To develop imaging-based measures for disease assessment in non-infectious posterior uveitis (NIPU). A mixed-methods design, beginning with a review of previously developed imaging recommendations formulated by separate subcommittees of the Multimodal Imaging in Uveitis (MUV) initiative, followed by a structured consensus process using the Nominal Group Technique (NGT), facilitated by an independent expert committee. An expert committee reviewed and extracted all consensus-based imaging recommendations by the MUV subcommittee manuscripts focused on five major NIPU entities. The primary objective was to categorize imaging features as suggestive of active disease (SAD), suggestive of inactive disease (SID), or equivocal. This process was conducted using the NGT to reach consensus-based imaging measures. These recommendations were further voted upon by members of the full task force. A total of 49 imaging statements were deliberated using two rounds of NGT and independent voting. For the five included diseases, a total of 21 statements qualified as features of SAD, whereas 12 statements were classified as SID. The remaining 16 statements were categorized as equivocal features, that need further investigation to determine whether the disease is active. This study builds upon the multinational efforts of the MUV initiative to extend the Standardization of Uveitis Nomenclature (SUN) work through the integration of additional multimodal imaging information. By defining clear imaging-based outcome measures for NIPU, it establishes a structured framework supporting objective disease assessment. These standardized imaging measures are expected to enhance the utility of multimodal imaging in both routine uveitis care and future clinical trials.

Non-infectious posterior and panuveitides (NIPUs) comprise a heterogeneous group of inflammatory disorders of the outer retina and choroid, historically referred to as "white dot syndromes." Recent consensus efforts by the Multimodal Imaging in Uveitis (MUV) Task Force have established standardized diagnostic criteria for the major NIPUs, including multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis and panuveitis/punctate inner choroiditis (MFCPU/PIC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis, and birdshot chorioretinopathy (BSCR). Nevertheless, a substantial proportion of cases deviate from classical presentations and fall into diagnostic "grey zones", blurring boundaries between diseases entities and complicating both differential diagnosis and management. This review aims to describe the broad spectrum of atypical, variant, and secondary forms of NIPUs as well as masquerade syndromes. Atypical MEWDS includes bilateral presentations or complicated courses, while MFCPU/PIC with outer retinal atrophy emerges as a notable entity with unclear therapeutic implications. Inflammatory reactions resembling both MEWDS and MFCPU/PIC may also occur as secondary phenomena, triggered by other chorioretinal disorders, most notably inherited retinal diseases (IRDs). Placoid chorioretinopathies, including APMPPE, persistent placoid maculopathy, serpiginous choroiditis, and relentless placoid chorioretinitis, are often distinguished only a posteriori based on disease course, but likely represent a continuum of disorders unified by choroidal ischemia. Atypical presentations of BSCR may feature extensive outer retinal damage, mimicking IRDs. Equally important is the consideration of masquerade syndromes in all suspected cases of NIPUs, as they can present with similar features yet require entirely different treatments. Infectious masquerades include tuberculosis-associated serpiginous-like choroiditis, acute syphilitic posterior placoid chorioretinopathy, and West Nile virus chorioretinitis, whereas vitreoretinal lymphoma is the most frequent neoplastic masquerade. In conclusion, integrating clinical context with high-quality multimodal imaging remains essential to navigate the jungle of differential diagnosis in NIPUs, while future studies should aim to link imaging phenotypes with immune and molecular biomarkers to refine classification and guide targeted therapies.

Intraocular dual infection by Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM) is rarely reported. This study describes the clinical features, aetiology, and treatment outcomes of patients with dual infection from MTBC and NTM-related uveitis. A retrospective study was conducted on 146 clinically suspected tubercular uveitis (TBU) patients who underwent diagnostic or therapeutic pars plana vitrectomy as plan of laboratory diagnosis-based management between June 2023 and December 2024. Undiluted vitreous samples were analysed with nested MTBC-NTM multiplex real-time PCR assay kit. Six out of 146 patients (4.11%) were found infected with dual infection from MTBC and NTM. All six cases showed severe clinical presentation characterised by bilateral panuveitis (5/6 patients), with significant structural sequelae. Optic atrophy was universal and occurred more frequently than in isolated TBU, while complicated cataract and hypotony-related maculopathy were also common. Despite the dual etiology, all patients achieved inflammatory resolution and visual recovery (mean BCVA improving from 20/400 to 20/100) following standard anti-tubercular therapy (ATT) and corticosteroids, with no recurrence during follow-up. Concurrent MTBC and NTM infection drives a distinct, aggressive form of panuveitis characterized by optic nerve pallor, anterior segment complications of complicated cataract or uveitic membranes and maculopathy. Despite this severity, standard ATT remained an effective first-line strategy, likely either due to therapeutic cross-coverage against NTM or MTBC being the primary driver of uveitis in the present study. The concurrent positivity also highlights the need for vitreous molecular profiling and further research in co-infections in infectious posterior uveitis.

