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Purpose: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies., Methods: Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score., Results: Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases., Conclusion: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

Introduction: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU., Areas Covered: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated., Expert Opinion: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Purpose: To describe the various ocular clinical features and visual outcomes in Tubulointerstitial Nephritis and Uveitis Syndrome (TINU)., Methods: The medical records of 13 patients (26 eyes) diagnosed with TINU were reviewed., Results: Twenty-six (26) eyes of 13 patients with TINU were reviewed in this study. The median age at onset of uveitis was 14 (range, 9-45). Eight (61.5%) subjects were female. The median follow-up of patients was 30 months (range, 6-89 months). Posterior segment findings were seen in 18 eyes of 9 patients (69.2%). The most common posterior findings were optic nerve head inflammation (16 eyes, 88.8%) and retinal vasculitis (13 eyes, 72.2%). Other posterior findings included vitritis (8 eyes, 44.4%), macular edema (6 eyes, 33.3%), snowball (4 eyes, 22.2%), and chorioretinal lesions (2 eye, 11.1%). Eight patients had fluorescein angiography (FA) data available and most eyes had retinal capillary leakage (13 eyes, 81.2%) followed by optic disc staining/leakage (12 eyes, 75%). Twelve (12) patients (92.3%) were treated with immunomodulatory treatment (IMT) and/or biologics. Five patients (%38.4) required biologics to control intraocular inflammation., Conclusion: Posterior segment involvement may be common in patients with TINU syndrome. FA provides significant information for detecting posterior segment involvement and disease activity in TINU. The majority of patients required systemic treatment in order to control intraocular inflammation and prevent relapses., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Aims: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide., Methods: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used., Results: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints., Conclusions: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates., Areas Covered: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated., Expert Opinion: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Purpose: To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients., Methods: Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales., Results: Mean change in LFP was correlated to those in BCVA ( p = .018), SUN scale ( p < .001), and MSUN scale ( p = .008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p < .05)., Conclusions: LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.

Purpose: To study the efficacy and safety of suprachoroidal CLS-TA (proprietary suspension of triamcinolone acetonide) in uveitic macular edema (UME) with and without concurrent systemic corticosteroid or steroid-sparing therapy (ST)., Methods: Post hoc analysis of the PEACHTREE phase 3 randomized trial., Results: Among UME patients receiving no ST, at week 24, mean BCVA change was +15.6 letters in 68 CLS-TA patients versus +4.9 letters in 49 sham-control patients ( p < .001), while mean CST change was -169.8 µm versus -10.3 µm, respectively ( p < .001). Among patients receiving ST, at week 24, mean BCVA change was +9.4 letters in 28 CLS-TA patients versus -3.2 letters in 15 sham-control patients ( p = .019), while mean CST change was -108.3 µm versus -43.5 µm, respectively ( p = .190). No SAEs related to treatment were reported., Conclusions: A clinically meaningful benefit of CLS-TA was noted in UME patients, regardless of concurrent ST usage. Abbreviation and Acronyms CST = central subfield thickness; BCVA = best corrected visual acuity; ME = macular edemaI; IVT = intravitreal; AE = adverse event; FA = fluocinolone acetonide; SD-OCT = spectral-domain optical coherence tomography; NIU = noninfectious uveitis; SAE = serious adverse event; TEAE = treatment emergent adverse event; ITT = intent to treat; CI = confidence interval.

