Optical coherence tomography as a potential surrogate marker of dopaminergic modulation across the life span.

The retina has been considered a "window to the brain" and shares similar innervation by the dopaminergic system with the cortex in terms of an unequal distribution of D1 and D2 receptors. Here, we provide a comprehensive overview that Optical Coherence Tomography (OCT), a non-invasive imaging technique, which provides an "in vivo" representation of the retina, shows promise to be used as a surrogate marker of dopaminergic neuromodulation in cognition. Overall, most evidence supports reduced retinal thickness in individuals with dopaminergic dysregulation (e.g., patients with Parkinson's Disease, non-demented older adults) and with poor cognitive functioning. By using the theoretical framework of metacontrol, we derive hypotheses that retinal thinning associated to decreased dopamine (DA) levels affecting D1 families, might lead to a decrease in the signal-to-noise ratio (SNR) affecting cognitive persistence (depending on D1-modulated DA activity) but not cognitive flexibility (depending on D2-modulated DA activity). We argue that the use of OCT parameters might not only be an insightful for cognitive neuroscience research, but also a potentially effective tool for individualized medicine with a focus on cognition. As our society progressively ages in the forthcoming years and decades, the preservation of cognitive abilities and promoting healthy aging will hold of crucial significance. OCT has the potential to function as a swift, non-invasive, and economical method for promptly recognizing individuals with a heightened vulnerability to cognitive deterioration throughout all stages of life.

Introducing a customized low-cost macular buckle.

PURPOSE: To demonstrate a novel surgical technique that is a low-cost alternative to commercial implants for macular buckling in high myopia. METHODS: A silicon encircling band serves as the anchor. A second silicon circling band is employed, with a 10mm silicon strip to widen the posterior scleral indentation. This band is inserted posteriorly the lateral and inferior rectus muscles and pushed behind the globe, orienting it in a superior-temporal to inferio-nasal position with the silicone strip directly under the macula. For better visualization, the placement of the macular buckle is done under the microscope. RESULTS: The placement of the macular buckle led to reattachment of the central retina in treated patients during long-term follow-up. This technique eliminates the need for detaching a rectus muscle. Visual acuity remained stable throughout the follow-up period. CONCLUSION: This customized macular buckle technique can improve the anatomical outcome in patients with central retinal detachment due to high myopia.

The clinical evaluation of a widefield lens to expand the field of view in optical coherence tomography (OCT-A).

This study aimed to evaluate the clinical benefits of incorporating a widefield lens (WFL) in optical coherence tomography angiography (OCT-A) in patients with retinal vascular diseases in comparison to standard single-shot OCT-A scans. Sixty patients with retinal vascular diseases including diabetic retinopathy (DR) and retinal vein occlusion (RVO) were recruited. OCT-A imaging (PlexElite 9000) with and without WFL was performed in randomized order. The assessment included patient comfort, time, field of view (FoV), image quality and pathology detection. Statistical analysis included paired t-tests, Mann-Whitney U-tests and Bonferroni correction for multiple tests, with inter-grader agreement using the kappa coefficient. Using a WFL did not lead to statistically significant differences in DR and RVO group test times. Patient comfort remained high, with similar responses for WFL and non-WFL measurements. The WFL notably expanded the scan field (1.6× FoV increase), enhancing peripheral retinal visibility. However, image quality varied due to pathology and eye dominance, affecting the detection of peripheral issues in RVO and DR cases. The use of a WFL widens the scan field, aiding vascular retinal disease imaging with minor effects on comfort, time, and image quality. Further enhancements are needed for broader view angles, enabling improved quantification of non-perfused areas and more reliable peripheral proliferation detection.

TRPP2 is located in the primary cilia of human non-pigmented ciliary epithelial cells.

