The human corneal endothelium (HCE) is critical for maintaining corneal transparency. Dysfunctions due to cell loss are linked to altered intracellular calcium ([Ca2+]i) homeostasis. Transient receptor potential channels (TRPs) are key regulators of [Ca2+]i, and both L-ascorbic acid (Asc) and cannabinoid receptor (CB) agonists have been implicated in modulating TRP activity. This study investigated the effects of 1 mM Asc and the CB agonist WIN 55,212-2 (WIN) (10 µM) on [Ca2+]i regulation in human corneal endothelial cells (HCECs). HCEC-12 was used as the established HCE cell model. [Ca2+]i dynamics were assessed by fura-2/AM fluorescence imaging, and membrane currents were analyzed using planar patch-clamp recordings. Adding 1 mM Asc increased [Ca2+]i, which was partially suppressed by the TRPV1 blocker AMG-9810 (AMG) (20 µM) and the TRPV4 blocker GSK2193874 (GSK219) (10 µM). Furthermore, 1 mM Asc increased whole-cell currents. WIN also induced [Ca2+]i transients that were partially attenuated by AMG, the TRPM8 blocker AMTB (20 µM), GSK219, and the CB1 inverse agonist AM251 (10 µM). In addition, combined treatment with Asc and WIN enhanced [Ca2+]i elevations compared with either treatment alone. These findings provide the first evidence for a functional interaction between TRP channel activity and CB signaling in HCECs. The inhibitory effect of AM251 suggests a predominant contribution of CB1 receptors. Given the central role of Ca2+ homeostasis in corneal endothelial function and disease, these results may contribute to a better understanding of endothelial pathophysiology and support further investigation of TRPs and cannabinoid signaling as potential targets in corneal disorders.

NGF plays important roles in ocular surface homeostasis and different pathological conditions. One effect includes promoting conjunctival epithelial cell differentiation and mucin secretion. This study characterizes the individual roles of TRPV1 and TRPM8 channel activity in mediating the effects of NGF on intracellular Ca2+ regulation and its alteration of regulatory cell volume responses to anisosmotic challenges in human conjunctival epithelial cells (IOBA-NHC). With fura-2/AM-loaded cells, the effects of 40 µM capsaicin and 20 µM AMG 9810 on Ca2+ regulation confirm functional TRPV1 expression. TRPM8 expression is evident since 500 µM menthol and 20 µM AMTB have opposing effects on [Ca2+]i. AMG 9810 and AMTB (both 20 µM) suppress the responses to NGF (100 ng/mL). With calcein/AM-loaded cells, the effects of these mediators are evaluated on apparent cell volume responses induced by an anisosmotic challenge. NGF decreases the apparent cell volume that AMG 9810 suppresses, whereas AMTB (both 20 µM) augments this response. Therefore, NGF interacts with TRPV1 and TRPM8 to induce opposing effects on cell volume regulatory behavior. These opposing effects suggest that the signaling pathways and effectors that mediate responses to TRPV1 and TRPM8 activation are not the same.

Approximately 0.5-1% of patients with multiple sclerosis (MS) have co-existing uveitis. Both intraocular inflammation and MS mainly affect women in younger adulthood. The MS in patients is most frequently associated with an often bilateral intermediate uveitis with typical concomitant retinal vasculitis. Both diseases share similar characteristics with chronic inflammatory diseases with a relapsing course and an immune-mediated pathogenesis; however, it is still unclear whether the co-occurrence of uveitis and MS in the same patient represents a coincidence of two separate disease entities or whether uveitis is a rare clinical manifestation of MS. In the differential diagnostics of intermediate uveitis, clinical symptoms and signs of MS should be considered. As both diseases are considered to be immune-mediated, immunotherapy is the main treatment option. In recent years the range of medications has expanded and includes several disease modifying drugs (biologics). When selecting the active substance it must be taken into account that tumor necrosis factor (TNF) alpha blockers are contraindicated in patients with MS.

INTRODUCTION:This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts. METHODS:This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey. RESULTS:Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors. CONCLUSIONS:This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.

Background/Aim This study evaluated real-life adalimumab impact in patients with active non-infectious intermediate, posterior, or panuveitis (NIIPPU). Methods Adults with active NIIPPU received adalimumab in this prospective, observational study (06/2017–04/2020). Patients were evaluated at baseline (V0) and four follow-up visits over 12 months (V1–V4). Primary endpoint: proportion of patients achieving quiescence (anterior chamber (AC) cells grade and vitreous haze (VH) grade≤0.5+ in both eyes, no new active chorioretinal lesions) at any follow-up visit. Secondary endpoints: proportion of patients achieving quiescence at each visit; proportion of patients maintaining response; and proportion of patients with flares. Workability, visual function, healthcare resource utilisation, and safety were evaluated. Results Full analysis set included 149 patients. Quiescence at any follow-up visit was achieved by 129/141 (91%) patients. Quiescence at individual visits was achieved by 99/145 (68%), 110/142 (77%), 102/131 (78%), and 99/128 (77%) patients at V1–V4, respectively. Number of patients in corticosteroid-free quiescence increased from 51/147 (35%; V1) to 67/128 (52%; V4; p<0.05). Proportion of patients with maintained response increased from 89/141 (63%; V2) to 92/121 (76%; V4; p<0.05) and proportion of patients with flare decreased from 25/145 (17%; V1) to 13/128 (10%; V4; p=0.092). Workability and visual function improved throughout the study. Proportion of patients with medical visits for uveitis decreased from 132/149 (89%; V0) to 27/127 (21%; V4). No new safety signals were observed. Conclusion These results demonstrated adalimumab effectiveness in improving quality of life while reducing economic burden of active NIIPPU.