Autoimmune uveitis is an orphan disease with a prevalence of 0.4% and normally very effectively prevented by the immune privilege of the eye. The immune privilege can be overcome, because an immune response that is activated outside the eye against foreign antigens enables T cells to enter the eye and also recognises intraocular antigens via cross-reactivity (antigenic mimicry) and thus triggers uveitis. This leads to the migration of lymphocytes into the eye, followed by the invasion of inflammatory cells that cause the destruction of intraocular structures. Antigenic mimicry can also be used therapeutically to induce oral tolerance. The discovery of the tolerance-inducing but non-pathogenic mimicry epitope B27PD made it possible to treat therapy-refractory uveitis patients by inducing oral tolerance. All 8 treated patients were able to reduce their steroid therapy, with stable or improved visual acuity, and two have been free of recurrence and therapy since oral tolerance induction 30 years ago. Later, the establishment of two new animal models for spontaneously recurrent and chronic uveitis has provided new insights into the role of different T cell types in the eye and allowed us to develop and test new therapies in ongoing autoimmune reactions, as corresponding to the situation in uveitis patients. These new animal models also enabled the development of a small molecule dihydroorotate dehydrogenase (DHODH) inhibitor PP-001/KIO-100 for the treatment of uveitis, which inhibits lymphocytes but has no toxic effects on intraocular cells (in vivo: rat) and human retinal pigment epithelial cells (RPE, in vitro). This was followed by a successful phase I trial for patients with non-infectious posterior uveitis, by intraocular application of PP-001/KIO-100 - without side effects, but with improvement of visual acuity and reduction in inflammation and CME. Die autoimmune Uveitis gehört mit einer Prävalenz von 0,4% der Bevölkerung zu den seltenen Erkrankungen und wird normalerweise durch das Immunprivileg des Auges effektiv verhindert. Das Immunprivileg kann überwunden werden, da eine Immunantwort, die außerhalb des Auges gegen Fremdantigene aktiviert wird, T-Zellen ermöglicht, in das Auge zu gelangen und über Kreuzreaktivität (antigene Mimikry) auch intraokuläre Antigene erkennt und eine Uveitis auslöst. Es kommt zur lymphozytären Einwanderung ins Auge, gefolgt von der Invasion von Entzündungszellen, die die Destruktion der intraokulären Strukturen verursachen. Antigene Mimikry erklärt nicht nur die Induktion der Uveitis, sondern kann auch therapeutisch für orale Toleranzinduktion genutzt werden. Die Entdeckung des toleranzinduzierenden, aber nicht pathogenen Mimikry-Epitops B27PD im Uveitismodell der Ratte ermöglichte einen Heilversuch für therapierefraktäre Uveitispatienten durch orale Toleranzinduktion. Alle 8 Patienten konnten bei stabilem oder verbessertem Visus ihre Steroidtherapie reduzieren, 2 sind seit der oralen Toleranzinduktion vor 30 Jahren rezidiv- und therapiefrei. Später brachte die Etablierung zweier neuer Tiermodelle für eine spontan rezidivierende bzw. chronische Uveitis neue Erkenntnisse über die Rolle von verschiedenen T-Zell-Typen im Auge und erlaubte uns die Entwicklung und Testung neuer Therapien bei bereits laufender Autoimmunreaktion, entsprechend der Situation bei Uveitispatienten. Diese Tiermodelle ermöglichten auch die Entwicklung eines kleinmolekularen Dihydroorotat-Dehydrogenase-Inhibitors PP-001/KIO-100 (DHODH-Inhibitors) für die systemische und intraokuläre Uveitisbehandlung, der Lymphozyten hemmt, aber keine toxischen Effekte für intraokuläre Zellen (in vivo: Ratte) und humane retinale Pigmentepithelzellen (RPE, in vitro) zeigte. Es folgte eine erfolgreiche Phase-I-Studie für Patienten mit nicht infektiöser posteriorer Uveitis durch intraokuläre Applikation von PP-001/KIO-100 ohne Nebenwirkungen, aber mit Visusverbesserung sowie Rückgang von Entzündung und CMÖ.

Ocular toxoplasmosis is the leading cause of infectious posterior uveitis worldwide and a daily challenge for ophthalmologists. Most cases of ocular toxoplasmosis are acquired postnatally, mainly through ingestion of contaminated meat or contact with cat feces. The diagnosis relies on clinical findings such as focal retinochoroiditis, vitritis and retinal scarring. The treatment can include antiparasitic drugs and in selected cases requires the combination with corticosteroids. The recurrence rates are high, particularly in older or immunocompromised patients. Early diagnosis and individualized treatment strategies significantly improve the prognosis and visual function. Die okuläre Toxoplasmose (OT), eine schwere Manifestation der Toxoplasma gondii-Infektion, ist weltweit die häufigste Ursache einer infektiösen posterioren Uveitis und eine alltägliche Herausforderung in der augenärztlichen Praxis. Die Mehrzahl der OT-Fälle wird – insbesondere über kontaminiertes Fleisch oder Kontakt mit Katzenfäkalien – postnatal erworben. Die Diagnose basiert klinisch auf typischen Befunden wie fokaler Retinochoroiditis, Glaskörperentzündung und narbigen Veränderungen der Netzhaut. Die Therapie kann den Einsatz von antiparasitärer Medikation und in ausgewählten Fällen die Kombination mit Kortikosteroiden erfordern. Die Rückfallrate ist hoch, insbesondere bei älteren oder immunsupprimierten Patienten. Frühzeitige Diagnostik und individuell angepasste Therapieschemata verbessern die Prognose und die Sehfunktion signifikant.