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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.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the clinical features of patients with uveitis associated with latent tuberculosis (TB) and examine the effect of anti-TB treatment (ATT) on uveitis outcome., Design: Retrospective cohort study., Methods: One hundred ninety-nine eyes of 129 patients diagnosed with uveitis associated with latent TB were evaluated for recurrence of disease following treatment. Eighty-nine of the patients (69%) received ATT and information was gathered retrospectively regarding clinical outcome, vision, and treatment. Outcome measures included best-corrected visual acuity (BCVA) and rate of disease recurrence., Results: This study included 89 patients (69%) who received ATT and 40 patients who did not. The uveitis was treated with local and systemic anti-inflammatory and immunosuppressive therapy in all patients. The mean change in BCVA following treatment was 4.5 ± 1.4 letters over the follow-up period, with no difference between eyes of patients receiving ATT and those who did not. Sixty-eight eyes (34.9%) had a recurrence of uveitis (0.64 ± 0.08 recurrences per year), with eyes of patients receiving ATT less likely to develop a recurrence compared to those not receiving ATT (29.5% vs 48.2%, odds ratio 0.47, 95% confidence interval 0.29-0.77, P = .003). Eyes treated with ATT recurred at an estimated median of 120 months, compared with 51 months in eyes with no treatment (P = .005)., Conclusions: Treatment with ATT halved the risk of uveitis recurrence and delayed the onset of the first recurrence in eyes with uveitis associated with latent TB., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy., Method: The approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease., Conclusion: We recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To ascertain whether patients on long-term systemic immunosuppressive therapy for inflammatory eye disease (IED) are at increased risk of malignancy., Design: A single-center, retrospective cohort study., Participants: We included 190 adults with IED treated with corticosteroids only (n = 58) or systemic immunosuppression (n = 132) for ≥6 months between 1985 and 2007. Immunosuppressed patients were treated with antimetabolites, T-cell inhibitors, and/or alkylating agents., Methods: Incident malignancies were ascertained by self-report and confirmed by medical record review. Multiple malignancies in a single patient were counted, except for nonmelanoma skin cancer (NMSC), where only the first was counted. Standardized incidence ratios (SIRs) were calculated by malignancy type. Cox regression models were used to compare malignancy incidence by treatment type., Main Outcome Measures: Risk of malignancy relative to the general population and within the cohort., Results: During a median 7.34 years of follow-up, 25 malignancies were observed in 17 patients, namely, 2.10 per 100 person-years and 0.43 per 100 person-years in the immunosuppressed and corticosteroid only groups, respectively. In the immunosuppressed group, the most common malignancies were NMSC (n = 11) and non-Hodgkin's lymphoma (NHL; n = 4) and malignancy risk was significantly increased compared with the general population for any malignancy (SIR, 4.39; 95% CI, 2.78-6.59) and for any malignancy excluding NMSC (SIR, 4.16; 95% CI, 1.67-8.57). Significantly elevated SIRs were observed for NMSC and NHL in those treated with immunosuppressive agents. Compared with the corticosteroid treatment-only group, the immunosuppressed group was at an increased risk of any malignancy (adjusted hazard ratio, 4.36; 95% CI, 1.02-18.7), but not first malignancy (n = 17; adjusted hazard ratio, 2.56; 95% CI, 0.57-11.5). No cancer-related deaths were observed., Conclusions: Our findings suggest that patients with IED treated with systemic immunosuppressive therapy are at increased risk of malignancy; however, the increase in absolute risk was modest. The types of malignancies observed at excess risk are similar to those observed in solid organ transplant recipients and patients with autoimmune diseases treated with systemic immunosuppression. Immunosuppressive therapy remains an important treatment modality in IED; however, patients may benefit from targeted malignancy-prevention strategies and long-term clinical follow-up. These findings require validation by a prospective, long-term, population-based cohort study., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure., Design: Retrospective cohort study., Participants: Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia., Methods: Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained., Main Outcome Measures: For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined., Results: A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients., Conclusions: Our data suggest that control of inflammation can be achieved after switching or combining ISAs., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the outcomes of the intravitreal administration of methotrexate in uveitis., Methods: Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy., Results: Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection., Conclusion: In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

Inflammatory eye diseases (IED) such as uveitis affect females and males in the prime of their reproductive life. Despite their propensity to lead to significant visual loss, there have been very few studies of the management of patients with IED who are pregnant or plan a pregnancy during the course of therapy. The first trimester and postpartum period may be associated with an exacerbation of IED and it is important to have available medications that control the disease and do not cause miscarriage or fetal abnormalities. Several immunosuppressive drugs are contraindicated in pregnancy (methotrexate and alkylating agents), while others (corticosteroids, azathioprine, and cyclosporin) may be considered for use in pregnancy. Most drugs are excluded from use in pregnancy not because of proven teratogenicity but because of the lack of available evidence of their safety for the fetus.

