Search

The conjunctiva has immune-responsive properties to protect the eye from infections. Its innate immune system reacts against external pathogens, such as fungi. The complement factor C5a is an important contributor to the initial immune response. It is known that activation of transient-receptor-potential-vanilloid 1 (TRPV1) and TRP-melastatin 8 (TRPM8) channels is involved in different immune reactions and inflammation in the human body. The aim of this study was to determine if C5a and mucor racemosus e voluminae cellulae (MR) modulate Ca 2+ -signaling through changes in TRPs activity in human conjunctival epithelial cells (HCjECs). Furthermore, crosstalk was examined between C5a and MR in mediating calcium regulation. Intracellular Ca 2+ -concentration ([Ca 2+ ] i ) was measured by fluorescence calcium imaging, and whole-cell currents were recorded using the planar-patch-clamp technique. MR was used as a purified extract. Application of C5a (0.05-50 ng/mL) increased both [Ca 2+ ] i and whole-cell currents, which were suppressed by either the TRPV1-blocker AMG 9810 or the TRPM8-blocker AMTB (both 20 µM). The N-terminal peptide C5L2p (20-50 ng/mL) blocked rises in [Ca 2+ ] i induced by C5a. Moreover, the MR-induced rise in Ca 2+ -influx was suppressed by AMG 9810 and AMTB, as well as 0.05 ng/mL C5a. In conclusion, crosstalk between C5a and MR controls human conjunctival cell function through modulating interactions between TRPV1 and TRPM8 channel activity.

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., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: In recent years artificial intelligence (AI), as a new segment of computer science, has also become increasingly more important in medicine. The aim of this project was to investigate whether the current version of ChatGPT (ChatGPT 4.0) is able to answer open questions that could be asked in the context of a German board examination in ophthalmology., Methods: After excluding image-based questions, 10 questions from 15 different chapters/topics were selected from the textbook 1000 questions in ophthalmology (1000 Fragen Augenheilkunde 2nd edition, 2014). ChatGPT was instructed by means of a so-called prompt to assume the role of a board certified ophthalmologist and to concentrate on the essentials when answering. A human expert with considerable expertise in the respective topic, evaluated the answers regarding their correctness, relevance and internal coherence. Additionally, the overall performance was rated by school grades and assessed whether the answers would have been sufficient to pass the ophthalmology board examination., Results: The ChatGPT would have passed the board examination in 12 out of 15 topics. The overall performance, however, was limited with only 53.3% completely correct answers. While the correctness of the results in the different topics was highly variable (uveitis and lens/cataract 100%; optics and refraction 20%), the answers always had a high thematic fit (70%) and internal coherence (71%)., Conclusion: The fact that ChatGPT 4.0 would have passed the specialist examination in 12 out of 15 topics is remarkable considering the fact that this AI was not specifically trained for medical questions; however, there is a considerable performance variability between the topics, with some serious shortcomings that currently rule out its safe use in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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.)

Inflammatory changes in the retinal vessels can be attributed to a wide range of etiologies. These include infections, intraocular and systemic autoimmune processes, general diseases and iatrogenic factors. As the endothelium of the retinal capillaries forms the inner blood-retinal barrier, a disruption of this structure is directly associated with consequences for the fluid electrolyte balance of the retina. Clinical sequelae can include leakage of the retinal vessels and macular edema, which are often functionally threatening and significantly reduce the quality of life of patients. As the eye can be affected as an "index organ", a work-up of the patient by the ophthalmologist is of great importance. In the age of "precision medicine", efforts are being made to gain new insights into the pathogenetic mechanisms of vasculitis through "omics" in order to develop innovative treatment concepts., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objective: This study aims to describe the outcome of corneal grafts, both low risk and high risk, after successfully reversed immunological rejection., Methods: Datasets on reversed rejection episodes in penetrating and endothelial keratoplasties between 2014 and 2019 (n=876) were extracted from the Adverse Immune Signatures and their Prevention in Corneal Transplantation database, which contains the prospectively and consecutively collected corneal transplants from five European centres. Stratified by the preoperatively determined risk status for immunological rejection, the outcome parameters analysed included visual acuity, intraocular pressure, endothelial cell density and central corneal thickness before and after reversed rejection episodes., Results: Fourty-seven (52%) out of a total of 91 identified rejection episodes were successfully reversed and were available for analysis (23 penetrating and 24 endothelial keratoplasties). No statistically significant change was found for any of the parameters studied between the values before and the values 3 months after the rejection episode, irrespective of the preoperative risk status., Conclusion: The outcome of corneal grafts that survive immunological rejection may be clinically indistinguishable from the state before immunological rejection, irrespective of graft type and risk status. These findings support clinicians by providing information on prognosis after reversed rejection episodes and by giving patients realistic expectations regarding the outcome., Competing Interests: Competing interests: One of the co-authors is an editor., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN ® ) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period ( p < 0.01). An IOP increase ( p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older ( p = 0.004) and had been treated with more dexamethasone (DEX) implants ( p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone ( p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 ( p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.

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.

