A case of AZOOR under immunomodulatory treatment.

PURPOSE: To describe the clinical course and treatment response of a case of Acute Zonal Occult Outer Retinopathy (AZOOR). METHODS: This is an observational case report. The examinations included ophthalmic examination, longitudinal multimodal imaging, visual field testing, electrophysiological recordings, serologic analyses and whole genome sequencing. RESULTS: In this report, the authors present the case of an otherwise healthy 33-year-old female with bilateral AZOOR manifestation. Other possible causes of the observed retinal lesions were ruled out by extensive diagnostic work-up. Treatment with oral prednisolone therapy led to temporal disease control but progression was observed after prednisolone discontinuation. A tapered oral prednisolone therapy in combination with adalimumab initiation prevented further progression for at least 21 months. CONCLUSION: Diagnosis of AZOOR is frequently complicated by the unspecific symptoms of the disease and significant number of differential diagnoses. Complete diagnostic work-up is important to rule out other etiologies. Due to the lack of randomized controlled trials, therapeutic decisions obligatorily rely on empiric treatment decisions in combination with frequent follow-up examinations.

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years.

PURPOSE: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants' baseline characteristics after the first 3 years. METHODS: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment. The data are collected in the electronic data capture software REDCap and include ophthalmological and general medical history as well as clinical findings. RESULTS: Between 24.10.2019 and 27.12.2022, 628 patients were enrolled at 25 clinical sites in Germany and Austria. Patients with intermediate uveitis were most frequently included (n=252; 40.1%) followed by posterior uveitis (181; 28.8%), panuveitis (n=154; 24.5%) and retinal vasculitis (n=41, 6.5%). At baseline, 39.6% were treated with systemic corticosteroids, 22.3% with conventional synthetic (cs) DMARDs, 20.5% with biological (b) DMARDs and 3.6% with other systemic treatments. Average best corrected visual acuity (BCVA) was 0.69 decimal. Patients with panuveitis had the worst BCVA with 0.63 decimal. Overall, only 8 patients (1.3%) suffered from severe visual impairment. CONCLUSIONS: Less than half of participants required DMARD treatment at baseline, with csDMARDs used more frequently than bDMARDs. The presence of severe visual impairment was low, mostly affecting patients with panuveitis. These findings are in line with comparable monocentric cross-sectional studies of tertiary uveitis centres in Germany and will allow us to generate generalisable evidence in TOFU.

Real-world insights and outcomes related to ciclosporin A 0.1% cationic emulsion for the long-term treatment of dry eye disease in Germany: Country-level sub-analysis of the PERSPECTIVE study.

PURPOSE: The PERSPECTIVE study was a real-world European, non-interventional, multicenter, observational study that evaluated the effectiveness, tolerability, and safety of ciclosporin A (CsA) 0.1% cationic emulsion (CE) in routine clinical practice as a treatment for adults with severe keratitis and dry eye disease (DED) that remained insufficiently controlled with artificial tears. This sub-analysis examined data from ophthalmology clinics in Germany to provide more precise insights into treatment patterns, outcomes, and clinical decision-making related to CsA 0.1% CE. METHODS: Study data were collected from adults starting CsA 0.1% CE (one drop in both eyes at bedtime) and followed up at Week 4, 12, and 24, and Month 12. The primary endpoint was mean change from baseline in corneal fluorescein staining (CFS) score (Oxford Grade Scale) at Month 12. Secondary endpoints examined the severity of ocular signs and symptoms, and adverse events (AEs). RESULTS: A total of 236 patients from 20 ophthalmology clinics in Germany participated in the PERSPECTIVE study (69.9% female; mean age 60.8 years). Following treatment with CsA 0.1% CE, patients experienced significant reductions in CFS score from Week 4, which were maintained through to Month 12 (P < 0.0001). From baseline, 81.6% of patients experienced an improvement in CFS score at Month 12. CsA 0.1% CE provided significant reductions in the severity of eyelid and conjunctival erythema at Month 12 compared with baseline (P < 0.001), as well as significant reductions in the severity of subjective ocular symptoms (all P ≤ 0.015). Safety data were consistent with the known safety profile of CsA 0.1% CE. Tolerability was rated as "satisfactory," "good," or "very good" by 97.2% of physicians and 95.7% of patients. CONCLUSION: Outcomes in Germany were similar to those reported for the overall European study population and are indicative of the treatment results that ophthalmologists may expect to see with CsA 0.1% CE treatment in real-life clinical practice. Treatment with CsA 0.1% CE provided long-term improvements over 12 months and was generally well tolerated.

[Association of the different forms of uveitis with inflammatory rheumatic diseases and their treatment]. / Assoziation der verschiedenen Uveitisformen mit entzündlich rheumatischen Erkrankungen und ihre Therapie.