Purpose: To report the use of methotrexate therapy as first-line systemic therapy in the treatment of ocular-cicatricial pemphigoid and drug-induced ocular-cicatricial pemphigoid., Design: Retrospective, noncomparative, interventional case series., Participants: Twelve patients with ocular-cicatricial pemphigoid and 5 patients with drug-induced ocular-cicatricial pemphigoid treated with low-dose oral methotrexate as the sole systemic agent. In 14 of the 17 patients, methotrexate was the first systemic agent used., Methods: Clinical data abstracted from patient medical records., Main Outcome Measures: Visual acuity, conjunctival inflammation, progression of cicatrization, and treatment-related side effects., Results: After a mean follow-up duration of 30.2 months (range, 6-78 months), complete control or suppression, or both, of conjunctival inflammation was achieved in 89% of eyes with ocular-cicatricial pemphigoid and in 100% of eyes with drug-induced ocular-cicatricial pemphigoid using methotrexate monotherapy as the first-line systemic agent. Progression of conjunctival cicatrization was prevented in 72% of eyes with ocular-cicatricial pemphigoid and 90% of eyes with drug-induced ocular-cicatricial pemphigoid. Visual acuity was maintained or improved in 85% of total eyes treated with methotrexate monotherapy, and a final visual acuity of 6/18 or better was achieved in 74% of the eyes. Methotrexate therapy was well tolerated, with 92% of patients maintained on continued treatment experiencing no side effects. The most common side effects were gastrointestinal (50%), and most (78%) were reversible on dose reduction. In 4 of 17 cases, methotrexate was ceased as a result of possible treatment-related side effects., Conclusions: Low-dose oral methotrexate monotherapy is both highly efficacious and well tolerated as the first-line systemic agent in the treatment of ocular-cicatricial pemphigoid and drug-induced ocular-cicatricial pemphigoid.

Purpose: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. Methods: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF). Results: 228 subjects (120 males; mean age of 42.82 ± 14.73 years) were included. Most common phenotype of uveitis was posterior (n = 81; 35.53%), and panuveitis (n = 76; 33.33%). Fifty-two patients (22.81%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, p =.003), vitreous haze (OR: 2.14, p =.018), and use of immunosuppressive therapies (OR: 5.45, p =.003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; p =.02). Conclusions: Majority of subjects (>75%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory eye diseases (IED), which encompasses uveitis and scleritis, often require systemic immunosuppressive therapy (IMT) to induce disease control or remission. Immunosuppressive therapy, including glucocorticoids, has been implicated in accelerating atherosclerosis and increasing cardiovascular morbidity and mortality in patients with rheumatic diseases or solid organ transplant recipients. Areas covered: Literature review conducted with the use of PubMed, MEDLINE and Cochrane library for peer reviewed articles then stratified for strength of evidence in reference to traditional risk factors such as hypertension, lipid profile and insulin resistance. Evidence of cardiovascular events were included. Commonly used immunosuppressive agent used in the treatment of IED including azathioprine, methotrexate, mycophenolate, cyclosporine, tacrolimus and the biologics. Each immunosuppressive agent was considered in terms of effects on hypertension, lipid profile, insulin resistance and cardiovascular outcomes. Expert commentary: Cyclosporine is associated with increased risk of hypertension and tacrolimus with insulin resistance. There is little evidence of cardiovascular disease with the use of methotrexate, azathioprine or mycophenolate. There is some evidence that the newer biologics may have protective effects on cardiovascular parameters. However, there is heterogeneity of the study populations and limited evidence in the ophthalmological setting. [ABSTRACT FROM PUBLISHER]

Purpose: To assess the vision-related (VR) and health-related (HR) quality-of-life (QoL) of patients with uveitis.Methods: In total, 60 patients with uveitis, 81 patients with diabetic retinopathy (DR), and 70 healthy subjects completed the National Eye Institute Visual Functioning Questionnaire and the Medical Outcome Study 36-Item Short Form.Results: Patients with uveitis reported lower HR- and VR-QoL than healthy subjects (p<0.05) and lower VR-QoL (p<0.001) than patients with DR. For patients with uveitis, multiple linear regression analyses indicated that lower HR-QoL scores were predicted by younger age (p<0.01), while lower VR-QoL scores were predicted by poorer visual acuity (p<0.001), ocular comorbidities (p<0.05), and female sex (p<0.05).Conclusions: Patients with uveitis have significantly poorer VR- and HR-QoL than healthy control subjects. Uveitis has a more debilitating impact on VR-QoL than DR. [ABSTRACT FROM AUTHOR]