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Importance: Randomized clinical trials are conducted to establish both drug safety and efficacy. However, evidence of adverse events associated with these drugs in the clinical practice setting can be of value at generating hypotheses regarding less common safety issues, even if causality cannot be determined., Objective: To present and analyze cases of intraocular inflammation associated with faricimab therapy in patients referred to a single European institution., Design, Setting, and Participants: This was a review starting in April of 2024 of an observational case series. Patients were from a single academic-based tertiary referral center in Switzerland. Included in the analysis were patients referred for intraocular inflammation soon after receiving a faricimab intravitreal injection between June 1, 2022, and March 5, 2024., Exposure: Faricimab, 6 mg (0.05 mL of a 120-mg/mL solution), administrated for neovascular age-related macular degeneration or diabetic macular edema., Main Outcomes and Measures: The systemic and ocular histories and imaging data available were reviewed. The following were evaluated: visual acuity measured with habitual correction using the Early Treatment of Diabetic Retinopathy Study charts before and after the event; intraocular pressure; patient symptoms; anterior, intermediate, or posterior location of the intraocular inflammation; and the presence of retinal vasculitis. Multimodal imaging including color fundus photographs, fluorescein angiograms, indocyanine green angiograms, and optical coherence tomography were reviewed., Results: A total of 12 eyes from 7 patients (mean [SD] age, 73.3 [16.7] years; 4 female [57.1%]) over 22 months were identified as having noninfectious intraocular inflammation after intravitreal faricimab injections. Among these cases, in 2 eyes, retinal vasculitis was present together with anterior and posterior inflammation. One of the 2 eyes had an occlusive form of vasculitis of the arteries and veins, leading to subsequent macular capillary nonperfusion and clinically relevant irreversible vision deterioration from 20/80 to 20/2000. The remaining eyes were characterized by moderate anterior segment inflammation without substantial vision changes. The intraocular inflammation event occurred after a median (IQR) of 3.5 (2.0-4.3) faricimab injections. The median (IQR) interval between the last faricimab injection and the diagnosis of inflammation was 28 (24-38) days. Increased intraocular pressure of 30 mm Hg or higher was found in 3 eyes., Conclusions and Relevance: This case series highlights the occurrence of rare, but potentially severe, intraocular inflammation associated with faricimab therapy. Although these findings do not prove causality and can only generate hypotheses for future investigations, these results suggest the importance of continuous surveillance and monitoring for patients undergoing faricimab therapy to promptly identify and manage potential adverse events.

This study analyzes the dynamics of short-term treatment response to the first intravitreal faricimab injection in eyes with diabetic macular edema (DME). This retrospective, single-center, clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich. Patients with treatment-naïve and pretreated DME were included. Patient chart data and imaging were analyzed. Safety and efficacy (corrected visual acuity (CVA), central subfield thickness (CST), and signs of intraocular inflammation (IOI)) of the first faricimab intravitreal therapy (IVT) were evaluated weekly until 4 weeks after injection. Forty-three eyes (81% pretreated) of 31 patients were included. Four weeks after the first faricimab IVT, CVA remained stable and median CST (µm) decreased significantly ( p < 0.001) from 325.0 (293.5-399.0) at baseline to 304.0 (286.5-358.0). CVA at week 4 was only associated with baseline CVA ( p < 0.001). CST was the only predictive variable ( p = 0.002) between baseline and week 4 CST. Weekly safety assessments did not show any sign of clinically significant IOI. This study suggests faricimab is an effective treatment for (pretreated) DME, showing structural benefit 1 month following the first injection without short-term safety signals.

Competing Interests: D. B. is a consultant and speaker for Novartis and Bayer, and a consultant for Alcon. D. R. M. is a consultant for Bayer and Roche. B. L. is outside of the submitted work member of the steering committee of HOS, a post-marketing registry for Hunterʼs disease and received honoraria and travel grants by Shire, Takeda, Genzyme-Sanofi, and Alexion for various presentations. None of the declarations represent a conflict of interest related to the presented study. S. S., J. M. G., J. V. M. H., K. F., F. B., and S. A. Z. declare no conflict of interest related to the topic.

