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In July 2023, cases of highly pathogenic avian influenza (HPAI) were reported at 2 shelters for stray cats in Seoul, South Korea. The cause of infection was suspected to be improperly sterilized raw food made from domestic duck meat, which was manufactured in South Korea. All viruses isolated from cats at the shelters and from the raw food belonged to HPAI A(H5N1) clade 2.3.4.4b. The gene constellation of all viruses was most similar to that of viruses isolated in Korea in November 2022. Of note, the viruses isolated from infected cats harbored mutations E627K or D701N in polymerase basic 2, which are indicative of adaptation to mammals. Postmortem examination revealed systemic pathologic lesions and the presence of widespread virus in different tissues. Thus, consumption of raw duck meat contaminated with HPAI virus likely caused systemic symptoms and death in cats, indicating the introduction of mammal-adapted mutations of the virus.

Introduction: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions., Methods: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline., Results: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively., Conclusions: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment., (© 2024. The Author(s).)

Purpose: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups., Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution., Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The avian influenza A virus (H7N9), first detected in China in 2013, is a zoonotic virus that remains persistent in bird populations despite a decline in human cases owing to control measures. Therefore, this study aimed to develop a vaccine as one preventive strategy in anticipation of the potential entry of H7N9 into Korea. Using the hemagglutinin and neuraminidase consensus sequences of H7N9 from 2018-2019, a recombinant H7N9 vaccine, rgAPQAH7N9, was developed, and its protective efficacy in specific pathogen-free chickens was evaluated. The rgAPQAH7N9 vaccine exhibited proliferation in eggs and demonstrated high immunogenicity, with a hemagglutination inhibition titer of 9.3 log 2 . Furthermore, the vaccine provided complete protection, as vaccinated chickens did not exhibit clinical signs or viral shedding. Moreover, when the rgAPQAH7N9 vaccine was boosted, the resulting immunity was long-lasting, with hemagglutination inhibition titers > 7 log2 persisting after 6 months. Therefore, the rgAPQAH7N9 vaccine virus may be considered a potential candidate for inclusion in the avian influenza antigen bank to ensure preparedness for emergency vaccination in poultry., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

This study evaluates the efficacy of photodynamic therapy (PDT) in treating central serous chorioretinopathy (CSC) based on the number of engorged vortex vein draining macula visualized on ultra-widefield (UWF) indocyanine green angiography (ICGA). Thirty-six eyes of 36 patients with treatment-naïve CSC were included. Macula-draining vortex veins were assessed in each quadrant using UWF ICGA. The resolution of subretinal fluid (SRF), pigment epithelial detachment (PED), ellipsoid zone (EZ) disintegrity, and retinal pigment epithelium (RPE) irregularity were evaluated at 3 months after PDT. Visual and anatomical improvements were monitored for 12 months. Logistic regression analysis was performed to identify factors associated with poor visual outcomes. A higher number of macula-draining vortex vein was associated to persistent SRF (p = 0.004), PED (p = 0.001), EZ disintegrity (p = 0.011), and RPE irregularity (p = 0.001). Macula-draining vortex veins were also correlated with poor EZ restoration and limited best corrected visual acuity (BCVA) improvements. In multivariate analysis, the number of macula-draining vortex vein (B = 0.197, p = 0.047) was a risk factor for worse BCVA at 12 months. Increased macula-draining vortex vein was related with unfavorable anatomical and poor visual outcomes after PDT in CSC patients., (© 2024. The Author(s).)

The aim of this study is to evaluate the visual outcomes and quality of an enhanced monofocal intraocular lens (IOL), compared to a conventional monofocal IOL in patients with epiretinal membrane (ERM). This retrospective comparative study reviewed medical records of 110 eyes of 110 patients with photoreceptor-preserving ERM (55 patients in each group) who underwent phacovitrectomy and received either a conventional monofocal IOL (Tecnis PCB00) or an enhanced monofocal IOL (Tecnis Eyhance ICB00) from March 2021 to October 2021. Baseline examination included corrected (CDVA) and uncorrected (UDVA) distance visual acuity, and measurement of pupil size. Postoperative evaluation included uncorrected intermediate (UIVA) and near (UNVA) visual acuity, and defocus curve. Contrast sensitivity was assessed using CGT-2000 (Takagi, Seiko, Japan). The baseline parameters showed no difference between PCB00 and ICB00 groups. At 3 months, there was no difference of UDVA and CDVA, but UIVA (0.27 vs. 0.39 LogMAR; p = 0.001) and UNVA (0.35 vs. 0.45 LogMAR; p = 0.014) were better in ICB00 group. On the defocus curve, the ICB00 group demonstrated a slower slope decrease, with higher visual acuity from - 1.5 to -3.0 diopters when compared to the PCB00 group. The distant contrast sensitivity showed no significant difference between two groups. In conclusion, the enhanced monofocal IOL improved intermediate visual outcomes, achieving equivalent distance visual acuity and similar contrast sensitivity to the conventional monofocal IOL. It could be an alternative option to conventional monofocal IOL when planning combined phacovitrectomy for patients with photoreceptor-preserving ERM., (© 2024. The Author(s).)

