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Retinal vascular diseases represent a broad field of ocular pathologies. Retinal imaging is an important tool for diagnosis, prognosis and follow up of retinal vascular diseases. It includes a wide variety of imaging techniques ranging from colour fundus photography and optical coherence tomography to dynamic diagnostic options such as fluorescein angiography, and optical coherence tomography angiography. The newest developments in respective imaging techniques include widefield imaging to assess the retinal periphery, which is of especial interest in retinal vascular diseases. Automatic image analysis and artificial intelligence may support the image analysis and may prove valuable for prognostic purposes. This review provides a broad overview of the imaging techniques that have been used in the past, today and maybe in the future to stage and monitor retinal vascular disease with focus on the main disease entities including diabetic retinopathy, retinal vein occlusion, and retinal artery occlusion.

Purpose To develop a consensus nomenclature for OCT angiography (OCTA) findings in retinal vascular diseases. Design Online survey using the Delphi Method. Participants Members of The Retina Society, the European Society of Retina Specialists, and the Japanese Retina and Vitreous Society. Methods An online questionnaire on OCTA terminology in retinal vascular diseases was sent to members of The Retina Society, the European Society of Retina Specialists, and the Japanese Retina and Vitreous Society. The respondents were divided into 2 groups (“experts” vs. “users”) according to the number of their publications in this field. The respondents who had more than 5 publications in the field of OCTA and retinal vascular diseases were considered the OCTA “experts” group. Main Outcome Measures Consensus and near consensus on OCTA nomenclature. Results The complete responses of 85 retina specialists were included in the analysis. Thirty-one were categorized as “experts.” There was a consensus in both groups that OCTA parameters such as foveal avascular zone (FAZ) parameters, areas of nonperfusion, and presence of neovascularization (NV) should be implemented in the identification and staging of diabetic retinopathy (DR) and that OCTA can be applied to differentiate between ischemic and nonischemic retinal vein occlusion (RVO). Diabetic macular ischemia (DMI) also can be assessed via OCTA. Further, there was consensus that the terminology should differ on the basis of the underlying causes of decreased vascular flow signal. There was disagreement in other areas, such as which terms should be applied to describe decreased OCTA signal from different causes, the definition of wide-field OCTA, and how to quantify DMI and area of decreased flow signal. These discrepancies form the basis for the upcoming expert Delphi rounds that aim to develop a standardized OCTA nomenclature. Conclusions Although there was agreement in some areas, significant differences were found in many areas of OCTA terminology among all respondents, but also between the expert and user groups. This indicates the need for standardization of the nomenclature among all specialists in the field of retinal vascular diseases.

We review the current literature on the use of wide-field optical coherence tomography (OCT) and wide-field optical coherence tomography angiography (OCTA) in different uveitic phenotypes as well as various sequelae of uveitis and discuss the limitations of this evolving technology.Current consensus guidelines on nomenclature in wide-field OCT and OCTA are described. The specific utility of wide-field OCT and OCTA in assessment of the retina and choroid using different en-face and cross-sectional slabs in various inflammatory diseases is reviewed. Furthermore, we discuss widefield OCT and OCTA in assessment of retinal ischemia and its limitations in assessing retinal vascular leakage.Wide-field OCT and OCTA deliver more sensitive measures of inflammation. With continued advancement in both hardware technology and software processing, these modalities will allow for more accurate assessment of uveitis, better understanding of disease mechanisms, and precise monitoring of treatment response.

The choroid is directly adjacent to the retina and consists of a dense vascular network that supplies the outer retina. Pathologies in the choroid can lead to changes in the retinal pigment epithelium (RPE) and photoreceptors. Thus, the choroid plays a crucial role in the development of retinal diseases such as age-related macular degeneration (AMD), central serous chorioretinopathy (CSCR), pathologic myopia, and inflammatory diseases such as Vogt-Koyanagi-Harada syndrome (VKH). Basic knowledge of the structure and physiology of the choroid, as well as diagnostic options for visualizing choroidal changes, provides a better understanding of the physiology and pathology of choroidal processes. This review provides an overview of the anatomy and function of the choroid, and describes the diagnostic techniques currently available to characterize and visualize the choroid. It also includes an overview of various retinal conditions, which are associated with choroidal changes.Die Aderhaut oder Choroidea liegt direkt außerhalb der Netzhaut an und besteht aus einem dichten Gefäßnetz, das die äußere Netzhaut versorgt. Pathologien im Bereich der Aderhaut können zu Veränderungen des retinalen Pigmentepithels (RPE) und der äußeren Netzhautschichten führen. Die Aderhaut spielt somit eine entscheidende Rolle bei der Entstehung von Netzhauterkrankungen wie der altersabhängigen Makuladegeneration (AMD), der Chorioretinopathia centralis serosa (CRCS, CSCR, RCS), der pathologischen Myopie und bei inflammatorischen Erkrankungen wie dem Vogt-Koyanagi-Harada-Syndrom (VKH). Die grundlegende Kenntnis des Aufbaus und der Physiologie der Aderhaut sowie der diagnostischen Optionen zur Darstellung von choroidalen Veränderungen ermöglicht ein besseres Verständnis der Physiologie und Pathologie choroidaler Prozesse. Diese Arbeit bietet einen Überblick der Anatomie und Funktion der Choroidea und beschreibt die aktuell verfügbaren diagnostischen Verfahren zur Charakterisierung und Darstellung der Aderhaut. Anschließend werden verschiedene Krankheitsbilder, die mit choroidalen Veränderungen assoziiert sind, beleuchtet.