Purpose: To investigate differences in the retinal vessel area density (VAD) on optical coherence tomography angiography (OCTA) between eyes with unilateral herpetic viral anterior uveitis (VAU) (herpes-simplex virus (HSV) and varicella-zoster virus (VZV)) and the non-affected fellow eye., Methods: In this monocentric, observational, prospective case series we analyzed the VAD of the macula, optic disc, and peripapillary region in affected and non-affected eyes of 22 patients with HSV-positive and 22 patients with VZV-positive VAU using OCTA. We analyzed also the visual field mean deviation (MD), the retinal nerve fiber layer (RNFL) thickness, Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW), and ganglion cell layer (GCL) thickness on OCT and correlated the results with the different VADs., Results: The macular VAD in the superficial vascular plexus (SVC) was significant lower in the affected compared to the non-affected eye for both viruses (HSV: 33.0% ± 3.3% vs. 34.7% ± 2.6%, p  = 0.011; adjusted p  = 0.040; VZV: 33.1% ± 3.2% vs. 34.3% ± 2.8%, p  = 0.012; adjusted p  = 0.050). Additionally, the VAD of the peripapillary SVC differed between the affected and non-affected eye for VZV-positive VAU (47.1% ± 6.2% vs. 50.5% ± 6.3%, p  = 0.048, adjusted p  = 0.100). For both HSV-positive and VZV-positive VAU, there were correlations between macular or peripapillary SVC VAD and BMO-MRW, GCL thickness, RNFL thickness or MD of the affected eye., Conclusion: We observed vascular dysfunction characterized by decreased macular and peripapillary VAD in the superficial plexus on OCTA in eyes with HSV- and VZV-positive VAU compared to non-affected fellow eyes. These changes might be an early sign of glaucomatous damage or may be a direct consequence of the herpes viruses themselves.

Purpose: This study aimed to investigate the association between age, immune response, and clinical presentation of ocular toxoplasmosis (OT)., Design: This was a monocentric, retrospective, observational cohort study., Methods: A review of the medical records of patients with active OT at the Uveitis Center, Charité Universitätsmedizin, was conducted. Baseline parameters included age at presentation, visual acuity, intraocular pressure (IOP), size and location of active lesions, inflammatory activity, antibody index (AI), and complications of intraocular inflammation. The data were presented as the mean ± standard deviation (SD). The level of significance was set at a p -value of <0.05., Results: Between 1998 and 2019, 290 patients with active OT were diagnosed at our tertiary reference center. The mean age of the participants was 37.7 ± 17.1 years, 53.8% of them were female individuals, and 195 patients (70.9%) showed recurrent disease. Older age was associated with lower baseline visual acuity ( p  = 0.043), poor visual outcome ( p  = 0.019), increased inflammatory activity ( p  < 0.005), and larger retinal lesions ( p  < 0.005). Older patients presented a lower AI (<35 years: 45.1 ± 82.7, median: 12.1; ≥35 years: 18.6 ± 50.5, median: 5.8; p  = 0.046), confirmed by a decrease in AI with increasing age ( R 2  = 0.045; p  = 0.024). Finally, AI was correlated with lesion size (multiple linear regression analysis: p  = 0.043). Macular involvement (24.3% of patients) was positively correlated with complications (macular/peripapillary edema and retinal detachment, p  < 0.005) and poor visual outcome ( p  < 0.005) and was negatively correlated with inflammatory activity ( p  < 0.005)., Conclusion: We found a strong and clinically relevant impact of age on the clinical presentation and course of OT. While an unspecific inflammatory response increased with age, the specific, local humoral immune response declined. These findings are well in line with the concept of immunosenescence and inflammaging in uveitis., Competing Interests: The 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Eraghi, Garweg and Pleyer.)

Physiological wound healing of the cornea is a complex process and involves numerous multifactorial tissue processes. A proper wound healing, especially without the formation of light-scattering scars, is essential to preserve the integrity and function of the cornea. Misdirected wound healing is of vast clinical relevance as it can lead to corneal fibrosis and the loss of optical transparency with subsequent reduction of visual acuity, up to blindness. In addition to the understanding of the pathophysiological mechanisms, the knowledge of therapeutic concepts and options for treating corneal wound healing disorders and fibrosis is essential to counteract a permanent damage of the cornea as early as possible. Nowadays, various pharmacological and surgical options are available for treatment. The decision, appropriate selection and indication for the optimal treatment depend primarily on the genesis and clinical appearance of the corneal wound, fibrosis or scar. The treatment of wound healing disorders ranges from the use of topical therapy and supportive measures up to tissue replacement procedures. As long as the mechanical stability of the cornea is intact and wound healing processes are still ongoing, a pharmacological modulation is reasonable, which is discussed in this article., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