Construction of a robust artificial solid-electrolyte interphase (SEI) layer has proposed an effective strategy to overcome the instability of the lithium (Li). However, existing artificial SEI layers inadequately controlled ion distribution, leading to dendritic growth and penetration. Furthermore, the environmental impact of the manufacturing process and materials of the artificial layer is often overlooked. In this work, a chemically and physically reinforced membrane (C-Li@P) composed of the biocompatible Li + coordinated carboxymethyl guar gum (CMGG) and polyacrylamide (PAM) polymers serves as an artificial SEI membrane for dendrite-free Li. This membrane with hollow channels not only directs ion flux along the interspace of fibers, fostering uniform Li plating but also induces a desirable interface chemistry. Consequently, artificial SEI membrane-covered Li exhibits stable electrochemical plating/stripping reactions, surpassing the cycle life of ≈750% of bare Li. It demonstrates exceptional capacity retention of ≈93.9%, ≈88.1%, and ≈79.18% in full cells paired with LiNi 0.8 Mn 0.1 Co 0.1 O 2 (NMC811), LiNi 0.6 Mn 0.2 Co 0.2 O 2 (NMC622) and S cathodes, respectively over 200 cycles at 1 C rate. Additionally, the water-based green manufacturing and biodegradability of the membrane demonstrated the sustainable development and disposal of electrodes. This work provides a comprehensive framework for the design of an artificial layer chemically and physically regulating dendritic growth., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Treatment with atezolizumab and bevacizumab is the first-line therapy for unresectable hepatocellular carcinoma. Although immune checkpoint inhibitors are novel and effective treatments, they can induce immune-related adverse events. However, neurological immune-related adverse events have rarely been reported. We report the case of a man in his 40s with hepatocellular carcinoma who developed life-threatening encephalitis after atezolizumab plus bevacizumab was administered. The patient presented with fever, headache, altered mentality, and general epileptic seizures, ten days after administration. Cerebrospinal fluid analysis showed elevated white blood cells and elevated protein levels, but revealed no infection or malignancy. Brain magnetic resonance imaging showed diffuse leptomeningeal enhancement in both the cerebrum and cerebellum. As immune checkpoint inhibitor-induced encephalitis was strongly suspected, steroid pulse therapy was initiated and neurological symptoms quickly improved. The patient was discharged after 66 days of hospitalization, and administration of sorafenib and radiotherapy was started for the hepatocellular carcinoma on an outpatient basis. This case demonstrates the importance of recognizing neurological immune-related adverse events following atezolizumab and bevacizumab treatment for early intervention. We discuss this case in comparison to available literature and previous two cases of Atezolizumab- and bevacizumab- induced encephalitis in hepatocellular carcinoma., (© 2024. The Author(s).)

It has been reported that the retinal vessel and macular region of the retina are displaced after macular hole (MH) surgery. However, there is no detailed information for correlations between retinal and choroidal displacements. We obtained optical coherence tomography angiography (OCTA) and en-face optical coherence tomography (OCT) images from 24 eyes to measure the retinal and choroidal vascular displacement before and after surgery. These images were merged into infrared images using blood vessel patterns. The same vascular bifurcation points were automatically selected for each follow-up image, and the displacements of the bifurcation points were analyzed as a vector unit for prespecified grid regions in a semi-automated fashion. The results showed displacements of the choroidal intermediate vessels and retinal vessels following MH surgery (p = 0.002, p < 0.001). The topographic changes showed inferior, nasal, and centripetal displacement of the retina and inferiorly displaced choroid. The ILM peeling size and basal MH size were significantly associated with the retinal displacement (p < 0.001 and p = 0.010). Additionally, changes in the amount of the choroidal displacement were significantly correlated with that of the retinal displacements (p = 0.002). Clinicians should keep in mind that there might be topographic discrepancies of the displacement between retina and choroid when analyzing them following surgery., (© 2024. The Author(s).)

The development of intravitreally injected biologic medicines (biologics) acting against vascular endothelial growth factor (VEGF) substantially improved the clinical outcomes of patients with common VEGF-driven retinal diseases. The relatively high cost of branded agents, however, represents a financial burden for most healthcare systems and patients, likely resulting in impaired access to treatment and poorer clinical outcomes for some patients. Biosimilar medicines (biosimilars) are clinically equivalent, potentially economic alternatives to reference products. Biosimilars approved by leading health authorities have been demonstrated to be similar to the reference product in a comprehensive comparability exercise, generating the totality of evidence necessary to support analytical, pre-clinical, and clinical biosimilarity. Anti-VEGF biosimilars have been entering the field of ophthalmology in the US since 2022. We review regulatory and scientific concepts of biosimilars, the biosimilar development landscape in ophthalmology, with a specific focus on anti-VEGF biosimilars, and discuss opportunities and challenges facing the uptake of biosimilars., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Neil M Bressler reported receiving grants from Samsung Bioepis to Johns Hopkins University and receiving grants from Bayer, Biogen, Boehringer Ingelheim, F. Hoffman-LaRoche, Genentech, and Regeneron and having a patent to System and Method for Automated Detection of Age-Related Macular Degeneration and Other Retinal Abnormalities issued. Dr Peter Kaiser reported being a consultant for Allergan, Allgenesis, Bayer, Bausch and Lomb, Biogen Idec, Boehringer Ingelheim, Carl Zeiss Meditec, Coherus, Genentech/Roche, Innovent, Kanghong, Kodiak, Novartis, Ocular Therapeutix, Regeneron, RegenxBio, and Samsung Bioepis. Dr Kyu Hyung Park reported receiving lecture fee and being a consultant for Bayer, Novartis, Roche and Samsung Bioepis. Dr Se Joon Woo reported being a consultant for Samsung Bioepis, Janssen, Novartis, Curacle, Novelty Nobility, Sometech, Rznomics; being an equity owner of Retimark and Panolos Bioscience; receiving grants from Samsung Bioepis, Novelty Nobility, Pharmabcine, Novartis, Alteogen, Geneuintech, and Curacle; and receiving lecture fees from Novartis, Bayer, Allergan, Abbvie, Retimark, and Alcon outside the submitted work. Dr Min Sagong reported being a consultant for and receiving grant support from Samsung Bioepis, Novartis, Bayer, Roche, Allergan/Abbvie, Celltrion, Alteogen, Alcon and Curacle, and receiving lecture fee from Novartis, Bayer, Roche, and Allergan/Abbvie. Dr Mario Bradvica obtained honoraria for presentations by Novartis and Abbvie. He is part of the advisory board of Novartis and obtained grants for clinical trials from Iveric Bio (former Optotech), Novartis, Roche, Ophthea, and Samsung Bioepis. Mercy Yeeun Kim and Seungkee Kim are reported being employees of Samsung Bioepis. Dr SriniVas R Sadda reported receiving honoria as a consultant for 4DMT, Abbvie/Allergan, Alexion, Amgen, Apelis, Astellas, Bayer, Biogen, Boerhinger Ingelheim, Catalyst, Centervue, Roche/Genentech, Gyroscope, Heidelberg, IvericBio, Jannsen, Merck, Nanoscope, Novartis, Optos, Oxurion, Osyterpoint, Eyepoint, Pfizer, Regeneron, Samsung Bioepis, and Vertex Pharmaceuticals. He has also received honoraria for talks given at symposia sponsored by Roche, Novartis, Apellis, Heidelberg, Optos, and Nidek. He has received research funding from Carl Zeiss Meditec and he has received research instruments from Optos, Nidek, Centervue, Topcon, Heidelberg, and Carl Zeiss Meditec. Dr Diana Do and Dr Quan Dong Nguyen declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To demonstrate the therapeutic similarity of CT-P42 compared with reference aflibercept (Eylea) in adult patients with diabetic macular edema (DME)., Design: Randomized, active-controlled, double-masked, phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus with DME involving the center of the macula., Methods: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 ml) by intravitreal injection every 4 weeks (5 doses), then every 8 weeks (4 doses), in the main study period. Results up to week 24 are reported herein., Main Outcome Measures: The primary end point was mean change from baseline at week 8 in best-corrected visual acuity (BCVA) using the ETDRS chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the 2-sided 95% confidence interval (CI) (global assumptions) and 2-sided 90% CI (United States Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set., Results: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). Best-corrected visual acuity improved from baseline to week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the predefined equivalence margin of ±3 letters (95% CI, -0.73 to 1.88 [global]; 90% CI, -0.52 to 1.67 [FDA]). Through week 24, other efficacy results for the 2 groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing ≥1 treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups., Conclusions: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 ml) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P < 0.001). Sarcopenia was associated with extended hospitalization (median: 8 vs. 6 days, P < 0.001) and fasting periods (4 vs. 3 days, P = 0.004), as well as prolonged antibiotic use (9 vs. 7 days, P = 0.039). Sarcopenia was linked to a higher risk of surgery or mortality (9.0% vs. 0%, P = 0.001) and independently predicted this outcome (odds ratio [OR], 11.17; 95% confidence interval [CI], 1.24‒1467.65, P = 0.027). It was prevalent among hospitalized patients with IC, potentially indicating severe IC and a worse prognosis. This underscores the importance of meticulous monitoring, immediate medical intervention, and timely surgical consideration., (© 2024. The Author(s).)

