvement of visual acuity (VA) to ≥20/40, improvement of VA loss attributed to macular edema (ME), incident cataract affecting VA, cataract surgery, ocular hypertension, and glaucoma surgery. Results Among 914 patients (1192 eyes) who received ≥1 periocular injection during follow-up, 286 (31.3%) were classified as having anterior uveitis, 303 (33.3%) as intermediate uveitis, and 324 (35.4%) as posterior or panuveitis. Cumulatively by ≤6 months, 72.7% (95% CI, 69.1–76.3) of the eyes achieved complete control of inflammation and 49.7% (95% CI, 45.5–54.1) showed an improvement in VA from Conclusions Periocular injections were effective in treating active intraocular inflammation and in improving reduced VA attributed to ME in a majority of patients. The response pattern was similar across anatomic locations of uveitis. Overall, VA improved in one half of the patients at some point within 6 months. However, cataract and ocular hypertension occurred in a substantial minority.

Objective To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory noninfectious scleritis. Design Prospective, dose-ranging, randomized, double-masked phase I/II clinical trial. Participants Twelve patients with noninfectious scleritis refractory to systemic corticosteroid and ≥1 other systemic immunosuppressive agent were enrolled from January 2007 to March 2010. Intervention Subjects were randomly assigned to 500 (n = 5) or 1000 mg (n = 7) dosing arms of rituximab intravenous infusions (500 or 1000 mg), given at study days 1 and 15. Initial responders with breakthrough inflammation after study week 24 were offered treatment with an additional cycle of 2 open-label rituximab 1000 mg infusions. Main Outcome Measures Primary outcomes were reduction of inflammation, as measured with a validated scleritis disease grading scale (SGS) and reduction in corticosteroid dose by ≥50%. Patients were characterized as responders to study therapy if ≥1 of these endpoints showed improvement and neither showed evidence of worsening. Secondary outcomes were improvement in visual acuity, reduction in pain, and improvement in patient and physician-reported global health assessment. Results Of 12 enrolled patients, 9 met the SGS endpoint at or before week 24, and 4 additionally were able to reduce corticosteroid dose by ≥50%. With regard to secondary outcome measures, 11 and 9 patients showed improvement in patient and physician global health scores, respectively, and 7 patients had reduction in pain. Of 9 initial responders, 7 experienced breakthrough inflammation after 24 weeks and were treated with a second cycle of rituximab infusions. Four patients had significant objective or subjective worsening within 8 weeks of receiving rituximab; this event was averted in subsequent patients by treatment with peri-infusional oral corticosteroid. No other significant adverse events were noted. No differences in efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. Conclusions Rituximab was effective treatment for 9 of 12 enrolled patients with refractory, noninfectious scleritis at 24 weeks, although 7 required reinfusion with rituximab to maintain inflammatory control. The treatment was well-tolerated, and peri-infusional inflammatory exacerbations were managed successfully with oral corticosteroids. Further long-term studies are warranted to determine the safety and efficacy of rituximab in treating noninfectious scleritis and other ocular inflammatory diseases.

BACKGROUND AND OBJECTIVE: Acute retinal necrosis (ARN) may lead to severe visual loss because of its rapid progression and high likelihood of retinal detachment (RD). This study investigates whether combination systemic and intravitreal antiviral therapy is superior to systemic antiviral therapy alone. PATIENTS AND METHODS: Single-center, interventional, comparative case series of patients with ARN treated with combination systemic antiviral and intravitreal foscarnet injection therapy or systemic antiviral therapy alone. Survival analysis and incidence rates of visual acuity (VA) gain of two lines or greater, severe visual loss of 20/200 or worse, and RD were assessed. RESULTS: Twelve patients received combination therapy and 12 received systemic therapy alone. Patients receiving combination therapy were more likely to gain two or more lines of VA and showed decreased incidences of severe visual loss and RD. CONCLUSION: Combination oral and intravitreal antiviral therapy may improve the likelihood for VA gain and decrease the risk of RD in patients with ARN. Clinicians should consider administering combination systemic and intravitreal antiviral therapy for patients with the ARN syndrome. [ Ophthalmic Surg Lasers Imaging Retina . 2014;45:399–407.]

Purpose To characterise uveitis in association with multiple sclerosis (MS). Methods We conducted a retrospective chart review of patients with uveitis and MS at two uveitis centres (Portland, Oregon, USA and Heidelberg, Germany). Baseline characteristics and ophthalmic data were collected at the patient9s first and last visits. Additionally, neurological records were obtained when possible. Results We identified 113 patients (196 eyes) with uveitis and MS. Of these, 53 had a diagnosis of MS confirmed by review of neurological records, 50 additional patients fulfilled the Poser criteria for MS and 10 with MS were referred by an outside neurologist. Among them, 83 (73%) were women and the mean age of presentation was 40.6 years (range 13–64 years). The average visual acuity in affected eyes at presentation was 20/39. There were 90 patients (80%) who presented with intermediate uveitis and 24 patients (15%) with anterior uveitis. Posterior and pan-uveitis were found in four patients (3%) and two patients (2%), respectively. During a median follow-up of 3.2 years (range 0.04–21 years), visual acuity improved –0.09 logMar/year. Compared with our location-matched controls with idiopathic intermediate uveitis (n=16), patients with MS and intermediate uveitis were significantly older when diagnosed with uveitis (p=0.027) and more likely to be female (p=0.01). There was no statistical difference in visual acuity or rate of vision change between our cases and controls (p=0.58 and p=0.36, respectively). Conclusions Uveitis with MS generally presents as intermediate uveitis with a minority presenting with anterior uveitis. Patients are significantly older and more likely to be women than patients with idiopathic intermediate uveitis. The visual prognosis is generally favourable.

