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In accordance with worldwide data, the Robert Koch Institute (RKI) has reported a constant increase of syphilis cases in Germany over the past decade. We analysed the data of all patients, referred to a Department of Ophthalmology in a tertiary referral centre in Düsseldorf, Germany between 2008 and 2019, who were tested for syphilis. The epidemiologic, demographic, clinical, diagnostic and therapeutic data were retrieved from the records and evaluated in a retrospective, descriptive, non-comparative study. Syphilis serology was positive in 32/1840 (1.7%) patients, and was evenly distributed over this period. 26 (81.3%) were male, 19 (59.4%) belonged to a risk group. Ocular syphilis was the primary diagnosis for 29 patients (90.6%). The most frequent manifestation was uveitis (n = 20, 62.5%). By the end of therapy, 19 patients (59.4%) had an improved visual acuity. The incidence of ocular syphilis cases has remained stable over the last decade. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to capture images that form on the human retina after the simulated implantation of an intraocular lens (IOL). White light was used rather than the commonly used near-infrared light, which is unsuitable for the examination of diffractive IOLs. For this purpose, a special optical setup was developed to investigate the influence of the IOL design on two-dimensional retinal images in vivo ., Materials and Methods: A double-pass ophthalmoscopic setup with a scientific CCD camera system was developed. Imaging the retinal image of a white LED located at infinity provides access to the double-pass point spread function of the natural eye. Subsequently, a see-through device for simulated IOL implantation (VirtIOL, 10Lens S. L. U., Terrassa, Spain) was integrated to investigate the influence of the IOL design on the retinal image quality of complex scenarios., Results: Retinal images were acquired from an incoherent white point light source. Combined with simulated IOL implantation, retinal images were acquired from the point light source, letters, and a United States Airforce target on a 6-m distant monitor. As expected, the double-pass images obtained with a monofocal IOL were sharper than those obtained with a multifocal IOL., Conclusion: The method opens up access to double-pass point spread function for white light, thus solving the problem of infrared light-based methods providing incorrect results when examining diffractive IOLs. This approach may be helpful for the investigation of perception in the future., Competing Interests: Mario Gerlach is employee of Carl Zeiss Meditec AG, Berlin, Germany., (Thieme. All rights reserved.)

Background: Large language models (LLMs) such as ChatGPT-4 and Google Gemini show potential for patient health education, but concerns about their accuracy require careful evaluation. This study evaluates the readability and accuracy of ChatGPT-4 and Google Gemini in answering questions about retinal detachment., Methods: Comparative study analyzing responses from ChatGPT-4 and Google Gemini to 13 retinal detachment questions, categorized by difficulty levels (D1, D2, D3). Masked responses were reviewed by ten vitreoretinal specialists and rated on correctness, errors, thematic accuracy, coherence, and overall quality grading. Analysis included Flesch Readability Ease Score, word and sentence counts., Results: Both Artificial Intelligence tools required college-level understanding for all difficulty levels. Google Gemini was easier to understand (p = 0.03), while ChatGPT-4 provided more correct answers for the more difficult questions (p = 0.0005) with fewer serious errors. ChatGPT-4 scored highest on most challenging questions, showing superior thematic accuracy (p = 0.003). ChatGPT-4 outperformed Google Gemini in 8 of 13 questions, with higher overall quality grades in the easiest (p = 0.03) and hardest levels (p = 0.0002), showing a lower grade as question difficulty increased., Conclusions: ChatGPT-4 and Google Gemini effectively address queries about retinal detachment, offering mostly accurate answers with few critical errors, though patients require higher education for comprehension. The implementation of AI tools may contribute to improving medical care by providing accurate and relevant healthcare information quickly., (© 2024. The Author(s).)