To assess the potential of machine learning to predict low and high treatment demand in real life in patients with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), and diabetic macular edema (DME) treated according to a treat-and-extend regimen (TER).Retrospective cohort study.Three hundred seventy-seven eyes (340 patients) with nAMD and 333 eyes (285 patients) with RVO or DME treated with anti-vascular endothelial growth factor agents (VEGF) according to a predefined TER from 2014 through 2018.Eyes were grouped by disease into low, moderate, and high treatment demands, defined by the average treatment interval (low, ≥10 weeks; high, ≤5 weeks; moderate, remaining eyes). Two random forest models were trained to predict the probability of the long-term treatment demand of a new patient. Both models use morphological features automatically extracted from the OCT volumes at baseline and after 2 consecutive visits, as well as patient demographic information. Evaluation of the models included a 10-fold cross-validation ensuring that no patient was present in both the training set (nAMD, approximately 339; RVO and DME, approximately 300) and test set (nAMD, approximately 38; RVO and DME, approximately 33).Mean area under the receiver operating characteristic curve (AUC) of both models; contribution to the prediction and statistical significance of the input features.Based on the first 3 visits, it was possible to predict low and high treatment demand in nAMD eyes and in RVO and DME eyes with similar accuracy. The distribution of low, high, and moderate demanders was 127, 42, and 208, respectively, for nAMD and 61, 50, and 222, respectively, for RVO and DME. The nAMD-trained models yielded mean AUCs of 0.79 and 0.79 over the 10-fold crossovers for low and high demand, respectively. Models for RVO and DME showed similar results, with a mean AUC of 0.76 and 0.78 for low and high demand, respectively. Even more importantly, this study revealed that it is possible to predict low demand reasonably well at the first visit, before the first injection.Machine learning classifiers can predict treatment demand and may assist in establishing patient-specific treatment plans in the near future.

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). 1 , 2 , 3 , 4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment. 1 , 2 , 3 , 4 , 5 , 6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms “optical coherence tomography angiography” or “OCT angiography” or “OCT-A”, AND “neovascular macular degeneration” or “neovascular age-related macular degeneration” or “neovascular AMD” or “nAMD” or “wet age-related macular degeneration” or “wet AMD” or “wet ARMD”. A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

PURPOSE To compare the differences between clinical, demographic, and multimodal imaging features of choroidal granulomas associated with tuberculosis and sarcoidosis. DESIGN Retrospective comparative case series. METHODS Clinical features and fundus imaging including fluorescein and indocyanine green angiography, and optical coherence tomography of patients with tuberculomas and sarcoid choroidal granulomas seen at three tertiary care centers were reviewed. The differences between clinical appearance including morphology of the lesions (size, shape, extent), vascularity, and multimodal imaging features were compared. Repeated measures logistic regression with a multi-level random effects model was used to assess characteristics of individual granulomas that could predict the underlying etiology. RESULTS The study included 47 eyes of 38 patients (22 with tuberculomas and 16 with sarcoid granulomas; total of 138 granulomas). Patients with tuberculoma were significantly younger (33.8±10.1 versus 48.6±14.3 years; p=0.002), but no gender differences were observed. In comparison with sarcoid granulomas, tuberculomas were solitary (p

Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Topic The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). Clinical Relevance The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Methods Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Results Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. Discussion The COTS consensus guidelines were generated based on the evidence from published literature, specialists’ opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME).This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of3 years duration, ETDRS central subfield thickness ≥ 310 μm by SD-OCT, and ETDRS letter score ≤ 73 and ≥ 24 in the study eye were randomized 2:1 to OCS-01 or matching vehicle, 1 drop 3 times/day for 12 weeks. Efficacy was evaluated as change from baseline to Week 12 of ETDRS letter score and central macular thickness (CMT). The primary analysis used a linear model with baseline ETDRS letters as a covariate, and missing data imputed using multiple imputation pattern mixture model techniques. Active treatment was considered superior to vehicle if the one-sided p-value was0.15 and the difference in mean change from baseline in ETDRS letters was0.Mean CMT showed a greater decrease from baseline with OCS-01 (N = 99) than vehicle (N = 45) at Week 12 (-53.6 vs -16.8 μm, p = 0.0115), with significant differences favouring OCS-01 from Weeks 2 to 12. OCS-01 was well-tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS-01 and 1 letter with vehicle (p = 0.125). In a post-hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS-01 group improved 3.8 letters compared with 0.9 letters with vehicle.Topical OCS-01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Junta de Andalucia Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in humans. Genetic and genomic analyses have recently demonstrated that the homeobox transcription factor Pitx2 plays a fundamental role regulating expression of distinct growth factors, microRNAs and ion channels leading to morphological and molecular alterations that promote the onset of AF. Here we address the plausible contribution of long non-coding (lnc)RNAs within the Pitx2>Wnt>miRNA signaling pathway. In silico analyses of annotated lncRNAs in the vicinity of the Pitx2, Wnt8 and Wnt11 chromosomal loci identified five novel lncRNAs with differential expression during cardiac development. Importantly, three of them, Walaa, Walras and Wallrd, are evolutionarily conserved in humans and displayed preferential atrial expression during embryogenesis. In addition, Walrad displayed moderate expression during embryogenesis but was more abundant in the right atrium. Walaa, Walras and Wallrd were distinctly regulated by Pitx2, Wnt8, and Wnt11, and Wallrd was severely elevated in conditional atrium-specific Pitx2-deficient mice. Furthermore, pro-arrhythmogenic and pro-hypertrophic substrate administration to primary cardiomyocyte cell cultures consistently modulate expression of these lncRNAs, supporting distinct modulatory roles of the AF cardiovascular risk factors in the regulation of these lncRNAs. Walras affinity pulldown assays revealed its association with distinct cytoplasmic and nuclear proteins previously involved in cardiac pathophysiology, while loss-of-function assays further support a pivotal role of this lncRNA in cytoskeletal organization. We propose that lncRNAs Walaa, Walras and Wallrd, distinctly regulated by Pitx2>Wnt>miRNA signaling and pro-arrhythmogenic and pro-hypertrophic factors, are implicated in atrial arrhythmogenesis, and Walras additionally in cardiomyocyte cytoarchitecture.

This work aims to summarize predictive biomarkers to guide treatment choice in DME. Intravitreal anti-VEGF is considered the gold standard treatment for centers involving DME, while intravitreal steroid treatment has been established as a second-line treatment in DME. However, more than 1/3 of the patients do not adequately respond to anti-VEGF treatment despite up to 4-weekly injections. Not surprisingly, insufficient response to anti-VEGF therapy has been linked to low-normal VEGF levels in the serum and aqueous humor. These patients may well benefit from an early switch to intravitreal steroid treatment. In these patients, morphological biomarkers visible in OCT may predict treatment response and guide treatment decisions. Namely, the presence of a large amount of retinal and choroidal hyperreflective foci, disruption of the outer retinal layers and other signs of chronicity such as intraretinal cysts extending into the outer retina and a lower choroidal vascular index are all signs suggestive of a favorable treatment response of steroids compared to anti-VEGF. This paper summarizes predictive biomarkers in DME in order to assist individual treatment decisions in DME. These markers will help to identify DME patients who may benefit from primary dexamethasone treatment or an early switch

Purpose To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro-re-nata (PRN) regimen over 4-years in a real-life setting. Design 4-year, multicenter, retrospective comparative study PARTICIPANTS: 264 patients with treatment-naive nAMD. Methods Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n=163) or PRN (n=101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4-years and had annual fundus autofluorescence (FAF) and optical coherence tomography (OCT) imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. Main outcomes measures MA incidence and progression over 4-years, association between treatment strategy, and number of injections. Results At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (p=0.32). At year-4, 27% (34/124) and 25% (20/81) eyes without baseline MA had detectable MA, in the T&E and PRN groups respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4±0.2 and 0.4±0.1mm/year in the T&E and PRN groups, respectively (p=0. 23). Multivariate analysis for baseline predictors of MA growth demonstrated older age, poorer baseline VA and presence of RAP, had a higher risk of greater MA progression (P=0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of developing new MA during the four years of follow-up or the progression of pre-existing MA at year-4 (p=0.692). Conclusion Over four years, neither incidence nor progression of macular atrophy in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and had better visual outcomes compared to those treated with a PRN approach.

