Background: Primary Sjögrens syndrome (pSS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by mononuclear cell infiltration of exocrine glands, notably the lacrimal gland. These lymphoid infiltrations lead to dryness of the eyes, also known as keratoconjunctivitis sicca. However, it is uncertain whether ocular microvascular alterations are associated with this disease. Objectives: This study aims to investigate the macular microvasculature and explore the OCTA (OCT Angiography) metrics as potential retinal biomarkers in a large cohort of patients with primary Sjögrens syndrome. Methods: From September 2022 to July 2023, pSS patients from the outpatient clinic of our hospital were consecutively included after informed consent. In addition, age- and sex-matched control subjects were recruited. All pSS patients fulfilled current EULAR classification criteria for pSS and had a disease duration of at least 5 years. Participants with additional diabetes mellitus, tumor diseases in the last five years (with chemotherapeutic treatment), glaucoma or increased intraocular pressure or known eye diseases (not pSS related) were excluded from this study. Data collection was performed by a standardized questionnaire, slit lamp, Schirmer I and II test, tensio, vision test, OCT and OCTA. A prospective study of 100 eyes of 50 pSS patients compared to 80 eyes of 40 healthy, age-matched controls. All participants underwent 2.9 mm × 2.9 mm imaging of the macula using the OCTA (Heidelberg Spectralis II, Heidelberg, Germany). The outcome variables were vessel Area Density (VAD) in circular sectors (c1, c2, and c3) and foveal avascular zone (FAZ). Both variables were measured in three layers: superficial (SVP), intermediate (ICP) and deep capillary Plexus (DCP). All scans were analyzed with the EA-Tool (coded in MATLAB, The MathWorks Inc, and R2017b). Results: VAD was significantly lower in the innermost circle of DCP c1 in the pSS group compared to healthy controls (29.14± 7.07 vs. 31.78± 9.55, p=0.03). FAZ was larger in both SVP (0.41± 0.13 vs.0.34± 0.11, p< 0.001; Cohens |d| = 0.55) and DCP (0.45± 0.15 vs. 0.4± 0.14, p=0.01; Cohens |d| = 0.38) in pSS group compared to healthy controls. Conclusion: Our findings indicate microvascular changes in the deep capillary layers of pSS patients, showing reduced vessel area density and enlarged FAZ. This could be due to inflammatory or arteriosclerotic etiology. OCTA could be beneficial as retinal biomarker for vascular risk stratification in pSS. Further longitudinal studies need to be considered in future studies for validation and implementation of the OCTA in the course of pSS. REFERENCES: [1] Yang QC, Yao F, Li QY, Chen MJ, Zhang LJ, Shu HY, Liang RB, Pan YC, Ge QM, Shao Y. Ocular microvascular alteration in Sjögren syndrome. Quant Imaging Med Surg. 2022 Feb;12(2):1324-1335. doi: 10.21037/qims-21-234. PMID: 35111627; PMCID: PMC8739119. [2] Yu C, Zou J, Ge QM, Liao XL, Pan YC, Wu JL, Su T, Zhang LJ, Liang RB, Shao Y. Ocular microvascular alteration in Sjögren's syndrome treated with hydroxychloroquine: an OCTA clinical study. Ther Adv Chronic Dis. 2023 Apr 17;14:20406223231164498. doi: 10.1177/20406223231164498. PMID: 37114215; PMCID: PMC10126603. [3] Lee OL, Tepelus TC, Huang J, Irvine AG, Irvine C, Chiu GB, Sadda SR. Evaluation of the corneal epithelium in non-Sjögren's and Sjögren's dry eyes: an in vivo confocal microscopy study using HRT III RCM. BMC Ophthalmol. 2018 Dec 4;18(1):309. doi: 10.1186/s12886-018-0971-3. PMID: 30514255; PMCID: PMC6278105. [4] Roszkowska AM, Oliverio GW, Aragona E, Inferrera L, Severo AA, Alessandrello F, Spinella R, Postorino EI, Aragona P. Ophthalmologic Manifestations of Primary Sjögren's Syndrome. Genes (Basel). 2021 Mar 4;12(3):365. doi: 10.3390/genes12030365. PMID: 33806489; PMCID: PMC7998625. [5] Hosari S, Hohberger B, Theelke L, Sari H, Lucio M, Mardin CY. OCT angiography: measurement of retinal macular microvasculature with spectralis II OCT angiography: reliability and reproducibility. Ophthalmologica. 2020;243(1):75–84 Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Patients with primary Sjögren Syndrome (pSS) can have different manifestations of the disease e.g. the inflammatory occultations of the eye, which can lead to to a change in corneal tropism (e.g. of the subbasal corneal nerve plexus (SNP)) and damage to the trigeminal nerve. This can correlate with the loss of retinal nerve fibers. Objectives: The aim of our study was to investigate the corneal and optic nerve metrics as well as the peripapillary microvasculature and to identify potential ocular biomarkers for neuro/microvascular changes in patients with pSS. Methods: Central cornea images were prospectively captured from 48 eyes with clinically diagnosed pSS and 38 eyes of age-matched healthy controls using in-vivo corneal confocal microscopy (IVCCM) (Heidelberg Retina Tomograph Rostock Cornea Module - HRT III RCM). Corneal nerve fiber length (CNFL), fiber density (CNFD), branching density (CNBD), total fiber branching density (CTBD), fiber area (CNFA), fiber width (CNFW) and fractal dimension (CNFrac) were measured with ACC Metrics software. OCTA and SD-OCT scans were obtained using SPECTRALIS® II (Heidelberg Engineering, Germany). RNFL and BMO were analyzed with the built-in software. Peripapillary OCTA images (2.9x2.9mm) were analyzed using Erlangen-Angio-Tool. Peripapillary Vessel Area Density (pVAD) was measured at the level of nerve fibre layer plexus (NFLVP) in the innermost circle c1. Results: Patients with pSS had significantly lower values of CNFD and a higher value of CNFW compared to controls (CNFD: (22.4±8.3 vs. 26.2±7.6 fibres/mm2, Cohen`s D 0.47; CNFW: 0.022±0.001 vs. 0.021±0.001 mm/mm2, Cohen`s D 0.52; always p<0.05). There were no statistically significant differences between groups for RNFL, BMO and pVAD measurements. No correlation was found between pVAD and RNFL/ SNP. Correlation analysis for RNFL showed a significant correlation with CNFL (ρ =.246), CTBD (ρ =.245), and CNFrac (ρ =.311) (always p< 0.05). Correlation analysis for BMO showed a significant correlation with CNFD (ρ =.291), CNFL (ρ =.289) and CNFrac (ρ =.252) (always p< 0.05). Conclusion: Patients with pSS have a lower CNFD and thicker corneal nerves compared to healthy eyes. Nerve fibre loss and swelling indicate an ongoing corneal inflammatory process. A low to moderate positive correlation between the SNP and optic nerve metrics suggest a link between peripheral and central nerve changes. Peripapillary microvasculature does not seem to be altered in patients with pSS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

