New and Updated Recommendations for the Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Idiopathic Chronic Anterior Uveitis.

OBJECTIVE: The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce this document to guide clinicians managing children with juvenile idiopathic arthritis-associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU). METHODS: The group analyzed the literature published between December 2014 and June 2020 after a systematic literature review conducted by 2 clinicians. Pediatric rheumatologists were paired with ophthalmologists to review the eligible 37 publications. The search criteria were selected to reflect those used for the 2018 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, in order to provide an update, rather than a replacement for that publication. The summary of the current evidence for each SHARE recommendation was presented to the expert committee. These recommendations were then discussed and revised during a video consensus meeting on January 22, 2021, with 14 voting participants, using a nominal group technique to reach consensus. RESULTS: JIAU treatment was extended to include CAU. Fourteen recommendations regarding treatment of JIAU und CAU with >90% agreement were accepted. CONCLUSION: An update to the previous 2018 SHARE recommendations for the treatment of children with JIAU with the addition of CAU was created using an evidence-based consensus process. This guideline should help support clinicians to care for children and young people with CAU.

COVID-19 Vaccination and Uveitis: Epidemiology, Clinical Features and Visual Prognosis.

PURPOSE: To study the epidemiological and clinical features of uveitis post-COVID-19 vaccination. PATIENTS AND METHODS: Retrospective chart review of patients presenting with uveitis after COVID-19 vaccination in tertiary uveitis services. RESULTS: In total, 25 patients, 76% females, mean age 43.2 years, were included. Uveitis occurred after Pfizer, Moderna, Astra-Zeneca and Covaxin vaccination. Anterior uveitis was the most frequent type of uveitis (56%). History of uveitis was found in 19 cases (76%), among whom 90.9% of the tested patients developed anti-Sars-CoV-2 spike antibodies after vaccination. In a mean follow-up of 5 months, one-line decrease in visual acuity was found in 12% of patients. During post-vaccine uveitis, 15.8% of cases needed an increase in their systemic therapy. According to Naranjo score, new-onset uveitis had a higher probability of being associated with vaccination (p < .01). CONCLUSION: COVID-19 vaccination can cause uveitis but has no significant impact on the visual prognosis after resolution.

Enteric-coated mycophenolate sodium in the treatment of non-infectious intermediate uveitis: results of a prospective, controlled, randomised, open-label, early terminated multicentre trial.

BACKGROUND/AIMS: To evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis (IU). METHODS: Open-label, prospective, controlled, randomised multicentre trial. Patients were randomised in a 1:1 ratio to either the treatment group (prednisolone plus EC-MPS) or control group (prednisolone monotherapy). Patients in the control group who relapsed within 6 months changed to the crossover group (prednisolone plus EC-MPS). Maximum treatment duration was 15 months. The primary endpoint was the time to first relapse in the treatment group and control group. RESULTS: Forty-one patients at eight sites were analysed. Twenty-two patients were allocated to the treatment group, with 19 patients in the control group. A first relapse occurred in 9 patients (40.9%) in the treatment group and 15 patients (78.9%) in the control group (p=0.03). The median time to the first relapse was >15 months for the treatment group and 2.8 months for the control group (p=0.07). The probability of relapse-free survival at month 15 was estimated to be 52.9% in the treatment group and 19.7% in the control group (p=0.01). 15 patients changed to the crossover group. Of these, only four patients developed a second relapse. No safety concerns arose during the trial. Only one patient had to discontinue EC-MPS due to increased liver enzymes. CONCLUSION: EC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU. TRIAL REGISTRATION NUMBER: EUDRACT number: 2009-009998-10, Results.

Tocilizumab in Uveitic Macular Edema Refractory to Previous Immunomodulatory Treatment.

PURPOSE: To analyze the efficacy of tocilizumab in uveitic macular edema (ME) resistant to various immunomodulatory drugs. METHODS: Patients received tocilizumab every 4 weeks intravenously. Central foveal thickness (CFT) was assessed by optical coherence tomography (OCT). RESULTS: Five patients (8 eyes) who were ineffectively pretreated with systemic prednisolone, at least one immunosuppressive drug, and at least one biologic drug for uveitic macular edema were included in the study. At 3 months, a response of ME (≥25% reduction in CFT) was observed in 6 eyes (75.0%) of 5 patients. During follow-up, complete resolution of ME was achieved in 5 eyes (62.5%) of 4 patients. Improvement of BCVA was observed in 3 eyes of 3 patients, and stabilization in 3 eyes of 3 patients. Tocilizumab was well tolerated, and no severe side effects occurred. CONCLUSIONS: Treatment with tocilizumab can be considered in chronic uveitic macular edema even if previous immunomodulatory therapy has failed.