To report a case of frosted branch angiitis in a patient with granulomatosis with polyangiitis.Clinical case report. Imaging was obtained with pseudo-color scanning laser ophthalmoscope photographs, fluorescein angiography, spectral domain optical coherence tomography, and B-scan ultrasound.A 24-year-old woman with a clinical history of granulomatosis with polyangiitis who presented with acute vision loss was found to have frosted branch angiitis with concurrent posterior scleritis and orbital inflammation. These findings improved rapidly after initiation of high-dose intravenous solumedrol.This is a unique case of frosted branch angiitis associated with granulomatosis with polyangiitis. The authors are not aware of a previous report of this association. Although rare, retinal vasculitis should be recognized as a potential complication of granulomatosis with polyangiitis and can respond rapidly to prompt initiation of therapy.

Yevgeniy V Sychev,1 Elizabeth A Verner-Cole,2 Eric B Suhler,2 J Timothy Stout,2 G Atmaram Vemulakonda1 1Department of Ophthalmology, University of Washington, Seattle, WA, USA; 2Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA Abstract: Intraocular foreign bodies (IOFBs) can complicate globe trauma and are associated with a high incidence of severe vision loss. Occult IOFBs present a particular challenge as they are not diagnosed promptly and tend to present with advanced complications, including endophthalmitis and retinal detachment. In this report, we present three cases of occult nonmetallic IOFBs presenting as fulminant uveitis, and we also review the literature. Keywords: intraocular foreign body, endophthalmitis, vitrectomy, trauma

Scleritis is an inflammatory condition affecting the eye wall that may be associated with a number of systemic inflammatory diseases. Because scleritis can be refractory to standard treatment, knowledge of the body of available and emerging therapies is paramount and is reviewed here.This review focuses on both traditional and emerging therapies for noninfectious scleritis. The authors cover the mechanisms of action and potential adverse effects of each of the treatment modalities. In addition, a summary of the significant MEDLINE indexed literature under the subject heading 'scleritis', 'treatment', 'immunomodulator' will be provided on each therapy, including commentary on appropriate use and relative contraindications. Novel treatments and potential drug candidates that are currently being evaluated in clinical trials with therapeutic potential will also be reviewed.While oral nonsteroidal anti-inflammatory drugs and oral corticosteroids are widely used, effective, first-line agents for inflammatory scleritis, refractory cases require antimetabolites, T-cell inhibitors, or biologic response modifiers. In particular, there is emerging evidence for the use of targeted biologic response modifiers, and potentially, for local drug delivery.

Importance Noninfectious uveitis (NIU) is a collection of intraocular inflammatory disorders that may be associated with significant visual impairment. To our knowledge, few studies have investigated NIU prevalence overall or stratified by inflammation location, severity, presence of systemic conditions, age, or sex. Objective To estimate NIU prevalence using a large, retrospective, administrative claims database. Design, Setting, and Participants This analysis used the OptumHealth Reporting and Insights database to estimate 2012 NIU prevalence. Analysis was conducted in September 2016. The large administrative insurance claims database includes 14 million privately insured individuals in 69 self-insured companies spanning diverse industries. Included in the study were patients with NIU with 2 or more uveitis diagnoses on separate days in 2012 and continuous enrollment in a health plan for all of 2012 and categorized by inflammation site. Main Outcomes and Measures We estimated overall NIU prevalence by inflammation site, severity, sex, and age. Patients with anterior NIU were categorized by the presence of systemic conditions. Results Of the approximately 4 million eligible adult patients, approximately 2.1 million were women, and of the 932 260 children, 475 481 were boys. The adult prevalence of NIU was 121 cases per 100 000 persons (95% CI, 117.5-124.3). The pediatric NIU prevalence was 29 cases per 100 000 (95% CI, 26.1-33.2). Anterior NIU accounted for 81% (3904 cases) of adult NIU cases (98 per 100 000; 95% CI, 94.7-100.9) and 75% (207 cases) of pediatric NIU cases (22 per 100 000; 95% CI, 19.3-25.4). The prevalences of noninfectious intermediate, posterior, and panuveitis were, for adults, 1 (95% CI, 0.8-1.5), 10 (95% CI, 9.4-11.5), and 12 (95% CI, 10.6-12.7) per 100 000, respectively, and for pediatric patients, 0 (95% CI, 0.1-1.1), 3 (95% CI, 1.8-4.1), and 4 (95% CI, 2.9-5.6) per 100 000, respectively. The prevalence of NIU increased with age and was higher among adult females than males. Application of these estimates to the US population suggests that NIU affected approximately 298 801 American adults (95% CI, 290 512-307 324) and 21 879 children (95% CI, 19 360-24 626) in 2015. Conclusions and Relevance The estimated prevalence of NIU was 121 cases per 100 000 for adults (95% CI, 117.5-124.3) and 29 per 100 000 for children (95% CI, 26.1-33.2). Prevalence was estimated using administrative claims from a commercially insured population, which may have a different prevalence than other segments of the US population. A better understanding of the prevalence of NIU will help to determine the number of patients affected.