PURPOSE: Mechanosensitive channels (MSCs) and primary cilium possess a possible relevance for the sensation of intraocular pressure (IOP). However, there is only limited data on their expression and localization in the ciliary body epithelium (CBE). The purpose of this study was to characterize the expression and localization of TRPP2 in a human non-pigmented ciliary epithelial cell (HNPCE) line. METHODS: The expression of the TRPP2 was studied by quantitative (q)RT-PCR and in situ hybridization in rat and human tissue. Protein expression and distribution were studied by western blot analysis, immunohistochemistry, and immunoelectron microscopy. Cellular location of TRPP2 was determined in rat and human CBE by immunofluorescence and immunoblot analysis. Electron microscopy studies were conducted to evaluate where and with substructure TRPP2 is localized in the HNPCE cell line. RESULTS: The expression of TRPP2 in rat and human non-pigmented ciliary epithelium was detected. TRPP2 was mainly located in nuclei, but also showed a punctate distribution pattern in the cytoplasm of HNPCE of the tissue and the cell line. In HNPCE cell culture, primary cilia did exhibit different length following serum starvation and hydrostatic pressure. TRPP2 was found to be colocalized with these cilia in HNPCE cells. CONCLUSION: The expression of TRPP2 and the primary cilium in the CB may indicate a possible role, such as the sensing of hydrostatic pressure, for the regulation of IOP. Functional studies via patch clamp or pharmacological intervention have yet to clarify the relevance for the physiological situation or aqueous humor regulation.

The Psychological, Social and Behavioral Impact of Intravitreal Anti-VEGF Therapy: An Analysis from the ALBATROS Data.

BACKGROUND: Retinal diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or branch/central retinal vein occlusion (B/CRVO) have significant implications for patients' social and psychological well-being. The ALBATROS study aimed to assess the care situation of patients who received anti-VEGF (vascular endothelial growth factor) treatment. To gain a comprehensive understanding of patients' backgrounds and attitudes, we developed an exploratory, structured questionnaire, the Basic Care and Patient Satisfaction Questionnaire (BPZ-9). METHODS: The data collection took place at the beginning and after twelve months of anti-VEGF therapy. The BPZ-9 questionnaire comprises nine questions to evaluate patients' psychological and social situation and satisfaction with treatment. RESULTS: Data were collected from 1478 nAMD (mean 78 years), 445 DME (67 years), 233 BRVO (70 years), and 144 CRVO (71 years) patients at 102 study centers throughout Germany. One in four patients had difficulties walking, and one in five needed an accompanying person for treatment. Anxiety about losing vision was present in three out of four patients at the beginning, and it slightly decreased to two out of three patients over the 12-month treatment period. The distress of having a retinal disease was generally higher than the distress related to the treatment. Most patients reported high treatment satisfaction (73%) and felt well-informed (81%). CONCLUSIONS: There is a relevant social and psychological impact related to anti-VEGF treatment. The patients' perception, attitudes, and commitment need further investigation.

Postoperative RNFL-Changes after Successful Trabeculectomy: 2-Year Outcomes. / Zwei-Jahres-Ergebnisse postoperativer RNFL-Entwicklung nach erfolgreicher Trabekulektomie.

BACKGROUND: The most important tool in glaucoma therapy is to lower the intraocular pressure to slow down the apoptosis of retinal ganglion cells. Trabeculectomy (TE) is considered the gold standard in glaucoma surgery. The aim of this study was to analyse the postoperative changes in retinal nerve fibre layer (RNFL) using optical coherence tomography (OCT) after TE. MATERIAL AND METHODS: We examined 40 patients naïve to prior glaucoma surgery retrospectively, who received a TE for medically uncontrolled primary open-angle glaucoma (POAG). Intraocular pressure (IOP), IOP-lowering medication, mean deviation of perimetry, visual acuity and peripapillary RNFL-thickness using OCT were evaluated during the first 24 month after TE. RESULTS: In total 40 eyes from 40 patients were treated with TE. Mean IOP decreased from 25.0 ± 0,9 to 13.9 ± 0.6 (p < 0.01), and the mean number of IOP-lowering eye drops from 3.3 ± 0.2 to 0.5 ± 0.2 (p < 0.01). Visual acuity and mean deviation in perimetry remained stable while mean global RNFL-thickness decreased from 67.8 ± 2.9 to 63.7 ± 2.9 (p < 0.01) and 63.4 ± 2.9 µm (p < 0.01) 12 and 24 months after TE. CONCLUSION: The TE is an effective method to reduce the IOD and the amount of IOP-lowering medication. Nevertheless, a significant further loss in RNFL thickness was observed in the first 12 months after TE. Thus, RNFL changes seem to stabilise only after a protracted period.

Impact of A-Scan Rate on Image Quality and Acquisition Time in OCT.