Background: Childhood blindness remains a neglected issue in eye care within low-income countries, with congenital and juvenile cataracts being the most common treatable causes. This study aims to investigate the factors influencing the management of congenital and juvenile bilateral cataracts, provide data on general outcomes and postoperative findings, and discuss treatment in a low-income country context., Methods: In this prospective study, data from clinical care were continuously entered into a database, and one follow-up examination of a cohort of 91 patients with congenital and juvenile bilateral cataracts in Kinshasa, Democratic Republic of the Congo, was conducted. Multiple factors that affect the first clinical presentation, the clinical management, and outcome were investigated., Results: Most patients (88.5%) who received medical treatment were identified by cataract finders. A patient's presentation time was independent of the parent's education, social status, income, and sex of the child. The median age at first presentation was 5.8 years (ranging from 0 days to 17.3 years). The best visual acuity outcomes were achieved by patients who underwent surgery during early childhood. According to WHO grades and on an eye level basis, 51.1% (93 out of 182 eyes) showed improvement, while 34.6% (63 eyes) had unchanged results post-surgery. Among the cases without improvement, 76.2% were blind prior to surgery. Postoperative findings were observed in 56% of the patients, with secondary cataracts being the most common, affecting 26.37% of the operated eyes., Conclusions: Optimal management of childhood cataracts involves early identification, efficient hospital infrastructure, high-quality medical care, and long-term follow up. In sub-Saharan Africa, this approach must be adapted to the context of available resources, which differs significantly from those in high- and middle-income countries.

Rationale: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question., Aims: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO., Methods: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial., Study Outcomes: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted., Sample Size: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm., Discussion: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology., Trial Registration: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Alteplase/placebo is provided by Boehringer Ingelheim at no costs. Boehringer Ingelheim was given opportunity to review the manuscript for medical/scientific accuracy and intellectual property considerations. The authors did not receive any payment related to trial/manuscript development.

Purpose: To analyze changes in demographic parameters and retreatment patterns over a 10-year period in a clinical routine setting of infants with retinopathy of prematurity (ROP) requiring treatment documented in the German Retina.net ROP registry., Design: Multicenter, noninterventional, observational registry study recruiting patients treated for ROP., Subjects: A total of 692 eyes of 353 infants treated for ROP were documented in the Retina.net ROP registry over a 10-year period between 2011 and 2020. These cases cover about 15% of all infants treated for ROP in Germany., Methods: The Retina.net ROP registry was established in 2012 to jointly collect information on infants treated for ROP. The database collects information on demographic parameters (gestational age [GA], birth weight, neonatal comorbidities) as well as treatment parameters (type of treatment, weight and age at treatment, and stage of ROP). A total of 19 centers contributed to the analysis. This is the 10-year analysis of data from 2011 to 2020, in which we focus on changes over time regarding the respective parameters., Main Outcome Measures: Changes over time in demographic parameters and treatment patterns for ROP in Germany., Results: The overall incidence of treatment requiring ROP was 3.5% of all infants screened for ROP at participating centers. Gestational age, weight at birth, and weight at treatment remained stable over the 10-year period, whereas postmenstrual and postnatal age at treatment increased moderately but statistically significantly over the years. The most prevalent ROP severity stage at treatment was stage 3+ in zone II (76.6% of all treated eyes). Treatment patterns changed considerably from predominantly laser treatments in 2011 (75% of all treated eyes) to predominantly ranibizumab treatments in 2020 (60.9% of all treated eyes). The overall retreatment rate was 15.6%. Retreatment rates differed between initial treatment modalities (14.1% after laser coagulation, 12% after bevacizumab and 24.5% after ranibizumab). Treatment-associated systemic or ophthalmic complications were rare., Conclusions: This data analysis represents one of the largest documented cohorts of infants treated for ROP. The data on demographic parameters and treatment patterns provide useful information for further improvement of ROP management., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD)., Methods: The authors measured laser flare values of all 3,048 prescreened patients excluding those with comorbidities. A mixed regression analysis evaluated the strength of the influencing factors like age, sex, lens status, and presence and extent of RRD on laser flare., Results: Rhegmatogenous retinal detachment was more frequent in men (65.8%) than in women (34.2%, P < 0.001) and in right (52%) than in left eyes (48%, P = 0.045). Phakic RRD affected less quadrants and was less likely to be associated with macula-off status than pseudophakic RRD (48.4% vs. 58.0% macula off, 23% vs. 31% ≥3 quadrants, P < 0.001). Laser flare of affected eyes was significantly higher compared with fellow eyes (12.6 ± 15.2 vs. 8.3 ± 7.4 pc/ms, P < 0.001). The factors age, sex, lens status, presence of RRD, and the number of quadrants affected were independent influencing factors on laser flare. R 2 was 0.145 for phakic and 0.094 for pseudophakic eyes., Conclusion: The results indicate that there may be more factors affecting laser flare than previously assumed. This might limit flare as predictive value for PVR and retinal redetachment.

