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Nikolaos Gkalapis,1,2,&ast; Simon Dulz,1,&ast; Carsten Grohmann,1 Miriam Nickel,3 Christoph Schwering,3 Eva Wibbeler,3 Martin Stephan Spitzer,1 Angela Schulz,3 Yevgeniya Atiskova1 1Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Department of Ophthalmology, University Hospital of Martin Luther University Halle/Wittenberg, Halle (Saale), Germany; 3Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany&ast;These authors contributed equally to this workCorrespondence: Yevgeniya Atiskova, Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany, Tel +49 (0) 40 7410 – 52301, Fax +49 (0) 40 7410 – 42301, Email y.atiskova@uke.dePurpose: To investigate the presence of peripapillary retinal nerve fiber layer (pRNFL) degeneration in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease and to evaluate the role of optical coherence tomography (OCT) assessed pRNFL thickness as a biomarker for CLN2 disease progression.Patients and Methods: Forty eyes of 20 patients with genetically and enzymatically confirmed diagnosis of late-infantile CLN2 disease were included in this retrospective cohort study. All patients received 300 mg of intracerebroventricular enzyme replacement treatment (cerliponase alfa) once every two weeks. OCT imaging was performed under general anesthesia using spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany). PRNFL thickness and central retinal thickness (CRT) values were manually confirmed with the Heidelberg Eye Explorer software. Corresponding pediatric data were extracted from the DEM-CHILD database. Spearman correlation coefficient values (rs) were calculated between pRNFL and CRT values, age at examination, the Weill Cornell Late Infantile Neuronal Ceroid Lipofuscinosis (Weill Cornell LINCL) Scale and the Hamburg Motor and Language (HML) Scale.Results: Fourteen of 20 patients underwent serial examinations resulting in a total of 84 OCT Scans and 42 Weill Cornell LINCL and HML Scale scores. Mean age was 6.90 years and mean follow-up time was 1.38 years. Mean global pRNFL (G-pRNFL) thickness was 77.02 μm presenting a significant decrease compared to normative values from healthy children (106.45 μm; p < 0.0001). G-pRNFL displayed significant correlations towards age at examination (rs = - 0.557, p < 0.01), the Weill Cornell LINCL Scale (rs = 0.849, p < 0.01), and the HML Scale (rs = 0.833, p < 0.01). Repeated measurements indicated decreases in pRNFL thickness over time in most patients.Conclusion: Patients with late-infantile CLN2 disease exhibit early onset progressive pRNFL loss regardless of outer retinal degeneration, highlighting the potential of pRNFL as an independent ocular biomarker for retinal pathology in late-infantile CLN2 disease.Keywords: neuronal ceroid lipofuscinosis, optic nerve, optical coherence tomography, retina, neurodegeneration, eye

Antony William, Martin S Spitzer, Deshka Doycheva, Spyridon Dimopoulos, Martin Alexander Leitritz, Bogomil Voykov Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany Background: The aim of this study was to compare the long-term outcomes of ab externo trabeculotomy in primary open-angle glaucoma (POAG) and uveitic glaucoma (UG). Design: This was a retrospective single-center case series study. Participants: Twenty eyes of 17 patients with POAG and 22 eyes of 18 patients with UG were included in this study. Patients and methods: The medical records of all consecutive patients with POAG and UG who underwent ab externo trabeculotomy since 2004 were reviewed. Main outcome measure: The main outcome measure was change in median intraocular pressure (IOP). Success was defined as IOP ≤21 mmHg (success 1) and IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). Results: In the POAG group, the median IOP decreased significantly from 22 mmHg (95% CI 21–25 mmHg; n=20) at baseline to 14 mmHg (95% CI 12–16; n=13) after 4 years, P

There is an active and controversial debate about the role of intravitreal bevacizumab versus approved drugs in the treatment of neovascular age-related macular degeneration (AMD). Because bevacizumab was available prior to the launch of ranibizumab, off-label use of the former became widespread and the cancer drug bevacizumab is the most commonly used medication in ophthalmology nowadays. This review considers every publication identified in MEDLINE using the keywords 'bevacizumab' and 'Avastin' between 1 June 2005 and 31 July 2008. The search identified 511 papers that were evaluated. In 33 studies, there was consistent and clear evidence for the efficacy of bevacizumab in neovascular AMD. However, the highest grade studies (three prospective, randomized, controlled trials) did not attain better than grade 2b level of evidence, and objective evaluation of the benefit of bevacizumab relative to representative controls was therefore not possible. Certainly, the available evidence is inferior to that obtained from the approval studies of ranibizumab and this should influence treatment selection and guidance of patients. These considerations indicate that important quality criteria need to be included in future studies to ensure more meaningful conclusions can be drawn. These include clearly defined inclusion criteria, information about the recruitment procedure (including data on withdrawals, excluded patients, concealed treatment allocation, use of intention-to-treat analyses and blinded assessment procedures). Although preclinical studies have almost exclusively found bevacizumab to be safe, the design utilized in clinical case series cannot rule out a possible increase in adverse events, which already show a high spontaneous incidence in elderly AMD patients. The superior evidence level for ranibizumab and the limited safety data for bevacizumab must be taken into consideration when evaluating the costs that a healthcare system is willing to spend. However, the superior grade of evidence for ranibizumab should not be confused with the (still missing) evidence for superior efficacy. The results of ongoing randomized, controlled, comparative trials will provide further data on the efficacy and cost effectiveness of bevacizumab and ranibizumab in the treatment of AMD. In the meantime, patients should be informed about the alternatives, the price differences and the restricted liability issue when off-label use of bevacizumab is offered. [ABSTRACT FROM AUTHOR]

