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.

Fundus Autofluorescence in Posterior and Panuveitis-An Under-Estimated Imaging Technique: A Review and Case Series.

Fundus autofluorescence (FAF) is a prompt and non-invasive imaging modality helpful in detecting pathological abnormalities within the retina and the choroid. This narrative review and case series provides an overview on the current application of FAF in posterior and panuveitis. The literature was reviewed for articles on lesion characteristics on FAF of specific posterior and panuveitis entities as well as benefits and limitations of FAF for diagnosing and monitoring disease. FAF characteristics are described for non-infectious and infectious uveitis forms as well as masquerade syndromes. Dependent on the uveitis entity, FAF is of diagnostic value in detecting disease and following the clinical course. Currently available FAF modalities which differ in excitation wavelengths can provide different pathological insights depending on disease entity and activity. Further studies on the comparison of FAF modalities and their individual value for uveitis diagnosis and monitoring are warranted.

Recommended data elements for health registries: a survey from a German funding initiative.

BACKGROUND: The selection of data elements is a decisive task within the development of a health registry. Having the right metadata is crucial for answering the particular research questions. Furthermore, the set of data elements determines the registries' readiness of interoperability and data reusability to a major extent. Six health registries shared and published their metadata within a German funding initiative. As one step in the direction of a common set of data elements, a selection of those metadata was evaluated with regard to their appropriateness for a broader usage. METHODS: Each registry was asked to contribute a 10%-selection of their data elements to an evaluation sample. The survey was set up with the online survey tool "LimeSurvey Cloud". The registries and an accompanying project participated in the survey with one vote for each project. The data elements were offered in content groups along with the question of whether the data element is appropriate for health registries on a broader scale. The question could be answered using a Likert scale with five options. Furthermore, "no answer" was allowed. The level of agreement was assessed using weighted Cohen's kappa and Kendall's coefficient of concordance. RESULTS: The evaluation sample consisted of 269 data elements. With a grade of "perhaps recommendable" or higher in the mean, 169 data elements were selected. These data elements belong preferably to groups' demography, education/occupation, medication, and nutrition. Half of the registries lost significance compared with their percentage of data elements in the evaluation sample, one remained stable. The level of concordance was adequate. CONCLUSIONS: The survey revealed a set of 169 data elements recommended for health registries. When developing a registry, this set could be valuable help in selecting the metadata appropriate to answer the registry's research questions. However, due to the high specificity of research questions, data elements beyond this set will be needed to cover the whole range of interests of a register. A broader discussion and subsequent surveys are needed to establish a common set of data elements on an international scale.

Fluocinolone acetonide 0.2 µg/day intravitreal implant in non-infectious uveitis affecting the posterior segment: EU expert user panel consensus-based clinical recommendations.

BACKGROUND: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants. METHODS: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS. RESULTS: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice. CONCLUSIONS: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes.

Piloting Rasch model scoring of the National Eye Institute Visual Function Questionnaire in uveitis.

INTRODUCTION: The National Eye Institute Visual Function Questionnaire (NEI VFQ) is a common patient-reported outcome measure (PROM) in uveitis trials. Its psychometric properties using state-of-the-art scoring based on Rasch models, a latent trait model that improves accuracy of PROMs assessment, has not yet been investigated. METHODS: The study participants were recruited online from uveitis patient organizations, where individuals self-reported their uveitis diagnosis and visual acuity level. These participants then completed the NEI VFQ-25. The visual function (VF) and socioemotional (SE) subscales were psychometrically analysed in terms of item fit, targeting, internal consistency, dimensionality, and differential item functioning (DIF), using Rasch models. Criterion validity was examined based on associations between NEI VFQ person measures and recent visual acuity (VA) levels. RESULTS: Ninety-nine participants recruited online from uveitis patient organizations (68 women, 31 men; mean age 50 ± 15 years; 46.5% self-reported receiving systematic therapy for uveitis, 0.6% NEI VFQ-25 missing data) were included. The mean difficulty of items was lower than the average person ability. None of the items demonstrated misfit to an extent that would induce noise into the measurement. The consistency metrics person reliability and person separation index of the subscales were 0.85 and 2.34 (NEI VFQ-VF), 0.86 and 2.52 (NEI VFQ-SE), respectively. There was no evidence of multidimensionality and none of the items showed DIF by gender. The differences between item and person measures were 1.44 (NEI VFQ-VF) and 1.03 (NEI VFQ-SE). NEI VFQ-25 person measures were significantly lower in participants with visual impairment (all p values ≤ 0.007). CONCLUSION: Rasch model-based scoring of the re-engineered NEI VFQ-25 demonstrates acceptable internal consistency, item fit and construct validity for assessing two key domains of quality of life in individuals self-reporting uveitis. The PROM was targeted at a higher level of difficulty than present in our heterogeneous sample.