Objective: Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology., Methods: We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder. Discriminatory statistical methods were used to disentangle microbial disease signals from one another and a wide range of potential confounders. Patients were naive to or had not received treatment with biological disease-modifying antirheumatic drugs (DMARDs) for >3 months before enrollment, providing a better approximation of a true baseline disease signal., Results: We identified a shared, immune-mediated disease signal represented by low abundances of Lachnospiraceae taxa relative to controls, most notably Fusicatenibacter, which was most abundant in controls receiving nonsteroidal antiinflammatory drug monotherapy and implied to partially mediate higher serum C-reactive protein. Patients with SpA showed an enrichment of Collinsella, whereas human leukocyte antigen (HLA)-B27+ individuals displayed enriched Faecalibacterium. CD patients had higher abundances of a Ruminococcus taxon, and previous conventional/synthetic DMARD therapy was associated with increased Akkermansia., Conclusion: Our work supports the existence of a common gut dysbiosis in SpA and related inflammatory pathologies. We reveal shared and disease-specific microbial associations and suggest potential mediators of disease activity. Validation studies are needed to clarify the role of Fusicatenibacter in gut-joint inflammation, and metagenomic resolution is needed to understand the relationship between Faecalibacterium commensals and HLA-B27., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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., Competing Interests: Competing interests: UP has served as a principal investigator or consultant for AbbVie, Alcon, Allergan, Dompé, Novartis, Santen, Shire, and Thea. CM received research grant funding, speaker fees and honoraria, and conference sponsorship from AbbVie. RH received research grant funding from AbbVie, speaker fees from AbbVie and Amgen, and served as a consultant for Novartis. KJ has served as a principal investigator and consultant for AbbVie. YG-C has served as a principal investigator for AbbVie. SH is an employee of AbbVie and may hold AbbVie stock or options. ON was an employee of AbbVie at the time of the study and is a current contractor of AbbVie and may hold AbbVie stock or options. ZH-W served as a consultant and received speaker fees from AbbVie. SA received research support from AbbVie, Alcon, Allergan, Bayer, Novartis, Roche, Servier, and Xoma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To analyse differences in the retinal microvasculature in eyes with cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS) compared to the non-affected eyes using optical coherence tomography angiography (OCTA)., Methods: In this monocentric, observational prospective case series, 25 patients with unilateral CMV-positive PSS were included. We compared the vessel area densities (VAD) in the macula, optic disc, and peripapillary region in PSS-affected and non-affected eyes using OCTA. We compared the visual fields (VF) of the affected and healthy eyes of each patient. The mean deviation (MD) of the VF was analysed together with the retinal nerve fibre layer (RNFL) thickness to evaluate the strength of correlation with the VAD parameters., Results: The VAD of the peripapillary superficial vascular complex (SVC) is significantly reduced in CMV-positive PSS-affected eyes (46.1 ± 9.3% versus 50.1 ± 6.3%, p = 0.008, adjusted p = 0.048). The VAD of the deeper macular, papillary, and peripapillary layers showed no differences between the affected and non-affected eyes. The mean deviation and the retinal nerve fibre layer thickness had correlations with the VAD of the macula (r = 0.451, p = 0.001, r = 0.553, p < 0.001), the peripapillary SCV (r = 0.430, p = 0.002, r = 0.723, p < 0.001), and the papillary region (r = 0.512, p < 0.001, r = 0.292, p = 0.039). Patients receiving systemic antiviral therapy (SAT) showed better VAD of the peripapillary choriocapillary layer (p = 0.001, no therapy: 31.4 ± 1.9%, SAT: 35.0 ± 1.6%), and choroidal layer (p = 0.009, no therapy: 34.2 ± 0.3%, SAT: 36.3 ± 1.8%) compared to those with no SAT., Conclusion: A lower peripapillary VAD in the SVC might indicate vascular dysfunction as a sign of glaucomatous damage. SAT might have positive effects on the microcirculation in the deep retinal and choroidal layers., Trial Registration: TRN: DRKS00028266, https://www.drks.de/drks&#95;web/ ., (© 2023. The Author(s).)

Background: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany., Methods: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used., Results: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%)., Conclusion: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term., Competing Interests: Martina Herwig-Carl: Forschungsförderung: EPIC-XS (Projektnr. 823839, gefördert durch das Horizon 2020 Programm der EU), Deutsche Forschungsgemeinschaft (HE5775/5-1); Beratung und Vortragstätigkeit: GlaxoSmithKline. Ich erkläre, dass die anderen Autoren während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne angeben./ Martina Herwig-Carl: Research grant: EPIC-XS (project no. 823839, funded by the Horizon 2020 programme of the EU), German Research Foundation (HE5775/5-1); lectures and consultancy work: GlaxoSmithKline. I declare that the other authors have not declared any economic or personal connections as defined above in the past 3 years., (Thieme. All rights reserved.)

Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activation by blocking heat- or capsaicin-induced increases in Ca 2+ influx or hyperosmotic stress-induced cell volume shrinkage in a human corneal epithelial cell line (HCE-T). Single-cell fluorescence imaging of calcein/AM-loaded cells or fura-2/AM-labeled cells was used to evaluate cell volume changes and intracellular calcium levels, respectively. Planar patch-clamp technique was used to measure whole-cell currents. TRPV1 activation via either capsaicin (20 µmol/L), hyperosmolarity (≈450 mosmol/L) or an increase in ambient bath temperature to 43 °C induced intracellular calcium transients and augmented whole-cell currents, whereas hypertonicity induced cell volume shrinkage. In contrast, either capsazepine (10 µmol/L) or L-carnitine (1-3 mmol/L) reduced all these responses. Taken together, L-carnitine and capsazepine suppress hypertonicity-induced TRPV1 activation by blocking cell volume shrinkage.