Background/aims: To use a composite endpoint scoring system in assessing efficacy of two doses of intravenous tocilizumab (TCZ), in eyes with non-infectious uveitis., Methods: Data from STOP-Uveitis Study (a phase 2 multicentre, randomised, interventional clinical trial), where monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month 6 (M6) were administered, were used. Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiographic and (5) steroid taper. Each component of grading system was graded as ((+1) improvement, (-1) worsening or (0) no change) based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups., Results: Thirty-seven patients were analysed. At M6, 31 (83.8%) subjects demonstrated a positive clinical response (Group 1=14 (77.8%) and Group 2=17 (89.5%)). Three (8.1%) subjects (all Group 1) met the criteria for treatment failure, whereas three (8.1%) subjects showed a stable clinical response (Group 1=1 and Group 2=2). The difference in clinical responses between study groups was not significant (p>0.05)., Conclusions: Both doses of intravenous TCZ were effective in either improving or maintaining stability in patients using the composite endpoint scoring system. A composite scoring system as used in this study may be a better measure to assess efficacy outcomes as compared with only vitreous haze or other single outcome measures., Competing Interests: Competing interests: YJS has received research support from Astellas, Genentech and Optovue, and serves on the Scientific Advisory Board for Genentech/Roche, Optos and Regeneron. QDN serves on the Scientific Advisory Board for AbbVie, Bayer, Genentech, Regeneron and Santen, among others, also chaired the Steering Committee for the STOP-Uveitis study and was on the Steering Committee for other studies sponsored by Genentech and Regeneron. DVD serves on the Scientific Advisory Board for Allergan, Genentech, Kodiak, Regeneron and Santen and has received research support from Genentech and Regeneron. No other authors have received any financial funding or support., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the efficacy of infliximab (IFX, 5-10 mg/kg) (Group 1) and tocilizumab (TCZ, 4-8 mg/kg) (Group 2) infusions in non-infectious retinal vasculitis (RV) using Angiographic Scoring for the Uveitis Working Group fluorescein angiography (FA) scoring system., Methods: Records of 14 patients (24 eyes) in Group 1 and 8 patients (11 eyes) in Group 2 were retrospectively evaluated to assess visual acuity (VA), anterior chamber cell and flare, vitreous haze, central subfield thickness (CST), and FA scoring at baseline and 6 months of follow-up. The measurements were employed to grade in each group., Results: In Group 1 and 2, respectively, there was no underlying disease in 9 (60%) and 3 (42.9%) patients. Three (42.9%) patients in Group 2 had juvenile idiopathic arthritis (JIA) as the most common identified cause. Mean improvement in VA (log MAR) and CST were 0.04 ± 0.14 and 40.3 ± 78.5 µm in Group 1; 0.04 ± 0.09 and 47.3 ± 82.3 µm in Group 2, respectively. Mean FA scores were significantly reduced from 12.4 ± 5.2 and 11.6 ± 4.4 at baseline to 6.4 ± 5.0 and 5.8 ± 3.9 at 6-month in Group 1 and 2, respectively. In Group 2, 9 eyes of 6 patients (75%) had the history of IFX use prior to TCZ initiation. There was no significant safety concern requiring treatment discontinuation during the follow-up in either group., Conclusion: IFX and TCZ infusions showed statistically significant improvement of non-infectious RV as shown by ASUWOG FA Scoring System. TCZ, as well as IFX, appeared to be effective treatment options for non-infectious RV., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: To evaluate effect of maximal anterior cortical lens density, iris scatter and anterior chamber depth on laser flare photometry., Methods: Patients diagnosed with clinical uveitis were enrolled in the study. Clinical flare gradings were recorded upon the Standardization of Uveitis Nomenclature. Aqueous flare was measured with an automated device (Kowa FM-700). Back-scattering from anterior cortical lens and anterior iris surface was calculated from Scheimpflug images. A curvilinear regression model was used to calculate estimated values for each clinical grade. These values were used to split cases in Group I (laser flare photometry lower than estimated) and Group II (laser flare photometry higher than estimated). Mean anterior chamber depth, pupil aperture, maximal anterior cortical lens density and iris scatter values were compared between two groups. A stepwise multiple regression analysis was performed to determine the effect of clinical flare gradings and ocular parameters on aqueous flare measurements., Results: The study included 228 eyes of 114 cases. Scheimpflug images were obtained from 105 eyes. Estimated aqueous flare measurements (in photons/milliseconds) were 4.87, 8.50, 14.81, 25.83, 45.04 and 136.93 for 0, 0.5+, 1+, 1.5+, 2+ and 3+ clinical flare respectively. Group II had higher maximal anterior cortical lens density than Group I (96.6 ± 37.1 vs 77.9 ± 17.1 pixel unit, p  = 0.001). The measured aqueous flare was significantly related to clinical flare, maximal anterior cortical lens density and pupil aperture (adjusted R 2 : 0.480, p  < 0.001)., Conclusion: The back-scattered light from anterior cortical lens could affect laser flare photometry measurements. This effect might be quantified by Scheimpflug imaging.

