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Hakan Kaymak,1,2 Marion R Munk,3– 5 Stephanie E Tedford,6 Cindy L Croissant,6 Clark E Tedford,6 Rene Ruckert,4,6 Hartmut Schwahn1 1I.I.O.GbR Breyer Kaymak Klabe, Duesseldorf, Germany; 2Experimental Ophthalmology, University Hospital and Medical Faculty of the University of Saarland, Homburg/Saar, Germany; 3Department of Ophthalmology, Inselspital University Hospital Bern, Bern, Switzerland; 4Eyegnos Consulting, Bern, Switzerland; 5Augenarzt-Praxisgemeinschaft Gutblick AG, Pfäffikon, Switzerland; 6LumiThera, Inc, Poulsbo, WA, USACorrespondence: Stephanie E Tedford, LumiThera, Inc, Poulsbo, WA, USA, Email setedford@lumithera.comPurpose: Diabetes is associated with ocular complications including diabetic macular edema (DME). Current therapies are invasive and include repeated intravitreal injections and laser therapy. Photobiomodulation (PBM) is a treatment (Tx) that utilizes selected wavelengths of light to induce cellular benefits including reduction of inflammation and edema. This single-center, open-label, post-hoc analysis explored the utility of multiwavelength PBM in subjects with DME.Methods: Analysis included review of data from patients undergoing standard clinical care with an approved and marketed PBM medical device, the Valeda® Light Delivery System. Subjects with early-stage DME with good vision (Best-corrected visual acuity (BCVA) > 20/25, logMAR > 0.1) were evaluated in clinic and treated with one series of multiwavelength PBM (Tx delivered 3x/week over 3– 4 weeks; total of 9 Tx sessions). Clinical, anatomical, and safety parameters were assessed in addition to subjective quality of life.Results: A total of 30 eyes (19 subjects) were analyzed. Subjects were predominately male (68.4%) with a mean age of 56 ± 14 years. Reductions in central retinal thickness (CRT), resolution of intraretinal fluid (IRF) and improvement in diabetic retinopathy severity scale scores were observed following PBM treatment in select patients. Baseline BCVA remained stable over the follow-up observation period of 3 months post-PBM. Approximately 64% of patients reported subjective improvements in their ocular condition and decreased influence in everyday life. Detailed OCT evaluations confirmed no safety issues related to phototoxicity up to 16 months.Conclusion: Early-stage DME subjects treated with Valeda multiwavelength PBM showed improvements in clinical and anatomical parameters. The Valeda multiwavelength PBM approach demonstrates a favorable safety profile with no signs of phototoxicity following an independent OCT review. PBM therapy may offer an alternative, non-invasive treatment strategy with a unique mechanism and modality for patients with early-stage DME.Keywords: photobiomodulation, diabetic macular edema, low level light therapy, diabetic retinopathy, central retinal thickness, Valeda Light Delivery System, DME, PBM, DR, CRT

Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is the primary cause of vision impairment in affected patients. Anti-VEGF agents have become the standard treatment, showing efficacy in improving visual acuity (VA) and reducing ME. However, a subset of patients exhibit a suboptimal response to anti-VEGF therapy, necessitating alternative treatments. Corticosteroids, which address inflammatory pathways implicated in ME, have shown promise, particularly in cases resistant to anti-VEGF. This review aims to identify biomarkers that predict treatment response to corticosteroids in RVO-associated ME, utilizing multimodal imaging and cytokine assessments. Baseline imaging, including SD-OCT and OCT-A, is essential for evaluating biomarkers like hyperreflective foci (HRF), serous retinal detachment (SRF), and central retinal thickness (CRT). Elevated cytokine levels, such as IL-6 and MCP-1, correlate with ME severity and poor anti-VEGF response. Early identification of these biomarkers can guide timely transitions to corticosteroid therapy, potentially enhancing treatment outcomes. The practical conclusion of this review is that integrating biomarker assessment into clinical practice enables personalized treatment decisions, allowing for earlier and more effective management of RVO-associated ME by transitioning patients to corticosteroid therapy when anti-VEGF agents are insufficient. Advanced diagnostics and machine learning may further refine personalized treatment strategies, improving the management of RVO-associated ME.