Purpose: To evaluate the increase in retinal thickness as a marker in predicting the onset of central retinal artery occlusions., Methods: Retrospective clinical study conducted at one Swiss hospital. Electronic records were filtered for patients with artery occlusions. Optical coherence tomography data, including time between the imaging and ischemic event, were reviewed. Increase in relative retinal thickness was measured, defined as an increase in retinal thickness compared to the unaffected partner eye. This was correlated with the time from symptom onset. A cutoff value of relative increase of < 24.5% was applied, as suggested in previous studies. The results were compared to the time gathered from the electronic records, and sensitivity, specificity, positive predictive value as well as negative predictive value were calculated for predicting an ischemia time of < 4.5 h., Results: Forty-two eyes from 41 patients with central artery occlusions were identified. Fourteen were female. Mean age was 66.4 ± 15.8 years. Initial corrected visual acuity was 2.41 ± 0.68 logMAR, and 2.13 ± 0.87 logMAR at the last follow-up (p > 0.05). Of eyes with a visual acuity of counting fingers (n = 38) or worse, 89.5% showed no improvement during follow-up, while eyes with logMAR 1 or better (n = 4) improved. Thirteen eyes (13 patients) presented within 4.5 h of the ischemic event. Four patients received i. v. thrombolysis, with visual recovery in one. In 12 eyes with an ischemia time of < 4.5 h, relative increase was below 24.5%. In the remaining 29 eyes with > 4.5 h, relative increase was below 24.5% in 4 eyes and above 24.5% in 25 eyes. This yielded a sensitivity of 92.3%, a specificity of 86.2%, with a positive predictive value of 75.0% and a negative predictive value of 96.2%., Conclusion: Central retinal artery occlusion is associated with severe vision loss. There is no current established therapy. Parameters that objectify the presence of a therapeutic window for thrombolysis are gaining in importance as patient history is often imprecise. Relative retinal thickness increase proved a noninvasive imaging parameter demonstrating adequate performance in detecting patients within the therapeutic window of thrombolysis. Further investigation of this parameter in central retinal occlusion is warranted., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: To report ophthalmological outcomes and treatment regimen in patients with Susac syndrome., Methods: This is a retrospective analysis of patients with Susac syndrome treated between November 2015 and March 2023. Multimodal imaging findings, ophthalmic examination data, information on neurological and sensorineural involvement, and therapeutic regimen were reviewed. Visual acuity was recorded as the logarithm of the minimum angle of resolution (logMAR). Ophthalmological manifestations and disease severity were assessed using the previously described clinical activity score (CAS)., Results: Ten patients with Susac syndrome m : f = 5 : 5 were identified. The mean follow-up time was 31.2 ± 23.3 months (range 1 to 78 months). The mean age was 41.4 ± 13.8 years (range 21 to 59 years). At baseline, corrected distance visual acuity (CDVA) was 0.03 ± 0.08 logMAR. At the last follow-up, CDVA improved to 0.00 ± 0.03 logMAR (p = 0.029). Three of 20 eyes showed an improvement of 5 letters, while no loss of visual acuity was recorded during the follow-up time. Baseline CAS was 10.65 ± 12.69, and CAS at the last follow-up was 5.15 ± 5.49 (p = 0.068). Except for one patient, all were initially treated with intravenous (i. v.) steroids and subsequent oral tapering. Depending on the treatment response, cyclophosphamide (n = 4), i. v. immunoglobulins (IVIGs) (n = 4), anti-CD20 antibodies (n = 3), or plasmapheresis (n = 1) were applied. All patients under treatment for more than 1 month (n = 9) showed improvement in CAS and CDVA., Conclusion: Susac syndrome is a rare autoimmune vascular endotheliopathy. Treatment of Susac syndrome appears to result in improving CAS and CDVA. The majority of patients, in addition to the systemic steroids, required systemic immunosuppressive agents. Interdisciplinary communication is crucial to reduce the time to diagnosis and initiation of therapy in patients with Susac syndrome., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: D. B. is a consultant and speaker for Novartis and Bayer, and a consultant for Alcon. D. R. M. is a speaker for Bayer and Roche. S. S., R. S., K. F., S. A. Z., and F. B. declare no conflict of interest related to the topic.

