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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To retrospectively assess the development of visual acuity and the frequency and duration of relapse-free periods in patients who were treated with interferon-[alpha] (IFN[alpha]) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of >=2 years. METHODS: IFN alfa-2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission. RESULTS: Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0-12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long-term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered. CONCLUSION: Our findings indicate that IFN[alpha] induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis of tuberculosis as an etiological factor in patients with uveitis is difficult because of lack of specific diagnostic tests. The authors report 2 cases of occlusive retinal vasculitis, in which 18F-FDG-PET/CT was helpful for the diagnosis of tuberculosis as a presumptive cause of intraocular inflammation. Methods: In 2 patients with severe occlusive retinal vasculitis and positive QuantiFERON TB-Gold test, 18F-FDG-PET/CT, transbronchial needle-aspiration biopsy, and microbiological investigation were performed. Results: 18F-FDG-PET/CT showed increased fluorodeoxyglucose uptake in some mediastinal and hilar lymph nodes. After needle-aspiration biopsy of PET-positive lymph nodes, M. tuberculosis was recovered in culture in both cases. Remission of uveitis was achieved only after a combination therapy with 3 anti-tubercular agents and systemic steroids. Conclusion: The authors favor the use of 18F-FDG-PET/CT in patients with sight-threatening intraocular inflammation and positive interferon-gamma release assay. Anti-tubercular therapy, together with anti-inflammatory treatment, may lead to a remission in such patients. [ABSTRACT FROM AUTHOR]

Purpose: To describe treatment of chronic Irvine-Gass syndrome (CME) with interferon (IFN) alpha. Methods: Interventional retrospective case series. IFN alpha-2a was administered at a dose of 3 million IU/day subcutaneously for 4 weeks, and was tapered thereafter. Treatment efficacy was assessed by best-corrected visual acuity (BCVA) and by optical coherence tomography (OCT). Results: Three patients (4 eyes) with chronic Irvine-Gass syndrome were treated. Ineffective pretreatment included local and systemic corticosteroids. Within 4 weeks, IFN alpha led to resolution of CME in all eyes. BCVA improved in 3 eyes and remained unchanged in 1 eye. During follow-up of 3--11 months no relapse of CME occurred. No systemic or local side effects were noted. Conclusions: IFN alpha has been demonstrated to be a successful and well-tolerated treatment option for resistant chronic pseudophakic CME. Further studies are necessary to evaluate the role of IFN alpha in Irvine-Gass syndrome. [ABSTRACT FROM AUTHOR]

Purpose: To report on the occurrence of tubulointerstitial nephritis and uveitis (TINU) and HLA typing in two siblings. Design: Retrospective case study. Methods: HLA typing from two siblings with TINU syndrome and their parents was performed on DNA from peripheral blood mononuclear cells (PBMC). Results: The boy developed TINU syndrome in 2001, his sister 5 years later. Both siblings inherited the HLA alleles HLA-DRB1*1401 and HLA-DQB1*0503 on the maternal haplotype, a haplotype that had rarely been observed in patients with TINU. Conclusions: The observations support inheritance of HLA-linked risk factors of TINU, but indicate heterogeneity of the risk phenotype due to linkage with different reported haplotypes. [ABSTRACT FROM AUTHOR]

Purpose: In acute retinal necrosis, which is caused by herpes virus, urgent treatment is essential. Design and Methods: Here we present a 47years 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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Competing interests: CH is a consultant for Alimera Sciences (Aldershot, Hampshire, UK) and received Honoria from AbbVie and Novartis. MWMW is a consultant for Heine Optotechnik GmbH and glaucare GmbH, has received honoraria from ASKIN & CO GmbH, Bayer AG, Berlin-Chemie AG, Heidelberg Engineering, Novartis Pharma GmbH, Pro Generika e.V., Eyepress Fachmedien GmbH, and Science Consulting in Diabetes GmbH, and research funding from CenterVue SpA, Carl Zeiss Meditec, and Novartis Pharma GmbH. RPF is a consultant for Alimera, Apellis, Biogen, Böhringer-Ingelheim, Bayer, Caterna, Novartis, ODOS, ProGenerika, Roche/Genentech, has received honoraria from Roche and research funding from Biogen. He is member of the advisory board of Stada Pharm, Roche and Opthea. CMED is a member of the advisory board of Alimera and he has received honoraria from AbbVie, Novartis, Santen and Thea. His institution received funding for clinical trials from Tarsier and Roche. UP received study support from Abbvie and honoraria from Abbvie, Alimera and Novartis. None of the following authors have any proprietary interests or conflicts of interest related to this submission: DJF, JD, TH, MB, MS, HR, KTB and TKL., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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]., Competing Interests: Authors FO, SS, and RS-Z were employed by Kiora Pharmaceuticals Inc. (previously Panoptes Pharma GmbH). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thurau, Deuter, Heiligenhaus, Pleyer, Van Calster, Barisani-Asenbauer, Obermayr, Sperl, Seda-Zehetner and Wildner.)

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.

Behçet's disease (BD) is a systemic immune-mediated vasculitis of unclear origin. Major symptoms include oral aphthous ulcers, genital ulcerations, skin lesions, and ocular lesions. Eye involvement, which affects 60-80% of BD patients, is characterized by posterior or panuveitis with occlusive retinal vasculitis. The pathogenesis of BD remains unclear, but research of the last decades has shown a complex role of genetic factors (HLA-B51) predisposing to inflammation with involvement of the innate-immune system (neutrophils, NK cells), perpetuated by the adaptive immune response, most importantly T cells, against infectious- and/or auto-antigens. Despite aggressive immunosuppressive treatment, the visual prognosis of ocular BD was generally poor to date. Recently, novel biologic drugs, including interferon-alpha and tumour necrosis factor (TNF)-alpha-antagonists have been introduced in the treatment of ocular BD with very promising results and seem for the first time to improve the prognosis of the disease. This article will provide a current review of BD including recent developments in epidemiology, immunology, genetics, and treatment.

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.

Background: In clinical practice ophthalmologists often need a tonometer which is independent of a slit lamp. Such a hand-held device is the Tono-Pen. We compared the precision of two equal Tono-Pens with Goldmann applanation tonometry., Material and Methods: Measurement of intraocular pressure (IOP) was done in 100 eyes of 51 patients (mean age 63 +/- 15 years) suffering from ocular hypertension or glaucoma. According to a random table either the right or left eye was measured using Goldmann tonometer first and the Tono-Pen second. For the other eye the measurement was reversed. One of the two equal Tono-Pens (Solan/USA) was used according to a second random table. Three measurements were obtained with each instrument on both eyes within 15 minutes subsequently. Patients were placed in an upright position for all measurements., Results: Even for well-trained ophthalmologists a learning curve of approximately 10 measurements was observed using the Tono-Pen. The Tono-Pen measured an average IOP of 16.9 mm Hg in all 100 eyes. The Goldmann tonometer measured an average IOP of 17.7 mm Hg. The difference was not statistically significant. The standard deviation for all measurements was better for the Tono-Pen (4.7 mm Hg vs 5.8 mm Hg for Goldmann tonometer). No reduction of the IOP after Tono-Pen measurement was observed (in contrast to the Goldmann tonometer). The reproducibility of the Tono-Pen on the same eye was inferior to the Goldmann tonometer by a factor of 2. There was an almost significant difference in reproducibility between two equal Tono-Pens., Conclusions: Measurement of IOP with the Tono-Pen is comparable to Goldmann applanation tonometry if an average of 3 measurements is used. The difference between two equal Tono-Pens indicates the need for improvement of the quality check during production.