PURPOSE: This study aims to examine the impact of the A-scan rate in optical coherence tomography (OCT) on scan quality and acquisition time. METHODS: Two horizontal OCT scans per scan rate (20, 85, 125 kHz) of the right eye were captured with the same OCT device (Spectralis SHIFT, HRA + OCT, Heidelberg Engineering GmbH, Heidelberg, Germany) of patients who presented to the inherited retinal dystrophies consultation, thus predominantly challenging patients due to reduced fixation ability. Scan quality was measured by the Q score, a signal-to-noise-ratio (SNR). Acquisition time was measured in seconds. RESULTS: Fifty-one patients were included in the study. The highest quality was seen for an A-scan rate of 20 kHz (44.49 dB), succeeded by scans of an A-Scan rate of 85 kHz (38.53 dB) and of 125 kHz (36.65 dB). Differences in scan quality between the various A-scan rates were statistically significant. The acquisition time seen for an A-scan rate of 20 kHz (6.45 s) was significantly longer than those seen for an A-Scan rate of 85 kHz (1.51 s) and of 125 kHz (1.69 s). CONCLUSION: An A-scan rate of 20 kHz resulted in a significantly higher scan quality but also a significantly longer acquisition time compared to scan rates of 85 kHz and 125 kHz. Differences between an A-scan rate of 85 kHz and 125 kHz were marginal.

Impact of Routinely Performed Optical Coherence Tomography Examinations on Quality of Life in Patients with Retinal Diseases-Results from the ALBATROS Data Collection.

The use of OCT to monitor intravitreal treatment varies in clinical practice and is not always mandatory. The ALBATROS data collection aimed to clarify the impact of routinely implemented OCT on clinical outcomes and its impact on vision-related quality of life (VRQoL). METHODS: An observational cohort study included patients with retinal diseases starting an intravitreal anti-vascular endothelial growth factor treatment in Germany. Treatment followed clinical practice except mandatory OCT examination during the 12-month observation period. VRQoL was assessed by NEI VFQ-25 and compared with respect to OCT examinations and number of intravitreal injections in the different diseases (nAMD, DME, BRVO, CRVO). RESULTS: 1478 patients (74.5 ± 10.9 years, 54.9% female) were included in the analysis. Patients had neovascular AMD (65.2%), DME (18.4%), BRVO (9.5%), or CRVO (6.9%). 8.8 ± 2.6 OCT examinations and 6.1 ± 3.2 intravitreal injections were performed within 12 months. VRQoL differed between indications at baseline, with substantially lower values for neovascular AMD and CRVO. After twelve months, an increase in visual acuity and visual functional scale was observed for nAMD, DME, and BRVO, while in DME only, there was an association between number of OCT examinations and VRQoL. CONCLUSION: Intravitreal treatment was able to maintain VRQoL over twelve months in a real-world setting. Regular OCT examinations were associated with higher gain in VRQoL in DME patients after 12 months.

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

Multitask Learning for Activity Detection in Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to provide a comparison of performance and explainability of a multitask convolutional deep neuronal network to single-task networks for activity detection in neovascular age-related macular degeneration (nAMD). Methods: From 70 patients (46 women and 24 men) who attended the University Eye Hospital Tübingen, 3762 optical coherence tomography B-scans (right eye = 2011 and left eye = 1751) were acquired with Heidelberg Spectralis, Heidelberg, Germany. B-scans were graded by a retina specialist and an ophthalmology resident, and then used to develop a multitask deep learning model to predict disease activity in neovascular age-related macular degeneration along with the presence of sub- and intraretinal fluid. We used performance metrics for comparison to single-task networks and visualized the deep neural network (DNN)-based decision with t-distributed stochastic neighbor embedding and clinically validated saliency mapping techniques. Results: The multitask model surpassed single-task networks in accuracy for activity detection (94.2% vs. 91.2%). The area under the curve of the receiver operating curve was 0.984 for the multitask model versus 0.974 for the single-task model. Furthermore, compared to single-task networks, visualizations via t-distributed stochastic neighbor embedding and saliency maps highlighted that multitask networks' decisions for activity detection in neovascular age-related macular degeneration were highly consistent with the presence of both sub- and intraretinal fluid. Conclusions: Multitask learning increases the performance of neuronal networks for predicting disease activity, while providing clinicians with an easily accessible decision control, which resembles human reasoning. Translational Relevance: By improving nAMD activity detection performance and transparency of automated decisions, multitask DNNs can support the translation of machine learning research into clinical decision support systems for nAMD activity detection.

Normative data for macular and retinal nerve fibre layer thickness in healthy German children and adolescents using optical coherence tomography.