[Intermediate and Posterior Uveitis - Disease entities]. / Intermediäre und posteriore Uveitis ­ Teil 2.

Intermediate and posterior uveitis can have multiple infectious and noninfectious causes, and posterior uveitis in particular is clinically multifaceted. Some entities require prompt initiation of therapy to ensure visual prognosis. This article presents typical characteristics of intermediate and posterior uveitides and explains special features of their treatment.

[Intermediate and Posterior Uveitis - Classification, diagnostics, complications, and therapeutic algorithms]. / Intermediäre und posteriore Uveitis ­ Teil 1.

Intermediate and posterior uveitis describes a broad variety of different types of intraocular inflammation. Before starting treatment of intermediate or posterior uveitis, a differentiation between infectious or non-infectious uveitis must always be made. Pathognomonic symptoms do not exist, visual loss and vitreous floaters are the most common symptoms. The indication for therapy is influenced by the anatomical localization, the degree of inflammation, an association, complications and the activity of the inflammation. In addition to clinical ophthalmological standard examination, angiography and OCT are the most important investigations to classify and assess the course of inflammation. Macular edema is the most common complication of intermediate or posterior uveitis and should be treated at first onset, recurrence, or worsening. Oral, intravenous, or intravitreal corticosteroids are usually the primary therapy for intermediate or posterior uveitis. Systemic immunosuppression is indicated after steroid failure in non-infectious uveitis.

Cross-Registry Benchmarking of Data Quality: Lessons Learned.

Feedback of data quality measures to study sites is an established procedure in the management of registries. Comparisons of data quality between registries as a whole are missing. We implemented a cross-registry benchmarking of data quality within the field of health services research for six projects. Five (2020) and six (2021) quality indicators were selected from a national recommendation. The calculation of the indicators was adjusted to the registries' specific settings. Nineteen (2020) and 29 results (2021) could be included in the yearly quality report. Seventy-four per cent (2020) and 79% (2021) of the results did not include the threshold in their 95%-confidence-limits. The benchmarking revealed several starting points for a weak-point analysis through a comparison of results with a predefined threshold as well as through comparisons among each other. In the future, a cross-registry benchmarking might be part of services provided through a health services research infrastructure.

Surgical Glaucoma Treatment in Patients with Juvenile Idiopathic Arthritis-Associated Uveitis: Results after Trabeculectomy or Ahmed Glaucoma Valve Implantation.

PURPOSE: Patients with juvenile idiopathic arthritis (JIA) associated uveitis (JIAU) are at risk for secondary glaucoma, frequently requiring surgical management. We compared the success rates for trabeculectomy (TE) and Ahmed glaucoma valve (AGV) implantation. METHODS: We conducted a retrospective analysis of TE (45 eyes), primary AGV (pAGV) (7 eyes), or secondary AGV (sAGV) implantation after TE (11 eyes) in JIAU at the 2-year follow-up. RESULTS: All groups achieved significant pressure reduction. After 1 year, the overall success rate was higher in the Ahmed groups (p = 0.03). After adjusting the p-value according to Benjamin Hochberg, there is no significant difference between the groups in the Kaplan-Meier, despite a significant logrank test between all groups (p = 0.0194) and a better performance in the Ahmed groups. CONCLUSION: Slightly better success rates were achieved with pAGV in managing JIAU patients with glaucoma refractory to medical treatment.

Cataract Surgery-Indications, Techniques, and Intraocular Lens Selection.

