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PurposeTo characterise the history, clinical and histopathological features of patients with bilateral nasal and temporal peripheral hypertrophic subepithelial corneal degeneration in a German population.MethodsA detailed ophthalmological and dermatological history and clinical findings were recorded of nine patients with bilateral simultaneous nasal and temporal peripheral corneal degeneration from two centers in Germany. Excised tissues were studied by histopathology, immunohistochemistry, and transmission electron microscopy.ResultsForeign body sensation and need of artificial tear substitutes were the only symptoms reported regularly. Schirmer's and Jones-test were normal in all, but fluorescein break-up time of >10 s was found in five eyes of four patients. Best corrected visual acuity was reduced only under glare conditions. Corneal topography revealed irregular astigmatism in 13 of 14 eyes. Follow-up median time was 35 months. Most cases were stable within the follow-up period. Light and electron microscopy revealed the findings of superficial vascularised corneal hypertrophic scars, oxytatlan fibers, and discontinued Bowmans layer.ConclusionIn this series of German patients with peripheral hypertrophic subepithelial corneal degeneration, the changes were predominantly located in the palpebral aperture and often present in both eyes. No associated surface disease could be established in this study. Light and transmission electron microscopy showed histological features that are similar to Salzmann's corneal changes without any inflammation. We hypothesise that light exposure and a localised limbal insufficiency could be involved in the pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: A nationwide, comparative survey of the physician-reported usability of electronic medical record (EMR) software used by ophthalmologists in Germany using the System Usability Scale (SUS) as a standardized metric., Methods: A cross-sectional survey of members of the German Ophthalmological Society (DOG) and professional association of ophthalmologists (BVA) was conducted in May 2022. All 7788 physician members of both societies were invited to participate in an anonymous online-survey by individualized links. User-reported usability of the participants main software used for electronic medical recordkeeping was assessed using the SUS (range 0-100)., Results: A total of 881 participants with 51 different EMRs completed the entire questionnaire. Mean EMR-SUS score was 65.7 (SD ± 23.5). Significant differences in mean SUS of several EMR programs were observed with a range of 31.5 to 87.2 in programs with 10 or more responses. 31.8% of all main program SUS ratings were below 50 points. Female gender was associated with 4.02 higher SUS score (95% CI 0.46-7.59). Main program SUS was positively correlated with overall work-related satisfaction and work environment SUS but negatively correlated with the number of programs in the work environment. The SUS of the entire digital work environment including all programs used daily was closely correlated with the main EMR SUS, but not the number of programs used., Conclusion: Our survey revealed a fragmented pattern of EMR use by ophthalmologists in Germany with many competing software products and widely diverging mean System Usability Scale scores. A considerable share of ophthalmologists report EMR usability below what is commonly considered acceptable., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The purpose of this study was to present the determination of inter- and intra-day variations in tear flow rate, and tear fluid protein concentration, as well as protein composition regarding their impact for future biomarker studies., Methods: Tear fluid was collected noninvasively from 18 healthy subjects by performing Schirmer tests at 4 different time points repetitive in a period of 2 days. The tear flow rate on the Schirmer test strips was measured. Proteins were extracted from strips and quantified using amino acid analysis. Protein composition was analyzed by the strips data-independent (DIA) based mass spectrometry. To exclude any impairments to health, volunteers underwent a detailed neurological as well as an ophthalmological examination., Results: Whether tear fluid was collected from oculus sinister or oculus dexter did not affect the tear flow rate (P ≈ 0.63) or protein concentration (P ≈ 0.97) of individual subjects. Moreover, protein concentration was independent from the tear volume, so that a change in volume may only influence the total protein amount. When the examination days were compared, investigation of tear flow rate (P ≈ 0.001) and protein concentration (P ≈ 0.0003) indicated significant differences. Further, mass spectrometric analysis of tear fluid revealed 11 differentially regulated proteins when comparing both examination days., Conclusions: Our findings provide evidence of inter-day variation in tear flow rate, tear proteome concentration, and composition in healthy subjects, suggesting that inter-day variation needs to be taken into consideration in biomarker research of tear fluid. Identified proteins were assigned to functions in the immune response, oxidative and reducing processes, as well as mannose metabolism.

Purpose: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon- α 2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany., Methods: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon- α 2b eye drops and subconjunctival injections., Results: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon- α 2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon- α 2b eye drops but were more frequently reported after subconjunctival interferon- α 2b injections. In total, eight centres had experience with interferon- α 2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon- α 2b were its high cost and the reimbursement thereof., Conclusion: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon- α 2b being the standard second-line option. Interferon- α 2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon- α 2b are likely to have a profound impact on patient care and their quality of life., Competing Interests: The authors declare that they have no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Thieme. All rights reserved.)