Purpose: To evaluate the efficacy of a subthreshold micropulse laser (SML) in patients with central serous chorioretinopathy (CSCR)., Methods: Retrospective clinical study conducted at the Departments of Ophthalmology at a university and a municipal hospital in Zurich, Switzerland. We enrolled acute and chronic CSCR patients with persistent subretinal fluid (SRF) treated with SML. Two treatment protocols (fluorescein/indocyanine green angiography or optical coherence tomography guided) were evaluated for efficacy after 3 and 6 months. The primary outcomes of the study were reduction and percentage of eyes with complete resolution of SRF 3 and 6 months after SML treatment. Secondary endpoints included changes in central subfield thickness (CST) and visual acuity (VA) after 3 and 6 months., Results: The study involved 37 eyes (35 patients, 48.6% chronic). A statistically significant reduction in SRF height and CST could be shown, irrespective of SRF duration, type of CSCR, or chosen guidance after 3 and 6 months: SRF - 40 µm (p < 0.01), CST - 52 µm (p < 0.01). Percentage of eyes with complete resolution of fluid at 3 and 6 months after SML were 24.3 and 21.6%, respectively. No statistically significant functional improvement (VA) could be shown. Multivariable regression and linear mixed regression analyses did not identify statistically significant differences in SRF reduction, CMT change, or VA improvement with respect to the type of CSCR or the treatment plan used (p > 0.05)., Conclusion: The effectiveness of SML in CSCR is under continuous debate. Our study findings demonstrate structural but only little functional changes with SML. In view of the shortage of verteporfin for photodynamic therapy, SML remains an important therapeutic option for CSCR patients., Competing Interests: F. T.: Consultant for Bayer, Roche, Carl Zeiss Meditec; D. R. M.: Consultant for Bayer, Roche; G. M. S.: Consultant for Abbvie, Apellis, Bayer, Carl Zeiss Meditec, Novartis, Roche; S. Z.: Consultant/advisor for Bayer Healthcare Pharmaceuticals, Novartis Pharmaceuticals Corp., Roche, and Carl Zeiss Meditec AG; grant support from Novartis Pharmaceuticals Corp. and Bayer Healthcare Pharmaceuticals. All other authors declare that they have no conflicts of interest., (Thieme. All rights reserved.)

Supervised deep learning (DL) algorithms are highly dependent on training data for which human graders are assigned, for example, for optical coherence tomography (OCT) image annotation. Despite the tremendous success of DL, due to human judgment, these ground truth labels can be inaccurate and/or ambiguous and cause a human selection bias. We therefore investigated the impact of the size of the ground truth and variable numbers of graders on the predictive performance of the same DL architecture and repeated each experiment three times. The largest training dataset delivered a prediction performance close to that of human experts. All DL systems utilized were highly consistent. Nevertheless, the DL under-performers could not achieve any further autonomous improvement even after repeated training. Furthermore, a quantifiable linear relationship between ground truth ambiguity and the beneficial effect of having a larger amount of ground truth data was detected and marked as the more-ground-truth effect., (© 2023 Wiley-VCH GmbH.)

Aims of the Study: Vitamin A deficiency retinopathy is a potentially blinding disease. In developed countries, vitamin A deficiency due to malnutrition is rare. However, vitamin A deficiency can be caused by malabsorption resulting from bowel resection or medication. In this retrospective study, we present five cases of vitamin A deficiency retinopathy related to malabsorption secondary to medical interventions., Methods: Electronic charts over a ten-year period (2012-2022) were screened for vitamin A deficiency retinopathy. Only patients with vitamin A deficiency confirmed by laboratory tests were included. Symptoms, medical history, visual acuity, optical coherence tomography, fundus autofluorescence, electrophysiological examination, and vitamin A levels were reviewed., Results: Five eligible cases were identified. Median age was 44.7 years (range 22.2-88.9), median duration of ocular symptoms prior to diagnosis was 14 months, and median visual acuity was 1.0 (range 0.5-1.0, Snellen, decimal). Three patients had a history of bariatric surgery, one patient had a small bowel resection and was on octreotide treatment, and one patient suffered from cystic fibrosis and had a history of small bowel resection and severe hepatopathy. Optical coherence tomography showed various abnormalities, including a reduced interdigitation zone, subretinal drusenoid deposits, and a thinned outer nuclear layer. Electroretinogram findings ranged from abnormal oscillatory potentials to non-recordable rod responses., Conclusions: Vitamin A deficiency retinopathy can occur following medical interventions associated with malabsorption. In cases of night blindness, vitamin A levels should be measured.