BACKGROUND: Opacification of the lens of the eye (cataract) is usually due to aging. It is a painless, progressive condition that affects contrast and color perception and alters refraction, leading to visual loss that may be total. In cataract surgery, the turbid lens is replaced by an artificial lens. An estimated 600 000 to 800 000 such procedures are performed in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including meta-analyses, Cochrane reviews, and randomized controlled clinical trials (RCTs). RESULTS: Cataract is the most common reversible cause of blindness around the world (approximately 95 million people). The surgical replacement of a turbid lens with an artificial lens is usually carried out under local anesthesia. The standard technique for fragmentation of the nucleus of the lens is ultrasonic phacoemulsification. RCTs have not shown the superiority of the femtosecond laser over phacoemulsification for this purpose so far. The spectrum of artificial intraocular lenses, aside from the conventional type with a single focus, include lenses with multiple foci, extended-depth-of-focus (EDOF) lenses, and astigmatism-correcting lenses. CONCLUSION: In Germany, cataract surgery is usually performed on an outpatient basis under local anesthesia. Artificial lenses with various additional functions are available nowadays; the choice of lens depends on the needs of the individual patient. Patients must be adequately informed about the advantages and disadvantages of the different lens systems.

Comparing the Efficacy of Intravitreal Dexamethasone and Time-displaced Fluocinolone Acetonide on Central Retinal Thickness in Patients with Uveitis.

BACKGROUND: To compare the efficacy of intravitreally administered dexamethasone (Dex) and subsequent time-displaced fluocinolone acetonide (FA) on central subfield thickness (CST) in eyes with noninfectious uveitis. METHODS: Retrospective analysis of twenty-three eyes (18 patients) subsequently receiving intravitreal Dex and FA implants. The main outcome measures were CST, best-corrected visual acuity (BCVA), intraocular pressure (IOP), and status of inflammation. RESULTS: CST (Dex: p < .0001; FA: p = .0008) and BCVA (Dex: p = .0009; FA: p = .0005) improved significantly with both implants. Significantly better effects were noted with Dex for absolute and relative CST reduction (p = .0089 and p = .0051, respectively). Final BCVA did not differ between groups (p = .1893). Dex significantly increased IOP, whereas FA did not. One eye was actively inflamed after Dex and FA injection at follow-up (inflamed eyes before injection: [Dex: 2; FA: 6]). CONCLUSION: Both implants significantly reduced CST and induced a significant gain in visual acuity. Dex might be more effective in reducing CST.

Beneficial Effect of Upadacitinib in an Adult Patient with Juvenile Idiopathic Arthritis-associated Uveitis after Unsatisfactory Response to Tofacitinib: A Case Report.

OBJECTIVE: Several case reports have been published on the effect of janus kinase inhibitors (JAK-I) on juvenile idiopathic arthritis-associated uveitis (JIAU). Both tofacitinib and baricitinib have been described as therapeutically effective in JIAU. METHODS: We here present a case of a 24-years-old female with refractory course of JIAU receiving upadacitinib therapy. RESULTS: After failing multiple conventional and biologic disease-modifying antirheumatic drugs, the patient finally achieved clinical remission on upadacitinib monotherapy, despite a previously unsatisfactory clinical response of both arthritis and uveitis to tofacitinib monotherapy. CONCLUSION: This case suggests that switching JAK-I might be a successful strategy in the treatment of JIAU, despite previously incomplete response to other preparations.

Uveitis Registries - A Digital Tool for Patient Care, Education, Research, and Collaboration.

PURPOSE: Clinical registries are increasingly important in research and clinical advancement. This review explores and compares current uveitis registries and recommends future directions on how uveitis registries can complement one another for synergistic effect and benefit. METHODS: From a systematic search, 861 citations were screened for longitudinal, non-interventional, and multicenter uveitis-specific registries. Additional registries were identified via consultations with uveitis experts. Characteristics of all registries were analyzed and compared. RESULTS: Four registries were identified: Treatment Exit Options for Non-infectious Uveitis, AutoInflammatory Disease Alliance International Registry, Ocular Autoimmune Systemic Inflammatory Infectious Study, and Fight Uveitis Blindness!. Despite certain differences, these registries have the overarching goal of collecting large quantities of real-world, high-quality patient data to improve the understanding of uveitis. CONCLUSION: The four uveitis registries share similar goals and collect clinical data from overlapping geographical regions. There is vast potential for collaboration, including data sharing to further augment datasets for analysis.