Background: Medical registries have shown their potential for medical research in different areas of healthcare in the past. The United States of America uses the well-known national ophthalmology registry Intelligent Research in Sight (IRIS®), on the basis of which insights into the ophthalmological care situation in the USA can be gained. Comparable projects do not currently exist in Germany. The oregis is the first disease-independent registry to collect comprehensive data in the field of ophthalmology in Germany for the purpose of healthcare research., Methods: The oregis collects anonymized clinical patient information from all subfields of ophthalmology and makes it available for research purposes. Participating centers read their data into the registry free of charge and preferably in an automated fashion. Currently, the oregis parameter list contains about 600 parameters, of which about 100 are used in the current pilot phase., Results: Since its initiation, the German ophthalmological registry oregis has compiled data on more than 1.75 million physician visits for more than 400,000 patients from German ophthalmologic centers. As of late 2022, more than 2.8 million visual acuity measurements and an equal number of intraocular pressure measurements have been recorded., Discussion: The aim of the oregis project is to establish a nationwide ophthalmology databank that forms the basis for a learning healthcare system in the field of ophthalmology. With the help of continuous updating, oregis can also illustrate short-term innovations in ophthalmological care., (© 2023. The Author(s).)

Purpose: The use of face masks has been proposed to cause or exacerbate the symptoms of dry eye disease (DED), which has been widely discussed under the term mask-associated dry eye (MADE). However, no studies have systematically investigated tear film parameters during the use of different face masks. Therefore, the objective of the present study was to investigate clinically relevant parameters of the tear film before and during the short-time use of face masks in dry and normal eyes., Methods: In a prospective study, the tear film parameters of 42 DED patients and 42 healthy volunteers were examined while wearing different types of face masks in a randomized order. This included measurements of non-invasive tear break-up time (NIBUT), lipid layer thickness, tear meniscus height, and bulbar redness after 30 min of wearing no mask, a surgical face mask or an FFP2/K95 mask. The equivalence of the means was assessed using the two one-sided t-test (TOST) method., Results: In healthy volunteers' lipid layer thickness, NIBUT and tear meniscus height were not significantly altered by 30 min of surgical or FFP2 mask wear (p > 0.016). The use of either type of mask was significantly associated with decreased bulbar redness (p < 0.001) in healthy eyes. In patients with DED, none of the tear film parameters or bulbar redness were significantly altered by 30 min of mask wear (p > 0.016)., Conclusions: Based on these results, the short-term wearing of face masks, regardless of type, did not produce a significant difference in tear film parameters of lipid layer thickness, NIBUT, and tear meniscus in healthy or dry eyes, while bulbar redness was reduced after mask wear only in healthy volunteers., (© 2022. The Author(s).)

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD)., Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted., Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer ( n = 221), followed by ChadOx1/AstraZeneca ( n = 57), mRNA-1273/Moderna ( n = 21), and Ad26.COV2.S/Johnson & Johnson ( n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window., Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

Purpose: This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region., Methods: We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data., Results: A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME)., Conclusion: A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic., (© 2022. The Author(s).)

Objective of Surgery: A CyPass®-microstent (Alcon, Fort Worth, TX, USA) extending too far into the anterior chamber should be trimmed as close as possible to the scleral spur to avoid progression of endothelial cell reduction., Indications: After CyPass implantation, if there is a significant loss of corneal endothelial cells due to the Cypass microstent extending too far into the anterior chamber, trimming or removal of the CyPass stent is necessary., Contraindications: There are no contraindications., Surgical Technique: As shown in our video, which is available online, a special cutter (19 Gauge Ahmed Micro Stent Cutter, MicroSurgical Technology Inc, Redmond, WA, USA) is inserted into the anterior chamber via a 1.5-mm wide corneal paracentesis made directly opposite to the CyPass stent. It is then possible to trim the anterior part of the stent. The severed fragment is removed using the head of the forceps. Finally, the previously inserted viscoelastic agent can be aspirated and the paracentesis can be hydrated., Postoperative Treatment: After the surgery vision testing as well as control of intraocular pressure and location of the stent are carried out. Antibiotic eye drops and ointment are postoperatively applied., Evidence: There is still no standardized protocol for the procedure to trim the CyPass stent. Performing the trimming in our clinic using the procedure described here has so far not led to any complications. Long-term data about the development of the endothelial cell measurement after CyPass trimming are not yet available., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Intravitreal drug delivery belongs to the most common medical procedures, with approximately 1.5 million treatments per year in Germany. However, for this enormous challenge to provision of proper care, there is a lack of empirical data regarding the treatment process and its clinical and subjective effect., Materials and Methods: This publication presents the development and structure of the Hamburg register for intravitreal therapies (QIVOM). Patients undergoing intravitreal injection therapy were invited to join the register study. Patients were recruited from the Hamburg eye clinics in Heidberg-Nord and Barmbek as well as from the University Medical Center Hamburg-Eppendorf (UKE). Both subjective patient-reported information about the perception of their eye disease and its treatment as well as medical parameters were stored in a central electronic database., Results: Of the first 162 study patients (aged 41-95 years), 64% suffered from wet age-related macular degeneration (AMD), 22% had a retinal vein occlusion, and 11% a diabetic macula edema. Disease severity and subjective impairment were heterogenous. Among these patients, 31.8% had a visual acuity above 10/20 on the treated eye compared to 79.1% on the other eye. The reduced ability to read was the most relevant limitation for more than one third of patients. However, 62% were able to drive a vehicle. An improvement of vision through intravitreal therapy was experienced by 45%., Conclusion: Collection of patient-reported as well as treatment-related data comprises the advantage of the newly created register. This extension of the data basis should deliver new findings in the future and contribute to quality assurance in intravitreal care., (© 2021. The Author(s).)