Background: Heterogeneity in type 2 diabetes can be represented by a tree-like graph structure by use of reversed graph-embedded dimensionality reduction. We aimed to examine whether this approach can be used to stratify key pathophysiological components and diabetes-related complications during longitudinal follow-up of individuals with recent-onset type 2 diabetes., Methods: For this cohort analysis, 927 participants aged 18-69 years from the German Diabetes Study (GDS) with recent-onset type 2 diabetes were mapped onto a previously developed two-dimensional tree based on nine simple clinical and laboratory variables, residualised for age and sex. Insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, insulin secretion was assessed by intravenous glucose tolerance test, hepatic lipid content was assessed by 1 H magnetic resonance spectroscopy, serum interleukin (IL)-6 and IL-18 were assessed by ELISA, and peripheral and autonomic neuropathy were assessed by functional and clinical measures. Participants were followed up for up to 16 years. We also investigated heart failure and all-cause mortality in 794 individuals with type 2 diabetes undergoing invasive coronary diagnostics from the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort., Findings: There were gradients of clamp-measured insulin sensitivity (both dimensions: p<0·0001) and insulin secretion (p dim1 <0·0001, p dim2 =0·00097) across the tree. Individuals in the region with the lowest insulin sensitivity had the highest hepatic lipid content (n=205, p dim1 <0·0001, p dim2 =0·037), pro-inflammatory biomarkers (IL-6: n=348, p dim1 <0·0001, p dim2 =0·013; IL-18: n=350, p dim1 <0·0001, p dim2 =0·38), and elevated cardiovascular risk (n events =143, p dim1 =0·14, p dim2 <0·00081), whereas individuals positioned in the branch with the lowest insulin secretion were more prone to require insulin therapy (n events =85, p dim1 =0·032, p dim2 =0·12) and had the highest risk of diabetic sensorimotor polyneuropathy (n events =184, p dim1 =0·012, p dim2 =0·044) and cardiac autonomic neuropathy (n events =118, p dim1 =0·0094, p dim2 =0·06). In the LURIC cohort, all-cause mortality was highest in the tree branch showing insulin resistance (n events =488, p dim1 =0·12, p dim2 =0·0032). Significant gradients differentiated individuals having heart failure with preserved ejection fraction from those who had heart failure with reduced ejection fraction., Interpretation: These data define the pathophysiological underpinnings of the tree structure, which has the potential to stratify diabetes-related complications on the basis of routinely available variables and thereby expand the toolbox of precision diabetes diagnosis., Funding: German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, European Community, German Research Foundation, and Schmutzler Stiftung., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Injured axons in the central nervous system (CNS) usually fail to regenerate, causing permanent disabilities. However, the knockdown of Pten knockout or treatment of neurons with hyper-IL-6 (hIL-6) transforms neurons into a regenerative state, allowing them to regenerate axons in the injured optic nerve and spinal cord. Transneuronal delivery of hIL-6 to the injured brain stem neurons enables functional recovery after severe spinal cord injury. Here we demonstrate that the beneficial hIL-6 and Pten knockout effects on axon growth are limited by the induction of tubulin detyrosination in axonal growth cones. Hence, cotreatment with parthenolide, a compound blocking microtubule detyrosination, synergistically accelerates neurite growth of cultured murine CNS neurons and primary RGCs isolated from adult human eyes. Systemic application of the prodrug dimethylamino-parthenolide (DMAPT) facilitates axon regeneration in the injured optic nerve and spinal cord. Moreover, combinatorial treatment further improves hIL-6-induced axon regeneration and locomotor recovery after severe SCI. Thus, DMAPT facilitates functional CNS regeneration and reduces the limiting effects of pro-regenerative treatments, making it a promising drug candidate for treating CNS injuries., Competing Interests: ML, CZ, MP, PG, AH, AA, RG, DF No competing interests declared, (© 2023, Leibinger, Zeitler et al.)