Background Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. Methods This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. Results The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P

To identify the incidence and risk factors for corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases.Retrospective cohort study.Patients with ocular inflammation followed at 5 United States tertiary centers that initially were neither diabetic nor taking hypoglycemic medications.Eligible patients who used oral corticosteroids during follow-up were identified and followed longitudinally for initiation of hypoglycemic medication over 1 year after beginning corticosteroids. The remaining eligible patients were followed for 1 year after their initial visit. Survival analysis was used to calculate the risk of hyperglycemia requiring medical therapy and to identify potential risk factors.Initiation of hypoglycemic medications.Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%) initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence interval [CI], 1.68-11.5). The RR tended to be higher in association with higher initial doses (for initial doses40 mg of prednisone per day: RR, 3.23; 95% CI, 1.08-9.64; for initial prednisone dose ≥40 mg/d: RR, 5.51; 95% CI, 2.01-15.1). Other risk factors for the initiation of hypoglycemic therapy included older age (RR [per each additional 10 years], 1.46; 95% CI, 1.15-1.85; P = 0.002) and African-American race (RR, 2.94; 95% CI, 1.34-6.43; P = 0.007).These results suggest that the absolute risk of corticosteroid-induced hyperglycemia that is detected and treated with hypoglycemic therapy in the tertiary ocular inflammation setting is low (an excess cumulative risk on the order of 1% within 1 year), although on a relative scale it is approximately 4.4-fold higher than in patients not treated with oral corticosteroids. Older age and African-American race also were risk factors. Physicians who use systemic corticosteroids for ocular inflammatory diseases should be aware of this risk, and should consider surveillance for hyperglycemia among high-risk patients. However, given the low absolute risk, routine laboratory monitoring or referral for monitoring may not be necessary for low-risk patients.

Objectives Systemic vasculitis is often mistakenly assumed to be a common cause of retinal vasculitis. We sought to determine the relationship between retinal vasculitis and systemic vasculitis. Methods A selected review was performed on 1390 charts of patients attending the uveitis clinic at the Oregon Health and Science University between 1985 and 2010. Included in the review were all patients with diagnoses commonly associated with retinal vasculitis and all patients who were diagnosed with a systemic vasculitis. Retinal vasculitis was identified by perivascular exudates, intraretinal hemorrhage, or cotton wool spots as seen on clinical examination or by vascular occlusion or leakage as identified by fluorescein angiogram. Results Two hundred seven or 14.9% of patients with uveitis had retinal vasculitis as a component of the intraocular inflammation. Thirty-five patients had retinal vasculitis that was primary, ie, not associated with a systemic disease, and the dominant manifestation of the uveitis. Fourteen of the patients with retinal vasculitis had Behcet's disease. Only 11 of the 1390 patients with uveitis had a systemic vasculitis. Of these 11, four had retinal vasculitis including 1 secondary to a cytomegalovirus retinitis. Thus, systemic vasculitis was directly responsible for 1.4% or 3 of 207 cases of retinal vasculitis. Nonvasculitic systemic diseases such as sarcoidosis ( n = 13), syndromes confined to the eye such as pars planitis ( n = 36), and intraocular infections ( n = 29) were far more common causes of retinal vasculitis. Conclusions Retinal vasculitis is a relatively common feature of uveitis. Patients with retinal vasculitis, however, rarely suffer from 1 of the classical systemic vasculitides.

Purpose: To determine the efficacy of interferon alpha 2b in the treatment of refractory, uveitic cystoid macular edema (CME).Methods: Retrospective chart review of 4 patients attending the uveitis clinic at the Casey Eye Institute, Oregon Health & Science University.Results: All 4 patients had uveitis and refractory CME, resistant to a variety of immunosuppressants. All patients, except one with severe scleral thinning, had tried and failed therapy with locally injected corticosteroids. Treatment with systemic interferon alpha 2b produced dramatic improvement in CME (central macular thickness: 563 to 267 µm, p = .002) and visual acuity (logMAR: +0.81 to +0.45, p = .0004) in all 4 cases. All patients have been able to reduce the interferon dosage, but none has discontinued it completely. All patients had some mild adverse response that did not necessitate stopping therapy.Conclusions: Interferon alpha 2b is an effective option to treat refractory CME secondary to uveitis.