Optical coherence tomography angiography (OCTA) holds promise in enhancing the care of various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD). Given nAMD's vascular nature and the distinct vasculature of macular neovascularization (MNV), detailed analysis is expected to gain significance. Research in artificial intelligence (AI) indicates that en-face OCTA views may offer superior predictive capabilities than spectral domain optical coherence tomography (SD-OCT) images, highlighting the necessity to identify key vascular parameters. Analyzing vasculature could facilitate distinguishing MNV subtypes and refining diagnosis. Future studies correlating OCTA parameters with clinical data might prompt a revised classification system. However, the combined utilization of qualitative and quantitative OCTA biomarkers to enhance the accuracy of diagnosing disease activity remains underdeveloped. Discrepancies persist regarding the optimal biomarker for indicating an active lesion, warranting comprehensive prospective studies for validation. AI holds potential in extracting valuable insights from the vast datasets within OCTA, enabling researchers and clinicians to fully exploit its OCTA imaging capabilities. Nevertheless, challenges pertaining to data quantity and quality pose significant obstacles to AI advancement in this field. As OCTA gains traction in clinical practice and data volume increases, AI-driven analysis is expected to further augment diagnostic capabilities., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Gender medicine is a medical specialty that addresses gender differences in health and disease. Traditionally, medical research and clinical practice have often been focused on male subjects and patients. As a result, gender differences in medicine have been overlooked. Gender medicine considers the biological, psychological, and social differences between the genders and how these differences affect the development, diagnosis, treatment, and prevention of disease. For ophthalmological diseases epidemiological differences are known. However, there are not yet any gender-based ophthalmic treatment approaches for women and men. This review provides an overview of gender differences in retinal diseases. It is intended to make ophthalmologists, especially retinologists, more sensitive to the topic of gender medicine. The goal is to enhance comprehension of these aspects by highlighting fundamental gender differences. Integrating gender medicine into ophthalmological practice helps promote personalized and gender-responsive health care and makes medical research more accurate and relevant to the entire population., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To evaluate choriocapillaris (CC) and choroidal vascular changes in patients with posterior uveitis using swept-source (SS) wide-field optical coherence tomography angiography (OCTA)., Method: Consecutive 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., Results: Eighty-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., Conclusion: CC 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 Number: NCT02811536., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission., Design: Retrospective study., Methods: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering., Results: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04)., Conclusions: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To study visual function, retinal layer thickness changes, and tangential displacement after pars plana vitrectomy for epiretinal membrane., Methods: Retrospective series of patients undergoing pars plana vitrectomy for epiretinal membrane, with 6-month follow-up including best-corrected visual acuity, optical coherence tomography, M-charts, epiretinal membrane grading, and infrared fundus photograph at time 0 (T0, preop) at months 1 (T1), 3 (T3), and 6 (T6) postop (±1 week). Retinal layer thickness and tangential ( en face ) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En face displacement was calculated as optical flow of consecutive images., Results: Average best-corrected visual acuity improved from 0.28 ± 0.08 logarithm of Minimum Angle of Resolution at T0 to 0.16 ± 0.25 at T6 ( P = 0.05), best-corrected visual acuity improvement correlated with best corrected visual acuity (BCVA) at T0 ( P < 0.001). Vertical metamorphopsia decreased from 1.33° ± 0.70° at T0 to 0.82° ± 0.69° at T6 ( P < 0.05). Foveal thickness reduced from 453 ± 53 µ m at T0 to 359 ± 31 µ m at T6 ( P < 0.05) and reduction correlated with best-corrected visual acuity improvement ( P < 0.05). Foveal layers decreased ( P < 0.05) in all cases. The mean en face deformation was 155.82 ± 50.17 µ m and mostly occurred in the first month: T0-T1 displacement was 83.59 ± 30.28 µ m, T1-T3 was 36.28 ± 14.45 µ m, while T3-T6 was 39.11 ± 22.79 µ m ( P < 0.001) on average. Perifoveal and parafoveal deformation correlated with optical coherence tomography foveal thickness reduction at all time intervals (1, 3, and 6 months: P < 0.01)., Conclusion: Epiretinal membrane peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en face and in-depth changes correlate with visual function., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Background: 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., Main Body: 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., Conclusion: 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.

Purpose: Multiple evanescent white dot syndrome 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 multiple evanescent white dot syndrome, 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 multiple evanescent white dot syndrome patients for a better understanding and monitoring of their disease.