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

Background: Solar and laser-associated retinopathies are rare occurrences. The two retinopathies are both photo-induced but differ in the involved intensity and duration of exposure. The purpose of this study was to evaluate the clinical features and natural course of these two entities, with a focus on the changes in the outer retina over time., Patients and Methods: This retrospective analysis assessed patients with solar or laser maculopathy seen at the Department of Ophthalmology of the University Hospital Zurich in Switzerland over the last 10 years. Visual acuity (VA; Snellen) and optical coherence tomography (OCT) findings were reviewed and analyzed at baseline and last follow-up visit. Areas of damaged outer retina, identified on en face OCT images as hyporeflective areas, were tagged and compared between visits. Descriptive analysis was performed by calculating mean values ± standard deviation (SD). Statistical evaluation was done using the Wilcoxon signed rank test. A p value < 0.05 was considered statistically significant., Results: Five patients with solar retinopathy and six patients with laser-associated retinopathy were identified. In the solar retinopathy group, mean VA at baseline was 0.80 (SD ± 0.37) and improved to 0.90 (SD ± 0.36). This was not statistically significant (p = 0.066). In the laser-associated retinopathy group, mean VA at baseline was 0.89 (SD ± 0.18) and improved to 1.03 (SD ± 0.09), which was not statistically significant either (p = 0.063). At baseline, in OCT cross-sections, initial changes were observed in the interdigitation, myoid, and ellipsoid zone, as well as the outer nuclear layer and the Henle fiber layer. At follow-up, most cases presented an alteration in the residual ellipsoid zone, with the degree of the aforementioned alterations depending on the size of the initial defect. A decrease of the hyporeflective alterations measured in en face OCT scans was observed in both groups but was only statistically significant in the laser-associated retinopathy group (p = 0.018 versus p = 0.172)., Conclusions: OCT can help to detect and monitor solar and laser-associated retinal injuries. Most injuries are minor, with good functional restitution. Minor changes in the ellipsoid zone often persist, even in cases with full visual recovery., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Background: Fabry disease (FD) is a potentially lethal lysosomal disorder with systemic vascular changes. Previous studies demonstrated retinal vascular involvement using optical coherence tomography angiography (OCTA) in affected patients; Aim: To analyze and quantify the retinal vasculature measuring vessel density (VD), vessel length density (VLD), and the ratio of VD to VLD (VD/VLD) in superficial capillary plexuses (SCP) and deep capillary plexuses (DCP) using OCTA in patients with FD and to show whether they differ from healthy controls (HC); Patients and methods: Single-center, retrospective, consecutive cohort study of patients with genetically proven FD. Patients underwent an ophthalmological examination including OCTA. VD, VLD, foveal avascular zone (FAZ), and the VD/VLD were compared to an HC group using a linear mixed model; Results: A statistically significant difference in the VLD and VD/VLD of DCP was observed between the two groups ( p < 0.001). Using ROC curves with AUC and Youden's Index, a cut-off value for differentiating both groups using VD/VLD in DCP FD with high specificity and high sensitivity was established; Conclusions: FD and HC groups seem to be separable using the VD/VLD ratio in DCP. This new biomarker might differentiate changes in the retinal microvasculature that are not detectable by VD or VLD alone.

Background: To describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD)., Methods: Retrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections., Results: For our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient's better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes)., Conclusions: The chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background / Aims . This study evaluates changes of flow and structure of diabetic retinal neovascularization (NV) treated with intravitreal antivascular endothelial growth factor (VEGF) agents using optical coherence tomography angiography (OCTA). With OCTA, retinal blood vessels are visualized at high resolution to separately look at flow and structure information without the need for dye injection. We introduce a new measurement method including and combining information of flow and structure. Methods . Retrospective observational case series. Patients with proliferative diabetic retinopathy (PDR) were treated with intravitreal antiVEGF injections. Retinal NV were repeatedly imaged using swept-source OCTA (Zeiss PlexElite 9000) at baseline, after initial treatment block with 3-4 monthly injections, and during a follow-up period of up to 51 weeks. Change of size and flow density of the structural and angio area of NV was assessed. Results . Nine NV in eight eyes of five patients were analyzed with a median follow-up time of 45 weeks. After the initial treatment block, en face structural area regressed, 18.7% ± 39.0% (95% CI 44.2-6.8%, p =0.26), and en face angio area regressed, 51.9% ± 29.5% (95% CI 32.6 to 71.2%, p =0.007). Flow density within the en face structural area decreased by 33% ± 19.2% (95% CI 20.5-45.5%, p =0.0077). Flow density within the en face angio area decreased by mean 17.9% ± 25.2% (95% CI 1.4-34.4%, p =0.066). In two fellow eyes, NV recurrence could be observed before the onset of vitreous bleeding in one. Conclusion . Our study introduces a new quantitative measurement for NV in PDR, combining structure and flow measurement. The structure area remained after treatment, while its flow density and angio area regressed. We propose this measurement method as a more physiological and possibly more comparable metrics., Competing Interests: Sandrine A. Zweifel is a consultant for Bayer HealthCare, Novartis and Roche. She receives research support from Bayer HealthCare and Novartis. Daniel Barthelmes is a consultant for Bayer HealthCare, Novartis, and Alcon. He receives lecture fees and grant support from Bayer HealthCare and Novartis. Katrin Fasler has been an external consultant for DeepMind., (Copyright © 2021 Christof Haensli et al.)