Background and Aims: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2 EK ; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes., Methods and Results: Males with recent-onset type 2 diabetes with (TM6SF2 EK : n = 16) or without (TM6SF2 EE : n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6- 2 H 2 ]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with 1 H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2 EK had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2 EE . After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2 EE only., Conclusions: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD., Competing Interests: Declaration of competing interest M.R. is on scientific advisory boards of Boehringer-Ingelheim, Eli Lilly, NovoNordisk and Target RWE, and received investigator-initiated support from Boehringer Ingelheim, Nutricia/Danone and Sanofi–Aventis. All contributions to the manuscript by D.F.M. have been performed when affiliated to the German Diabetes Center, prior to current employment by Boehringer Ingelheim. All other authors have no potential conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: The aim of this study was to evaluate results after Descemet membrane endothelial keratoplasty (DMEK) and DMEK with cataract surgery (triple DMEK) in eyes with endothelial dysfunction and concomitant macular pathology., Methods: A monocentric, prospective clinical observational study of patients who underwent DMEK or triple DMEK surgery at the Department of Ophthalmology, University Hospital Düsseldorf, Germany, from June 2013 to February 2016 was conducted. Sex, age, best-corrected visual acuity (BCVA), central corneal thickness, endothelial cell density, and central retinal thickness in the 1 millimeter zone were analyzed., Results: A total of 209 eyes were included in the study. Forty-two eyes (20.1%) had vision-limiting concomitant maculopathies. These were age-related macular degeneration (n = 17, 8.1%), epiretinal gliosis (n = 13, 6.2%), chronic macular edema (n = 7, 3.3%), macular holes (n = 3, 1.4%), and macular scarring (n = 2, 1.0%). BCVA significantly increased in patients without maculopathy from 0.6 ± 0.33 logMAR to 0.1 ± 0.15 logMAR ( P < 0.001) and also in patients with maculopathy from 0.9 ± 0.38 logMAR to 0.27 ± 0.23 logMAR 12 months postoperatively ( P < 0.001). There was a significant central retinal thickness increase of 34.1 μm 6 weeks after triple DMEK in the central 1-mm zone ( P = 0.011). This increase was insignificant after DMEK. Postoperative macular edema occurred in 5.9% of cases after DMEK and 8.1% after triple DMEK, which was not significantly different., Conclusions: DMEK and triple DMEK significantly increase BCVA in eyes with concomitant maculopathy. Postoperative macular edema is a common disorder after lamellar keratoplasty; therefore, prophylactic treatment with nonsteroidal antiinflammatory drugs should be considered. Maculopathies did not predispose the development of postoperative macular edema., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: An increasing number of patients suffering from diabetes require regular ophthalmological check-ups to diagnose and/or treat potential diabetic retinal disease. Some countries have already implemented systematic fundus assessments including artificial intelligence-based programs in order to detect sight-threatening retinopathy. The aim of this study was to improve the detection of diabetic fundus changes in Germany without examination by a doctor and to create an easy access to ophthalmological examinations., Material and Methods: In this prospective monocentric study 93 patients in need for a routine check-up for diabetic retinopathy were included. The study participants took up an offer of an examination (visual examination, non-mydriatic camera-based fundus examination) without doctor-patient contact. Patient satisfaction with the organization and examinations was assessed using a questionnaire., Results: The mean age was 53.5 years (SD 13.6 years, 49.5% female) and 17 eyes (18.3%) showed a diabetic retinopathy which was detected using a camera-based examination. Within the small sample, no patient had to repeat the examination due to poor image quality. All categories of the questionnaire showed a good to very good satisfaction, indicating a high acceptance of the other examination form that took place at the ophthalmologist's premises., Conclusion: In our study in an ophthalmological practice a high level of acceptance among the patients interested in the screening for diabetic retinopathy without any direct patient-doctor contact was achieved. Our study shows a very good acceptance and feasibility. Future use of artificial intelligence in clinical practice may help to be able to screen many more patients as in this study imaging quality was very good., (© 2022. The Author(s).)