Beneficial Effect of Upadacitinib in a Refractory Course of Scleritis: A Case Report.

Noninfectious scleritis typically takes a chronic course, and systemic corticosteroids or disease-modifying anti-rheumatic drug (DMARD) treatment may be inevitable for a prolonged period. Janus kinase (JAK) inhibitors are a relatively new therapeutic option for inflammatory diseases, and three cases of successful treatment of scleritis with tofacitinib, a substance targeting JAK-1 and -3, have been published up to now. We here describe the case of a 51-years-old female patient with bilateral anterior and posterior scleritis who, after treatment failure of multiple DMARDs, finally achieved clinical quiescence of disease under treatment with upadacitinib, a selective JAK-1 inhibitor.

Elevated endothelin-1 levels as risk factor for an impaired ocular blood flow measured by OCT-A in glaucoma.

The purpose of this study was to ascertain whether a correlation exists between glaucoma-associated alteration of ocular vascular haemodynamics and endothelin-1 (ET-1) levels exist. Eyes of patients with cataract (n = 30) or glaucoma (n = 68) were examined with optical coherence tomography (OCT) and OCT-angiography (OCT-A; AngioVue™-RTVue-XR; Optovue, Fremont, California, USA). The peripapillary and the macular vessel density (VD) values were measured. Inferior and superior retinal nerve fibre layer (RNFL) thickness loss was used for further OCT staging. Aqueous humour of the examined eye and plasma were sampled during cataract or glaucoma surgery and analysed by means of ELISA to determine their ET-1 level. Glaucoma eyes are characterised by reductions in RNFL thickness and VD that correlate significantly with the OCT GSS score. Peripheral and ocular ET-1 level were significantly elevated in patients with glaucoma and correlate positively with the OCT-GSS score of the entire study population. Peripapillary and macula VD of glaucoma patients correlates negatively with plasma ET-1 levels. Multivariable analysis showed a subordinate role of intraocular pressure predictive factor for impaired retinal blood flow compared with plasma ET-1 level in glaucoma. Peripheral ET-1 level serves as risk factor for detection of ocular blood flow changes in the optic nerve head region of glaucomatous eyes.

Metadata Definition in Registries: What Is a Data Element?

Observational research benefits from a rich methodological foundation of registry development and operation published in international and national guidelines. Metadata management is an essential part of registry implementation based on concepts of data elements and value sets. The metadata from six German registries revealed vastly divergent interpretations of the concept of data elements. The different perspectives of research questions, data acquisition and data storage were all represented in the registries' catalogs of data elements. Consequently, the whole life cycle of a registry needs to be accompanied by a catalog of data elements, which has to be continuously adapted to the changing perspectives. A standard for the representation of those metadata is still missing. The FAIR Guiding Principles introduce important methodological requirements, but the tools for their fulfillment in respect to the management of metadata are still in its infancy.

Non-infectious uveitis affecting the posterior segment treated with fluocinolone acetonide intravitreal implant: 3-year fellow eye analysis.