Purpose: To (i) describe a series of patients with isolated or syndromic nanophthalmos with the underlying genetic causes, including novel pathogenic variants and their functional characterization and (ii) to study the association of retinal dystrophy in patients with MFRP variants, based on a detailed literature review of genotype-phenotype correlations., Methods: Patients with nanophthalmos and available family members received a comprehensive ophthalmological examination. Genetic analysis was based on whole-exome sequencing and variant calling in core genes including MFRP, BEST1, TMEM98, PRSS56, CRB1, GJA1, C1QTNF5, MYRF and FAM111A. A minigene assay was performed for functional characterization of a splice site variant., Results: Seven patients, aged between three and 65 years, from five unrelated families were included. Novel pathogenic variants in MFRP (c.497C>T, c.899-3C>A, c.1180G>A), and PRSS56 (c.1202C>A), and a recurrent de novo variant in FAM111A (c.1706G>A) in a patient with Kenny-Caffey syndrome type 2, were identified. In addition, we report co-inheritance of MFRP-related nanophthalmos and ADAR-related Aicardi-Goutières syndrome., Conclusion: Nanophthalmos is a genetically heterogeneous condition, and the severity of ocular manifestations appears not to correlate with variants in a specific gene. However, retinal dystrophy is only observed in patients harbouring pathogenic MFRP variants. Furthermore, heterozygous carriers of MFRP and PRSS56 should be screened for the presence of high hyperopia. Identifying nanophthalmos as an isolated condition or as part of a syndrome has implications for counselling and can accelerate the interdisciplinary care of patients., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate efficacy of eplerenone therapy vs. observation on resolution of subretinal fluid (SRF) in patients with acute and chronic central serous chorioretinopathy (CSCR) in routine clinical practice. Methods: Retrospective comparative case series of eyes diagnosed with CSCR treated with eplerenone or observation. Primary outcome measure was maximum height of SRF at 12 months. Secondary outcome was percentage of eyes with complete resolution of SRF, percentage of eyes with reduction of SRF ≥50%, and best corrected visual acuity (VA) at 12 months. Separate analysis was conducted for eyes with acute and chronic CSCR. Results: Sixty-eight eyes of 60 patients (82% male) were included. Eleven of the 38 eyes with acute CSCR, and seven of the 30 eyes with chronic CSCR, received eplerenone. Subretinal fluid decreased from baseline to 12 months in acute (287 ± 221 to 31 ± 63 µm) and chronic (148 ± 134 to 40 ± 42 µm) CSCR. Kaplan-Meier curves were similar for treated and observed eyes and COX regression analysis did not show a significant difference in SRF resolution in treated vs. observed eyes (p = 0.6 for acute, p = 0.2 for chronic CSCR). Conclusion: This routine clinical practice outcome study did not show evidence of efficacy of eplerenone on resolution of SRF in acute nor chronic CSCR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fasler, Gunzinger, Barthelmes and Zweifel.)

Background: To date, there are no studies associating the dried blood spot (DBS) levels of globotrioasylsphingosine (lysoGb3) with quantitative optical coherence tomography angiography (OCTA) parameters in Fabry disease (FD) patients. Here, we aimed to investigate the association between OCTA vessel density (VD), vessel length density (VLD) with DBS lysoGb3., Methods: A retrospective, single center analysis of all consecutive FD patients enrolled at the Department of Ophthalmology of the University Hospital of Zurich from 1 December 2017 to 9 September 2020. An association between VD and VLD detected by OCTA and lysoGb3 was investigated using a linear mixed model., Results: A total of 57 FD patients (23 male, 34 female; 109 eyes) were included. Forty-one patients suffered from the classic phenotype and 16 from the later-onset phenotype. LysoGb3 inversely correlated with VD and VLD in both the superficial (VD: p = 0.034; VLD: p = 0.02) and deep capillary plexus (VD: p = 0.017; VLD: p = 0.018) in the overall FD cohort., Conclusions: Our study shows an association between lysoGb3 and OCTA VD and VLD. This supports the hypothesis that quantitative OCTA parameters might be useful as diagnostic biomarkers for evaluating systemic involvement in FD, and possibly other diseases.