The etiology of uveitis greatly varies worldwide, whereby in industrial nations noninfectious causes occur relatively more frequently. In Germany, 44% of all cases of uveitis are due to systemic diseases. In rheumatology, uveitis or other kinds of ocular inflammation, such as scleritis or retinal vasculitis, most commonly occur in spondylarthritis, vasculitis and sarcoidosis. Vice versa, ophthalmologists often ask rheumatologists about an underlying rheumatic disease in patients with uveitis. It is of utmost importance to differentiate between the different forms of uveitis. This review article presents the associations with inflammatory rheumatic diseases as well as treatment options from the point of view of both ophthalmologists and rheumatologists.

A new small molecule DHODH-inhibitor [KIO-100 (PP-001)] targeting activated T cells for intraocular treatment of uveitis - A phase I clinical trial.

Uveitis is a T cell-mediated, intraocular inflammatory disease and one of the main causes of blindness in industrialized countries. There is a high unmet need for new immunomodulatory, steroid-sparing therapies, since only ciclosporin A and a single TNF-α-blocker are approved for non-infectious uveitis. A new small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), an enzyme pivotal for de novo synthesis of pyrimidines, has a high potency for suppressing T and B cells and has already proven highly effective for treating uveitis in experimental rat models. Systemic and intraocular application of KIO-100 (PP-001) (previously called PP-001, now KIO-100) could efficiently suppress rat uveitis in a preventive as well as therapeutic mode. Here we describe the outcome of the first clinical phase 1 trial comparing three different doses of a single intraocular injection of KIO-100 (PP-001) in patients with non-infectious posterior segment uveitis. No toxic side effects on intraocular tissues or other adverse events were observed, while intraocular inflammation decreased, and visual acuity significantly improved. Macular edema, a sight-threatening complication in uveitis, showed regression 2 weeks after intraocular KIO-100 (PP-001) injection in some patients, indicating that this novel small molecule has a high potential as a new intraocular therapy for uveitis. Clinical trial registration: [https://www.clinicaltrials.gov/ct2/show/NCT03634475], identifier [NCT03634475].

Update of evidence- and consensus-based guidelines for the treatment of juvenile idiopathic arthritis (JIA) by the German Society of Pediatric and Juvenile Rheumatic Diseases (GKJR): New perspectives on interdisciplinary care.

BACKGROUND: New therapeutic strategies for juvenile idiopathic arthritis (JIA) have evolved within the past ten years, and as a result, an update of the 2011 recommendations of the German management guidelines was initiated. METHODS: A systemic literature review was performed, overarching principles were proposed and pre-selected via an online survey followed by two multidisciplinary consensus conferences. Pharmacological and non-pharmacological treatments were discussed, statements were proposed and ultimately agreed upon by nominal group technique (NGT). RESULTS: 12 overarching therapeutic principles, as well as 9 recommendations on pharmacological and 5 on non-pharmacological treatments for JIA were agreed upon. CONCLUSION: This report summarizes the recent update of the interdisciplinary, consensus-based German guidelines on the management of JIA. The multi- and interdisciplinary participation of all caregivers was central for this patient-focused update. With these guidelines, physicians can choose an evidence-based approach, which allows better tailored treatment in this vulnerable cohort of children and adolescents.

[Clinical aspects, diagnostics and differential diagnostics of uveitis for rheumatologists]. / Klinik, Diagnostik und Differenzialdiagnostik der Uveitis für Rheumatologen.

This review article presents the different forms of uveitis and their clinical manifestations. The exact type and localization of the ocular inflammation is crucial for the probability of the underlying rheumatological disease and thus for a correct differential diagnosis. In this first part, in addition to the anatomy of the eye, the different forms of uveitis including the associated nomenclature, typical symptoms, diagnostics and possible complications are presented. In a following second part ("Association of the different forms of uveitis with inflammatory rheumatic diseases and their treatment"), the associations with rheumatological and other systemic diseases are explained and highlighted from an ophthalmological and rheumatological perspective.

[Association of the different forms of uveitis with inflammatory rheumatic diseases and their treatment]. / Assoziation der verschiedenen Uveitisformen mit entzündlich rheumatischen Erkrankungen und ihre Therapie.

The etiology of uveitis greatly varies worldwide, whereby in industrial nations noninfectious causes occur relatively more frequently. In Germany, 44% of all cases of uveitis are due to systemic diseases. In rheumatology, uveitis or other kinds of ocular inflammation, such as scleritis or retinal vasculitis, most commonly occur in spondylarthritis, vasculitis and sarcoidosis. Vice versa, ophthalmologists often ask rheumatologists about an underlying rheumatic disease in patients with uveitis. It is of utmost importance to differentiate between the different forms of uveitis. This review article presents the associations with inflammatory rheumatic diseases as well as treatment options from the point of view of both ophthalmologists and rheumatologists.