Vernal keratoconjunctivitis (VKC) is a severe ocular allergic disease characterized by chronic inflammation of the cornea and conjunctiva that may lead to loss of visual acuity and blindness. The disease occurs primarily in children and is more common in geographical regions characterized by warm temperatures and high humidity. The clinical manifestations of VKC, when inadequately treated, may lead to severe complications and corneal damage. The prevalence of allergen sensitization, specific serum immunoglobulin E (IgE), and specific tear IgE was reported in approximately 55%-60% of patients with VKC, confirming the involvement of IgE-mediated and non-IgE-mediated mechanisms in the pathophysiology of the condition. This article explores current knowledge on the immunological pathways of VKC and the role of the monoclonal anti-IgE antibody, omalizumab, in its management. The review evaluated the effects of omalizumab beyond the direct IgE-mediated reactions and discusses its potential as a therapeutic target for VKC. Multiple retrospective analyses, case series, and case reports have reported the effectiveness of omalizumab in the management of VKC. A summary of the clinical data from these studies revealed that in children with VKC omalizumab treatment was well tolerated with improvement or resolution of ocular symptoms, reduction in steroid use, and enhancement of quality of life. Omalizumab may serve as a promising treatment option for VKC due to its ability to target both IgE-mediated and non-IgE-mediated pathophysiological pathways. Larger, controlled clinical trials are needed to support these findings., (© 2023 The Authors.)

The diagnosis of ocular mucous membrane pemphigoid (MMP) remains a challenge as the timing and choice of diagnostic methods have a decisive influence on its quality. A systematic approach is required that includes a comprehensive medical history, critical evaluation of the clinical findings and targeted laboratory testing. The diagnosis is complicated by the fact that some patients present purely clinically the symptoms of MMP without fulfilling the required immunohistochemical and laboratory criteria. Basically, the diagnosis of ocular MMP is based on three pillars: 1) medical history and clinical findings, 2) positive immunohistological (direct immunofluorescence) tissue sample and 3) specific serological autoantibodies. As the diagnosis of ocular MMP often implies prolonged systemic immunomodulatory treatment in predominantly older patients, the accurate diagnosis and approach are of critical relevance. The aim of this article is to present the recently updated diagnostic procedure., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: To report the efficacy of systemic anti-TNF agents in Mooren's ulcer., Design: Retrospective, consecutive case series., Methods: We report on clinical characteristics and outcome of five patients with Mooren's ulcer with anti-TNF treatment., Results: During a mean follow-up of 30 months, relief of symptoms and arrest of corneal melting were observed in all eyes. Systemic corticosteroid treatment could be discontinued or reduced to threshold levels. No patient experienced adverse effects on bDMARDs., Conclusions: Our results suggest that bDMARDs are effective in Mooren's ulcer unresponsive to conventional treatment. This is in line with accumulating evidence in the current literature. Therefore, more targeted immunomodulatory approaches might be an effective first-line therapy in the future.