Photobiomodulation treatment in a randomized, sham-controlled, single-center, double-masked study conducted in 46 eyes of patients with dry age-related macular degeneration significantly improved functional (visual acuity and contrast sensitivity) and anatomical (drusen volume and central drusen thickness) outcomes. Patient improvements were reported in the VFQ-25 assessing activities of daily living., Purpose: The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. Methods: Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3–4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. Results: Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported. Conclusion: Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.

In this work we evaluated a postprocessing, customized automatic retinal OCT B-scan enhancement software for noise reduction, contrast enhancement and improved depth quality applicable to Heidelberg Engineering Spectralis OCT devices. A trained deep neural network was used to process images from an OCT dataset with ground truth biomarker gradings. Performance was assessed by the evaluation of two expert graders who evaluated image quality for B-scan with a clear preference for enhanced over original images. Objective measures such as SNR and noise estimation showed a significant improvement in quality. Presence grading of seven biomarkers IRF, SRF, ERM, Drusen, RPD, GA and iRORA resulted in similar intergrader agreement. Intergrader agreement was also compared with improvement in IRF and RPD, and disagreement in high variance biomarkers such as GA and iRORA.

Introduction: The inflammatory milieu after acute retinal necrosis (ARN) may lead to a breakdown of the inner and outer blood-retinal barrier and consequently to a cystoid macular edema (CME) with accumulation of intra- and subretinal fluid. Up to now, there is no established therapeutic approach for CME in ARN patients.Case report: We report a case of an immunocompetent 14-year-old female with chronic ARN-related CME, which was unresponsive to valacyclovir, prednisone and intravitreal ranibizumab injections. A combination treatment of tocilizumab, an interleukin-6 receptor inhibitor, and intravitreal aflibercept was successful to control the CME.Conclusion: In selected patients with treatment-refractory CME following ARN a therapy with tocilizumab and intravitreal aflibercept might be considered.

PURPOSE Multiple evanescent white dot syndrome (MEWDS) is a self-limiting inflammatory condition of the outer retina.Only little information is available how patients experience their symptoms. METHOD We report a case of a 28-year-old male graphic designer with MEWDS, who precisely illustrated the development and course of the characteristic symptoms while looking at the ceiling, at a face and on his phone. RESULT At onset, the scotoma was sparking/ shiny and appeared on the temporal field of view, consistent with an enlarged blind spot. Over the course of the disease, the scotoma decreased in intensity and moved superiorly and nasally until it completely faded. CONCLUSION Illustrations from a patient's perspective over the course of the disease can be beneficial for physicians and other MEWDS patients for a better understanding and monitoring of their disease.

PurposeTo evaluate choriocapillaris (CC) and choroidal vascular changes in patients with posterior uveitis using swept-source (SS) wide-field optical coherence tomography angiography (OCTA).MethodConsecutive patients with posterior uveitis were evaluated using 3×3 mm and 12×12 mm OCTA scan patterns and montage images of 5×12×12 mm or 2×15×9 mm, covering approximately 70°–90° of the retina. The images were quantitatively and qualitatively analysed and compared with healthy controls.ResultsEighty-six eyes of 56 patients with posterior uveitis (mean age 45.2±19.9 years; 58.9% female), and 38 eyes of 19 age-matched healthy controls (57.9% female) were included. The mean perfusion density (PD) in 3×3 mm and 12×12 mm CC scans was significantly lower in eyes with posterior uveitis compared with those of healthy controls. However, no significant difference in the mean PD of choroidal scans was found comparing eyes with posterior uveitis and healthy controls. The mean PD in eyes with active disease was significantly higher compared with the inactive eyes on 12×12 mm choroidal scans (55.61% vs 51.25%, p=0.02), while no difference was found in the CC slabs.ConclusionCC and choroidal assessment using OCTA provides useful information in patients with posterior uveitis. SS-OCTA metrics of the CC and choroidal slabs are promising tools in uveitis patients in the future.Trial registration numberNCT02811536.

Fifty-five degree wide-field spectral domain optical coherence tomography provides an alternative to standard 30° optical coherence tomography lens with comparable thickness values with a greater field of view., Purpose: To assess whether retinal thickness measurements with a standard 30° spectral domain optical coherence tomography (SD-OCT) are comparable with wide-field 55° SD-OCT. Methods: Thirty-three healthy individuals were scanned using 55° as well as 30° SD-OCT according to a standardized protocol. Automated retinal layer segmentation of standard and wide-field SD-OCTs was assessed using customized software. Results: Both lenses showed a high correlation when analyzing total retinal thickness within the central, the inner, and the outer retinal ring (r = > 0.9). Automated thickness measurements with the 55° system were marginally higher compared with the 30° lens. The thickness of each separate retinal layer using automated segmentation showed excellent correlations within the inner and outer rings (range: r = 0.6—r = 0.9 for the inner ring and range: r = 0.9—r = 1.0 for the outer ring). Conclusion: Fifty-five degree wide-field SD-OCT provides a good overview of the posterior pole and presents similar quantitative values as a standard 30° OCT lens. Therefore, thickness values are comparable when switching between these two lenses.