Background: In recent years, an increasing number of surgical microscopes fitted with an OCT module (intraoperative OCT, iOCT) have become available, providing high-resolution images of the surgical site in real time. While a 2018 survey at our hospital showed that iOCT delivered an additional intraoperative benefit in only 2.4% of all operations, considering that the manufacturer had since revised the hardware and software, we conducted a second user evaluation of this technology., Material and Methods: Prospective monocentric analysis of the application and user-friendliness of an EnFocus Ultra-Deep OCT (Leica Microsystems) over a period of 25 (2018) and 20 working days (2021). A standardized questionnaire was used to assess the surgeons' use of iOCT and its influence on the surgical course., Results: 118 operations were performed over a 25-day period in 2018 and 92 operations were performed over a 20-day period in 2021. In 2018, iOCT was used in 24.6% and in 2021 in 48.9% of all surgeries, with iOCT proving to be "critical" to the surgical course in 2.4% and 3.3% of cases, respectively, as assessed by the surgeons in both years. These were operations in which the intraocular view was limited, e.g., with decompensated cornea, vitreous hemorrhage, or after previous surgery, e.g., after penetrating keratoplasty., Conclusion: Further development of the user interface led to an improvement in usability, and the iOCT was used significantly more often. In both years, the iOCT proved to be critical for the course of the surgery in a comparably small number of operations, especially those involving complex situations., Competing Interests: GG: Leica Microsystems, die anderen Autoren und Autorinnen geben keine Interessenkonflikte an./GG: Leica Microsystems, the other authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Importance: One of the biggest challenges when using anti-vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment., Objective: To evaluate whether an artificial intelligence (AI)-based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment., Design, Setting, and Participants: This prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022., Interventions: An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images., Main Outcomes and Measures: Analysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation., Results: Among 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P < .001) and 2.9 (1.3) at week 4 (P < .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P < .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = -0.9997; P < .001)., Conclusions and Relevance: In this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.

Background: "Spaceflight associated neuro-ocular syndrome" (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS., Methods and Design: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness., Conclusions: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS.

Aims/hypothesis: Hyperbaric oxygen (HBO) therapy may improve hyperglycaemia in humans with type 2 diabetes, but underlying mechanisms are unclear. Our objective was to examine the glucometabolic effects of HBO on whole-body glucose disposal in humans with type 2 diabetes., Methods: In a randomised placebo-controlled crossover trial located at the German Diabetes Center, 12 male individuals with type 2 diabetes (age 18-75 years, BMI <35 kg/m 2 , HbA 1c 42-75 mmol/mol [6-9%]), randomly allocated by one person, underwent 2-h HBO, once with 100% (240 kPa; HBO) and once with 21% oxygen (240 kPa; control, CON). Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamps with D-[6,6- 2 H 2 ]glucose, hepatic and skeletal muscle energy metabolism were assessed by 1 H/ 31 P-magnetic resonance spectroscopy, while high-resolution respirometry measured skeletal muscle and white adipose tissue (WAT) mitochondrial capacity. All participants and people assessing the outcomes were blinded., Results: HBO decreased fasting blood glucose by 19% and increased whole-body, hepatic and WAT insulin sensitivity about one-third (p<0.05 vs CON). Upon HBO, hepatic γ-ATP concentrations doubled, mitochondrial respiratory control doubled in skeletal muscle and tripled in WAT (p<0.05 vs CON). HBO increased myocellular insulin-stimulated serine-473/threonine-308 phosphorylation of Akt but decreased basal inhibitory serine-1101 phosphorylation of IRS-1 and endoplasmic reticulum stress (p<0.05 vs CON)., Conclusions/interpretation: HBO-mediated improvement of insulin sensitivity likely results from decreased endoplasmic reticulum stress and increased mitochondrial capacity, possibly leading to low-dose reactive oxygen species-mediated mitohormesis in humans with type 2 diabetes., Trial Registration: ClinicalTrials.gov NCT04219215 FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, North-Rhine Westfalia Ministry of Culture and Science, European-Regional-Development-Fund, German-Research-Foundation (DFG), Schmutzler Stiftung., (© 2022. The Author(s).)