Purpose: To investigate the presence of ACE2, TMPRSS2 and Furin, i.e., a key player in the ocular infection with SARS-COV-2, in surgically obtained human retinal tissue samples from SARS-CoV-2-negative patients, using gene expression analysis., Methods: The mechanisms and entry paths of ocular infections have been ill-defined so far. To better understand the possible entry routes, we used surgically explanted retinal tissue from nine patients that were not infected with SARS-CoV-2 and analyzed the message expression of the three key molecules that confer viral entry into cells using polymerase chain reaction., Results: The median age of the patients (n = 9) included in the study was 52 years (IQR 48, 55). Eight patients underwent surgery for rhegmatogenous retinal detachment and one patient for tractional retinal detachment. Gene expression for the proteins studied was detected in all nine patients. The results of analysis by Livak's method (2001) demonstrated a median TMPRSS2 gene expression value of 20.9 (IQR 11.7, 33.7), a median ACE2 gene expression value of 2.09 (IQR 1.14, 2.79) and a median Furin gene expression value of 8.33 (IQR 5.90, 11.8)., Conclusion: In conclusion, TMPRSS2, Furin and ACE2 are expressed in the retina and may contribute to the retinal involvement in COVID-19 patients. Expression may vary among individuals, which may explain why some patients may be more prone to retinal involvement during SARS-CoV-2 infection COVID-19 patients than others. Variability in the expression of TMPRSS2, Furin and ACE2 proteins themselves may also explain the presence or development of retinal symptoms of varying severity., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To report a case series of herpetic uveitis following COVID-19 vaccinations., Methods: Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well., Results: Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes ( n  = 12, 50%) and recurrent episodes ( n  = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2., Conclusion: This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing., 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 © 2023 Ott, Nagamany, Zandi, Pichi, Agarwal, Carreño, Gupta, Grewal, Cunningham and Munk.)

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., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background/aims: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis., Methods: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%., Results: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'., Conclusions: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe multimodal imaging findings of vitamin A deficiency retinopathy., Methods: A retrospective study of patients with serum retinol < 0.3 mg/L. Fundus color photos, spectral domain-optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were reviewed and, when available, electrophysiological tests were analyzed., Results: Forty-five eyes (63.9 ± 15.7 years) were included. Ultra-widefield fundus photography showed drusen-like deposits (53.3%) and macular retinal pigment epithelium (RPE) mottling (40%). The deposits were hypoautofluorescent, and a perifoveal hyperautofluorescent ring was present in 8.9%. By SD-OCT, the ellipsoid zone had an irregular appearance (100%) and conical deposits anterior to the RPE (33.3%). Electroretinogram (ERG) (66.7%) showed a decrease in b-wave in the scotopic registers, and microperimetry (4.4%) showed decreased foveal sensitivity. After vitamin A supplementation, SD-OCT and FAF showed resolution of all findings. Forty percent of eyes had restoration of the scotopic registers in ERG and improved macular sensitivity by microperimetry (4.4%)., Conclusions: Vitamin A deficiency causes a mild cone dysfunction in addition to the more severe absent rod response. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:330-336.] .

Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile.

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., (© 2023 Royal Australian and New Zealand College of Ophthalmologists.)

Introduction: Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD., Methods: The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm)., Results: LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed., Conclusion: These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD., Trial Registration: Clinicaltrial.Gov Registration Identifier: NCT03878420., (© 2022. The Author(s).)

Purpose: To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME)., Methods: This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of <3 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 was <0.15 and the difference in mean change from baseline in ETDRS letters was >0., Results: 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., Conclusion: 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., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

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: To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts., Design: Delphi-based survey., Subjects, Participants, And/or Controls: Twenty-five retinal vascular disease and OCTA imaging experts., Methods, Intervention, or Testing: A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of "wide-field (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: "strong consensus" was defined as ≥85% agreement, "consensus" as 80% to 84%, and "near consensus" as 70% to 79%., Main Outcome Measures: Consensus and near consensus on OCTA nomenclature in retinal vascular disease., Results: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of "no-flow areas," and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round., Conclusions: This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report nine cases of multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy., Methods: A retrospective observational case series of eyes with multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. Multimodal imaging findings were reviewed and presented., Results: Fifteen eyes of 9 patients (6 women and 3 men), with a mean age of 48.1 years (median, 46 years; range, 23-74 years), presented with multifocal choroiditis serpiginous-like peripapillary chorioretinal atrophy. All 15 eyes presented with serpiginoid peripapillary changes and had discrete patches of atrophy or punched-out scars in the posterior pole or periphery. Eleven eyes (73.3%) had cone-shaped retinal pigment epithelium elevations on optical coherence tomography, 10 eyes (66.7%) had mild vitritis, and 4 eyes (26.7%) had peripheral curvilinear streak lesions. Three eyes (20%) had choroidal neovascularization. All patients responded well to treatment with systemic immunosuppression, local corticosteroid injections, and/or intravitreal anti-vascular endothelial growth factor injections., Conclusion: Multifocal choroiditis may present with peripapillary chorioretinal changes resembling a serpiginous-like choroiditis in addition to the classic findings of patches of atrophy or punched-out scars in the posterior pole or periphery, cone-shaped retinal pigment epithelium elevated on optical coherence tomography and peripheral curvilinear streak lesions.