Introduction: Individualized treatment regimen using currently available/approved anti-vascular endothelial growth factor (VEGF) agents for the therapy of neovascular age-related macular de...

Purpose: Differentiating the underlying pathology of macular edema in patients with diabetic retinopathy following cataract surgery can be challenging. In 2015, Munk and colleagues trained and tested a machine learning classifier which uses optical coherence tomography variables in order to distinguish the underlying pathology of macular edema between diabetic macular edema and pseudophakic cystoid macular edema. It was able to accurately diagnose the underlying pathology in 90%–96% of cases. However, actually using the trained classifier required dedicated software and advanced technical skills which hindered its accessibility to most clinicians. Our aim was to package the classifier in an easy to use web-tool and validate the web-tool using a new cohort of patients. Methods: We packaged the classifier in a web-tool intended for use on a personal computer or mobile phone. We first ensured that the results from the web-tool coincide exactly with the results from the original algorithm and then proceeded to test it using data of 14 patients. Results: The etiology was accurately predicted in 12 out of 14 cases (86%). The cases with diabetic macular edema were accurately diagnosed in 7 out of 7 cases. Of the pseudophakic cystoid macular edema cases, 5 out of 6 were correctly interpreted and 1 case with a mixed etiology was interpreted as pseudophakic cystoid macular edema. Variable input was reported to be easy and took on average 7 ± 3 min. Conclusion: The web-tool implementation of the classifier seems to be a valuable tool to support research into this field.

Purpose: This article investigates the optical coherence tomography (OCT) and fundus autofluorescence imaging findings in birdshot chorioretinopathy (BSCR) and their association with visual acuity (VA). Methods: In a retrospective, cross-sectional study, we evaluated OCT images for changes in retinal structure including cystoid macular edema (CME), epiretinal membrane, and outer retinal lesions. We assessed autofluorescence images for hypoautofluorescent and hyperautofluorescent changes and noted the distribution of the lesions. Demographic data and VA at the time of imaging were also collected. Associations between OCT and autofluorescence findings and logarithm of the minimum angle of resolution VA were tested using linear regression. Results: We conducted a chart review of 80 eyes from 40 patients with BSCR. Outer retinal lesions were found on OCT in 28 of 80 eyes (35%) and disruption of the outer segment ellipsoid zone (EZ) occurred in 23 eyes (28.7%). Macular hypoautofluorescent lesions were more common than hyperautofluorescent lesions, present in 58.8% and 13% of eyes, respectively. The presence of outer retinal lesions on OCT was significantly associated with reduced VA ( P = .006) as was EZ disruption ( P = .003). These associations remained significant after accounting for the presence of macular edema. There was a trend toward association of macular hypoautofluorescent lesions with decreased vision, although it was not statistically significant ( P = .17). Conclusions: The association of outer retinal lesions with decreased VA suggests a mechanism of central vision loss that is distinct from CME and may provide an additional objective finding to monitor disease activity in BSCR patients.

Ultra-wide-field (UWF) imaging has been used clinically in retina practices for nearly two decades to achieve rapid, single-frame photographic access to the mid- and far-retinal periphery.1–5 These...

AimTo describe the optical coherence tomography (OCT) characteristics and to identify and analyse the incidence of choroidal neovascular (CNV) network seen on optical coherence tomography angiography (OCTA) in eyes with cystoid macular degeneration (CMD) associated with central serous chorioretinopathy (CSCR).MethodsThis was a retrospective, observational study of 29 eyes of 25 patients who were previously diagnosed as CSCR with CMD. Baseline patient characteristics, best-corrected visual acuity (BCVA), evidence of CNV network and its pattern on OCTA, distribution of CMD changes and OCT parameters, such as height of the neurosensory retinal detachment (NSD), presence of double layer sign, central macular thickness, were analysed. The eyes were classified into two groups depending on the presence or absence of CNV network on OCTA. BCVA, OCT parameters and CMD distribution were compared in the two groups at baseline using independent t-test.ResultA total of 13 (44.8 %) eyes had a CNV network, while only 9 out of the 13 eyes had pattern-I CNV. Among the eyes with CNV network (13 eyes), mean height of NSD was of 65.2±22.7 µ, whereas, among the eyes without CNV (16 eyes), it was 134.6±77.4 µ. The difference was statistically significant (p=0.013). There was no statistically significant difference between eye having a CNV and eyes without CNV in terms of other parameters.ConclusionA CNV network is seen in a large subset of patients with CMD in CSCR. A shallower subretinal fluid may point towards the presence of an underlying CNV network.