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 μm to 336.38 ± 121.67 μm at the third visit ( p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution ( p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.

Background/aims: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD)., Design: Prospective, double-masked, randomised, phase 3 trial., Methods: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity., Results: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups., Conclusions: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants., Competing Interests: Competing interests: WC, IO and HJ are employed by Samsung Bioepis. Samsung Bioepis funded medical writing support and article processing charges. Additional potential conflicts of interest are listed below. SJW obtained consulting fees from Samsung Bioepis, Janssen, Novartis, Curacle, Novelty Nobility, Sometech, Rznomics and Pharmabcine, grants from Samsung Bioepis, Novelty Nobility, Novartis, Alteogen, Roche, Geneunitech, Bayer, Bio Bank Healing, and Curacle, and payments for lectures from Novartis, Bayer, and Allergan-Abbvie. He serves as equity owner of Retimark and Panolos Bioscience. SRS obtained consulting fees from Apellis, Amgen, Abbvie/Allergan, Samsung Bioepis, Biogen, Boerhinger Ingelheim, Iveric, Novartis, Roche, Bayer, Regeneron, Pfizer, Astellas, Nanoscope, Jannsen, Centervue, Optos and Heidelberg, and honoraria for lectures from Novartis, Roche, Optos, and Heidelberg. He is part of the Data Safety Monitoring/Advisory Board of Regeneron and holds leadership/fiduciary functions in ARVO and Macula Society. MB obtained honoraria for presentations by Novartis and Abbvie. He is part of the advisory board of Novartis and obtained grants for clinical trials from Iveric Bio (former Optotech), Novartis, Roche, Ophthea and Samsung Bioepis. AV obtained consulting fees and honoraria for lectures from Novartis, Roche, Pfizer, Bausch & Lomb, Zeiss, and Alcon. He also obtained support for meeting attendances by Novartis, Pfizer, Bausch & Lomb, Roche, Zeiss, Alcon, Iveric Bio, Amgen, Chengdu, Mylan, Panoptica, Formycon, Thrombogenics, Regeneron and Clearside. He is part of the Data Safety Monitoring/Advisory Board of Zeiss, Bayer, Novartis, Pfizer, and Roche. MS obtained grants from Allergan/Abbvie, Bayer and Novartis, consulting fees from Samsung Bioepis, Bayer, Novartis, Allergan/Abbvie, Roche, Alcon and Curacle, honoraria for lectures from Samsung Bioepis, Bayer, Novartis, Allergan/Abbvie, Roche, Alcon and Johnson & Johnson, and support for meeting attendances from Bayer, Allergan/Abbvie and Novartis. Min Sagong is part of the Data Safety Monitoring/Advisory board of Bayer, Novartis, and Allergan/Abbvie. JS obtained consulting fees from Abbvie and support for meeting attendances from Bayer. MV obtained consulting fees from Abbvie and Roche and support for meeting attendances from Bayer. EW obtained honoraria for lectures from Bayer, Roche, Alfa Sigma, Allergan, Zeiss and Thea, and is part of the advisory board of Allergan. SP obtained grants from Aerie, Aerpio, Allergan, Allgenesis, Apellis, Boehringer Ingelheim, Chengdu Kanghong, Clearside, EyePoint, Genentech-Roche, Ionis Pharmaceuticals, IVERIC Bio, KalVista, Kodiak Sciences, Mylan, Novartis, Oculis, Opthea, Ora, Oxurion, Regeneron, Samsung, SmileBiotek, Stealth Biotherapeutics, ThromboGenics, Xbrane Biopharma, consulting fees from AiViva, Allergan, Allgenesis, Genentech-Roche, Kala, Kodiak Sciences, Oxugenix, and RegenxBio, and support for travel expenses from EyePoint. He is part of the Data Safety Monitoring/Advisory Board of Allergan, Allgenesis Biotherapeutics, Genentech-Roche, Kodiak Sciences, and Iveric Bio and serves as equity owner and chief medical officer for Allgenesis Biotherapeutics. WC received consulting fees from Samsung Bioepis and payments for lectures from Bayer, Novartis and Chong Kun Dang., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the 2000s, the Y439 lineage of H9N2 avian influenza virus (AIV) has been the predominant strain circulating in poultry in Korea; however, in 2020, the Y280 lineage emerged and spread rapidly nationwide, causing large economic losses. To prevent further spread and circulation of such viruses, rapid detection and diagnosis through active surveillance programs are crucial. Here, we developed a novel H9 rRT-PCR assay that can detect a broad range of H9Nx viruses in situations in which multiple lineages of H9 AIVs are co-circulating. We then evaluated its efficacy using a large number of clinical samples. The assay, named the Uni Kor-H9 assay, showed high sensitivity for Y280 lineage viruses, as well as for the Y439 lineage originating in Korean poultry and wild birds. In addition, the assay showed no cross-reactivity with other subtypes of AIV or other avian pathogens. Furthermore, the Uni Kor-H9 assay was more sensitive, and had higher detection rates, than reference H9 rRT-PCR methods when tested against a panel of domestically isolated H9 AIVs. In conclusion, the novel Uni Kor-H9 assay enables more rapid and efficient diagnosis than the "traditional" method of virus isolation followed by subtyping RT-PCR. Application of the new H9 rRT-PCR assay to AI active surveillance programs will help to control and manage Korean H9 AIVs more efficiently., (© 2023. The Author(s), under exclusive licence to Microbiological Society of Korea.)