Acute Retinal Necrosis: Diagnostic and Treatment Strategies in Germany.

PURPOSE: To analyze the preferred practice respective diagnosis, treatment, and complications in patients with acute retinal necrosis in Germany. METHODS: The uveitis-section of the German Ophthalmologic Society developed a questionnaire with 12 questions concerning patients with acute retinal necrosis seen in the 5 years up to August 2009. RESULTS: In total, 35 eye hospitals answered the questionnaire and reported 213 patients with acute retinal necrosis. Diagnosis was made clinically in 86%. Anterior chamber tap, vitreous biopsy, diagnostic vitrectomy, and serology were performed for confirmation. Therapy was started with acyclovir in all institutions, and continued with ganciclovir, foscarnet and brivudine in some cases. Intravitreal injections were performed in 46%. Additional oral steroids were given in 80%. A following oral antiviral treatment was performed in 94%. CONCLUSIONS: Relevant variations were seen in diagnosis and treatment practices. The survey outlines the need for a unique diagnostic and therapeutic guideline.

Assesment of Conjunctival Microangiopathy in a Patient with Diabetes Mellitus Using the Retinal Function Imager.

Diabetes mellitus (DM) is notorious for causing retinal microangiopathy, but bulbar conjunctival microangiopathy (CM) mirroring the established retinal vessel changes, has also been observed. Recent studies suggest that CM occurs in all DM patients in various degrees depending on disease severity and occur even before non-proliferative retinopathy develops. Thus, CM might provide a means of early detection or even form a basis for early intervention of disease progression in DM patients. Herein we present - to our knowledge for the first time-the feasibility and applicability in diagnostic imaging of CM in a diabetic patient using a commercially available Retinal Function Imager (RFI, Optical Imaging Ltd, Rehovot, Israel).

Mycophenolic acid in the treatment of birdshot chorioretinopathy: long-term follow-up.

AIM: To assess the long-term efficacy and tolerability of both derivatives of mycophenolic acid, mycophenolate mofetil (MMF) and mycophenolate sodium (MPS), in the therapy of patients with birdshot chorioretinopathy (BSCR). METHODS: Retrospective analysis of 24 patients (48 eyes) with BSCR, treated with MMF or MPS with a follow-up of at least 1 year. The main outcome measures included control of inflammation, steroid-sparing potential and side effects. Secondary outcome measure was the development of retinal function during the therapy measured by best-corrected visual acuity (BCVA), visual field and/or electroretinography (ERG). RESULTS: Twelve patients (50%) were treated with MMF and 12 patients (50%) with MPS. Control of intraocular inflammation, defined as complete lack of clinical and angiographic signs of inflammatory activity, was achieved in 16 of 24 patients (67%). The angiographic signs of activity were significantly reduced during the follow-up (p<0.05). No significant difference was found in the mean BCVA, the visual field and the ERG parameters during the treatment compared with the baseline (p>0.05). In 20 out of 21 patients (95%) who received systemic corticosteroids, the corticosteroids could be tapered to a daily dose of ≤10 mg (rate 0.26/patient-year). Drug-related side effects occurred in 12 patients (50%, rate 0.16/patient-year). In four patients (17%), a therapy switch from MMF to MPS was undertaken due to gastrointestinal discomfort. CONCLUSIONS: Derivatives of mycophenolic acid are effective and safe drugs for the treatment of BSCR. In cases with gastrointestinal side effects, a therapy switch from MMF to MPS should be considered.

Immunomodulatory therapy with tumour necrosis factor α inhibitors in children with antinuclear antibody-associated chronic anterior uveitis: long-term results.