Purpose: To assess the relationship between best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) features in noninfectious uveitis (NIU)-related macular edema., Design: Clinical cohort study from post hoc analysis of 2 phase 3 clinical trials., Methods: Correlation and longitudinal treatment analyses were performed. Of 198 patients with NIU, 134 received suprachoroidal CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension), and 64 received sham, with 12.9% and 72%, respectively, receiving rescue therapy., Results: At baseline, mean BCVA progressively worsened with each ordinal drop in central subfield ellipsoid zone (EZ) integrity. Eyes with normal baseline EZ experienced greater 24-week change in BCVA versus those with some degree of baseline EZ disruption (11.9 vs 9.4 letters, P = .006). In contrast, eyes with baseline central subfield cystoid spaces and/or subretinal fluid showed more improvement (13.7 or 17.2 letters, respectively) at 24 weeks, versus those without such findings (5.5 [P = .012] or 9.5 letters [P < .001], respectively). Longitudinal modeling for CLS-TA-treated eyes showed that central subfield thickness (CST) reached 90% of maximal improvement by week 3, whereas 90% maximal response in BCVA was not reached until week 9. CLS-TA-treated eyes that showed CST reduction of ≥50 µm at 4 weeks experienced a greater 24-week improvement in BCVA versus those without such an early response (14.6 vs 6.5 letters, P = .006 for difference)., Conclusions: Pretreatment EZ integrity and the presence of central subfield cystoid spaces or subretinal fluid each predict improved therapeutic response to treatment in eyes with NIU. In CLS-TA treated eyes, longitudinal modeling shows CST improvement preceding BCVA improvement., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases., Methods: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree)., Results: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent., Conclusions: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged., Methods: A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine., Results: Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups., Conclusion: Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment is corticosteroid therapy. Corticosteroids remain the most potent and efficacious drugs for treating intraocular inflammation. However, their long-term use is limited by their medium- and long-term side effects, which are a major concern. The approach taken to limit corticosteroid side effects is to introduce steroid-sparing agents that suppress the inflammatory pathways and immune response differently than corticosteroids. There are several classes of such drugs that are affordable, effective, and generally well-tolerated. Relatively recently, an increasing range of biologic agents has become available to treat intraocular inflammation. However, the relatively expensive cost of these therapies limits their use in the developing world. This systemic review aimst to discuss the use of corticosteroids and different immunosuppressive regimens in the management of various uveitides., Competing Interests: None

This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS) and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction : The treatment strategies for noninfectious uveitis (NIU) aim to achieve disease remission, prevention of recurrences, and preserving vision, while minimizing the side effects associated with the therapies used. Areas covered : The index review aims to provide a detailed overview of the adverse events and safety parameters associated with the systemic therapies for the management of the NIU. Expert opinion : Despite being the cornerstone of management of acute cases of NIU, long-term corticosteroid use is associated with multi-system side effects, requiring the use of steroid-sparing agents. Adalimumab was recently approved by the FDA for the management of NIU based on the results of VISUAL studies. Similarly, newer drugs targeting various aspects of the inflammatory cascade are being developed. However, until we completely understand the molecular pathways of the inflammatory diseases, the therapeutic profile of these newer agents needs to be broad enough to suppress inflammatory cascade and narrow enough to spare normal cellular processes. Another strategy that has shown some potential in decreasing the systemic side effects is to provide local drug delivery. Therefore, the future of management of NIU is very bright with many novel therapeutic agents and strategies of drug delivery on the horizon.

Purpose: Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis., Methods: Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography., Results: Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure., Conclusion: A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

Uveitis is a spectrum of inflammatory disorders characterized by ocular inflammation and is one of the leading causes of preventable visual loss. The main aim of the treatment of uveitis is to control the inflammation, prevent recurrences of the disease and preserve vision while minimizing the adverse effects associated with the therapeutic agents. Initial management of uveitis relies heavily on the use of corticosteroids. However, monotherapy with high-dose corticosteroids is associated with side effects and cannot be maintained long term. Therefore, steroid-sparing agents are needed to decrease the burden of steroid therapy. Currently, the therapeutic approach for non-infectious uveitis (NIU) consists of a step-ladder strategy with the first-line option being corticosteroids in various formulations followed by the use of first-, second- and third-line agents in cases with suboptimal steroid response. Unfortunately, the agents currently at our disposal have limitations such as having a narrow therapeutic window along with their own individual potential side-effect profiles. Therefore, research has been targeted to identify newer drugs as well as new uses for older drugs that target specific pathways in the inflammatory response. Such efforts are made in order to provide targeted and safer therapy with reduced side effects and greater efficacy. Several specially designed molecular antibodies are currently in various phases of investigations that can potentially halt the inflammation in patients with NIU. In the review, we have provided a comprehensive overview of the current and upcoming therapeutic options for patients with NIU., (© 2019 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis., Methods: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF)., Results: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years)., Conclusions: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