Uveitis in Juvenile Idiopathic Arthritis - Case Reports on Guideline-based Diagnostic Work-up and Treatment. / Uveitis bei juveniler idiopathischer Arthritis ­ leitliniengerechte Diagnostik und Therapie anhand von Kasuistiken.

OBJECTIVES: Case report based presentation of the current German interdisciplinary guideline on the diagnosis and management of juvenile idiopathic arthritis-associated (JIA) uveitis. MATERIAL AND METHODS: Guideline of the German Society of Ophthalmology, the Society of Paediatric and Adolescent Rheumatology, the German Society of Rheumatology, the Professional Association of German Ophthalmologists, with the participation of patient representatives. Recent primary publications were critically graduated for evidence and recommendations; the methodology included consensus building through Delphi rounds and external peer review. The outcomes are presented with typical case studies. OUTCOMES: Once JIA is first diagnosed, periodic ophthalmological check-ups should promptly be instituted ensuring that uveitis is diagnosed before irreversible sequelae become manifest. High-quality patient care can be provided depending on the severity of each uveitis case. At present, anti-inflammatory treatment relies on corticosteroids, conventional synthetic (cs), biological (b) and other disease-modifying anti-rheumatic drugs (DMARDs). CONCLUSIONS: Timely diagnosis and state-of-the-art guideline-based management can significantly improve the long-term outcome of JIA-associated uveitis.

New pharmacotherapy options for noninfectious posterior uveitis.

INTRODUCTION: Noninfectious inflammation of the posterior eye segment represents an important cause of visual impairment. It often affects relatively young people and causes a significant personal and social impact. Although steroids and nonbiologic- Disease-Modifying Antirheumatic Drugs (nbDMARDs) are effective both in acute and long- lasting diseases, however they are increasingly being replaced by biologic (DMARDs). bDMARD. This article therefore aims to identify recent advances in the therapy of noninfectious posterior segment uveitis. METHODS: A Medline-search was conducted using the terms: nbDMARD, bDMARD, posterior uveitis, intermediate uveitis, treatment, corticosteroid. In addition, clinical studies were included as registered at ClinicalTrials.gov. RESULTS: Currently two major lines of treatments can be identified: (1) the intraocular application of anti-inflammatory agents and (2) the introduction of new agents, e.g., (bDMARDs) and small-molecule-inhibitors. Whereas intravitreal treatments have the advantage to avoid systemic side effects, new systemic agents are progressively earning credit on the basis of their therapeutic effects. CONCLUSION: Even when current treatment strategies are still hampered by the limited number of randomized controlled trials, promising progress and continuous efforts are seen.

Efficacy of Topical Ivermectin for the Treatment of Cutaneous and Ocular Rosacea.

Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods: Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5-12 months).Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea.

[Uveitis in Behçet's Syndrome in Germany - Prognosis During Current Therapy]. / Uveitis bei Behçet-Syndrom in Deutschland ­ Prognose unter aktueller Therapie.

Behçet's syndrome (BS) is an inflammatory systemic disease associated with multiple organ manifestations. Major symptoms include oral and genital ulcerations, skin lesions and uveitis. Diagnosis of Behçet's syndrome is based on clinical findings. A typical for ocular Behçet's syndrome is recurrent non-granulomatous panuveitis with occlusive retinal vasculitis. Treatment used to be based only on the use of systemic corticosteroids and conventional immunosuppressives, but most often this treatment did not appear to be sufficient. In consequence, prognosis of ocular BS was very poor over a long period of time - especially if occlusive retinal vasculitis was present. In recent years, the introduction of biologicals has revolutionised the therapeutic regime and consecutively visual prognosis of ocular Behçet's syndrome has dramatically improved.

[Macular Oedema in Uveitis: Pathogenesis, Diagnosis, and Treatment]. / Makulaödem bei Uveitis: Pathogenese, Diagnostik und Therapie.

Macular oedema is the most common cause of irreversible visual loss in patients with uveitis. The pathogenesis is caused by pro-inflammatory cytokines that lead to the breakdown of the blood-retina barrier. For the diagnosis of inflammatory macular oedema, optical coherence tomography is now mainly used, but cannot always replace fluorescein angiography. The therapy is mainly performed with intravitreally applied corticosteroids as well as systemic immunomodulators and should start as early as possible to prevent chronification of macular oedema.

Interferon Alpha for Refractory Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome).