Purpose: To evaluate real-life outcomes in treatment-naive patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) agents using a treat-and-extend regimen without a fixed loading phase. Methods: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measured using optical coherence tomography at baseline and after 1 year of treatment, intervals and number of injections were analyzed. Subgroup analysis was performed to compare anatomical and functional outcomes between patients receiving ranibizumab or aflibercept. Results: Seventy-five eyes of 61 patients met the inclusion criteria and had follow-up for 1 year. Baseline BCVA and CRT were 68.1 ± 13.2 letters and 424 ± 135 µm, retrospectively. After 1 year, there was a significant mean gain in BCVA of +5.8 ± 7.4 letters (paired t test: p < 0.0001) and a significant decrease in mean CRT of –117 ± 134 µm (paired t test: p < 0.0001). The mean number of anti-VEGF injections was 10.0 ± 1.6 (range 6–12). The mean maximum interval between injections was 8.5 ± 2.9 weeks (range 4–14) and the mean interval 6.0 ± 1.2 weeks (range 4.1–8.9). 96% of eyes could be extended after a mean of 5.3 injections and 17% of patients could be extended before reaching a formal loading dose of 3 injections. Subgroup analysis did not reveal any differences in outcomes between patients treated with ranibizumab or aflibercept. Subretinal fluid at baseline was associated with better BCVA gain after 1 year (stepwise forward regression analysis, p = 0.003). Conclusion: Our results suggest that not all patients with DME require a fixed loading phase when initiating anti-VEGF treatment. Finding anatomical predictors to identify this subgroup of patients would help to reduce treatment burden and optimize clinical outcomes.

To detect vascular abnormalities in diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) widefield images, and to compare the findings with color fundus photographs (CFPs) using Early Treatment Diabetic Retinopathy Study severity grading.3 mm × 3 mm and 12 mm × 12 mm scans were acquired to cover 70° to 80° of the posterior pole using a 100-kHz SS-OCTA instrument. Two masked graders assessed the presence of vascular abnormalities on SS-OCTA and the Early Treatment Diabetic Retinopathy Study level on CFP. The grading results were then compared.A total of 120 diabetic eyes (60 patients) were imaged with the SS-OCTA instrument. Cohort 1 (91 eyes; SS-OCTA grading only) showed microaneurysms in 91% (n = 83), intraretinal microvascular abnormalities in 79% (n = 72), and neovascularization in 21% (n = 19) of cases. Cohort 2 (52 eyes; CFP grading compared with SS-OCTA) showed microaneurysms on CFP in 90% (n = 47) and on SS-OCTA in 96% (n = 50) of cases. Agreement in intraretinal microvascular abnormality detection was fair (k = 0.2). Swept-source optical coherence tomography angiography detected 50% of intraretinal microvascular abnormality cases (n = 26), which were missed on CFP. Agreement in detecting neovascularization was moderate (k = 0.5).Agreement in detection of diabetic retinopathy features on CFP and SS-OCTA varies depending on the vascular changes examined. Swept-source optical coherence tomography angiography shows a higher detection rate of intraretinal microvascular abnormalities (P = 0.039), compared with Early Treatment Diabetic Retinopathy Study grading.

Purpose : To validate a custom algorithm for automated identification and quantification of clinically relevant inflammatory choriocapillaris (CC) lesions from en face swept source optical coherence tomography (SS-OCTA) images. Design : observational case series Methods : Twenty eyes of 14 patients with posterior uveitis were imaged using the PLEX® Elite 9000. The machine-generated en face OCTA CC slabs were exported to MATLAB where a custom algorithm performed unsupervised lesion boundary delineation and area quantification. Lesions identified by the algorithm (AG) were compared to those identified by two masked human graders (HG1 and HG2), using the Sorensen-Dice coefficient (DSC) and intraclass correlation coefficient (ICC). Intra-grader and intra-visit reliability were determined by coefficient of variation (CV) and DSC. Results : The AG demonstrated excellent agreement with both HGs in determination of lesion area (HG1 vs. AG ICC 0.92, 95% CI 0.81-0.97, HG2 vs. AG ICC 0.91, 95% CI 0.78-0.97). The AG demonstrated good spatial overlap (DSC≥0.70) with both HGs in 14/20 (70%) eyes and at least one HG in 16/20 (80%) eyes. Poor spatial overlap (DSC between 0.31 and 0.69) was associated with the presence of a choroidal neovascular membrane and low contrast lesion boundaries. Intra-visit repeatability for the AG was superior to both HGs (CV 2.6% vs >5%). Conclusion : This custom algorithm demonstrated a high degree of agreement with human graders in identification of inflammatory CC lesions, and outperformed human graders in reproducibility. Automated CC lesion delineation will support the development of objective and quantitative biomarker of disease activity in patients with posterior uveitis.

Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (TE) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the TE regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity.摘要: 积液作为新生血管性年龄相关黄斑变性治疗的关键性生物标志物: 文献回顾及共识建议摘要目前关于新生血管性年龄相关性黄斑变性 (nAMD) 患者的管理指南中缺乏相干光断层扫描 (OCT) 中积液的阐释, 也没有明确的建议将该信息纳入正在制定的疾病治疗策略中。本文旨在总结目前积液作为生物标志物在nAMD中治疗作用的相关指南及科学证据, 并基于欧洲视网膜专家共识, 开发以临床需求为导向的具有实用价值的诊断和管理的算法。我们检索了PubMed数据库并查找自2006年以来发表的关于积液在nAMD中作用的文献。共筛选654篇文章, 纳入66篇文章以综述回顾。其中, 14项为治疗指南、共识陈述、系统综述及meta分析, 其中OCT被一致推荐作为nAMD的初始诊断和后续管理的重要工具。然而, 在提供建议时, 很少有指南会区分不同类型的液体。共有52篇文献报道了来自临床试验、研究和图表评论的主要证据。这些观察结果有时是不一致的, 但在预测视力方面有一定特征性的趋势。基于这些发现, 我们提出了诊断建议和基于TE方案的治疗算法。这为nAMD的诊断提供了指导, 同时也为TE方案提供了一个简单的治疗途径, 即根据观察到的积液作为疾病活动的关键生物标志物来决定治疗方案。.

In this paper we analyse the performance of machine learning methods in predicting patient information such as age or sex solely from retinal imaging modalities in a heterogeneous clinical population. Our dataset consists of N = 135,667 fundus images and N = 85,536 volumetric OCT scans. Deep learning models were trained to predict the patient’s age and sex from fundus images, OCT cross sections and OCT volumes. For sex prediction, a ROC AUC of 0.80 was achieved for fundus images, 0.84 for OCT cross sections and 0.90 for OCT volumes. Age prediction mean absolute errors of 6.328 years for fundus, 5.625 years for OCT cross sections and 4.541 for OCT volumes were observed. We assess the performance of OCT scans containing different biomarkers and note a peak performance of AUC = 0.88 for OCT cross sections and 0.95 for volumes when there is no pathology on scans. Performance drops in case of drusen, fibrovascular pigment epitheliuum detachment and geographic atrophy present. We conclude that deep learning based methods are capable of classifying the patient’s sex and age from color fundus photography and OCT for a broad spectrum of patients irrespective of underlying disease or image quality. Non-random sex prediction using fundus images seems only possible if the eye fovea and optic disc are visible.

AimTo report long-term outcomes on best-corrected visual acuity (BCVA) and treatment intervals with a treat-and-extend (T&E) regimen in patients with neovascular age-related macular degeneration (nAMD).MethodsThis observational study included treatment-naïve patients with nAMD, treated with aflibercept. A specific T&E protocol without a loading phase and predefined exit criteria was administered. After reaching predefined ‘exit-criteria’, the treatment period was complete, and patients were observed three monthly.ResultsEighty-two patients with a follow-up period of ≥2 years were included. BCVA (mean±SD, ETDRS letters) increased from 51.9±25.2 at baseline to 63.7±17.7 (pConclusionsAfter 4 years of treatment, initial vision gains were maintained with a reasonable treatment burden, even without an initial loading phase. Our results on functional outcomes are comparable with large controlled studies.