Background: Diabetes prevalence is constantly rising, involving the eyes with damage including development of diabetic macular oedema. Since 2012, intravitreal anti-vascular endothelial growth factor medication is available for diabetic macular oedema treatment. Endocrinological studies have shown that fewer women are affected by diabetes. However, when affected, they exhibit more severe diabetic complications than men. We have investigated gender-related differences in diabetic macular oedema and outcome in an ophthalmological tertiary referral hospital., Methods: We included 88 patients (54 males and 34 females) with 112 eyes (68 male and 44 female) having clinically significant diabetic macular oedema, treated with anti-vascular endothelial growth factor medication. A 1 year follow-up was performed in all patients (visual acuity and optical coherence tomography). Previous retinal surgery was an exclusion criterion, as were other retinal pathologies., Results: The mean visual acuity and mean central retinal thickness at baseline were 0.53 logMAR (male 0.49 and female 0.595) and 469 μm (male 452 μm and female: 494 μm), respectively. After 360 days, mean visual acuity changed by -0.07 (±0.36) logMAR (male -0.11 and female +0.01) and mean central retinal thickness changed by -119 μm (male -113 μm and female -127 μm). For visual acuity, a significant difference was noted at baseline ( p  = 0.02) and at 1 year ( p   <  0.001). Males received 5.6 injections and females received 5.68 injections in 1 year., Conclusion: Our study showed that female patients with diabetic macular oedema were diagnosed with and treated for diabetic macular oedema at a stage when visual acuity and optical coherence tomography were worse than those in their male counterparts. This gender difference could not be reduced, despite similar numbers of injections. Female diabetic patients should therefore be assessed early for ophthalmological pathologies.

Progression to exudative 'wet' age-related macular degeneration (exAMD) is a major cause of visual deterioration. In patients diagnosed with exAMD in one eye, we introduce an artificial intelligence (AI) system to predict progression to exAMD in the second eye. By combining models based on three-dimensional (3D) optical coherence tomography images and corresponding automatic tissue maps, our system predicts conversion to exAMD within a clinically actionable 6-month time window, achieving a per-volumetric-scan sensitivity of 80% at 55% specificity, and 34% sensitivity at 90% specificity. This level of performance corresponds to true positives in 78% and 41% of individual eyes, and false positives in 56% and 17% of individual eyes at the high sensitivity and high specificity points, respectively. Moreover, we show that automatic tissue segmentation can identify anatomical changes before conversion and high-risk subgroups. This AI system overcomes substantial interobserver variability in expert predictions, performing better than five out of six experts, and demonstrates the potential of using AI to predict disease progression.

Background/aims: Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on 'fellow eyes' have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) antivascular endothelial growth factor treatment and timelines for fellow eye involvement., Methods: Retrospective, electronic medical record database study of the Moorfields AMD database of 6265 patients/120 286 single entries with data extracted between 21 October 2008 and 9 August 2018. The data set for analysis consisted of 1180 sequential, 807 non-sequential and 3410 unilateral eyes., Results: Mean VA (ETDRS letters±SD) of sequentially treated fellow eyes at baseline was significantly higher (63±13), VA gain over 2 years lower (0.37±14) and proportion of eyes with good VA (≥70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at 2 years 5.6±15, percentage of eyes with good VA 39%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at 2 years, and median time interval to fellow eye involvement was 71 (IQR: 27-147) weeks., Conclusion: This report shows that sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years., Competing Interests: Competing interests: KF has received fellowship support from Alfred Vogt Stipendium and Schweizerischer Fonds zur Verhütung und Bekämpfung der Blindheit. She has been an external consultant for DeepMind. SW is an academic clinical fellow funded by the National Institute of Health Research (NIHR). PAK has received speaker fees from Heidelberg Engineering, Topcon, Carl Zeiss Meditec, Haag-Streit, Allergan, Novartis and Bayer. He has served on advisory boards for Novartis and Bayer and has been an external consultant for DeepMind and Optos. PAK is supported by a UK NIHR Clinician Scientist Award (NIHR-CS-2014-12-023). RC received studentship support from the College of Optometrists and is a paid intern at DeepMind. PJP has received speaker fees from Novartis UK, Bayer UK and Roche UK and has received an advisory board honorarium from Novartis UK and Bayer UK. AYL has received research funding from Novartis, NVIDIA and Microsoft Corporation. He is supported by the National Institutes of Health (K23EY029246) and Research to Prevent Blindness., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of the study was to analyze imaging findings in spectral domain en face optical coherence tomography (SD OCT) in patients with laser-induced and solar maculopathies focusing on the possible regeneration of the ellipsoid zone. In a retrospective case series of 3 patients (4 eyes) with solar maculopathy and 2 patients (3 eyes) with laser-induced maculopathy who underwent a comprehensive ocular examination, ellipsoid zone (EZ) was segmented from SD OCT data. Evaluation of EZ in en face OCT revealed a hyporeflective lesion surrounded by a hyperreflective border. The area of EZ alteration was measured manually in en face OCT. All patients showed partial EZ regeneration. Mean EZ alteration decreased from 0.12 mm 2 (range: 0.05-0.32) at baseline to 0.07 mm 2 (range: 0.01-0.22) at last follow-up ( p = 0.018, mean follow-up: 372 days; range: 115-592). Mean best visual acuity (BVA) improved from 20/36 at baseline to 20/30 ( p = 0.018). In conclusion, en face OCT imaging clearly delineated the area of EZ alteration in patients with laser-induced and solar maculopathies. Follow-up showed significant reformation of the EZ as well as improvement of BVA., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Jeanne M. Gunzinger et al.)