AIM: The aim of the study was to assess the long-term efficacy and tolerability of tumour necrosis factor α (TNFα) inhibitors in the therapy of children with refractory antinuclear antibody (ANA)-associated chronic anterior uveitis. METHODS: Retrospective analysis of 31 children with ANA-associated uveitis, treated with TNFα inhibitors with a follow-up period of at least 2 years. The outcome measures included: control of inflammation, corticosteroid-sparing potential and side effects. RESULTS: Twenty-three children (74%) were treated with adalimumab, five children (16%) with infliximab and three children (10%) with etanercept. Control of uveitis, defined as 0 anterior chamber cells while on ≤2 drops/day topical corticosteroids, was achieved in 22 of 31 patients (71%) after 1 year (95% CI 52% to 86%), and in 21 of 29 patients (72%) after 2 years of treatment (95% CI 53% to 87%). Control of uveitis was observed in 18 of 23 children (78%) treated with adalimumab, and in two of five children (40%) treated with infliximab. In all children treated with etanercept, no sufficient inflammatory control was found. Systemic corticosteroids could be discontinued in 71% (12/17 children) and topical corticosteroids in 55% (17/31) of the patients. Treatment-related side effects were found in nine children (29%, rate: 0.10/patient-year). CONCLUSIONS: Our data show that adalimumab and infliximab have beneficial effects in the therapy of severe ANA-associated anterior uveitis in children.

Mycophenolate mofetil in the therapy of uveitic macular edema--long-term results.

PURPOSE: To assess the long-term efficacy of mycophenolate mofetil (MMF) in uveitic cystoid macular edema (CMO). METHODS: Thirty-eight uveitis patients with CMO treated with MMF with a follow-up of at least 5 years were analyzed. The patients were divided into two groups: group A, 24 patients with CMO that had occurred before initiation of MMF; group B, 14 patients who developed CMO for the first time during MMF. RESULTS: In group A, a complete remission of CMO without recurrences was observed in 12 of 24 patients (50%, rate: 0.12/patient-year). In group B, CMO occurred in 7 patients (50%) despite standard dosage of MMF, and in 7 patients (50%) during MMF dose reduction. CONCLUSIONS: The results show that MMF is not always sufficiently effective as a long-term treatment for uveitic macular edema. Moreover, in some uveitis patients MMF cannot prevent new development of CMO.

Long-term results of therapy with mycophenolate mofetil in ocular mucous membrane pemphigoid.

PURPOSE: To assess the long-term efficacy and tolerability of mycophenolate mofetil (MMF) in the therapy of ocular mucous membrane pemphigoid (OcMMP). METHODS: Ten patients (19 eyes) with OcMMP treated with MMF, who had a follow-up of at least 4 years, were retrospectively analyzed. Main outcome measures were inflammatory control, progression of cicatrization, and side effects. RESULTS: Control of inflammation was achieved in 11 eyes (58%) of 6 patients (rate: 0.11/PY). Mild inflammatory activity was observed in 8 eyes (42%) of 4 patients (rate: 0.07/PY). Progression of conjunctival cicatrization was prevented in 47% (9/19) of the eyes. Mild progression of cicatrization was found in 42% (8/19) of the eyes. Conjunctival cicatrization had progressed to stage IV in 1 patient (11%). Treatment-related side effects occurred in 7 patients (rate: 0.12/PY). CONCLUSION: MMF is an effective agent for treatment of OcMMP. However, the drug cannot always prevent disease progression.

Long-term results of therapy with mycophenolate mofetil in chronic non-infectious uveitis.

BACKGROUND: Short-term studies have shown mycophenolate mofetil (MMF) to be a useful immunosuppressive agent for the treatment of intraocular inflammation. The aim of our study was to assess the long-term efficacy and tolerability of MMF in patients with chronic non-infectious uveitis, as well as to analyze disease course following discontinuation of therapy. METHODS: This is a retrospective case series on 60 uveitis patients treated with MMF with a follow-up period of at least 5 years. The main outcome measures were: control of inflammation, corticosteroid-sparing potential, side-effects, ability to stop/taper MMF treatment because of effective control of inflammation and relapse rate after therapy discontinuation. RESULTS: Control of intraocular inflammation (efficacy of MMF), defined as inactive disease under prednisolone dose of ≤ 10 mg daily, was achieved in 43 of 60 patients (72%) after 1 year of MMF treatment at a rate of 0.72 per patient-year (PY), and in 45 of 55 patients (82%) after 2 years therapy (rate: 0.41/PY). An improvement (3 lines) or stabilization of visual acuity was observed in 49 patients (82%), and a worsening in 11 patients (18%, 95% CI: 10-30%). The probability of discontinuing prednisolone, estimated by the Kaplan-Meier method, was 40% after 5 years therapy. The probability of discontinuing mycophenolate mofetil due to efficacy was 33% after 5 years treatment. Recurrences of uveitis occurred in six of 21 patients (29%, rate: 0.11/PY) after MMF discontinuation due to efficacy. The treatment was stopped because of inefficacy in 12 patients (rate: 0.05/PY) and because of side-effects in four patients (rate: 0.02/PY). The rate of adverse effects during MMF therapy was 0.17/PY. CONCLUSIONS: Our data show that mycophenolate mofetil is generally effective and well tolerated in the treatment of chronic non-infectious uveitis.