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 indocyanine green angiography (ICGA) and swept-source wide-field optical coherence tomography angiography (SS-OCTA) for the assessment of patients with posterior uveitis., Method: SS-OCTA montage images of 5 x 12 x 12 mm or 2 x 15 x 9 mm, covering ~70-90 degree of the retina of consecutive patients with posterior uveitis were acquired. The choriocapillaries and choroidal slabs were compared to findings on ICGA., Results: Sixty-eight eyes of 41 patients were included (mean age 47.2 ± 20.4 years; 58.5% female). In 23 (34%) lesions were visible on OCTA, but not discernable on ICGA. In turn, out of the 45 eyes with clearly discernable lesions on ICGA, 22 (49%) and 21 (47%) eyes showed no corresponding areas of flow deficit on OCTA in the CC and choroidal slab, respectively. Lesion size strongly correlated among ICGA and OCTA choriocapillaries- (CC) (r = 0.99, p ≤ 0.0001) and choroidal slabs (r = 0.99, p ≤ 0.0001), respectively. The mean lesion size on the late frames of ICGA (8.45 ± 5.47 mm 2 ) was larger compared to the lesion size on OCTA CC scan (7.98 ± 5.47 mm 2 , p ≤ 0.0001) and choroidal scan (7.69 ± 5.10 mm 2 , p = 0.002), respectively. The lesion size on OCTA CC scan was significantly larger than on the OCTA choroidal scan ( p ≤ 0.0001)., Conclusion: SS-wide field OCTA may be a promising tool to assess posterior uveitis patients and may replace ICGA to a certain extent in the future., 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 © 2022 Tian, Zeng, Tappeiner, Zinkernagel, Wolf and Munk.)

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. The machine-generated en face OCTA CC slabs were exported to a computing platform, where a custom algorithm performed unsupervised lesion boundary delineation and area quantification. Lesions identified by the algorithm (AG) were compared to those identified by 2 masked human graders (HG1 and HG2), using the Sørensen-Dice coefficient (DSC) and intraclass correlation coefficient (ICC). Intragrader and intravisit 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 of 20 (70%) eyes and at least 1 HG in 16 of 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. Intravisit 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 HGs in identification of inflammatory CC lesions and outperformed HGs in reproducibility. Automated CC lesion delineation will support the development of objective and quantitative biomarker of disease activity in patients with posterior uveitis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the optical coherence tomography angiography (OCTA) features of fellow eyes of patients with unilateral choroidal neovascularisation (CNV) associated with chronic central serous chorioretinopathy (CSCR)., Methods: Medical records of patients with chronic CSCR who had undergone OCT angiography of both the eyes were reviewed. Patients with evidence of unilateral CNV detected by conventional imaging (OCT, fluorescein angiography and/or indocyanine green angiography) were included in the study. The OCT and OCTA characteristics of fellow eyes were analysed., Results: Forty patients (80 eyes-40 fellow eyes) with chronic CSCR with evidence of CNV in one eye were included. Mean age of the patients was 54.9±9.9 years and 82.5 % were males. Twenty-five (62.5%) fellow eyes had flat irregular pigment epithelial detachment on OCT, out of which 21 had internal hyper-reflectivity. A definite vascular network was picked up by OCTA in 9 of these 40 fellow eyes (22.5%) which was not detected on conventional imaging. In addition, two eyes had an ill-defined hyper-reflectivity, which could not be classified as a definite network at that point of time. The networks detected on OCTA in fellow eyes were mostly inactive, suggesting a subclinical neovascularisation., Conclusion: One-fourth of fellow eyes showed vascular network which could not be diagnosed on conventional imaging which highlights the importance of imaging both the eyes of chronic CSCR for early detection of CNV using OCTA. Further longitudinal studies are needed to assess the clinical course of such subclinical vascular networks in CSCR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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 (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity., (© 2021. The Author(s).)