We investigated predictors of visual outcomes and injection interval in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) treated with a treat-and-extend (TAE) regimen. All 48 patients in a multicenter study were followed for 52 weeks and received three monthly intravitreal aflibercept injections before the TAE regimen, with treatment intervals adjusted by 4 weeks, up to a maximum of 16 weeks. Various laboratory biomarkers and optical coherence tomography parameters were evaluated. Patients were classified into the extension failure group if they had ≥ 1 treatment interval decreased due to an increase in the central macular thickness compared to the previous visit and 18 patients were assigned to this group. In multivariate logistic analyses, presence of microaneurysms and prominent middle limiting membrane (p-MLM) sign, increased initial external limiting membrane (ELM) disruption, and higher total cholesterol were correlated with inhibiting a sustained extension in the injection interval (P = 0.015, P = 0.032, P = 0.037, P = 0.009, respectively). Therefore, in the patients with ME secondary to BRVO with these risk factors, early consideration of frequent injection may improve treatment outcome., (© 2023. The Author(s).)

Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy., Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD)., Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up., Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56., Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity., Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable., Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD., Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.

High pathogenicity avian influenza (HPAI) viruses of clade 2.3.4.4 H5Nx have been circulating in poultry and wild birds worldwide since 2014. In South Korea, after the first clade 2.3.4.4b H5N1 HPAI viruses were isolated from wild birds in October 2021, additional HPAIV outbreaks occurred in poultry farms until April 2022. In this study, we genetically characterized clade 2.3.4.4b H5N1 HPAIV isolates in 2021-2022 and examined the pathogenicity and transmissibility of A/mandarin duck/Korea/WA585/2021 (H5N1) (WA585/21) in chickens and ducks. Clade 2.3.4.4b H5N1 HPAI viruses caused 47 outbreaks in poultry farms and were also detected in multiple wild birds. Phylogenetic analysis of HA and NA genes indicated that Korean H5N1 HPAI isolates were closely related to Eurasian viruses isolated in 2021-2022. Four distinct genotypes of H5N1 HPAI viruses were identified in poultry, and the majority were also found in wild birds. WA585/21 inoculated chickens showed virulent pathogenicity with high mortality and transmission. Meanwhile, ducks infected with the virus showed no mortality but exhibited high rates of transmission and longer viral shedding than chickens, suggesting that they may play an important role as silent carriers. In conclusion, consideration of both genetic and pathogenic traits of H5N1 HPAI viruses is required for effective viral control.

An efficient synthetic approach for chiral malonates was established via enantioselective phase transfer catalysis. The α-alkylation of 2,2-diphenylethyl tert-butyl α-methylmalonates with (S,S)-3,4,5-trifluorophenyl-NAS bromide as a phase-transfer catalyst under phase-transfer catalytic conditions successfully produced corresponding α-methyl-α-alkylmalonates; these compounds are versatile chiral building blocks containing a quaternary carbon center in high chemical yields (up to 99%) with excellent enantioselectivities (up to 98% ee). α,α-Dialkylmalonates were selectively hydrolyzed to the corresponding chiral malonic monoacids under basic (KOH/MeOH) and acidic conditions (TFA/CH 2 Cl 2 ), showing the practicality of the method., 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 Guo, Oh, Sagong, Yang, Lee and Park.)

Worldwide, high pathogenic avian influenza viruses belonging to clades 2.3.4.4 and 2.3.2.1 have been circulating in both poultry and wild birds. Since 2018, Korea has built a national antigen bank to ensure preparedness in an emergency. In this study, we developed a bivalent vaccine candidate containing antigens derived from two reassortant KA435/2.3.2.1d and H35/2.3.4.4b strains for Korean national antigen bank. We evaluated its immunogenicity and protective efficacy in specific pathogen free chickens. The two vaccine strains, rgKA435-H9N2 PB2/2.3.2.1d and rgH35/2.3.4.4b, both of which were generated successfully by reverse genetics, were highly immunogenic (titres of haemagglutination inhibition: 8.3 and 8.4 log 2 , respectively) and showed good protective efficacy (100 and 147 50% protective dose, respectively) against lethal challenge with wild-type virus when delivered as a 1:1 mixture. Notably, the vaccine provided complete protection against viral shedding at a full dose (512 HAU) and a 1/10 dose (51.2 HAU), with no clinical signs, after challenge with H35/2.3.4.4b. The bivalent vaccine developed in this study may reduce the cost of vaccine production and could be used as a H5 subtype avian influenza vaccine candidate against two clades simultaneously., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Polypoidal choroidal vasculopathy (PCV) is characterized by choroidal vascular abnormalities including polypoidal lesion and branching vascular networks. Not only choroidal structural changes, but also choroidal hyperpermeability and congestion are also thought to be involved in pathogenesis of PCV. We investigated choroidal vascular brightness intensity (CVB) using ultra-widefield indocyanine green angiography (UWF-ICGA) images and analyzed its association with clinical features in patients with PCV. In this study, 33 eyes with PCV and 27 eyes of age-matched controls were included. CVB was measured by extracting the enhanced pixels of choroidal vessels after the reference brightness across the images was adjusted to be uniform. Associations between choroidal vascular features and the clinical features of PCV were also determined. The mean CVB was higher in PCV than control eyes, regardless of the segmented region (all p < 0.001). CVB was also higher at the posterior pole than at the periphery, and the inferior quadrants were brighter than the superior quadrants in both the PCV and control group (all p < 0.05). In affected eyes, CVB was higher than in unaffected fellow eyes at the posterior pole, whereas there was no difference at the periphery. Posterior pole CVB correlated significantly with subfoveal choroidal thickness (r = 0.502, p = 0.005), polyp number (r = 0.366 p = 0.030), and the greatest linear dimension (r = 0.680, p = 0.040). Greatest linear dimension was positively correlated with CVB at posterior pole (p = 0.040), whereas SFCT or CVD in all regions didn't show the significant correlation. The UWF ICGA results showed an increase in CVB at the inferior quadrants and posterior pole, suggesting venous outflow congestion in PCV eyes. CVB might provide more substantial information on the phenotype than other choroidal vascular features., (© 2023. The Author(s).)