Mycophenolate sodium for immunosuppressive treatment in uveitis.

PURPOSE: To assess the efficacy and tolerability of mycophenolate sodium (MPS) in patients with uveitis. METHODS: Retrospective analysis including uveitis patients treated with MPS (Myfortic) for at least 3 months duration. MPS was administered in a dose of 720 mg twice daily. RESULTS: We analyzed 35 patients (65 affected eyes) with anterior (n = 5), intermediate (n = 23), posterior (n = 6), and panuveitis (n = 1). Previous treatment consisted of systemic corticosteroids in all patients and at least one immunomodulating agent in 15 patients. Mean duration of MPS therapy was calculated as 9.6 months (3-31 months). MPS was able to control intraocular inflammation without relapse in 30 patients (85.7%). Stabilization or improvement of visual acuity was achieved in 60 eyes (92.3%). Tolerability of MPS was good or moderate in 34 patients (97.1%). CONCLUSIONS: MPS was demonstrated as an effective and well-tolerated immunosuppressive drug for different forms of uveitis.

Interferon-alpha-associated presumed ocular sarcoidosis.

BACKGROUND: Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha. METHODS: We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin. RESULTS: In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations. CONCLUSIONS: Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.

An unusual case of central serous chorioretinopathy in a patient with acute retinal necrosis.

PURPOSE: In acute retinal necrosis, which is caused by herpes virus, urgent treatment is essential. DESIGN AND METHODS: Here we present a 47 years old male patient, who developed an acute retinal necrosis in his left eye. Therapy was initiated with systemic aciclovir and corticosteroids. RESULTS: During the course of disease our patient achieved improvement of acute retinal necrosis but he developed central serous chorioretinopathy. CONCLUSIONS: The development of central serous chorioretinopathy in our patient was most probably due to the systemic corticosteroids he received. Especially in patients with an intraocular inflammation this diagnosis may lead to severe differential diagnostic problems.

Interferon alfa-2a: a new treatment option for long lasting refractory cystoid macular edema in uveitis? A pilot study.

PURPOSE: To perform a prospective pilot study to evaluate interferon alfa-2a (IFN alfa-2a) for the treatment of refractory cystoid macular edema (CME) in endogenous uveitis. METHODS: IFN alfa-2a was administered at an initial dose of 3 or 6 million IU (depending on body weight) per day subcutaneously. Afterwards IFN alfa-2a was tapered slowly over 6 months and finally discontinued. If CME relapsed IFN alfa-2a was reinstituted and tapered slowly again to evaluate the lowest maintenance dose to keep remission. RESULTS: A total of 15 eyes of 8 patients with refractory CME due to intermediate or posterior uveitis were included. Ineffective pretreatment consisted of systemic steroids and acetazolamide (all patients) and at least one additional immunosuppressant (6 patients). Six of 8 patients (11 eyes) responded well to IFN alfa-2a and CME resolved completely during 6 months treatment. One patient was lost to follow-up after IFN alfa-2a was stopped. In 1 patient (1 eye) even 19 months after cessation of IFN alfa-2a no recurrence of CME occurred. In 4 patients (8 eyes) IFN alfa-2a had to be reinstituted because CME relapsed. All 4 patients responded again. During a mean follow-up period of 16.4 months since restart of therapy we succeeded in all 4 patients to taper IFN alfa-2a to maintenance doses between 1.5 million IU every second and every sixth day without a recurrence of CME in any of the 8 eyes. CONCLUSION: IFN alfa-2a can be a treatment option for patients with otherwise treatment resistant uveitic CME.