AimTo standardise the nomenclature for reporting optical coherence angiography (OCT-A) findings in the field of uveitis.MethodsMembers of the International Uveitis Study Group, of the American Uveitis Society and of the Sociedad Panamericana de Infermedades Oculares that choose to participate responded to an online questionnaire about their preferred terminology when reporting on OCT-A findings in uveitis. The response of individuals with several publications on OCT-A (experts) was compared with uveitis specialists (users) who have less than five publications on the field of uveitis and OCT-A.ResultsA total of 108 uveitis specialists who participated in the survey were included in the analysis. Of those, 23 were considered OCT-A ‘experts’. There was an agreement in both groups for the definition of wide-field (WF)-OCT-A, and definition of neovascularisation in uveitis. Moreover, there was a difference in the responses in other areas, such as quantification of ischaemia, definition of ‘large’ areas of ischaemia or terms to describe decreased OCT-A signal from different causes. There was an unanimous need of ‘users’ and ‘experts’ to distinguish size of decreased OCT-A signal in uveitis, to implement a quantitative measurement of decreased flow specifically for WF-OCT-A and to use different terms for different causes of decreased OCT-A signal.ConclusionsWhile there was considerable agreement in the terminology used by all uveitis experts, significant differences in terminology were noted between ‘users’ and ‘experts’. These differences indicate the need for standardisation of nomenclature among all uveitis specialists both for the purpose of reporting and in clinical use.

Purpose: To evaluate longitudinal changes in retinal layer thickness and clinical outcome in patients with MEWDS.Methods: In 20 patients with MEWDS, SD-OCT images and BCVA were assessed at baseline, and at months 1, 3, and 12. SD-OCTs were segmented and measurements were performed within the fovea and a MEWDS lesion. Baseline and follow-up values in the affected eye were compared to measurements performed at the corresponding location in the fellow eye.Results: ONL thickness was 4.7% thicker in MEWDS-eyes compared with the baseline, with a significant decrease of 9% at 3 months. Within the lesion, INL thickness was 7.9% increased at baseline and decreased significantly over the follow-up of 12 months. BCVA was decreased at baseline (0.2 ± 0.18logMAR) and at the 3 months but after 12 months had increased to 0.01 ± 0.04 logMAR.Conclusion: MEWDS shows the involvement of different retinal layers and characteristic changes over the disease course.

Purpose: Placoid-pigment-epitheliopathies like Acute-Posterior-Multifocal-Placoid-Pigment Epitheliopathy (APMPPE) and Relentless-Placoid-Choroidopathy (RPC) usually show bilateral involvement. This retrospective case series describes the clinical features with unilateral disease onset. Methods: 21 patients from 9 tertiary referring institutions were collected and evaluated. Results: Seventeen patients were included: 11 (65%) had unilateral placoid-pigment-epitheliopathy consistent with APMPPE, 6 (35%) with RPC (mean age: 28.82 ± 9.1 years). Mean follow-up time was 45 ± 48 months. Forty-one percent fellow-eyes had initial inflammatory signs including vitreous-cells, vascular-sheathing, and ONH swelling. Thirty-five percent developed chorioretinal lesions during follow-up after 19.5 ± 16.9 months. Initial inflammation in fellow-eye was not associated with fellow-eye involvement (p =.5). However, subfoveal choroidal-thickness (SCT) at baseline was significantly thicker in fellow-eyes who developed chorioretinal lesion compared to fellow-eyes who did not (400 ± 70 µm versus 283 ± 127 µm,p =.047). Conclusion: Unaffected fellow-eyes may have inflammatory signs at initial disease-onset and may develop lesions over time. They should be carefully monitored, particularly if they present with an increased SCT.

We aimed to evaluate the neuroprotective efficacy of rasagiline in pseudophakic patients who had surgery for macula-off rhegmatogenous retinal detachment (RRD). This was a 6-month, prospective, randomized, double-blind, placebo-controlled pilot study. Patients presenting with acute macula-off RRD were recruited and randomized 1:1 to receive rasagiline 1 mg/day or placebo for 7 days. Best-corrected visual acuity (BCVA) and optical coherence tomography were acquired 1 day before as well as 2 days, 3 weeks, 3 months and 6 months after surgery. We screened 26 patients with RRD whereof 23 were eventually included and randomized. The primary outcome was final BCVA. Secondary outcomes included central retinal thickness (CRT) and adverse events (AE). We evaluated photoreceptor cells (prc) recovery through morphological measurements. The baseline characteristics were comparable between groups. BCVA significantly improved in both groups (letters gained: rasagiline 61.5 ± 18.1 vs placebo 55.3 ± 29.2, p = 0.56), but no significant inter-group difference was found at any visit. CRT was stable 3 weeks after surgery onwards, with no inter-group difference. No treatment-emergent AE occurred. Significant prc restoration was observed from 3 weeks to 6 months after surgery, without inter-group difference at either visit. Ellipsoid zone integrity (β = 0.517, p = 0.008) and foveal bulge (β = 0.387, p = 0.038) were significant predictors of good final BCVA. In conclusion, perioperative oral treatment with rasagiline 1 mg/day for 7 days did not show significant benefits on visual or anatomical outcomes in macula-off RRD patients.