Choroidal nevi are common benign melanocytic lesions often incidentally found during routine ophthalmic examinations. Patients with choroidal nevi are frequently referred to ocular oncology centers to differentiate these from choroidal melanoma and to exclude a malignant transformation which rarely occurs. However, this causes a high workload for referral centers and may delay diagnosis and treatment of patients with potentially severe conditions. To overcome this, the MOLES score was previously developed which may empower non-specialists to differentiate choroidal nevi from melanoma. In this retrospective study, the performance of the MOLES score was assessed in 695 patients with choroidal nevi and 53 with choroidal melanoma. With a specificity of 96% (choroidal nevi) and a sensitivity of 100% (melanoma) the MOLES score was highly successful in differentiating choroidal nevi from melanoma and may offer great potential to optimize monitoring and referral decisions, and for teleophthalmology applications. Furthermore, the TFSOM-DIM score using risk factors for determining tumor progression was applied and showed a good correlation with MOLES. A complementary use of MOLES and TFSOM-DIM may be beneficial for clinical routine: MOLES for screening by non-experts with limited diagnostic tools and TFSOM-DIM in a referral setting to counsel also regarding potential transformation., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: To investigate the presence of silicone oil (SO)-emulsification on the anterior iris surface with anterior segment optical coherence tomography (AS-OCT)., Methods: In this single-center cross-sectional study, vitrectomized eyes with SO tamponade that underwent AS-OCT imaging and gonioscopy examination during the postoperative follow-up visits, were reviewed., Results: 45 eyes of 42 consecutive patients were included. In 35.6% of the eyes (n = 16) emulsified SO droplets were detected in the anterior chamber (AC) angle by gonioscopy and in 55.6% (n = 25) on the anterior iris surface by AS-OCT imaging. The presence of SO emulsifications in the AC-angle correlated with the presence of SO emulsifications on the anterior iris surface (OR = 13.4, 95% CI [2.179-82.130]; p = 0.005). The accuracy of the AS-OCT predicting the presence of SO in the AC-angle was 71.0% and the sensitivity was 87.5%. No significant association between SO droplets in the AC and other clinical parameters including endotamponade-duration or type of silicone oil were found. The presence of emulsified SO droplets on the anterior iris surface detected by AS-OCT was significantly correlated to postoperative IOP rise (p = 0.027)., Conclusion: AS-OCT is a suitable method for the detection of SO on the anterior iris surface. SO droplets on the iris surface correlate with elevated postoperative IOP and with the presence of SO in the AC detected by gonioscopy, therefore AS-OCT might be used as a screening method for the detection of SO migration into the AC., Trial Registration Number: Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2023-300372-WF., (© 2024. The Author(s).)

Purpose: In October 2023, other cases with early silicone oil opacification within hours after intraocular implantation in the absence of emulsification occurred. While multiple, small series of this phenomenon are now documented during the last decade, the cause was never unmasked. In this study, we analyzed explanted patient samples, unused samples of the affected, and a control batch of the same silicone oil., Methods: The oils were examined on their optical and viscosimetric properties, interfacial tension and for presence of particles. Contamination was investigated using Inductively Coupled Plasma - Mass Spectrometry, thermogravimetric analyses, and Raman-spectroscopy. Cytotoxicity examination in ARPE-19 cells was performed. The oil's effect on pH-changes of aqueous solutions and the oil's defoaming ability were analyzed., Results: The affected batch passed all regulatory limits. However, the affected batch showed an elevated turbidity already before implantation. 3000-fold magnification revealed dispersed particles only in the affected batch. Contamination analyses revealed the absence of other elements indicating a silicon-containing contamination. The affected batch showed no in-vitro cytotoxicity but altered viscosimetric properties and a lower pH of the hydrophilic phase after inducing emulsification. Both batches did not show relevant defoaming properties., Conclusion: The results obtained combined with information from suppliers and the manufacturer suggest an elevated level of silica particles as the cause of the opacification. Based on these results, the manufacturer and suppliers of the latest affected batch adjusted cut-off values for turbidity measurements and introduced turbidity measurements of the raw material prior to distillation. Other manufacturers should follow these preventive measures.