For the early detection of avian influenza virus (AIV), molecular diagnostic methods such as real-time RT-PCR (rRT-PCR) are the first choice in terms of accuracy and speed in many countries. A laboratory's capability to perform this diagnostic method needs to be measured through external and independent assessment to ensure that the method is validated within the laboratory and in interlaboratory comparison. The Animal and Plant Quarantine Agency of Korea has implemented five rounds of proficiency testing (PT) for rRT-PCR targeting local veterinary service laboratories involved in the AIV national surveillance program from 2020 to 2022. In each round, a portion composed of six or more samples was selected from the entire PT panel consisting of H5, H7, and H9 viruses isolated in Korea and distributed to each participant, and at least one pair of samples was commonly included in each panel for interlaboratory comparison. During the five rounds of PT, a few incorrect and outlying results were detected that required immediate inspection or corrective actions. However, in the quantitative measurement of Ct values, the average standard deviation or coefficient of variation decreased as multiple PT rounds progressed, and a positive correlation between consecutive rounds of PT was observed since 2021. The better consistency or stability in the experimental performance appeared to contribute to the more harmonized results in the latest PTs, and it is assumed that the positive reaction of participants to the challenges of quantitative assessment reports showing their status intuitively might work. We need to continue operating the PT program for local laboratories because they play crucial roles at the front line of the national avian influenza surveillance program, and frequent changes in the human resources or environment for diagnosis in those laboratories are inevitable.

Importance: Until now, other than complex neurologic tests, there have been no readily accessible and reliable indicators of neurologic dysfunction among patients with Parkinson disease (PD). This study was conducted to determine the role of fundus photography as a noninvasive and readily available tool for assessing neurologic dysfunction among patients with PD using deep learning methods., Objective: To develop an algorithm that can predict Hoehn and Yahr (H-Y) scale and Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score using fundus photography among patients with PD., Design, Settings, and Participants: This was a prospective decision analytical model conducted at a single tertiary-care hospital. The fundus photographs of participants with PD and participants with non-PD atypical motor abnormalities who visited the neurology department of Kangbuk Samsung Hospital from October 7, 2020, to April 30, 2021, were analyzed in this study. A convolutional neural network was developed to predict both the H-Y scale and UPDRS-III score based on fundus photography findings and participants' demographic characteristics., Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) was calculated for sensitivity and specificity analyses for both the internal and external validation data sets., Results: A total of 615 participants were included in the study: 266 had PD (43.3%; mean [SD] age, 70.8 [8.3] years; 134 male individuals [50.4%]), and 349 had non-PD atypical motor abnormalities (56.7%; mean [SD] age, 70.7 [7.9] years; 236 female individuals [67.6%]). For the internal validation data set, the sensitivity was 83.23% (95% CI, 82.07%-84.38%) and 82.61% (95% CI, 81.38%-83.83%) for the H-Y scale and UPDRS-III score, respectively. The specificity was 66.81% (95% CI, 64.97%-68.65%) and 65.75% (95% CI, 62.56%-68.94%) for the H-Y scale and UPDRS-III score, respectively. For the external validation data set, the sensitivity and specificity were 70.73% (95% CI, 66.30%-75.16%) and 66.66% (95% CI, 50.76%-82.25%), respectively. Lastly, the calculated AUROC and accuracy were 0.67 (95% CI, 0.55-0.79) and 70.45% (95% CI, 66.85%-74.04%), respectively., Conclusions and Relevance: This decision analytical model reveals amalgamative insights into the neurologic dysfunction among PD patients by providing information on how to apply a deep learning method to evaluate the association between the retina and brain. Study data may help clarify recent research findings regarding dopamine pathologic cascades between the retina and brain among patients with PD; however, further research is needed to expand the clinical implication of this algorithm.

Prior to the identification of low pathogenic avian influenza H9N2 viruses belonging to the Y280 lineage in 2020, Y439 lineage viruses had been circulating in the Republic of Korea since 1996. Here, we developed a whole inactivated vaccine (vac564) by multiple passage of Y439 lineage viruses and then evaluated immunogenicity and protective efficacy in specific-pathogen-free chickens. We found that LBM564 could be produced at high yield in eggs (10 8.4 EID 50 /0.1 mL; 1024 hemagglutinin units) and was immunogenic (8.0 ± 1.2 log 2 ) in chickens. The vaccine showed 100% inhibition of virus in the cecal tonsil with no viral shedding detected in either oropharyngeal or cloacal swabs after challenge with homologous virus. However, it did not induce effective protection against challenge with heterologous virus. An imported commercial G1 lineage vaccine inhibited viral replication against Y280 and Y439 lineage viruses in major tissues, although viral shedding in oropharyngeal and cloacal swabs was observed up until 5 dpi after exposure to both challenge viruses. These results suggest that a single vaccination with vac564 could elicit immune responses, showing it to be capable of protecting chickens against the Y439 lineage virus. Thus, our results suggest the need to prepare suitable vaccines for use against newly emerging and re-emerging H9N2 viruses.