Noninfectious posterior uveitis (NPU) comprises a heterogeneous group of vision-threatening, immune-mediated ocular and systemic diseases. It is predominantly bilateral and recurrent and, if not treated properly, leads to severe tissue damage that threatens the eyesight. In industrialized countries ca. 10-20% of all cases of blindness are caused by NPU. An NPU can occur at any age but is most common between the ages of 20 and 50 years. Laboratory diagnostic and imaging procedures enable an increasingly better differentiation of the disease spectrum. This makes it possible to better assess the course and prognosis of individual disease entities. An increasing repertoire of systemic and intravitreal forms of treatment has already led to more favorable long-term treatment outcomes. It can be expected that further progress can be achieved with better knowledge of the pathophysiology of the different clinical disorders and appropriate, targeted treatment., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: This study was undertaken to analyze the prevalence of spondyloarthritis (SpA) in patients with acute anterior uveitis (AAU), to identify parameters associated with the presence of SpA, and to evaluate the performance of referral algorithms for identifying patients with a high probability of having SpA., Methods: Prospectively recruited consecutive patients with noninfectious AAU underwent structured rheumatologic assessment including magnetic resonance imaging of the sacroiliac joints, allowing a definitive diagnosis/exclusion of concomitant SpA. Fisher's exact test and Mann-Whitney U test were used to compare AAU patients with SpA and AAU patients without SpA. Furthermore, logistic regression analyses were performed. The predictive performance of SpA referral strategies was analyzed by calculating the sensitivity, specificity, positive predictive value, and positive and negative likelihood ratios., Results: Among the 189 AAU patients evaluated, 106 (56%) were diagnosed as having SpA. The majority of SpA patients (93%) had predominantly axial SpA and 7 patients had peripheral SpA. In 74 patients (70%), the SpA diagnosis was established for the first time. In multivariable logistic regression analysis, psoriasis (odds ratio [OR] 12.5 [95% confidence interval (95% CI) 1.3-120.2]), HLA-B27 positivity (OR 6.3 [95% CI 2.4-16.4]), elevated C-reactive protein level (OR 4.8 [95% CI 1.9-12.4]), and male sex (OR 2.1 [95% CI 1.1-4.2]) were associated with the presence of SpA. None of the ophthalmologic parameters were found to be predictive of SpA. The Dublin Uveitis Evaluation Tool (DUET) showed higher specificity for SpA recognition than the Assessment of SpondyloArthritis international Society (ASAS) tool for the early referral of patients with a suspected diagnosis of axial SpA (specificity for SpA 42% versus 28%), whereas the sensitivity of the ASAS tool was slightly higher than the DUET tool (sensitivity for SpA 80% versus 78%). However, more than 20% of the AAU patients in this study who were diagnosed as having SpA would have been missed by both referral strategies., Conclusion: Our study revealed a high prevalence of SpA in AAU patients overall, as well as a high prevalence of previously undiagnosed SpA in AAU patients. Therefore, we propose rheumatologic evaluation for all AAU patients with musculoskeletal symptoms., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Ocular toxoplasmosis (OT) is the most common infectious cause of posterior uveitis. This survey aimed to evaluate the current diagnostic and therapeutic approach to OT in Germany., Material and Methods: A detailed questionnaire with specific patient examples was sent in July 2021 to the members of the Uveitis Section of the German Ophthalmological Society (DOG) and the Retinological Society (RG)., Results: The questionnaire was answered by 53 (29 RG and 24 DOG) ophthalmologists. Of the respondents 16 (30%) work in private practice, 18 (34%) in a clinical facility and 19 (36%) in university hospital, 9 (17%) colleagues see < 50, 28 (53%) 50-200 and 16 (30%) more than 200 uveitis patients per year. The clinical results are still the gold standard (87%) for the diagnosis of OT and in cases of first manifestation 60% are supported by serological antibody investigations, while 10 out of 53 (19%) ophthalmologists rely on the clinical presentation only. An IgM test is requested by 25 (47%) respondents, 6 expected an increase in IgG titer (11%) and 1 the detection of specific IgA antibodies (2%). The majority (n = 28, 53%) of ophthalmologists would aim at confirming the diagnosis by an anterior chamber puncture, from which 20 (38%) prefer PCR, 3 (6%) determination of Goldmann-Witmer coefficients (GW) and 5 (9%) a combination of both methods. Clindamycin was most frequently used for treatment (n = 21, 40%), followed by pyrimethamine/sulfadiazine (n = 17, 32%) and trimethoprime + sulfamethoxazole (TMP/SMX) (n = 10, 19%); the latter was also used (n = 40, 75%) for secondary prophylaxis., Conclusion: The results show that apart from the clinical results as the gold standard for the diagnosis, there is no uniform approach to diagnosis and treatment of OT. The high request rate for serum IgM antibodies indicates a widespread uncertainty about the importance of serological findings. This should be viewed critically, given the continued high seroprevalence in Germany., (© 2022. The Author(s).)

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness. In addition to a clinical picture of predominant mucosal involvement, diagnosis is based on direct immunofluorescence of a peri-lesional biopsy and serology. The main target antigen is BP180 (collagen XVII), and reactivity with laminin 332 is associated with malignancy in approximately 25 % of MMP patients. The treatment of MMP is challenging. On the one hand, due to the involvement of different mucous membranes, good interdisciplinary cooperation is required; on the other hand, due to the rarity of the disease, no randomized controlled clinical trials are available. The aim of this guideline is to present the clinical picture, including severity and scoring systems, and to give guidance for diagnosing and treating this complex disease. In MMP, interdisciplinary cooperation plays an essential role as well as the prompt diagnosis and initiation of adequate therapy in order to avoid irreversible damage to the mucous membranes with serious complications., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

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.)