Purpose : To analyze the role of polymerase chain reaction (PCR) of ocular fluids in management of tubercular (TB) anterior, intermediate, posterior, and panuveitis. Methods: In Collaborative Ocular Tuberculosis Study (COTS)-1 (25 centers, n  = 962), patients with TB-related uveitis were included. 59 patients undergoing PCR of intraocular fluids (18 females; 53 Asian Indians) were included. Results: 59 (6.13%) of COTS-1 underwent PCR analysis. PCR was positive for Mycobacterium TB in 33 patients (23 males; all Asian Indians). 26 patients were PCR negative (18 males). Eight patients with negative PCR had systemic TB. Anti-TB therapy was given in 18 negative and 31 PCR cases. At 1-year follow-up, five patients with positive PCR (15.15%) and three with negative PCR (11.54%) had persistence/worsening of inflammation. Conclusions : Data from COTS-1 suggest that PCR is not commonly done for diagnosing intraocular TB and positive/negative results may not influence management or treatment outcomes in the real world scenario.

Purpose: The aim of this study was to examine regional variation management practices and outcomes for tubercular uveitis (TBU)., Methods: In this retrospective multinational cohort study, patients from 25 international eye care centers diagnosed with TBU with a minimum follow-up of 1 year were included. The geographic variation in treatment outcomes on survival analysis in patients with TBU were analyzed. Treatment failure is defined as a persistence or recurrence of inflammation within 6 months of completing antitubercular therapy, the inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy., Results: Records of 945 patients (1485 eyes) with TBU were analyzed. The mean age was 41.3 ± 15.0 years (range, 4-90 years), with more males (52.9%, n = 500/945) and predominant Asian ethnicity (74.4%, n = 690/927). Most patients had no symptoms (92.0%, n = 655/712) or history (76.7%, n = 604/787) suggestive of pulmonary tuberculosis (TB). Some patients had evidence of inactive pulmonary TB on chest X-rays (26.9%, n = 189/702) or chest computed tomography (68.6%, n = 109/159). Patients with western geographic origin (log-rank = 6.47, P = 0.010), African or Hispanic ethnicity (log-rank = 19.9, P < 0.001), and positive immigrant status (log-rank = 4.89, P = 0.027) had poorer survival outcomes., Conclusions: This is a first-ever multinational analysis of TBU that highlights regional differences in treatment outcomes for this elusive form of extrapulmonary TB. Our findings will help in the design of future collaborative studies together with internists to develop best practice guidelines for this early opportunity to address TB infection and strategies to target at-risk groups such as immigrants.