Objectives: To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up., Methods: Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year., Results: A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events., Conclusion: Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

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: Bilateral progressive, symmetrical loss of central retinal thickness (CRT) has been described in neuronal ceroid lipofuscinosis type 2 (CLN2) disease. This study details the pattern of morphological changes underlying CRT loss and disease progression in patients receiving intracerebroventricular (ICV) enzyme replacement therapy (ERT) with cerliponase alfa., Methods: Spectral-domain optical coherence tomography macular cube scans were collected from 16 patients with classic CLN2 disease receiving ICV ERT. Detailed retinal structure analyses were performed on manually segmented horizontal B-scans through the fovea to determine the thickness of six retinal parameters and the extent of ellipsoid zone (EZ) loss., Results: Anatomical changes primarily occurred in photoreceptor (PR)-related retinal parameters and correlated with ocular disease severity. Retinal degeneration began with initial focal parafoveal EZ discontinuities signaling the onset of rapid PR degeneration in a predictable pattern: parafoveal PR involvement with foveal sparing followed by profound parafoveal and foveal PR loss with additional thinning beyond the central retina. PR degeneration began with outer segment loss and progressed to outer nuclear layer (ONL) involvement. Longitudinal analyses confirmed these observations. The rate of PR loss was fastest at the fovea at ∼58 mm per year and became slower at locations farther away from the fovea., Conclusions: Retinal degeneration in CLN2 disease is primarily associated with PR loss in a predictable pattern, with EZ disruption signaling early PR stress. CRT, ONL thickness, and PR layer thickness are useful anatomical biomarkers for understanding disease progression and treatment efficacy in CLN2. Studies using en face images will further clarify CLN2-related retinal degeneration.

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.

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

Background: Intravitreal injections are one of the most commonly performed ophthalmic procedures. It is estimated that over 1 million intravitreal injections are performed in Germany annually. The aim of this study was to quantify the waste and carbon footprint associated with single-use injection sets, and to establish a waste reduction strategy., Material and Methods: The clinical waste and associated carbon footprint from standard disposable injection sets used by tertiary referral centres in Germany (n = 6) and the United Kingdom (n = 2) were assessed. The safety of performing intravitreal injections with a minimalistic material-sparing approach was evaluated., Results: The average weight of an injection set (and hence the waste generated from each injection) was 165 g. On average, each injection set comprised 145 g (88%) of plastic, 2.1 g (1.3%) of metal, 4.3 g (2.6%) of paper, and 12.9 g (7.8%) of gauze/swabs. The production of such injection sets was extrapolated to a CO 2 equivalent of 752.6 tonnes (t), and the incineration of the resulting waste to a CO 2 equivalent of 301.7 t. For 1 million injections, this equates to 145.2 t of plastic, 2.1 t of metal, 4.3 t of paper, and 12.9 t of gauze/swabs. A material-sparing approach can reduce injection set-associated waste by 99% without necessarily compromising patient safety., Conclusion: A resource-saving approach to intravitreal injections can minimise the generation of clinical waste and its associated carbon footprint, thereby supporting sustainability., 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.)

Background: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting., Methods: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications., Results: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24., Conclusion: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Artificial intelligence (AI) has the potential to increase the affordability and accessibility of eye disease screening, especially with the recent approval of AI-based diabetic retinopathy (DR) screening programs in several countries., Methods: This study investigated the performance, feasibility, and user experience of a seamless hardware and software solution for screening chronic eye diseases in a real-world clinical environment in Germany. The solution integrated AI grading for DR, age-related macular degeneration (AMD), and glaucoma, along with specialist auditing and patient referral decision. The study comprised several components: (1) evaluating the entire system solution from recruitment to eye image capture and AI grading for DR, AMD, and glaucoma; (2) comparing specialist's grading results with AI grading results; (3) gathering user feedback on the solution., Results: A total of 231 patients were recruited, and their consent forms were obtained. The sensitivity, specificity, and area under the curve for DR grading were 100.00%, 80.10%, and 90.00%, respectively. For AMD grading, the values were 90.91%, 78.79%, and 85.00%, and for glaucoma grading, the values were 93.26%, 76.76%, and 85.00%. The analysis of all false positive cases across the three diseases and their comparison with the final referral decisions revealed that only 17 patients were falsely referred among the 231 patients. The efficacy analysis of the system demonstrated the effectiveness of the AI grading process in the study's testing environment. Clinical staff involved in using the system provided positive feedback on the disease screening process, particularly praising the seamless workflow from patient registration to image transmission and obtaining the final result. Results from a questionnaire completed by 12 participants indicated that most found the system easy, quick, and highly satisfactory. The study also revealed room for improvement in the AMD model, suggesting the need to enhance its training data. Furthermore, the performance of the glaucoma model grading could be improved by incorporating additional measures such as intraocular pressure., Conclusions: The implementation of the AI-based approach for screening three chronic eye diseases proved effective in real-world settings, earning positive feedback on the usability of the integrated platform from both the screening staff and auditors. The auditing function has proven valuable for obtaining efficient second opinions from experts, pointing to its potential for enhancing remote screening capabilities., Trial Registration: Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2021-10574-BO-ff., (© 2024. The Author(s).)

Introduction: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns., Methods: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed., Results: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0-70.0). 28% of eyes were classified as acute (&lt;4 months duration) CSC, 28% as chronic (&gt;4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2-0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab., Conclusion: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV., (© 2024 The Author(s). Published by S. Karger AG, Basel.)