Introduction: The assessment of the corneal nerve fibre plexus with corneal confocal microscopy (CCM) is an upcoming but still experimental method in the diagnosis of early stage diabetic peripheral neuropathy (DPN). Using an innovative imaging technique-Heidelberg Retina Tomograph equipped with the Rostock Cornea Module (HRT-RCM) and EyeGuidance module (EG)-we were able to look at greater areas of subbasal nerve plexus (SNP) in order to increase the diagnostic accuracy. The aim of our study was to evaluate the usefulness of EG instead of single image analysis in diagnosis of early stage DPN., Methods: This prospective study was performed on 60 patients with type 2 diabetes mellitus, classified equally into two subgroups based on neuropathy deficient score (NDS): patients without DPN (group 1) or with mild DPN (group 2). The following parameters were analysed in the two subgroups: corneal nerve fibre length (CNFL; mm/mm 2 ), corneal nerve fibre density (CNFD; no./mm 2 ), corneal nerve branch density (CNBD; no./mm 2 ). Furthermore, we compared the data calculated with the novel mosaic, EG-based method with those received from single image analysis using different quantification tools., Results: Using EG we did not find a significant difference between group 1 and group 2: CNFL (16.81 ± 5.87 mm/mm 2 vs. 17.19 ± 7.19 mm/mm 2 , p = 0.895), CNFD (254.05 ± 115.36 no./mm 2 vs. 265.91 ± 161.63 no./mm 2 , p = 0.732) and CNBD (102.68 ± 62.28 no./mm 2 vs. 115.38 ± 96.91 no./mm 2 , p = 0.541). No significant difference between the EG method of analysing the SNP and the single image analysis of 10 images per patient was detected., Conclusion: On the basis of our results it was not possible to differentiate between early stages of large nerve fibre DPN in patients with type 2 diabetes mellitus via SNP analysis. To improve sensitivity and specificity of this method newer technologies are under current evaluation., Trial Registration: ClinicalTrials.gov Identifier NCT05326958., (© 2022. The Author(s).)

Background: For quantitative and qualitative evaluation of the imaging properties of IOLs, axial cross-sectional images can be obtained from the 3-dimensional light distribution by means of an optical bench, as is known from light sheet recordings in fluorescein baths. This paper presents a new image-processing algorithm to enhance the quality of generated axial cross-sectional images, and the two methods are then compared., Material and Methods: The 3-dimensional point spread function of a diffractive trifocal IOL (AT LISA tri 839MP, Carl Zeiss Meditec AG, Jena, Germany) was recorded on an optical bench developed in Rostock for different pupil diameters. A specially adapted image processing algorithm was then applied to the measurements, allowing through-focus curves to be generated. In addition, cross-sectional images of the IOLs studied were acquired using the light sheet method in a fluorescein bath., Results: The study clearly shows the superiority of the newly developed method over the light sheet method in terms of image quality. In addition to the individual focal points, fine focal structures as well as halos can be made visible in the cross-sectional images obtained using the new method. In the generated through-focus curves, 3 intensity peaks can be identified, which represent the near, intermediate and far focus of the tested MIOL and cannot be represented by light sheet methods., Conclusion: The interaction of the optical bench with the developed image processing algorithm allows a more detailed understanding of the image formation and false light phenomena of IOLs, which was restricted by the technical limitations of the existing light sheet method. In addition, other quantities such as the through-focus curve can be derived quantitatively., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Stummer et al. established fluorescence-guided surgery (FGS) for glioblastoma (GBM) using 5-aminolevulinic acid (5-ALA). Its metabolite, protoporphyrin IX (PPIX), is also a photosensitizer and can be used for photodynamic therapy (PDT) using a laser beam of 635 nm. The porphyrin derivate verteporfin (VP) was discovered to have properties to penetrate the brain, pharmacologically target glioma cells, and is approved for PDT of choroidal neovascularization in wet age-related macular degeneration at 689 nm., Objective: To elucidate whether GBM cell lines are susceptible to PDT with second-generation photosensitizer VP., Methods: Human glioma cell lines LN229, HSR-GBM1, and a low-passage patient-derived GBM cell line P1 were treated with variable concentrations of VP for 24 h, followed by PDT at 689 nm using a diode laser light. Cell viability was measured using the MTT assay and VP uptake was measured using a desktop cytometer., Results: Significantly higher cell death following PDT with VP compared to VP treatment alone or no treatment was detected in all cell models (LN229, HSR-GBM1, P1). Flowcytometric measurements revealed a concentration-dependent cellular uptake of VP after 24 h incubation up to 99% at 10 µM (HSR-GBM1)., Conclusion: This study demonstrates that PDT with VP causes cell death in GBM cells at marginal concentrations. Additionally, red spectrum fluorescence was detected at therapeutic concentrations in all cell lines, validating the cellular uptake of VP in GBM cells. VP, therefore, is not only a potential drug for targeting GBM pharmacologically but can be used as an optical imaging dye in surgery and photosensitizer to make GBM susceptible to PDT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD., Design: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis., Participants: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry., Methods: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy., Main Outcome Measures: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon., Results: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified., Conclusions: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

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: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1- and 2-year follow-up data focusing on long-term functional outcomes and safety., Methods: The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients., Results: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were -1.9 diopters (D) and -0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms., Conclusion: Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)