Ein 48-jähriger Patient mit langjährig bekannter Hornhautproblematik wurde als Notfall mit der Diagnose eines perforierten Hornhautulkus und bestehender Autotamponade des linken Auges vom Facharzt eingewiesen. Anamnestisch bestand eine linksseitige schmerzlose Sehminderung seit dem Vortag. Der Patient war in gutem Allgemeinzustand. Als Folge einer Fazialislähmung, welche seit der operativen Entfernung eines juvenilen Angiofibroms bestand, hatte er bereits eine Sicca-Symptomatik mit rezidivierenden Hornhauterosionen, eine Durchwanderungskeratitis sowie mehrere Herpeskeratitiden am betroffenen Auge erlitten. Deshalb waren mehrfach intensivierte antibiotische und antimykotische Lokaltherapien sowie mehrere Amniontransplantationen notwendig geworden. Im Oktober des vorherigen Jahres erfolgte bei fortgeschrittener Katarakt und hinteren Synechien eine Phakoemulsifikation mit Hinterkammerlinsenimplantation. Mehrere Wochen nach der Operation (4 Monate vor der Notfallvorstellung) wurde der Patient aufgrund eines Hornhautulkus bei uns vorstellig (. Abb. 1 links oben). Es wurde eine intensivierte antibiotische Lokaltherapie mit Kanamycinund Moxifloxacin-Augentropfen und Ganciclovir-Augengel begonnen. Bei der Verlaufskontrolle 2 Monate später zeigte sich im Vorderabschnitts-OCT neben einer Zunahme der zentralen Hornhautverdünnung auch eine inferiore Verdünnung (. Abb. 1 unten), sodass eineAmnionmembranaufnähung erfolgte. DerPatientwurde14TagevorNotfallvorstellung zur Befundkontrolle vorstellig. Zu diesem Zeitpunkt wies das Auge eine geschlossene Hornhaut sowie einen klaren Funduseinblick ohne Glaskörperreiz oder -infiltration auf (. Abb. 1 rechts oben). Die weitere Anamnese bezüglich Allgemeinerkrankungen und Allergien war bis auf eine Epilepsie infolge eines Angiofibroms unauffällig.