Background and Purpose: Approximately 1% of patients with multiple sclerosis (MS) have uveitis, but data on the effects of immunotherapies for MS on MS-associated uveitis are scarce. The aim of this study was to investigate the ophthalmological outcomes in patients with MS-associated uveitis treated with anti-CD20 therapy., Methods: A retrospective study of 12 eyes of six patients with MS-associated uveitis, refractory to previous immunotherapies, was conducted. Uveitis activity was assessed before initiation of anti-CD20 therapy and at regular follow-up visits. Primary outcome measures were: vitreous haze score; retinal vasculitis score, determined on fluorescein angiography images; macular edema, as quantified by central retinal thickness (CRT) on optical coherence tomography; and visual acuity (VA). Secondary outcomes included number of annualized uveitis or MS relapses, disease activity on cerebral magnetic resonance imaging (cMRI) and Expanded Disability Status Scale (EDSS) score., Results: After a median (interquartile range [IQR]) treatment time of 28.5 (8-43) months, anti-CD20 therapy was associated with an improvement of vitreous haze score (p = 0.002), retinal vasculitis score (p = 0.001), CRT (p = 0.002), and VA (p = 0.007). The median (IQR) annualized uveitis relapse rate declined from 0.59 (0.56-0.94) before to 0 (0-0.49) after the start of anti-CD20 therapy. The median (IQR) annualized MS relapse rate declined from 0.62 (0.26-2.84) before to 0 (0-0) after the start of anti-CD20 therapy. After initiation of anti-CD20 therapy, there was no disease activity on cMRI, and EDSS score improved (n = 2) or remained stable (n = 4). No severe adverse events were observed., Conclusion: These findings suggest that anti-CD20 therapy may be a valuable treatment option for MS-associated uveitis., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were collected from adults with clinically diagnosed AR of full-thickness (FT)-CT (n = 35) and posterior lamellar (PL)-CT (n = 21) along with Stable CT recipients (n = 177) and adults with non-transplanted corneal disease (n = 40). For those with AR, additional samples were collected 3 months later. Immune cell analysis was performed by whole-genome microarrays (whole blood) and high-dimensional multi-color flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT- but not PL-CT recipients, AR was associated with differences in B cell maturity and regulatory CD4 + T cell frequency compared to stable allografts. These data suggest that circulating B cell and T cell subpopulations may provide insights into the regulation of anti-donor immune response in human CT recipients with differing AR risk. Our results suggest that, in contrast to solid organ transplants, genetic or cellular assays of peripheral blood are unlikely to be clinically exploitable for prediction or diagnosis of AR., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Knowledge about artifacts in optical coherence tomography angiography (OCTA) is important to avoid misinterpretations. An overview of possible artifacts in posterior uveitis provides important information for interpretations. Methods: In this monocentric prospective study, OCTA images from a total of 102 eyes of 54 patients with posterior uveitis, and an age-matched control group including 34 healthy subjects (67 eyes), were evaluated (day 0, month 3, month 6). We assigned different artifacts to distinct layers. Various types of artifacts were examined in different retinal layers. The χ2 test for the comparison between the control and uveitis group and Cochran’s Q test for the longitudinal comparison within the uveitis group were used. Results: A total of 2238 images were evaluated; 1836 from uveitis patients and 402 from healthy subjects. A total of 2193 artifacts were revealed. Projection (812 [36.3%]), segmentation (579 [25.9%]), shadowing (404 [18.1%]), and blink artifacts (297 [13.3%]) were the most common artifact types. The uveitis group displayed significantly more segmentation artifacts and projection artifacts (p < 0.001). No segmentation artifacts were documented in healthy subjects. The consecutive examinations within the uveitis group revealed the same artifact types without significance (p > 0.1). Conclusions: The uveitis patients showed more segmentation and projection artifacts than the control group. Within the uveitis group, artifacts remained longitudinally constant in terms of artifact type and pattern. The artifacts therefore appear to be reproducible on an individual level.

This updated and upgraded S2k guideline deals with the diagnosis and treatment of rosacea, which is a common, chronic inflammatory skin disease mostly affecting the face. Initially, rosacea is characterized by recurrent erythema, telangiectasia and flushing. Later, the inflammatory component predominates, with persistent erythema with follicular papules, papulopustules and pustules. The development of phyma, which usually occurs on the acral localizations, is the most severe manifestation. For the treatment of rosacea, the interdisciplinary guideline committee, with representatives of the German Dermatological Society (DDG), the Professional Association of German Dermatologists (BVDD), the German Opthalmological Society (DOG), the Society for Dermopharmacy (GD), the Swiss Society for Dermatology and Venereology (SGDV) and the German Rosacea Aid e. V., recommends the avoidance of trigger factors and topical applications of metronidazole, azelaic acid or ivermectin. For symptomatic treatment of persistent centrofacial erythema, the topical vasoconstrictors brimonidine or oxymetazoline can also be used. Systemic therapy is recommended for therapy-resistant and severe forms of rosacea papulopustulosa. The drug of choice is low-dose doxycycline. Alternatively, low-dose isotretinoin can be recommended. Ocular rosacea should be treated with lid margin hygiene. For topical treatment, ciclosporin eye drops, azithromycin, ivermectin or metronidazole are suggested., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Rubella virus (RV) and cytomegalovirus (CMV) have both been implicated in anterior uveitis (AU). Clinical phenotypes can vary widely among both etiologies, including Fuchs uveitis syndrome (FUS) as a very distinct phenotype that has been associated with both RV and CMV. The Standardization of Uveitis Nomenclature (SUN) Working Group recently updated the classification criteria for FUS as unilateral AU, including either heterochromia or diffuse iris atrophy combined with stellate keratic precipitates as key findings. The aim of this study was to determine whether our patients adhere to the classification criteria of FUS as previously reported and whether RV- or CMV-associated uveitis can be differentiated by clinical findings. Therefore, this study investigated the clinical characteristics of patients with AU and intraocular presence of either RV or CMV determined by the Goldmann-Witmer coefficient (GWC). Our study included 100 patients (107 eyes) with AU and positive GWC for RV (86) and CMV (21). Clinical findings of RV-positive eyes were as follows: keratic precipitates (91.9%) with a predominantly diffuse distribution (81.4%), unilateral cataract (80.2%), pseudophakia (73.5%), and vitreous cells (59.7%), whereas heterochromia was present in only 39.5% of eyes and iris atrophy in 12.9% of eyes. In CMV-positive eyes, conversely, a higher incidence of ocular hypertension with markedly increased intraocular pressures above 30 mmHg (66.7%), keratic precipitates (81.0%), which were most commonly distributed in the center of the cornea (63.6%), an unaffected lens (55.0%), absent iris atrophy (100%), and absent posterior synechiae (90.5%) could be detected. This indicates a clinical presentation that was mainly compatible with Posner-Schlossman syndrome. In our cohort of RV-positive FUS patients, we saw a different cluster of clinical findings compared to the classification criteria suggested by the SUN Working Group. The main criteria, such as unilaterality, were mostly fulfilled. When applying all classification criteria, only 8.4% of 107 eyes and 10.5% of all 86 RV-positive eyes would qualify for the diagnosis of FUS. In addition, in our cohort of predominantly Caucasian patients, the clinical findings in patients with proven CMV infection differed from the clinical presentation typically associated with FUS., Competing Interests: The 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 Yermalitski, Rübsam, Pohlmann, Metzner and Pleyer.)