Importance: Eradication of systemic tuberculosis (TB) has been limited by neglected populations and the HIV pandemic. Whereas ocular TB often presents as uveitis without any prior evidence of systemic TB, the existing uncertainty in the diagnosis of TB uveitis may perpetuate missed opportunities to address systemic TB., Objective: To examine the clinical features of TB uveitis and the associations with response to antitubercular therapy (ATT)., Design, Setting, and Participants: This retrospective multinational cohort study included patients from 25 ophthalmology referral centers diagnosed with TB uveitis and treated with ATT from January 1, 2004, through December 31, 2014, with a minimum follow-up of 1 year., Main Outcomes and Measures: Treatment failure, defined as a persistence or recurrence of inflammation within 6 months of completing ATT, inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy., Results: A total of 801 patients (1272 eyes) were studied (mean [SD] age, 40.5 [14.8] years; 413 [51.6%] male and 388 [48.4%] female; 577 [73.6%] Asian). Most patients had no known history (498 of 661 [75.3%]) of systemic TB. Most patients had bilateral involvement (471 of 801 [58.8%]). Common clinical signs reported include vitreous haze (523 of 1153 [45.4%]), retinal vasculitis (374 of 874 [42.8%]), and choroidal involvement (419 of 651 [64.4%]). Treatment failure developed in 102 of the 801 patients (12.7%). On univariate regression analysis, the hazard ratios (HRs) associated with intermediate uveitis (HR, 2.21; 95% CI, 1.07-4.55; P = .03), anterior uveitis (HR, 2.68; 95% CI, 1.32-2.35; P = .006), and panuveitis (HR, 3.28; 95% CI, 1.89-5.67; P < .001) were significantly higher compared with posterior distribution. The presence of vitreous haze had a statistically significant association (HR, 1.95; 95% CI, 1.26-3.02; P = .003) compared with absence of vitreous haze. Bilaterality had an associated HR of 1.50 (95% CI, 0.96-2.35) compared with unilaterality (HR, 1 [reference]), although this finding was not statistically significant (P = .07). On multivariate Cox proportional hazards regression analysis, the presence of vitreous haze had an adjusted HR of 2.98 (95% CI, 1.50-5.94; P = .002), presence of snow banking had an adjusted HR of 3.71 (95% CI, 1.18-11.62; P = .02), and presence of choroidal involvement had an adjusted HR of 2.88 (95% CI, 1.22-6.78; P = .02)., Conclusions and Relevance: A low treatment failure rate occurred in patients with TB uveitis treated with ATT. Phenotypes and test results are studied whereby patients with panuveitis having vitreous and choroidal involvement had a higher risk of treatment failure. These findings are limited by retrospective methods. A prospectively derived composite clinical risk score might address this diagnostic uncertainty through holistic and standardized assessment of the combinations of clinical features and investigation results that may warrant diagnosis of TB uveitis and treatment with ATT.

Purpose: To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis., Design: Randomized, controlled, multicenter clinical trial., Methods: STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6., Results: A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 μm at month 6 (-131.5 ± 41.56 μm in Group 1 and -38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated., Conclusions: Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis)., Design: Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus., Participants: Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol., Methods: Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120., Main Outcome Measures: The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented., Results: A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated., Conclusions: Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids., Methods: We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838., Findings: Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group)., Interpretation: Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis., Funding: AbbVie., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years)., Conclusions: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Purpose: To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study., Methods: SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6)., Results: 24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42µm in group 1 and +81.5µm in group 2 at M6., Conclusions: Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months.

Chronic inflammation plays an important role in the pathogenesis of ocular diseases such as diabetic retinopathy, uveitis and age-related macular degeneration. Activation and proliferation of naïve T cells may result in pathological changes responsible for significant visual morbidity. Sirolimus (earlier termed rapamycin) is a novel drug that inhibits cellular kinases and, thereby, inhibits T-cell proliferation. Preclinical studies in experimental models have shown promising results with the use of this pharmacological agent in various ocular conditions. Subsequently, early phase I/II studies have provided encouraging safety and efficacy data. This chapter focuses on the mechanisms of action, preclinical study results and data from human clinical trials of sirolimus in human eye diseases. Key highlights from ongoing phase III clinical trials are also provided. Sirolimus, thus, appears to be an important addition to the armamentarium of steroid-sparing therapeutic agents that act on various steps in the inflammatory pathway., (© 2016 S. Karger AG, Basel.)

Importance: Elevated intraocular pressure (IOP) is a well-known adverse event associated with the fluocinolone acetonide implant (FAI), but no data are available regarding factors associated with increased risk of IOP elevation in patients treated with the FAI., Objective: To report risk factors that may predispose patients to elevated IOP after treatment with the FAI., Design, Setting, and Participants: Data from 3 multicenter, 3-year, prospective, randomized, phase 2b/3 clinical trials evaluating the safety and efficacy of the FAI were pooled and analyzed. Patients had no underlying glaucoma and at least one eye with a history of recurrent noninfectious uveitis affecting the posterior segment. Patients were treated with 1 or more of the following: systemic therapy (corticosteroids or other immunosuppressive drugs) for at least 3 months before enrollment, 2 or more sub-Tenon capsule corticosteroid injections for uveitis management during the 6 months before enrollment, or systemic corticosteroid or sub-Tenon capsule corticosteroid injection therapy required for at least 2 separate recurrences within 6 months before enrollment., Main Outcomes and Measures: Factors evaluated as risk factors for IOP elevation included age, sex, lens status, uveitis severity at enrollment, and location of uveitis., Results: Data analyses were based on 641 eyes. A total of 351 eyes did not receive the FAI, whereas 290 eyes had the 0.59-mg FAI placed. An increase in IOP of 10 mm Hg or elevation to 30 mm Hg was seen in 60 untreated eyes (17.1%) and 188 treated eyes (65.1%) (hazard ratio, 5.80; 95% CI, 4.28-7.70; P < .001). A total of 8 untreated eyes (2.3%) required surgical intervention for elevated IOP compared with 93 treated eyes (32.1%) (hazard ratio, 16.48; 95% CI, 8.24-32.96; P < .001). In patients with the FAI, younger age, male sex, and phakic lens status were associated with higher risk of IOP elevation and the need for glaucoma surgery (P = .003, P < .001, and P < .001, respectively)., Conclusions and Relevance: Patients receiving the FAI are at higher risk of developing an IOP increase of 10 mm Hg or an absolute IOP of 30 mm Hg when compared with patients without the FAI. Patients who are male, younger, and phakic are at an even higher risk for elevated IOP and possibly glaucoma surgery.