PURPOSE: To establish normative data for macular thickness, macular volume and peripapillary retinal nerve fibre layer (RNFL) thickness using Spectralis® spectral-domain optical coherence tomography (SD-OCT) in healthy German children and adolescents and investigate influencing factors. METHODS: The cross-sectional study included the right eye of 695 children with at least one complete retinal OCT scan. As part of the LIFE Child study, the children underwent an ophthalmological examination including axial length (AL), spherical equivalent (SE) and OCT measurements. Various questionnaires were answered by the children or their parents to identify media use or outdoor time. Multiple linear regression models were used to investigate the potential influencing factors. RESULTS: A total of 342 boys and 353 girls with an average age (SD) of 12.91 (3.29) years participated. The mean AL (SD) was 23.20 (0.86) mm. The mean macular thickness (SD) was 320.53 (12.29) µm and the mean RNFL thickness (SD) was 102.88 (8.79) µm. Statistical analysis revealed a significant correlation between average macular thickness and age (p < 0.001, ß = 0.77) as well as AL (p < 0.001, ß = -4.06). In addition, boys had thicker maculae (p < 0.001, ß = 5.36). The RNFL thickness showed no significant correlation with children's age (p > 0.05), but with AL (p = 0.002, ß = -2.15), birth weight (p = 0.02, ß = 0.003) and a gender-specific effect of the body mass index standard deviation score for male participants (p = 0.02, ß = 1.93). CONCLUSION: This study provides normative data and correlations between macular and RNFL thickness in healthy German children. Especially age, gender and AL must be taken into account when evaluating quantitative OCT measurements to classify them as normal.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, 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-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b 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-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b 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-α2b being the standard second-line option. Interferon-α2b 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-α2b are likely to have a profound impact on patient care and their quality of life.

Surgical Care in Specialist Ophthalmology Departments: Structure and Impact of the COVID-19 Pandemic.

BACKGROUND: Specialist ophthalmology departments contribute to the surgical care of German patients. Outpatient and inpatient surgeries were restricted during the COVID-19 pandemic and led to a sharp decline in the number of cases in ophthalmological care. The aim of this analysis was to improve the understanding of the logistic structures of medical facilities as well as the effects of the pandemic. MATERIAL AND METHOD: Based on reported process data, a sample of the specialist ophthalmological departments were examined based on operation and procedure codes (OPS) and data submitted between 01.01.2017 and 31.05.2021 according to the benchmarking programmes of the Professional Association of German Anaesthetists (BDA), the Professional Association of German Surgeons (BDC), and the Association for Operating Theatre Management (VOPM). RESULTS: Eighteen ophthalmology departments from Germany were analysed. After the decline in the number of cases (by temporarily up to 48%) during the first wave of the pandemic, the case numbers of all interventions assessed as nonurgent continued to be reduced. While intravitreal injections hardly decreased during the first wave (- 16%), significant drops in the coverage of cataract surgery (- 79%), vitrectomies (- 35%), glaucoma surgery (- 59%), strabismus surgery (- 95%), and eyelid surgery (- 52%) were found. One exception was intravitreal injection, which stabilised at a lower level early on during the pandemic. Overall, the number of cases during the later phases of the pandemic were significantly reduced below the level of previous years, despite the maintenance of emergency care. The underuse was variable for different interventions. CONCLUSION: In addition to self-reported figures, the analysed process data demonstrates the effect that various factors had on elective as well as urgent operations within hospital care during the pandemic. Despite partial stabilisation of some services, a relevant supply gap for outpatient and inpatient interventions was identified, with corresponding effects on the eye health of the population, while compensation or performance enhancement have not taken place to date. Facing the growing preload and the demographic development, future structures must therefore allow for an increase in the performance of specialist ophthalmological departments.

Legal obligation in the general population: face mask influence on endophthalmitis after intravitreal injection.

PURPOSE: To investigate whether compulsory face masking in public life changes the incidence or pattern of post-injection endophthalmitis (PIE). PATIENTS AND METHODS: All injections of bevacizumab, ranibizumab, aflibercept, dexamethasone or triamcinolone between 01/01/2015 and 12/31/2021 at the University Eye Clinic of Tuebingen were included in this retrospective analysis. The injection procedure itself was unchanged since 2015 and included the use of a sterile drape covering the head up to the shoulders which prevents airflow toward the eye. Furthermore, all staff wore a face mask and gloves at all times. The two study periods were defined by the introduction of a compulsory face masking rule in public life (01/01/2015 until 04/27/2020 vs. 04/28/2020 until 12/31/2021). RESULTS: A total of 83,543 injections were performed in the tertiary eye clinic, associated with a total of 20 PIE (0.024%, 1/4177 injections). Of these, thirteen PIE were documented during the pre-pandemic period (0.021%, 1/4773 injections) and seven PIE during the pandemic period (0.033%, 1/3071 injections). No significant difference in PIE risk was observed (p = 0.49), and there was no case of oral flora associated PIE. CONCLUSION: Although some potential confounders (wearing time, skin flora) could not be considered, there was no clear signal that the introduction of compulsory face masking in public life did alter the risk for PIE in our patient population. Three and six months after PIE, no difference in visual acuity was detectable between the two study periods.