Purpose: To report objective morphologic changes in cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS)., Design: Retrospective, consecutive case series., Methods: We reviewed the charts of patients with unilateral PSS tested positive for CMV by Goldmann-Witmer coefficients between 2007 and 2018 at our tertiary eye clinic. We report data on corneal endothelial cell (CEC) count, peripapillary retinal nerve fiber layer (RNFL), choroidal thickness (CT) using optical coherence tomography (OCT) as well as clinical findings and management. The unaffected eye served as control., Results: Fifty-two eyes of 52 patients were included and followed for 32.8 ± 28.3 months. The peak intraocular pressure was 45 ± 11 mm Hg. The CEC (2241.7 ± 381.1 cells/mm 2 vs 2529.4 ± 351.9 cells/mm 2 , P = .0004) and the global RNFL thickness (80.81 ± 21.01 µm vs 97.38 ± 9.75 µm, P = .0001) were significantly reduced, whereas CT was nonsignificantly higher (295.69 ± 45.46 µm vs 274.00 ± 67.85 µm, P = .156) in the affected eyes compared to the fellow eye. Forty (76.9%) patients were treated with oral valganciclovir (VGC), 2 (3.8%) with topical ganciclovir alone, and 10 (19.2%) received no antiviral therapy. Eight eyes (15.4%) underwent trabeculectomy with mitomycin C. After cessation of oral VGC, 23 patients (57.5%) had recurrences., Conclusions: In our cohort, CMV-positive PSS was often associated with RNFL thinning and CEC loss. Highly elevated intraocular pressures usually present the most relevant challenge. In conjunction with aqueous humor sampling, monitoring by OCT scans and endothelial microscopy may help to guide therapy decisions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Differential diagnosis of viral anterior uveitis (AU) based on the typical clinical findings (anterior chamber inflammation, morphology of the keratic precipitates, severity of IOP increase in relapse) is often straightforward. When differential diagnosis is difficult clinically, analysis of aqueous humour by PCR and/or antibody testing (Goldmann-Witmer coefficient) may be helpful. While both modalities are highly specific, they lack absolute sensitivity. Patients with HSV, VZV and CMV associated uveitis require both antiviral as well as antiinflammatory medication and often additional antiglaucomatous therapy, depending on IOP. In contrast, specific antiviral treatment is not possible in rubella associated AU and steroids should be administered with extreme caution due to their adverse effects. With all subtypes of virus associated AU, recurrent episodes put the patients at risk of developing secondary glaucoma, which often requires surgical treatment., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have also included newer advances in imaging in retinal vasculitis such as OCTA and widefield imaging.

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.

The cornea forms the anterior border of the eye and significantly contributes to a sharp optical image quality on the retina through its transparency, avascular nature and curvature. Because of its anatomical structure and as a barrier to the environment, the cornea is particularly exposed to various external factors, such as injuries and pathogens. A correct wound healing without the formation of light diverging scarring is therefore essential to preserve the integrity and function of the cornea. Misguided wound healing is of outstanding clinical relevance and can lead to corneal fibrogenesis. Corneal fibrosis results in scarring with a loss of optical transparency, which significantly reduces eyesight and can lead to blindness. Understanding the pathophysiological mechanisms of wound healing and fibrogenesis is of great importance for the diagnostics, treatment and evaluation of the subsequent healing process in order to prevent permanent damage as far as possible., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The standardization of uveitis nomenclature (SUN) working group is an international expert committee, which follows the aim to develop a standardized and internationally recognized terminology for the field of uveitis. This appears to be important in view of the demand for evidence-based medicine, especially for relatively rare diseases such as uveitis., Methods: A databank of > 4000 uveitis patients was compiled using formal consensus techniques, for whom a majority consensus was previously achieved in the diagnosis. The patient data were analyzed within the subclasses of uveitis and divided into a training set and a validation set. Multinomial logistic regressions with LASSO regularization were carried out on the training set with machine learning (ML). The accuracy of the rules that were developed to express the criteria of ML, were assessed by a masked observer in a random sample of 10%., Results: The estimations of total accuracy according to the uveitis classes in the validation set were high for all forms of uveitis: anterior uveitis 96.7% (95% confidence interval, CI 92.4-98.6%), intermediate uveitis 99.3% (95% CI 96.1-99.9%), posterior uveitis 98.0% (95% CI 94.3-99.3%), panuveitis 94.0% (95% CI 89.0-96.8%) and infectious posterior uveitis/panuveitis 93.3% (95% CI 89.1-96.3%)., Conclusion: Classification criteria are presented, which show a high degree of accuracy (low misclassification rates) and are therefore suitable for future clinical and translational research., (© 2021. The Author(s).)