Background/aim: Conjunctival malignant melanoma (CMM) is a rare, but very aggressive tumor with a high metastasis rate. Not much is known about the CMM metastasis mechanisms. So far, epidermal growth factor (EGF) and its receptor (EGF-R) as well as macrophages and matrix metalloproteinase 9 (MMP-9) have been reported to lead to metastasis by epithelial-mesenchymal-transition and tumor migration in different solid tumors. Therefore, we evaluated whether EGF and EGF-R, CD68 and MMP-9 are altered in CMM samples in comparison to conjunctival nevi and healthy conjunctiva., Patients and Methods: EGF, EGF-R, the macrophage marker CD68 and MMP-9 expression were analyzed in human conjunctival melanoma (CMM, n=16), human conjunctival nevi (n=13) and disease-free human conjunctiva (controls, n=14) by immunohistology. Staining of each sample was evaluated using a standardized score ranging from negative (0) to triple positive (3). The groups were then compared by ANOVA, followed by Tukey's post-hoc test., Results: A statistically significant increase of EGF was seen in CMM samples in comparison to conjunctival nevi (p=0.03). In contrast, no statistically significant differences in EGF-R expression were noted between the three groups. A statistically significant increase of CD68 was only seen in conjunctival nevi compared to controls (p=0.04). MMP-9 expression was similar in all groups., Conclusion: In CMM, the study data demonstrated an up-regulation of EGF in comparison to conjunctival nevi. Hence, EGF might promote proliferation of CMM cells and induce the epithelial-mesenchymal transition. Therefore, our data suggest that an interplay between EGF and CMM might have a critical role in the developing CMM tumors and metastasis., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Impairment of corneal nerves can lead to neurotrophic keratopathy accompanied with severe ocular surface damage, which due to limited treatment options, can result in severe visual deterioration. This study evaluates a possible new treatment by enhancing the corneal nerve regeneration using a Rho Kinase inhibitor (Y27632). ROCK is known to play an important role in regulating cell morphology, adhesion and motility but little is known about its role in corneal nerve regeneration., Methods: Effects of ROCK inhibition on murine peripheral nerves was assessed in single cell- and wound healing assays as well as a 3D in vitro model. Furthermore, Sholl analysis evaluating neuronal branching and life-death assays evaluating toxicity of the inhibitor were performed. An in vivo mouse model was established, with monitoring weekly corneal nerve regrowth using confocal microscopy. Additionally, corneal nerve fiber length was evaluated by immunofluorescence staining. Underlying pathways were examined by qrtPCR., Results: ROCK inhibition leads to a significant enhancement of fiber growth in vitro. Sholl analysis revealed a higher degree of branching of treated fibers. Cytotoxicity assay showed no influence of Y27632 on cellular survival. In vivo measurement revealed significant enhanced regeneration after injury in the treated group. QrtPCR of trigeminal ganglia confirmed ROCK knock-down as well as altered pathways., Conclusion: The inhibition of ROCK after corneal nerve injury resulted in an enhanced regrowth of fibers in vitro and in vivo. This might be a step towards a new therapeutic concept for the treatment of impaired corneal nerves in diseases such as neurotrophic keratopathy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: In a benchwork particle counting analytical evaluation, the number and type of particles in intravitreal injection formulations of three different agents against vascular endothelial growth factor were investigated., Methods: Commercially available ready-to-use aflibercept and brolucizumab glass syringes, vials containing bevacizumab (off-label use in ophthalmology), and repackaged ready-to-use plastic syringes containing bevacizumab were tested without filtration. Total visible, subvisible, and nanoparticles numbers and size distributions were quantified using light obscuration, flow imaging, resonant mass measurement (RMM), tunable resistive pulse sensing, and dynamic light scattering., Results: Repackaged bevacizumab showed overall low particle numbers, aflibercept showed high numbers of micrometer sized particles but low nanoparticle numbers, brolucizumab showed low to moderate numbers of micrometer sized particles but high nanoparticle numbers. RMM measurements identified particles in the nanometer range as either proteinaceous or silicon oil; the nature of the other particles was not further evaluated., Conclusions: Repackaged bevacizumab shows no inferior particle quality compared to ready-to-use products. It is relevant to study nanoparticle load of the products as the micrometer-sized particle numbers do not in all cases correlate to nanoparticle counts. Particularly for the high concentration product Beovu (brolucizumab), high nanoparticle numbers were found despite low numbers of micrometer sized particles. Silicone oil droplets did not account for high particle numbers as the measured numbers were low., Translational Relevance: Different side effects are registered in different frequencies with different intravitreal anti-VEGF-drugs and syringes, which are applied by injection by small 30G needles through the sclera directly to the intravitreal cavity. The study of nanoparticles and silicone oil droplets may be able to contribute to narrowing down the causes.