Bacterial orbital cellulitis is a life-threatening infection of the postseptal orbital tissue. It can occur in the context of sinusitis, particularly in children and adolescents. Ocular complications include exposure keratopathy, increased intraocular pressure, occlusion of the central retinal artery or vein and optic neuropathy. Rarely, a subperiosteal abscess can occur, and osteomyelitis can lead to spread of the infection to the cerebrum. A rapid diagnosis and targeted therapy are essential for saving the eye as well as the life of the patient.

According to the latest findings, macular oedema due to retinal vein occlusion is best treated safely and effectively with near-term intravitreal anti-VEGF therapy (aflibercept, bevacizumab [off label], ranibizumab). After an initial upload of 3monthly injections of anti-VEGF, the decision on re-injection should be based on OCT (rather than on visual acuity). After initial monthly injections, the pro-re-nata (PRN) and the treat-and-extend regimens have been predominantly used in the further course of therapy. Taking into account the side effect spectrum (in particular cataract progression, increased intraocular pressure), intravitreal therapy with a dexamethasone implant may be a reasonable alternative. The prognosis for visual acuity and the decline in macular oedema depend on starting treatment early and continuing it consistently. Before starting treatment, as well as during treatment, fluorescein angiography is necessary to detect ischemic retinal areas. There is evidence that early targeted laser coagulation of ischemic retina may reduce the frequency of necessary injections and improve the response of the oedema to therapy. Significant retinal ischemia may lead to proliferations, rubeosis iridis and secondary glaucoma and therefore requires laser treatment.

ZusammenfassungNach neuesten Erkenntnissen ist ein Makulaödem infolge eines retinalen Venenverschlusses am besten mit einer zeitnahen intravitrealen Anti-VEGF-Therapie (Aflibercept, Bevacizumab [off label], Ranibizumab) sicher und effektiv behandelbar. Nach einem anfänglichen Upload von monatlich 3 Injektionen Anti-VEGF sollte in regelmäßigen Kontrollen vor allem OCT-basiert (bevorzugt gegenüber visusbasiert) über eine erneute Injektion entschieden werden. Nach anfänglichen monatlichen Injektionen haben sich derzeit vor allem das „Pro-re-nata“- (PRN) und das „Treat-and-Extend“-Schema in Bezug auf den weiteren Therapieverlauf durchgesetzt. Unter Beachtung des Nebenwirkungsspektrums (insbesondere Kataraktprogression, Augeninnendruckerhöhung) kann auch eine intravitreale Therapie mit einem Dexamethason-Implantat sinnvoll sein. Die Prognose bez. Visus und Rückgang des Makulaödems hängt von einem frühen Behandlungsbeginn mit konsequenter Therapiefortführung ab. Vor Behandlungsbeginn sowie im Verlauf ist eine Fluoresceinangiografie nötig, um ischämische Netzhautareale zu detektieren. Es gibt Hinweise, dass eine frühe gezielte Laserkoagulation ischämischer Netzhautareale die Frequenz der nötigen Injektionen senkt und zu einem besseren Ansprechen des Ödems auf die Therapie führt. Bei signifikanter retinaler Ischämie, die in der Folge zu Proliferationen, Rubeosis iridis und einem Sekundärglaukom führen kann, ist eine Laserbehandlung unumgänglich.

Es erfolgte die Vorstellung einer Patientin mit zwei 21 cm langen, von der linken nasalen Orbita bis zur okzipitalen Kalotte reichenden Fremdkörpern. Fremdanamnestisch habe sich die Patientin zum Unfallzeitpunkt bei Handarbeiten befunden und sich vermutlich 2 Stricknadeln selbstständig in die linke Orbita eingeführt. Als Grunderkrankungen waren eine paranoide Schizophrenie sowie Demenz bekannt. Die zentrale Bildgebung stellte die Lage der Stricknadeln in Bezug zu den intrakraniellen Gefäßen als bedrohlich dar. Die operative Entfernung der Stricknadeln verlief ohne schwerwiegende Komplikationen wie intrakranielle Massenblutung.