Introduction: Uveitis is an intriguing group of disorders characterized by inflammation of the uveal tract. Due to the potential grave consequences of the disease process, it is important to assess the various therapeutic options available for treating uveitis, and their outcomes., Areas Covered: This review discusses the use of conventional agents in the management of uveitis, including discussion of the molecular and clinical properties of corticosteroids, antimetabolites, calcineurin inhibitors and alkylating agents and their side effects. In addition, it also discusses the molecular and clinical properties of novel biologic agents and their side effects. Moreover, recommendations as to when biologic agents should be employed are also discussed., Expert Opinion: We recommend that in general (except in selected cases of Adamantiades-Behçet's disease) biologics should not be used as a first-line therapy for uveitis due to inconvenience, high cost, and potential immunosuppressive effects. However, many biologics are potent in inducing drug-free remission of uveitis and may be employed to manage recurrent diseases or diseases not responsive to conventional agents.

Autoimmune uveitis is a group of sight-threatening inflammatory diseases associated with an exacerbated immunological response to ocular proteins. The Standardization of Uveitis Nomenclature Working Group Guidelines have recommended the use of corticosteroids as the first line of therapy for patients who present with active uveitis. However, long-term use of corticosteroids is associated with numerous adverse effects including cataract, glaucoma and metabolic disorders. In this context, new drugs developed to treat rheumatic diseases, and other autoimmune diseases, are being employed often as monotherapy or combined with other immunosuppressive drugs in order to decrease the corticosteroid burden on patients and to manage refractive uveitis. These drugs are currently being evaluated in the framework of uveitis and may open a new horizon with less side effects and more responsiveness for chronic cases. Among others, calcineurin inhibitor voclosporin, mammalian target of rapamycin inhibitor sirolimus, and the IL-1 trap rilonacept, are among these new agents and will be scrutinized in detail in this chapter. More efficient modes of drug delivery are also being employed to deliver high concentration of drug locally and to minimize systemic side effects. The new modes of drug delivery that we will describe in the index chapter include nanoparticles and iontophoresis., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: Corticosteroids (CS) are the only approved drug class for treatment of noninfectious uveitis by the U.S. Food and Drug Administration. Serious side effects are associated with chronic use of systemic CS; established guidelines recommend the use of steroid-sparing agents if control of uveitis cannot be achieved with ≤ 10 mg/day of prednisone (or equivalent) within 3 months. This study evaluated the treatment patterns among physicians who routinely manage patients with noninfectious uveitis to determine how treatment guidelines are followed., Design: Cross-sectional, multicenter study conducted across the United States., Participants: Sixty ophthalmologists and 3 rheumatologists were recruited using payer reimbursement International Classification of Diseases, Ninth Revision codes., Methods: Patient data were reported using a study-specific questionnaire. Physicians were also asked if they were aware of or used recommended treatment guidelines., Main Outcome Measures: Uveitis treatment patterns were compared with guidelines., Results: Physicians managed a mean of 5555 patients; patients with uveitis who required systemic CS treatment comprised approximately 5% of each physician's practice. A total of 580 patients with noninfectious uveitis were randomly selected for analyses. Anterior uveitis requiring systemic therapy was diagnosed in 168 patients (29%), intermediate uveitis was diagnosed in 140 patients (24%), posterior uveitis was diagnosed in 150 patients (26%), and panuveitis was diagnosed in 122 patients (21%); 199 patients (34%) had active disease. The mean time interval from the diagnosis of uveitis to the time of survey was 3.1 to 4.5 years. A systemic disorder was associated with uveitis in 16% to 54% of patients; 57% to 100% of patients received systemic immunosuppressive therapy. In all, 360 of 580 patients (62%) received systemic CS, with a mean initial daily dose of 44 mg, tapered to 34 mg prednisone (or equivalent) as maintenance dose. Among physicians surveyed, 75% did not use or were not aware of treatment guidelines for uveitis., Conclusions: The study reveals that the majority of physicians surveyed are not familiar with or do not adhere to currently recommended guidelines for management of uveitis. High CS doses are used to maintain control of disease, and there is a low level of awareness of recommended guidelines to treat noninfectious uveitis. The finding underscores the need to place further emphasis on educating the medical community and reinforcing treatment guidelines to improve the care of patients with uveitis., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