Purpose: To benchmark the human and machine performance of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) image segmentation, i.e., pixel-wise classification, for the compartments vitreous, retina, choroid, sclera., Methods: A convolutional neural network (CNN) was trained on OCT B-scan images annotated by a senior ground truth expert retina specialist to segment the posterior eye compartments. Independent benchmark data sets (30 SDOCT and 30 SSOCT) were manually segmented by three classes of graders with varying levels of ophthalmic proficiencies. Nine graders contributed to benchmark an additional 60 images in three consecutive runs. Inter-human and intra-human class agreement was measured and compared to the CNN results., Results: The CNN training data consisted of a total of 6210 manually segmented images derived from 2070 B-scans (1046 SDOCT and 1024 SSOCT; 630 C-Scans). The CNN segmentation revealed a high agreement with all grader groups. For all compartments and groups, the mean Intersection over Union (IOU) score of CNN compartmentalization versus group graders' compartmentalization was higher than the mean score for intra-grader group comparison., Conclusion: The proposed deep learning segmentation algorithm (CNN) for automated eye compartment segmentation in OCT B-scans (SDOCT and SSOCT) is on par with manual segmentations by human graders., Competing Interests: Authors BH, PK, SS are salaried employees of Supercomputing Systems, Zurich; this does not alter our adherence to PLOS ONE policies on sharing data and materials. Outside of the present study, the authors declare the following competing interests: PMM is a consultant at Zeiss Forum, Roche and holds intellectual properties for machine learning at MIMO AG, Berne, Switzerland. AYL has received funding from Novartis, Microsoft Corporation, NVIDIA Corporation and grant number from NEI: K23EY029246. CE and AT received a financial grant from the National Institute for Health Research (NIHR) Biomedical Research Centre, based at Moorfields Eye Hospital, and also from the NHS Foundation Trust and the UCL Institute of Ophthalmology. The views expressed in this article are those of the authors and not necessarily those of the National Eye Institute, NHS, the NIHR, or the Department of Health. AT is a consultant for Heidelberg Engineering and Optovue and has received research grant funding from Novartis and Bayer. CE is a consultant for Heidelberg Engineering and has received research grant funding from Novartis. MO has received travel and honorarium from Allergan. KF has received fellowship support from Alfred Vogt Stipendium and Schweizerischer Fonds zur Verhütung und Bekämpfung der Blindheit and has been an external consultant for DeepMind. JZ-V declares the following (where C: Consultant, S: Speaker; TG: Travel Grant, G: Research Grant, IP: Intellectual Properties): Alcon (C,S, TG, Alimera Sciences (C, S, TG), Allergan (C, S, TG, G), Bausch & Lomb (S, TG), Bayer (C,S, TG), Brill Pharma (C, S9, Novartis (S, TG), Topcon (S, TG, Zeiss (S). These do not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: To analyse treatment outcomes and share clinical data from a large, single-centre, well-curated database (8174 eyes/6664 patients with 120 756 single entries) of patients with neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (VEGF). By making our depersonalised raw data openly available, we aim to stimulate further research in AMD, as well as set a precedent for future work in this area., Setting: Retrospective, comparative, non-randomised electronic medical record (EMR) database cohort study of the UK Moorfields AMD database with data extracted between 2008 and 2018., Participants: Including one eye per patient, 3357 eyes/patients (61% female). Extraction criteria were ≥1 ranibizumab or aflibercept injection, entry of 'AMD' in the diagnosis field of the EMR and a minimum of 1 year of follow-up. Exclusion criteria were unknown date of first injection and treatment outside of routine clinical care at Moorfields before the first recorded injection in the database., Main Outcome Measures: Primary outcome measure was change in VA at 1 and 2 years from baseline as measured in Early Treatment Diabetic Retinopathy Study letters. Secondary outcomes were the number of injections and predictive factors for VA gain., Results: Mean VA gain at 1 year and 2 years were +5.5 (95% CI 5.0 to 6.0) and +4.9 (95% CI 4.2 to 5.6) letters, respectively. Fifty-four per cent of eyes gained ≥5 letters at 2 years, 63% had stable VA (±≤14 letters), 44% of eyes maintained good VA (≥70 letters). Patients received a mean of 7.7 (95% CI 7.6 to 7.8) injections during year 1 and 13.0 (95% CI 12.8 to 13.2) injections over 2 years. Younger age, lower baseline VA and more injections were associated with higher VA gain at 2 years., Conclusion: This study benchmarks high quality EMR study results of real life AMD treatment and promotes open science in clinical AMD research by making the underlying data publicly available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The increasing incidence of medical retinal diseases has created capacity issues across UK. In this study, we describe the implementation and outcomes of virtual medical retina clinics (VMRCs) at Moorfields Eye Hospital, South Division, London. It represents a promising solution to ensure that patients are seen and treated in a timely fashion METHODS: First attendances in the VMRC (September 2016-May 2017) were included. It was open to non-urgent external referrals and to existing patients in a face-to-face clinic (F2FC). All patients received visual acuity testing, dilated fundus photography and optical coherence tomography scans. Grading was performed by consultants, fellows and allied healthcare professionals. Outcomes of these virtual consultations and reasons for F2FC referrals were assessed., Results: A total number of 1729 patients were included (1543 were internal and 186 external referrals). The majority were diagnosed with diabetic retinopathy (75.1% of internal and 46.8% of external referrals). Of the internal referrals, 14.6% were discharged, 54.5% continued in VMRC and 30.9% were brought to a F2FC. Of the external referrals, 45.5% were discharged, 37.1% continued in VMRC and 17.4% were brought to a F2FC. The main reason for F2FC referrals was image quality (34.7%), followed by detection of potentially treatable disease (20.2%)., Conclusion: VMRC can be implemented successfully using existing resources within a hospital eye service. It may also serve as a first-line rapid-access clinic for low-risk referrals. This would enable medical retinal services to cope with increasing demand and efficiently allocate resources to those who require treatment., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Amiodarone-associated optic neuropathy (AAON) is a controversial diagnosis with possible impact on vital cardiac therapy decisions. This retrospective case series aims for application of distinguishing features of AAON versus non-arteritic ischaemic optic neuropathy (NAION): Bilaterality, mode of onset, degree of optic nerve dysfunction, structure of uninvolved disc (unilateral cases), and systemic toxic effects. Applying these criteria to patients with disc swelling under amiodarone, the authors identified four unilateral disc swellings, one with NAION-typical features only and three with one or more NAION-atypical features. All three sequential and six bilateral cases showed one or more NAION-atypical features. The 12 cases highlight the persisting diagnostic dilemma arising from diversity of presentation, lack of plausible pathomechanism, and controversial existence of the entity itself.