Purpose: 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)., Design: Retrospective cohort study., Participants: 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., Methods: 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)., Main Outcome Measures: Mean area under the receiver operating characteristic curve (AUC) of both models; contribution to the prediction and statistical significance of the input features., Results: 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., Conclusions: Machine learning classifiers can predict treatment demand and may assist in establishing patient-specific treatment plans in the near future., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: To standardise the nomenclature for reporting optical coherence angiography (OCT-A) findings in the field of uveitis., Methods: Members 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., Results: A 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., Conclusions: While 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare the differences among 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 3 tertiary care centers, were reviewed. The differences among clinical appearances, including morphology of the lesions (size, shape, extent), vascularity, and multimodal imaging features, were compared. Repeated logistic regression measurements with a multilevel random effects model was used to assess characteristics of individual granulomas that could predict the underlying cause., Results: The study included 47 eyes of 38 patients (22 with tuberculomas and 16 with sarcoid granulomas; total of 138 granulomas). Patients with tuberculomas were significantly younger (33.8 ± 10.1 vs. 48.6 ± 14.3 years, respectively; P = .002), but no sex differences were observed. In comparison with sarcoid granulomas, tuberculomas were solitary (P <.001), intense yellow, lobulated, full thickness, and located in the perivascular region (all P <.001); they were also larger (16.01 ± 9.7 mm 2 vs. 2.7 ± 4.5 mm 2 , respectively; P <.001) and were vascularized (P <.001). Sarcoid granulomas were associated with retinal vasculitis (P = .003) and disc hyperfluorescence (P <.001). Logistic regression showed that multiple granulomas were associated with sarcoidosis (odds ratio [OR]: 3.5; 95% confidence interval: 1.8-6.9; P <.001). Granulomas larger than 6.45 mm 2 had the highest area under the receiver operating curves (0.94) for differentiating tuberculomas from sarcoid granulomas., Conclusions: Tuberculomas and sarcoid choroidal granulomas have various clinical and imaging features that help differentiate between the 2 entities with high predictability and can supplement immunological and radiological tests in a diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Although severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection have emerged globally, findings related to ocular involvement and reported cases are quite limited. Immune reactions against viral infections are closely related to viral and host proteins sequence similarity. Molecular Mimicry has been described for many different viruses; sequence similarities of viral and human tissue proteins may trigger autoimmune reactions after viral infections due to similarities between viral and human structures. With this study, we aimed to investigate the protein sequence similarity of SARS CoV-2 with retinal proteins and retinal pigment epithelium (RPE) surface proteins. Retinal proteins involved in autoimmune retinopathy and retinal pigment epithelium surface transport proteins were analyzed in order to infer their structural similarity to surface glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), envelope protein (E), ORF1ab polyprotein (orf1ab) proteins of SARS CoV-2. Protein similarity comparisons, 3D protein structure prediction, T cell epitopes-MHC binding prediction, B cell epitopes-MHC binding prediction and the evaluation of the antigenicity of peptides assessments were performed. The protein sequence analysis was made using the Pairwise Sequence Alignment and the LALIGN program. 3D protein structure estimates were made using Swiss Model with default settings and analyzed with TM-align web server. T-cell epitope identification was performed using the Immune Epitope Database and Analysis (IEDB) resource Tepitool. B cell epitopes based on sequence characteristics of the antigen was performed using amino acid scales and HMMs with the BepiPred 2.0 web server. The predicted peptides/epitopes in terms of antigenicity were examined using the default settings with the VaxiJen v2.0 server. Analyses showed that, there is a meaningful similarities between 6 retinal pigment epithelium surface transport proteins (MRP-4, MRP-5, RFC1, SNAT7, TAUT and MATE) and the SARS CoV-2 E protein. Immunoreactive epitopic sites of these proteins which are similar to protein E epitope can create an immune stimulation on T cytotoxic and T helper cells and 6 of these 9 epitopic sites are also vaxiJen. These result imply that autoimmune cross-reaction is likely between the studied RPE proteins and SARS CoV-2 E protein. The structure of SARS CoV-2, its proteins and immunologic reactions against these proteins remain largely unknown. Understanding the structure of SARS CoV-2 proteins and demonstration of similarity with human proteins are crucial to predict an autoimmune response associated with immunity against host proteins and its clinical manifestations as well as possible adverse effects of vaccination., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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-world setting., Design: Four-year, multicenter, retrospective comparative study., Participants: Two hundred sixty-four 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 undergone annual fundus autofluorescence (FAF) and 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: Macular atrophy incidence and progression over 4 years, association between treatment strategies, 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 = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed 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 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation 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 new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692)., Conclusions: Over 4 years, neither incidence nor progression of MA 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 achieved better visual outcomes compared with those treated with a PRN approach., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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: 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.

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.