Purpose: To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH., Design: Multicenter, retrospective, observational case series of patients with AIH and uveitis., Methods: One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment., Results: Clinical information was obtained for seven individuals (four females and three males; age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression., Conclusion: Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some individuals.

Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity ofcorticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale.

Purpose: To evaluate treatment outcomes with mycophenolate mofetil in patients with inflammatory eye disease., Design: Retrospective case series., Participants: Eighty-four consecutive patients with inflammatory eye disease treated with mycophenolate mofetil at an academic referral center., Methods: Medical records were reviewed for treatment with mycophenolate mofetil. Dose of mycophenolate mofetil, response to therapy, dose of prednisone, use of other immunosuppressive drugs, and side effects associated with the use of mycophenolate mofetil were recorded., Main Outcome Measures: Ability to control ocular inflammation with mycophenolate mofetil and to taper prednisone to < or =10 mg daily, and incidence of treatment-related side effects., Results: Of the 84 patients treated with mycophenolate mofetil, 61% had uveitis, 17% had scleritis, 11% had mucous membrane pemphigoid, and 11% had orbital or other inflammatory disease. Forty-three percent of patients treated with mycophenolate mofetil had been treated with at least one other immunosuppressive drug previously. The median dose of prednisone at the start of mycophenolate mofetil therapy was 40 mg, and 82% of the patients were considered a treatment success, as judged by the ability to control the inflammation and taper prednisone to < or =10 mg daily. Median time to treatment success was 3.5 months. Mycophenolate mofetil therapy was discontinued due to insufficient efficacy at a rate of 0.10 per person-year (PY) and due to side effects at a rate of 0.08/PY. The most frequent side effect was gastrointestinal upset, with a rate of 0.19/PY., Conclusions: These data suggest that mycophenolate mofetil may be an effective corticosteroid-sparing agent in the treatment of inflammatory eye disease with a manageable side effect profile.

Purpose: To describe the prevalence and characteristics of posterior segment manifestations in patients with HLA-B27-associated uveitis using wide field imaging. Methods: Medical records of patients diagnosed with HLA-B27-associated uveitis from a tertiary uveitis clinic were reviewed. Posterior segment involvements including but not limited to peripheral vasculitis, optic disc inflammation, and macula edema documented based on medical records and various imaging modalities including wide field fluorescein angiography and optical coherence tomography, were noted. Demographic characteristics, accompanied with systemic diseases as well as duration and chronicity of uveitis, were also evaluated. Patients with significant systemic and ocular comorbidities were excluded. Statistical analyses including chi-squared tests and paired t-tests were employed. Results: Of the 44 patients with HLA-B27 associated uveitis, 22 patients (50%) were noted to demonstrate posterior segment involvement. Disc leakage and peripheral vasculitis were the most common findings of posterior involvement. Those with anterior chamber inflammation were found to have a significantly increased risk of posterior involvement. Those with posterior involvement were also noted to have a statistically significant decreased visual acuity. No significant association was found between documented duration of disease and posterior segment involvement. Conclusion: The prevalence of posterior segment involvement in HLA-B27 associated uveitis is higher compared to previous reports when evaluated with wide angle imaging modalities. Careful examination of the posterior segment is required in patients with HLA-B27 associated uveitis. [ABSTRACT FROM AUTHOR]