Although many studies demonstrated the differences of clinical features, natural course, and response to treatment between typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), differential microRNAs (miRNAs) expression in the aqueous humor (AH) between them has not been reported yet. We investigated the roles of miRNAs in the AH of patients with typical AMD and PCV using next-generation sequencing (NGS) and quantitative PCR (qPCR). Target genes and predicted pathways of miRNAs were investigated via pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database. A total of 161 miRNAs from eyes with typical AMD and 185 miRNAs from eyes with PCV were differentially expressed. 33 miRNAs were commonly upregulated, and 77 miRNAs were commonly downregulated in both typical AMD and PCV groups. Among them, hsa-miR-140-5p, hsa-miR-374c-3p, and hsa-miR-200a-5p were differentially expressed and were predicted to regulate proteoglycans in cancer, p53 signaling pathway, Hippo signaling pathway, and adherens junction. The differential expression profiles and target gene regulation networks of AH miRNAs may contribute to the development of different pathological phenotypes in typical AMD and PCV. The results of this study provide novel insights into the pathogenesis, associated prognostic biomarkers, and therapeutic targets in AMD and PCV., (© 2023. The Author(s).)

Introduction: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD)., Methods: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid., Results: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months., Conclusion: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months., (© 2023 S. Karger AG, Basel.)

Purpose: To evaluate plasma antiretinal autoantibody (ARA) profiling and diagnostic efficacy for autoimmune retinopathy (AIR)., Design: A multicenter, diagnostic evaluation study., Methods: Forty-nine patients with a clinical diagnosis of AIR, disease controls including 20 patients with retinitis pigmentosa (RP), and 30 normal controls were included. Plasma samples from patients were analyzed for the presence of 6 ARAs, including recoverin, α-enolase, carbonic anhydrase II, heat shock protein 60, aldolase C, and cone-rod homeobox/cone-rod retinal dystrophy 2 using western blotting., Results: Autoantibody detection rates against cone-rod homeobox/cone-rod retinal dystrophy 2, heat shock protein 60, and aldolase C in AIR were 67.3%, 40.8%, and 42.9%, respectively, which were higher than those in RP and normal controls (P < .001, P < .001, and P = .007, respectively), but recoverin, α-enolase, and carbonic anhydrase II were not different from other control groups (P = .117, P = .774, and P = .467, respectively). Among ARAs, antirecoverin antibody was the most specific, as it was found in 3 (6.1%) patients with AIR and none of the control groups. As the number of detected ARAs increased, the probability of AIR increased (odds ratio: 1.913; P < .001; 95% confidence interval: 1.456-2.785). The positive number of ARAs was significantly higher when photoreceptor disruption was observed on optical coherence tomography, or severe dysfunction was observed in electroretinography (P = .022 and P = .029, respectively)., Conclusions: The profiles of ARAs in the AIR group were different from those in the RP and normal controls. The higher number of positive ARAs suggests a higher possibility of AIR diagnosis. ARAs should be used as adjunct tools for the clinical diagnosis of AIR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The H9N2 avian influenza (AI) has become endemic in poultry in many countries since the 1990s, which has caused considerable economic losses in the poultry industry. Considering the long history of the low pathogenicity H9N2 AI in many countries, once H9N2 AI is introduced, it is more difficult to eradicate than high pathogenicity AI. Various preventive measures and strategies, including vaccination and active national surveillance, have been used to control the Y439 lineage of H9N2 AI in South Korea, but it took a long time for the H9N2 virus to disappear from the fields. By contrast, the novel Y280 lineage of H9N2 AI was introduced in June 2020 and has spread nationwide. This study reviews the history, genetic and pathogenic characteristics, and control strategies for Korean H9N2 AI. This review may provide some clues for establishing control strategies for endemic AIV and a newly introduced Y280 lineage of H9N2 AI in South Korea., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Korean Society of Veterinary Science.)

Purpose: To investigate features of central serous chorioretinopathy with choroidal neovascularization (CNV) on multimodal imaging and analyze their association with treatment response., Methods: A total of 37 patients with chronic central serous chorioretinopathy complicated by CNV were divided into bevacizumab and photodynamic therapy groups, and each group was subdivided into responders and nonresponders according to subretinal fluid status at 3 months. We assessed multimodal imaging parameters (subfoveal choroidal thickness; vortex vein engorgement; choroidal vascular hyperpermeability; and CNV morphologic pattern, area, and vessel density) and analyzed their association with treatment responses., Results: Responders in the bevacizumab group showed thinner subfoveal choroidal thickness (384.0 ± 103.2 vs. 398.3 ± 87.1 µm, P = 0.042), smaller CNV area (0.512 ± 0.267 vs. 1.323 ± 0.481 mm2, P = 0.007), open-circuit pattern (84.6% vs. 12.5%, P < 0.001), and capillary fringe (69.2% vs. 37.5%, P = 0.001) than nonresponders. Responders in the photodynamic therapy group had thicker subfoveal choroidal thickness (420.1 ± 93.5 vs. 395.7 ± 6.5 µm, P = 0.021), more quadrants with engorged vortex veins extending to the macula (P = 0.012), and intense choroidal vascular hyperpermeability (57.1% vs. 50.0%, P = 0.026) than nonresponders. Choroidal neovascularization showing closed-circuit pattern (85.7% vs. 0%, P = 0.001) and peripheral loop (64.3% vs. 0%, P = 0.001) demonstrated a good response to photodynamic therapy., Conclusion: Heterogeneous features of choroidal hyperpermeability, thickness, and CNV morphology in CNV accompanying central serous chorioretinopathy are associated with different therapeutic responses to bevacizumab and photodynamic therapy treatments.