[Photo-based examination for diabetic eye pathologies in a German ophthalmological practice without personal doctor-patient contact]. / Fotobasierte Untersuchung auf diabetische Augenveränderungen in einer deutschen Augenarztpraxis ohne direkten Arzt-Patienten-Kontakt.

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.

Refractive Changes after Glaucoma Surgery-A Comparison between Trabeculectomy and XEN Microstent Implantation.

Best-corrected visual acuity often decreases temporarily or permanently after trabeculectomy (TE). The purpose of this study was to compare visual acuity and refractive changes after TE or XEN microstent implantation (XEN) in primary open-angle glaucoma (POAG) or pseudoexfoliation glaucoma (PEX) cases naïve to prior glaucoma surgery over a 24-month follow-up period. We analyzed 149 consecutive glaucoma patients who received either TE or XEN because of medically uncontrollable POAG or PEX. Intraocular pressure (IOP), IOP-lowering medication use, subjective and objective refraction and best-corrected visual acuity were evaluated. In addition, surgically induced astigmatism (SIA) was calculated and compared using the vector analysis method described by Jaffe and Clayman. A total of 93 eyes (85 POAG; 8 PEX) were treated with TE and 56 eyes (50 POAG; 6 PEX) with XEN. After 24 months, the mean IOP and number of IOP-lowering medications used decreased significantly after TE (p < 0.01) and XEN (p < 0.01). In the TE group, mean best-corrected visual acuity (BCVA) changed from 0.16 ± 0.26 to 0.23 ± 0.28 logMAR (p < 0.01) after 24 months, while mean BCVA did not change significantly in the XEN group (preoperative: 0.40 ± 0.50 logMAR, postoperative: 0.36 ± 0.49 logMAR; p = 0.28). SIA was almost the same in both groups at the end of the 24-month follow-up period (0.75 ± 0.60 diopters after TE and 0.81 ± 0.56 diopters after XEN; p = 0.57). In addition, there was no significant correlation between SIA and the observed BCVA changes or SIA and IOP reduction 12 or 24 months after TE or XEN. Our results demonstrate that TE and XEN are effective methods for reducing IOP and IOP-lowering medication use. The SIA was nearly similar in both groups. The SIA does not seem responsible for the decreased visual acuity after TE.

Two Year Functional and Structural Changes-A Comparison between Trabeculectomy and XEN Microstent Implantation Using Spectral Domain Optical Coherence Tomography.

The aim of this study was to analyze retinal nerve fiber layer (RNFL) thickness after trabeculectomy (TE) versus XEN microstent implantation (XEN) in primary open-angle glaucoma (POAG) cases naïve to prior incisional glaucoma surgery. We examined 119 consecutive glaucoma patients retrospectively, who received a TE or XEN for medically uncontrolled POAG. Intraocular pressure (IOP), amount of IOP-lowering medication, mean deviation of standard automated perimetry and peripapillary RNFL thickness were evaluated during the first 24 months after surgery. Fifty eyes were treated with TE and 69 eyes with XEN. Mean IOP decreased from 25.1 ± 0.8 to 13.3 ± 0.6 mm Hg (p < 0.01) and mean number of IOP-lowering eye drops from 3.2 ± 0.2 to 0.4 ± 0.1 (p < 0.01) 24 months after TE. In 69 eyes undergoing XEN, mean IOP dropped from 24.8 ± 0.6 to 15.0 ± 0.4 mm Hg (p < 0.01) and medication from 3.0 ± 0.1 to 0.6 ± 0.1 (p < 0.01) during the 24 months follow-up. Mean deviation of standard automated perimetry remained stable in TE (8.5 ± 0.7 to 8.1 ± 0.8 dB; p = 0.54) and XEN group (11,0 ± 0.5 to 11.5 ± 0.5 dB; p = 0.12) after 24 months, while mean RNFL thickness further deteriorated in the TE (−2.28 ± 0.65 µm/year) and XEN (−0.68 ± 0.34 µm/year) group. Postoperative RNFL loss develops after TE and XEN despite effective and significant lowering of IOP and amount of IOP-lowering medication. RNFL loss was more pronounced in the first year after glaucoma surgery.

Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study.

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.

Morphology of foveal hypoplasia: Hyporeflective zones in the Henle fiber layer of eyes with high-grade foveal hypoplasia.

BACKGROUND: Foveal hypoplasia is characterized by the persistance of inner retinal layers at the macular center. We evaluated using spectral-domain optical coherence tomography (SD-OCT) morphological parameters of the macular center of eyes with foveal hypoplasia and describe the presence of hyporeflective zones in the Henle fiber layer (HFL) of eyes with high-grade foveal hypoplasia. METHODS: Eyes with foveal hypoplasia were classified into two groups: high-grade foveal hypoplasia with thick inner retinal layers at the macular center (thickness above 100 µm; 16 eyes of 9 subjects) and low-grade foveal hypoplasia with thinner inner retinal layers at the macular center (thickness below 100 µm; 25 eyes of 13 subjects). As comparison, SD-OCT images of normal control eyes (n = 75) were investigated. RESULTS: Eyes with foveal hypoplasia displayed shorter central photoreceptor outer segments (POS), a thinner central myoid zone, and a thicker central HFL compared to control eyes. Eyes with high-grade foveal hypoplasia also displayed a thinner central outer nuclear layer (ONL) compared to eyes with low-grade foveal hypoplasia and control eyes. There was a negative correlation between the thicknesses of the central ONL and HFL in eyes with foveal hypoplasia; however, the total thickness of both ONL and HFL was similar in all eye populations investigated. Visual acuity of subjects with foveal hypoplasia was negatively correlated to the thickness of the central inner retinal layers and positively correlated to the length of central POS. In contrast to central POS, the length of paracentral POS (0.5 and 1.0 mm nasal from the macular center) was not different between the three eye populations investigated. The paracentral ONL was thickest in eyes with high-grade foveal hypoplasia and thinnest in control eyes. Hyporeflective zones in the HFL were observed on SD-OCT images of eyes with high-grade foveal hypoplasia, but not of eyes with low-grade foveal hypoplasia and control eyes. OCT angiography images recorded at the level of the HFL of eyes with high-grade foveal hypoplasia showed concentric rings of different reflectivity around the macular center; such rings were not observed on images of eyes with low-grade foveal hypoplasia and control eyes. CONCLUSIONS: It is suggested that the hyporeflective zones in the HFL of eyes with high-grade foveal hypoplasia represent cystoid spaces which are surrounded by Henle fiber bundles. Cystoid spaces are likely formed because there are fewer Henle fibers and a thinner central ONL despite an unchanged thickness of both ONL and HFL. Cystoid spaces may cause the concentric rings of different reflectivity around the macular center in the HFL of eyes with high-grade foveal hypoplasia.

Clinical validation of saliency maps for understanding deep neural networks in ophthalmology.

Deep neural networks (DNNs) have achieved physician-level accuracy on many imaging-based medical diagnostic tasks, for example classification of retinal images in ophthalmology. However, their decision mechanisms are often considered impenetrable leading to a lack of trust by clinicians and patients. To alleviate this issue, a range of explanation methods have been proposed to expose the inner workings of DNNs leading to their decisions. For imaging-based tasks, this is often achieved via saliency maps. The quality of these maps are typically evaluated via perturbation analysis without experts involved. To facilitate the adoption and success of such automated systems, however, it is crucial to validate saliency maps against clinicians. In this study, we used three different network architectures and developed ensembles of DNNs to detect diabetic retinopathy and neovascular age-related macular degeneration from retinal fundus images and optical coherence tomography scans, respectively. We used a variety of explanation methods and obtained a comprehensive set of saliency maps for explaining the ensemble-based diagnostic decisions. Then, we systematically validated saliency maps against clinicians through two main analyses - a direct comparison of saliency maps with the expert annotations of disease-specific pathologies and perturbation analyses using also expert annotations as saliency maps. We found the choice of DNN architecture and explanation method to significantly influence the quality of saliency maps. Guided Backprop showed consistently good performance across disease scenarios and DNN architectures, suggesting that it provides a suitable starting point for explaining the decisions of DNNs on retinal images.