Current recommendations for treatment of macular edema secondary to BRVO or CRVO favour intravitreal anti-VEGF agents compared to intravitreal steroids. An upload of 3 injections is reasonable to address intravitreal VEGF levels. Prognosis for visual improvement is good and time to treatment is crucial. There is evidence that an early targeted laser photocoagulation of ischemic areas may lead to additional treatment effects, less injections and improved prognosis if administered early after RVO. In the course of the disease patients must be frequently monitored for recurrence of edema to initiate re-treatment and for conversion to ischemic RVO. Ischemia, proliferations and rubeosis iridis must not be treated with intravitreal anti-VEGF alone. Laser treatment of peripheral retina remains the standard-of-care to treat ischemia. In this article we review up-to-date information on intravitreal anti-VEGF therapy in RVO, international guidelines, safety and efficacy of treatment. We discuss new insights on factors that may improve prognosis or burden of intravitreal treatment. And we discuss the role of ischemia in RVO.

Presentation of a patient with two foreign bodies each 21 cm long in left nasal orbit and penetrating as far as the sinciput. The patient had been knitting at the time of the accident and had probably autonomously thrust the two knitting needles into the left orbit, as assessed by questioning of other parties. The patient had a known history of paranoid schizophrenia and dementia. Central imaging revealed the position of the knitting needles with respect to the intracranial vessels to be threatening. The surgical removal of the knitting needles was carried out without any serious complications, such as intracranial hemorrhage.

Heat shock proteins (HSPs) play a regulatory role for maturation of antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. Whereas HSP70 has been shown to enhance the maturation of human DCs via a nuclear factor kappa-B (NF-κB)-dependent pathway, the regulatory role of calreticulin (CRT), which is a HSP with similar functions to HSP70, is not well studied. To investigate the role of CRT as adjuvant in cell activation and co-stimulatory responses we determined the effects of CRT on human APC maturation in comparison to that of HSP70. To facilitate eukaryotic endotoxin-free CRT protein expression, three different methods were compared. We demonstrate that CRT induces the maturation of human DCs and increases the production of proinflammatory cytokines via the NF-κB pathway. CRT-mediated maturation was qualitatively similar to that induced by HSP70. Interestingly, priming of monocytes with HSPs showed an even more prominent effect on maturation than exposure of immature DCs to these compounds. A higher expression of CD86, CD83 and CCR7 on mature DCs were found in response to CRT. Our data provide novel insights into the role of extracellular HSPs as chaperokines in the processes of APC generation and may thus be useful to improve adoptive immunotherapy.

Calreticulin (CRT), an endoplasmic reticulum (ER) resident protein, is involved in critical cellular functions, such as protein folding and antigenic peptide cross presentation. Furthermore, this chaperone has been proposed to act as an adjuvant during the activation of dendritic cells (DCs) in vivo. We assessed human eukaryotically expressed CRT for its potential to induce NF-kappa B regulated maturation of monocyte-derived DCs. In order to facilitate eukaryotic expression procedures, we established and compared three different methods to express recombinant endotoxin-free CRT to be secreted in the supernatant of HEK 293 cells: (1.) the complete, unmodified CRT coding sequence was cloned into the pcDNA3.1V5/His vector (euCRT), (2.) the C-terminal ER-retrieval KDEL amino acid sequence was mutated into KDQL in order to disturb the endoplasmic retention and support the protein secretion (euCRT_KDQL) and (3.) a shRNA was designed to knock down the expression of aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP-1), which is known to regulate protein retention in the ER. An efficient shRNA sequence specific to AIMP-1 transcripts was delivered to HEK 293 cells, which were afterwards transfected with the CRT-expressing vector (euCRT). No relevant differences between these different approaches were observed in regard to mRNA levels of the transfected CRT determined by Real Time RT-PCR as well as protein expression levels of CRT determined by V5/HIS ELISA in the cell culture supernatants. Thus, for large scale expression of CRT the first strategy with the unmodified CRT sequence (euCRT) was chosen. The functional capability of the expressed calreticulin to induce maturation of DCs was tested. By flow cytometry the translocation of NF-kappa B into the nuclei of the monocytes after stimulation with the recombinant CRT could be demonstrated. Using low-dose CRT (10 μg/ml) the phenoptype of the immature DCs changed to a more matured one, as indicated by an increased surface expression of CD40, CD86, CD83. In summary, our first data indicate, that this recombinant CRT can act as an adjuvant for in vitro maturation of DCs and therefore has the potential to assist in T cell stimulation and expansion protocols.