BACKGROUND: Prevention of non-infectious uveitis of the posterior segment (NIU-PS) recurrence using 0.2 µg/day fluocinolone acetonide implant (FAi) was assessed over 3 years (NCT01694186). Outcomes for FAi-treated and fellow eyes with NIU-PS were compared, to evaluate FAi versus conventional treatment strategies. METHODS: Eligible subjects had >1-year recurrent NIU-PS history and either ≥2 separate recurrences requiring treatment, or corticosteroid therapy (systemic or ocular) in the 12 months preceding study entry. Bilateral disease was present and analysed in 59/87 FAi-treated participants. Recurrence rates, best-corrected visual acuity (BCVA) changes, cataract surgery, intraocular pressure (IOP) events and adjunctive medication use were compared for FAi-treated and fellow eyes. RESULTS: Over 36 months, more FAi-treated than fellow eyes remained recurrence-free (28.8% vs. 5.1%, P = 0.001; mean 1.9 vs. 4.7 recurrences, respectively, P < 0.0001). FAi-treated eyes gained +9.6 letters BCVA, versus a loss of -4.4 in fellow eyes (P < 0.0001). Systemic medications were given to 42.4% of subjects. Intra/periocular adjunctive injections were lower in FAi-treated than fellow eyes (20.3% vs. 66.1%, P < 0.0001); topical corticosteroid use was also lower in FAi-treated than fellow eyes (27.1% vs 52.5%, P = 0.0041). IOP-related events occurred at similar rates in both FAi-treated and fellow eyes, excepting IOP-lowering surgery (5.1% vs. 15.3%, respectively; P = 0.1251). Cataract surgery occurred in 72.0% of FAi-treated and 37.0% of fellow eyes. CONCLUSIONS: In subjects with bilateral NIU-PS, continuous, low-dose corticosteroid with 0.2 µg/day FAi reduced recurrence and adjunctive medication requirements, and improved vision over 36 months, providing greater protection against ocular inflammation than a reactive approach using standard of care.

Treatment Exit Options for Non-infectious Uveitis (TOFU): Study Protocol for a Prospective Clinical Registry.

PURPOSE: Currently, there is limited evidence regarding clinical management of non-anterior non-infectious uveitis including treatment outcomes of disease-modifying anti-rheumatic drugs (DMARDs) and their combinations. Treatment guidelines or recommendations on preferred choice of DMARD combinations and reduction and/or discontinuation strategies in quiescent uveitis are lacking. The TOFU (Treatment exit options for non-infectious uveitis) registry aims to document disease courses and to provide recommendations on DMARD treatment exit strategies. METHODS: The registry is an observational, non-commercial, and non-interventional study and targets patients who are ≥18 years of age with non-infectious uveitis of the posterior segment or retinal vasculitis on or starting DMARD treatment. Data are entered prospectively at study sites through a web-based interface into electronic case report forms (eCRF) implemented in the electronic data capture software RedCap (Version 9, Vanderbilt University, USA). The collated data include ophthalmological, general medical history and patient-reported outcomes (PROs). Assessment of uveitis classification and activity follows the international Standardization of uveitis nomenclature (SUN) criteria. Patient appointment and treatment decisions remain at the discretion of the managing physician and are completely independent of participation in the registry. The study follows the tenets of the declaration of Helsinki. CONCLUSIONS: The TOFU registry captures real-life data of patients with non-infectious uveitis of the posterior segment, involving both medical personnel and patients. The study adheres to international standards and will provide important evidence and guidance in the development of guidelines.

[The Treatment Exit Options for Uveitis (TOFU) Registry: Involving Patients in the Generation of Evidence]. / Das Treatment Exit Options for Uveitis (TOFU) Register: Einbindung von Patienten in die Evidenzgenerierung.

Uveitis comprises a group of rare diseases characterised by intraocular inflammation which may cause vision impairment and blindness and mostly affects people of working age. Non-infectious uveitis involving the posterior pole or the entire eye is often treated with different immunomodulating or disease-modifying anti-rheumatic drugs (DMARDs). However, the evidence on long-term management strategies and reduction/termination of treatment is limited. To help develop treatment exit strategies for patients with quiescent uveitis on long-term DMARD treatment, the Treatment Exit Options for Non-infectious Uveitis registry was initiated by the German ophthalmological society. A key aspect of the registry is active participation of patients (patient-reported outcomes, PROs). In a pilot study involving members of patient organizations, a combination of questionnaires covering vision- and general health-related quality of life, adherence to treatment, productivity and effects of treatment were evaluated. As the pilot study showed coverage of relevant patient-related aspects of the disease and its effect on daily life, the evaluated questionnaires were implemented in the registry's patient module. The registry including the patient module uses the electronic data capture (EDC) software REDCap (Version 9, Vanderbilt University, USA). By involving patients in both conceptualization and ongoing data collection, the TOFU registry emphasizes the patients' perspectives, and the inclusion of patient-relevant evidence for such as the development of guidelines and treatment recommendations is ensured.

Structural Endpoints and Outcome Measures in Uveitis.

Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and "core outcomes" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current "core modalities" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.