Ocular involvement is present in up to 79% of sarcoid patients. Uveitis is the main ocular manifestation and presents as a chronic intraocular inflammatory condition with potentially detrimental effects on visual acuity and quality of life. This retrospective study was conducted to explore the incidence and characteristics of ocular sarcoidosis in a single tertiary ophthalmology center. Medical records of 84 patients presenting between June 2007 and March 2021 were analyzed. Based on the “International Workshop on Ocular Sarcoidosis” (IWOS) criteria, ocular sarcoidosis was determined as: definite (n = 24; 28.6%), presumed (n = 33; 39.3%), probable (n = 10; 11.9%), and indefinite (n = 17; 20.2%) in our study population. In 43.9% of the definite and presumed cases, the eye was primarily affected. In addition to specific ocular findings, the diagnosis was supported by biopsy (28.6%) and chest x-ray or computer tomography (66.7%). Moreover, an increased soluble interleukin-2 receptor (sIL-2R) expression (76.2%), elevated angiotensin-converting enzyme (ACE) levels (34.8%), and lymphocytopenia (35.1%) were valuable laboratory findings. Co-affected organs were lungs (60.7%), skin (15.5%), and central nervous system (8.3%). Our findings support the prominent role of the eye in the early detection of sarcoidosis. In addition to the IWOS criteria, sIL-2R, in particular, was shown to be relevant in establishing the diagnosis.

Despite the immune-privilege of the cornea, transplant rejection remains the leading cause for graft failure following penetrating keratoplasty. This is particularly true in the high-risk recipients, e.g. following previous graft failure due to rejection, infectious keratitis and vascularized corneas. Several strategies including local and systemic immune modulatory agents are currently used to increase the success rate of high-risk corneal grafts. Although corticosteroids are still a major component of our immunopharmacological armentarium, they might be supplemented by other more specific immunomodulating agents. The spectrum includes agents such as methotrexate calcineurin inhibitors affecting T-cells (cyclosporin A, FK506), mycophenolate mofetil and more selective monoclonal antibodies directed against T-cell subpopulations and other targets. New options may include JAK kinase and anti-Rho directed approaches that remain under investigation. In addition, preoperative MHC and non-MHC antigens matching have been investigated as strategy to reduce immune-mediated graft rejection however, results still remain controversial. In order to better evaluate the risks and benefit of these approaches the properties of established and forthcoming options are presented.

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].

ZusammenfassungICD-10-Code: L12 Pemphigoidkrankheit, L12.1 Vernarbendes Pemphigoid, H13.3 Okuläres Pemphigoid

ZusammenfassungICD-10-Code B83 Toxokariasis

ZusammenfassungDie anteriore Uveitis umfasst eine Entzündung der Iris und/oder des Ziliarkörpers und ist die häufigste Form der intraokularen Entzündung in der augenärztlichen Praxis. Anamnese und (Leit-)Befunde bei der Spaltlampenuntersuchung bieten oft bereits wichtige Hinweise zur Pathogenese und damit zur weiteren diagnostischen Abklärung und Therapie.

Purpose: To describe a case of acute macular neuroretinopathy (AMN) in a 23-year-old Caucasian female after a COVID-19 vaccination (Vaxzevira). Observations: Our patient perceived visual symptoms in both eyes one day after COVID-19 vaccination. Hyporeflective petalloid shaped perifoveal lesions appeared in infrared reflectance (IR) imaging, and Spectral domain-optical coherence tomography (SD-OCT) revealed structural alterations of outer retinal layers that resulted in persistent disruption of the ellipsoid zone (EZ) and the interdigitation zone (IZ). Conclusions and importance: We report a novel association between AMN and COVID-19 vaccination. In addition to a febrile infection and oral contraception, previous vaccination should also be considered a potential risk factor for AMN.

ZusammenfassungICD-10-Code H30.9 Chorioretinale Entzündung, unspezifisch

Zusammenfassung Die akute anteriore Uveitis (AAU) ist die häufigste Form intraokularer Entzündungen, die v. a. Personen im erwerbsfähigen Alter betrifft und mit erheblichen sozioökonomischen Auswirkungen verbunden ist. Etwa die Hälfte der AAU-Patienten sind HLA-B27 positiv und teilen ein hohes Risiko zu HLA-B27-assoziierten Erkrankungen, insbesondere zur Spondyloarthritis (SpA). Sowohl die SpA als auch die AAU sind komplexe entzündliche Erkrankungen, deren genaue Pathogenese unbekannt ist. Da bei bis zu 40% der AAU-Patienten eine nicht diagnostizierte SpA vorliegt, bietet die AAU die Möglichkeit einer frühzeitigen Erkennung der zugrundeliegenden rheumatologischen Erkrankung. Die klinische Präsentation der AAU bei SpA weist eine Reihe typischer Augenbefunde auf, die diagnostisch wegweisend sind und auf eine systemische Grunderkrankung hindeuten können. Daher ist eine abgestimmte Überweisungsstrategie zur zügigen Diagnostik und Behandlung notwendig. Dieser Beitrag fokussiert daher auf die interdisziplinäre Zusammenarbeit und bietet gleichzeitig Hinweise für die differentialdiagnostische Abklärung.

ZusammenfassungICD-10-Code H16 Keratitis