Purpose: To compare the clinical features, treatments, and outcomes between bullous and chronic variants of central serous chorioretinopathy (CSC)., Design: Retrospective, observational case series., Participants: Sixty-two eyes of 44 patients with bullous-variant CSC (bvCSC) and 97 eyes of 85 patients with nonbullous CSC., Methods: We conducted a national survey between September 1, 2020, and March 31, 2021, of members of the Korean Retina Society and obtained data of patients with bvCSC from 11 retinal centers. A comparator group comprised consecutive chronic CSC patients without bullous detachment., Main Outcome Measures: Baseline demographics and patient characteristics were compared between groups. Secondary outcomes included factors associated with visual prognosis within the bvCSC group., Results: Compared with the nonbullous CSC group, the bvCSC group presented at a younger age (49 vs. 52 years; P = 0.047) and with more bilateral involvement (41% vs. 14%; P < 0.001). Systemic corticosteroid use was more prevalent in the bvCSC group, both in terms of any exposure (50% vs. 20%; P = 0.001) and long-term exposure (36% vs. 9%; P <  0.001). The bvCSC group had distinct imaging features (all P < 0.05): retinal folding (64% vs. 1%), subretinal fibrin (75% vs. 13%), multiple retinal pigment epithelium tears (24% vs. 2%), and multifocal fluorescein leakages with terminal telangiectasia (36% vs. 1%). Although bvCSC patients had worse vision at diagnosis (20/80 vs. 20/44; P =  0.003), treatment response was more robust (fluid resolution by final follow-up, 84% vs. 68%; P = 0.034) even with conservative management, resulting in similar final vision (20/52 vs. 20/45; P =  0.52). History of kidney-related (odds ratio [OR] 5.4; 95% confidence interval [CI] 1.3-18.5; P =  0.045) and autoimmune/rheumatoid diseases (OR 25.4, 95% CI 2.8-195.0; P =  0.004) showed associations with the bvCSC group. Apart from vision at diagnosis (OR 0.1, 95% CI 0.05-0.36; P  <  0.001), a history of renal transplantation was most predictive of visual prognoses for bvCSC eyes (OR 0.2, 95% CI 0.04-0.75; P  =  0.020)., Conclusions: Bullous-variant CSC may be associated with pathogenic risk factors based on underlying medical conditions and systemic corticosteroid use. Poor vision at diagnosis and history of renal transplantation were associated with poor visual outcome., (Copyright © 2022. Published by Elsevier Inc.)

The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P < 0.001). Only baseline BCVA was associated with VA gain at 12 months (Odds ratio = 3.53, P < 0.001). This study demonstrated that there was no difference in 12 month visual outcomes among treatments and a better early visual outcome can be expected with anti-VEGF monotherapy., (© 2022. The Author(s).)

High pathogenicity H5N1 avian influenza viruses pose a threat to both animal and human health worldwide. In late 2020, outbreaks of H5 high pathogenicity avian influenza viruses belonging to clade 2.3.4.4b emerged in Europe, following on from outbreaks in East Asia in earlier years. However, very recent studies show that clade 2.3.4.4b H5N1, rather than 2.3.4.4b H5N8, has become predominant in wild birds and has infected poultry in several countries. In this study, we describe isolation of a novel H5N1 virus from a captured mandarin duck in South Korea, and another H5N1 virus from a quail farm. We performed genetic analysis of these two viruses to identify their origin and to determine their relationship with the clade 2.3.4.4b H5N1 viruses currently circulating in Europe. Based on our results, it is presumed that the novel H5N1 virus isolated in Korea originated from an unknown reassortant between clade 2.3.4.4b H5N8 viruses circulating from 2020 and other Eurasian viruses, with additional reassortment of genes and point mutations that discriminate them from the recently reported H5N1 virus in Europe., (© 2022 Wiley-VCH GmbH.)

To evaluate the real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) in Korea, focusing on retinal fluid resolution. This multi-institutional retrospective chart review study, analyzed medical records of patients with nAMD (age ≥ 50 years) who received their first anti-vascular endothelial growth factor (VEGF) treatment in ophthalmology clinics across South Korea between January 2017 and March 2019. The primary endpoint was the proportion of patients with retinal fluid after 12 months of anti-VEGF treatment. The association between fluid-free period and VA gains was also evaluated. A total of 600 patients were enrolled. At baseline, 97.16% of patients had retinal fluid; after 12 months of anti-VEGF treatment, 58.10% of patients had persistent retinal fluid. VA improvements were relatively better in patients with absence of retinal fluid compared with presence of retinal fluid (+ 12.29 letters vs. + 6.45 letters at month 12; P < .0001). Longer duration of absence of retinal fluid over first 12 months correlated with better VA gains at month 12 (P < .01). More than half of the study patients with nAMD had retinal fluid even after 12 months of treatment with their current anti-VEGF. Presence of retinal fluid was associated with relatively worse VA outcomes., (© 2022. The Author(s).)

Aims: To investigate the structure of multilayered pigment epithelial detachment (m-PED) in neovascular age-related macular degeneration, and its association with visual prognosis and the progression of fibrotic scars at 12 months., Methods: We retrospectively analysed 68 eyes of 63 patients with m-PED that included a prechoroidal cleft. The compartments within m-PED were divided into neovascular tissue (layer 1), a hyper-reflective band (layer 2), and a prechoroidal cleft (layer 3). Clinical variables were compared between patients manifesting layer 2 and those who did not. Multiple regression analyses were used to find the factors related to visual outcome and fibrotic scar formation., Results: Layer 2 was detected in 38 (55.9 %) of 68 eyes. With continuous treatment, the group with layer 2 showed gradual visual deterioration (p<0.001 at month 12), while the group without layer 2 showed visual improvement (p<0.001 at month 12). In the group with layer 2, the thickness of layer 2 significantly increased, and in the group without layer 2, if it formed, it increased gradually (p=0.004 at month 12). In both groups, other layers significantly decreased by month 12. The presence of layer 2 at baseline was significantly associated with a poor visual outcome (p=0.009) and fibrotic scar formation (p=0.023)., Conclusions: The m-PED with layer 2 had a higher risk of fibrotic scar formation and was associated with a poor visual prognosis. Layer 2 may be an early stage precursor of a fibrotic scar., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetic retinopathy (DR) is characterized by microvascular changes including ischemia. Degradation and metabolic changes of various retinal cells occur during ischemia. Ischemic region containing more cells will lead to greater metabolic impairment. We analyzed the non-perfusion region (NPR) by integrating histologic mapping with ultra-widefield fluorescein angiography (UWF FA) images. We also investigated the correlations of the weighted ischemic index (ISI) considering the regional distribution of retinal cells with cytokines, macular edema (ME), and neovascularization (NV). In this study, 32 patients with treatment-naïve DR and 21 age-matched control participants were included. The difference between the non-weighted and weighted ISI of NPR with leakage was greatest at the posterior region. The weighted ISI of NPR with leakage was correlated with MCP-1, IL-8, IL-6, PlGF, and VEGF-A levels, while the non-weighted ISI of NPR with leakage was correlated with IL-8 and IL-6 levels. The presence of baseline ME or NV in patients with DR was associated with the weighted ISI, with a stronger association when cones and rods were weighted. The weighted ISI reflecting both metabolic activity and cell distribution demonstrated a better correlation with clinical features and was more valuable in NPR with leakage than non-weighted ISI, which previous studies conventionally used., (© 2022. The Author(s).)