Purpose: To assess the efficacy and safety of systemic interferon alpha-2a (IFN) for refractory pseudophakic cystoid macular edema (PCME).Methods: Retrospective observational study. The primary outcome was the decrease of central retinal thickness (CRT). Secondary endpoints were the improvement of best-corrected visual acuity (BCVA) and the assessment of IFN-related side effects.Results: Twenty-four eyes of 20 patients were included. The median CRT was 513 µm (range 220-980 µm) at baseline and decreased to 190 µm (range 140-520 µm) at the last follow-up visit (p < 0.001). Reduction of CRT greater than 100 µm was observed in 22 eyes (92%). The median BCVA (logMAR) increased statistically significant from 0.5 (range 0.2-1.5) at baseline to 0.3 (0-0.8) at the last follow-up (p < 0.001). The BCVA improved in 18 eyes (75%) and remained stable in five eyes (21%). No severe treatment-related side effects occurred.Conclusion: IFN is a very effective agent for treatment of refractory PCME.

[Topical Corticosteroids and Non-steroidal Anti-inflammatory Drugs in the Therapy of Non-infectious Uveitis]. / Topische Kortikosteroide und nicht steroidale Antiphlogistika zur Behandlung der nicht infektiösen Uveitis.

Topical corticosteroids are effective anti-inflammatory drugs in the treatment of anterior uveitis. The intraocular efficacy of topical corticosteroids mostly depends on their intraocular permeability through the cornea. Lipophile derivatives such as dexamethasone and prednisolone acetate penetrate better into the anterior chamber than hydrophilic derivatives. Prednisolone acetate 1% is the first choice in the therapy of patients with anterior uveitis. Loteprednole and fluorometholone have a slightly weaker anti-inflammatory effect, but they induce less elevation of intraocular pressure and might be helpful in the treatment of patients with steroid response. Topical corticosteroid therapy has to be individually adapted, depending on the clinical course and severity of uveitis. The most common side effects of topical corticosteroids are corticosteroid-induced glaucoma and corticosteroid-induced cataracts. Non-steroidal anti-inflammatory drugs inhibit the enzyme cyclooxygenase that is responsible for the formation of pro-inflammatory prostaglandins. These have an adjunctive role in the treatment and prevention of post-operative inflammation after cataract surgery. A therapeutic role of topical NSAID to treat uveitis and cystoid macular oedema secondary to uveitis has not yet been established.

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.

Long-term Follow-up of Patients with Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome.

PURPOSE: To evaluate the response to treatment in patients with tubulointerstitial nephritis and uveitis (TINU) syndrome over a long-term follow-up period. METHODS: Nine patients with TINU syndrome were retrospectively reviewed. The mean follow-up was 54.8 months (range: 24-133 months). RESULTS: The mean number of recurrences per year declined from 1.7 in the 1st year to 0.66 in the 2nd year of treatment. The ocular inflammation responded to local corticosteroids in two patients, systemic corticosteroids in two patients, immunosuppressive therapy in four patients, and anti-TNF-α blocking agent in one patient. The therapy could be discontinued in six (67%) patients after a mean treatment period of 29.5 months. In five patients, remission with the recurrence-free period of 12.8 months was achieved. CONCLUSIONS: TINU syndrome was characterized by limited responsiveness to corticosteroid therapy and less by severe complications. A long-term course of immunosuppressants or biologics was necessary to control the uveitis and led to induction of remission.

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.

Outcomes of Primary Transconjunctival 23-Gauge Vitrectomy in the Diagnosis and Treatment of Presumed Endogenous Fungal Endophthalmitis.

PURPOSE: To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE). METHODS: Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center. RESULTS: Nineteen eyes of 15 patients with EFE were included in the study. Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15 patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture, polymerase chain reaction, and histopathologic examinations. All affected eyes were treated with intravitreal amphotericin B 5 µg/0.1 mL. Fourteen patients received additional systemic antifungal therapy. Diagnostic 23-G vitrectomy confirmed the diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes). CONCLUSIONS: EFE can be easily confirmed using primary 23-G vitrectomy.

Outcomes of Ahmed Glaucoma Valve Implantation for Glaucoma Secondary to Fuchs Uveitis Syndrome.

PURPOSE: To present the outcomes of Ahmed glaucoma valve implantation (AGV) in glaucoma secondary to Fuchs uveitis syndrome (FUS). METHODS: In this retrospective chart review, two definitions of success were used: 6 mmHg ≤intraocular pressure (IOP) ≤21 mmHg (success 1), and 6 mmHg ≤ IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). Depending on the need of postoperative antiglaucoma medication, success was defined as either complete or qualified. RESULTS: In total, 17 eyes of 17 patients were included. Complete success rates (both definitions) were 23.5% (n = 17) after 1 year and 23% (n = 13) after 3 years. Qualified success rates (both definitions) were 58.3% (n = 17) after 1 and 38.4% (n = 13) after 3 years. Encapsulated bleb formation was the most common complication (47% of eyes). CONCLUSIONS: AGV was moderately successful in the management of glaucoma secondary to FUS. Success rates are improved by medications, needling, and cycloablative procedures.