Background: Cardiopulmonary resuscitation (CPR) causes significant stress for the rescuers which may cause deficiencies in attention and increase distractibility. This may lead to misjudgements of priorities and delays in CPR performance, which may further increase mental stress (vicious cycle). This study assessed the impact of a task-focusing strategy on perceived stress levels and performance during a simulated CPR scenario., Methods: This prospective, randomized-controlled trial was conducted at the simulator-center of the University Hospital Basel, Switzerland. A total of 124 volunteer medical students were randomized to receive a 10 minute instruction to cope with stress by loudly posing two task-focusing questions ("what is the patient's condition?", "what immediate action is needed?") when feeling overwhelmed by stress (intervention group) or a control group. The primary outcome was the perceived levels of stress and feeling overwhelmed (stress/overload); secondary outcomes were hands-on time, time to start CPR and number of leadership statements., Results: Participants in the intervention group reported significantly less stress/overload levels compared to the control group (mean difference: -0.6 (95% CI -1.3, -0.1), p=0.04). Higher stress/overload was associated with less hands-on time. Leadership statements did not differ between groups, but the number of leadership statements did relate to performance. Hands-on time was longer in the intervention- group, but the difference was not statistically significant (difference 5.5 (95% CI -3.1, 14.2), p=0.2); there were no differences in time to start CPR (difference -1.4 (95% CI -8.4, 5.7), p=0.71)., Conclusions: A brief stress-coping strategy moderately decreased perceived stress without significantly affecting performance in a simulated CPR. Further studies should investigate more intense interventions for reducing stress., Trial Registration: NCT01645566.

National Quality Forum safe-practice guidelines encourage hospitals to integrate disclosure, patient safety and risk management activities. Combining collaborative law with a patient safety program in a parallel process makes it possible to achieve this integration. This combination provides for physician-led guidance in determining whether disclosure is required - and, if so, provides mentor assistance with actual disclosure. It offers proactive error prevention by offering a means to quickly utilize information to make safety changes. Additionally, the combination provides an opportunity to access collaborative law at a time when it is still possible to resolve issues without resort to litigation.