Toxoplasmosis is a zoonotic infection contracted through Toxoplasma gondii-contaminated food, soil, or water. Seroprevalence in Germany is high, but estimates of disease incidence are scarce. We investigated incidences for various toxoplasmosis manifestations using anonymized healthcare claims data from Germany for 2011-2016. Patients with a toxoplasmosis diagnosis during the annual observational period were considered incident. The estimated incidence was adjusted to the general population age/sex distribution. We estimated an annual average of 8,047 toxoplasmosis patients in Germany. The average incidence of non-pregnancy-associated toxoplasmosis patients was 9.6/100,000 population. The incidence was highest in 2011, at 10.6 (95% CI 9.4-12.6)/100,000 population, and lowest in 2016, at 8.0 (95% CI 7.0-9.4)/100,000 population. The average incidence of toxoplasmosis during pregnancy was 40.3/100,000 pregnancies. We demonstrate a substantial toxoplasmosis disease burden in Germany. Public health and food safety authorities should implement toxoplasmosis-specific prevention programs.

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.

Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK). We determined TRPV1-induced intracellular calcium transients using fluorescence calcium imaging, channel currents by planar patch-clamping, and cell migration by scratch assay for wound healing. The potential L-carnitine effect on TRPV1-induced myofibroblast transdifferentiation was evaluated by immunocytochemical detection of alpha smooth muscle actin. RT-PCR analysis confirmed TRPV1 mRNA expression in HCK. L-carnitine (1 mmol/l) inhibited either capsaicin (CAP) (10 µmol/l), hypertonic stress (450 mOsmol/l), or thermal increase (>43 °C) induced Ca 2+ transients and corresponding increases in TRPV1-induced inward and outward whole-cell currents. This was accompanied by suppression of injury-induced increases in myofibroblast transdifferentiation and cell migration. In conclusion, L-carnitine contributes to inhibit stromal scarring through suppressing an injury-induced intrinsic TRPV1 activity that is linked with induction of myofibroblast transdifferentiation in HCK cells.

Purpose: Studies on the occurrence of ocular toxoplasmosis (OT) in a general population are rare. Therefore, we conducted this pilot study to assess whether a nonmydriatic ultra-wide-field (UWF) scanning laser ophthalmoscope (SLO) is suitable for a simple, rapid screening procedure., Methods: The population of this cross-sectional study was randomly recruited from a cohort of hospital-based patients in an urban geriatric hospital. Ophthalmologic evaluation was performed on 201 eyes from 101 participants through nonmydriatic UWF-SLO (Optos Daytona) and assessed for suspicious lesions and other relevant ocular findings. All images were evaluated by two independent examiners. Individuals who presented lesions with a morphological appearance suggestive of OT underwent fundoscopy and serological analysis of Toxoplasma gondii-specific antibodies., Results: The mean age of the study group was 76 years, and 63 (62%) were female. Despite many health restrictions, the SLO examination was carried out easily in this geriatric population. Three participants presented findings by SLO suspicious for T. gondii-related injury. Further clinical examination and serological investigation confirmed the diagnosis, with funduscopic evaluation and positive T. gondii ELISA testing. In addition, a high rate of arterial hypertension and dyslipidemias within the cohort led to a high incidence of vascular changes and age-related fundus findings., Conclusion: In our study, we confirm that UWF-SLO technology is helpful in the rapid detection of peripheral retinal injuries in elderly patients such as OT and may be used as a routine screening tool.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe and often life-threatening reactions of the skin and mucous membranes. They are considered as a single disease entity with different expressions of severity and are summarized under the term epidermal necrolysis (EN). There is a high risk of ocular involvement, which can lead to long-lasting eye problems and even blindness without immediate ophthalmological treatment. The acute occurrence, the unpredictable course and extreme variation in the manifestation of complications require an interdisciplinary approach. A rapid diagnosis of eye involvement and initiation of an intensive lubricating and anti-inflammatory surface treatment is of utmost importance for the long-term outcome. This article should help ophthalmologists to have a better understanding of this condition and therefore lead to substantial improvement in visual outcome and the quality of life of patients.