Purpose: This study aims to evaluate choroidal vascular alterations in patients with central serous chorioretinopathy (CSC) using ultra-widefield (UWF) indocyanine green angiography (ICGA)., Methods: This was a retrospective case-control study conducted at a single tertiary eye center. In total, 36 eyes in patients with either unilateral (24 patients) or bilateral (six patients) treatment-naïve CSC and 30 eyes in 24 age-matched controls were evaluated. The number of quadrants with vortex vein engorgement on UWF ICGA was evaluated. Dilated choroidal vessels affecting the macula were regarded as extended vortex vein engorgement. Choroidal vascular hyperpermeability (CVH) area on late-phase ICGA was quantified using stereographic projection. The parameters were compared with clinical and optical coherence tomographic findings., Results: Eyes with CSC had larger CVH area, thicker choroid, and more quadrants with vortex vein engorgement and extended vortex vein engorgement compared with control eyes (all P < 0.001). In patients with unilateral CSC, affected eyes had larger CVH area, thicker choroid, and more extended vortex vein engorgements compared with unaffected fellow eyes (all P < 0.001), but vortex vein engorgement did not significantly differ. CVH was significantly correlated with extended vortex vein engorgement (P < 0.001) and subfoveal choroidal thickness (P = 0.007)., Conclusions: The increased number and binocular symmetry of engorged vortex veins suggest an anatomical predisposition for CSC. CVH area and extended vortex vein engorgement were indicators of choroidal outflow congestion. These parameters may serve as diagnostic clues or predictors of disease development in eyes with CSC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To develop an automated diabetic retinopathy (DR) staging system using optical coherence tomography angiography (OCTA) images with a convolutional neural network (CNN) and to verify the feasibility of the system., Methods: In this retrospective cross-sectional study, a total of 918 data sets of 3 × 3 mm2 OCTA images and 917 data sets of 6 × 6 mm2 OCTA images were obtained from 1118 eyes. A deep CNN and four traditional machine learning models were trained with annotations made by a retinal specialist based on ultra-widefield fluorescein angiography. Separately, the same images of the test data sets were independently graded by two human experts. The results of the CNN algorithm were compared with those of traditional machine learning-based classifiers and human experts., Results: The proposed CNN achieved an accuracy of 0.728, a sensitivity of 0.675, a specificity of 0.944, an F1 score of 0.683, and a quadratic weighted κ of 0.908 for a six-level staging task, which were far superior to the results of traditional machine learning methods or human experts. The CNN algorithm showed a better performance using 6 × 6 mm2 rather than 3 × 3 mm2 sized OCTA images and using combined data rather than a separate OCTA layer alone., Conclusions: CNN-based classification using OCTA images can provide reliable assistance to clinicians for DR classification., Translational Relevance: This CNN algorithm can guide the clinical decision for invasive angiography or referrals to ophthalmology specialists, helping to create more efficient diagnostic workflow in primary care settings.

As the prevalence of diabetes increases, millions of people need to be screened for diabetic retinopathy (DR). Remarkable advances in technology have made it possible to use artificial intelligence to screen DR from retinal images with high accuracy and reliability, resulting in reducing human labor by processing large amounts of data in a shorter time. We developed a fully automated classification algorithm to diagnose DR and identify referable status using optical coherence tomography angiography (OCTA) images with convolutional neural network (CNN) model and verified its feasibility by comparing its performance with that of conventional machine learning model. Ground truths for classifications were made based on ultra-widefield fluorescein angiography to increase the accuracy of data annotation. The proposed CNN classifier achieved an accuracy of 91-98%, a sensitivity of 86-97%, a specificity of 94-99%, and an area under the curve of 0.919-0.976. In the external validation, overall similar performances were also achieved. The results were similar regardless of the size and depth of the OCTA images, indicating that DR could be satisfactorily classified even with images comprising narrow area of the macular region and a single image slab of retina. The CNN-based classification using OCTA is expected to create a novel diagnostic workflow for DR detection and referral., (© 2021. The Author(s).)

Purpose: Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region., Methods: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region., Results: Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable., Conclusions: T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients., Competing Interests: Conflicts of interest: VC: honoraria from Bayer, Novartis, Roche for lecture fees and research grants from Bayer, Roche; MS: honoraria from Allergan, Bayer, Novartis, Roche for lecture fees, consultancy and board membership, research grants from Allergan, Bayer, Novartis; TL: honoraria from Allergan, Bayer, Boehringer Ingelheim, Novartis, Roche for consultancy, research grants from Novartis and Roche; GT: honoraria from Allergan, Bayer, Roche, Novartis, Topcon, and research grant from Leica and Santen; NF: honoraria from Bayer, Novartis, and Allergan for lecture fees; MO: honoraria from Bayer, Novartis, Santen, Kowa, Otsuka for lecture fees, research grants from Alcon, Bayer, Hoya, Novartis, Otsuka, Santen, Senju, and consultancy fees from Allergan, Bayer, Chengdu Kanghong Biotechnology, Chugai, Novartis; PM: N/A;, (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Zoonotic infection with avian influenza viruses (AIVs) of subtype H7, such as H7N9 and H7N4, has raised concerns worldwide. During the winter of 2020-2021, five novel H7 low pathogenic AIVs (LPAIVs) containing different neuraminidase (NA) subtypes, including two H7N3, an H7N8, and two H7N9, were detected in wild bird feces in South Korea. Complete genome sequencing and phylogenetic analysis showed that the novel H7Nx AIVs were reassortants containing two gene segments (hemagglutinin (HA) and matrix) that were related to the zoonotic Jiangsu-Cambodian H7 viruses causing zoonotic infection and six gene segments originating from LPAIVs circulating in migratory birds in Eurasia. A genomic constellation analysis demonstrated that all H7 isolates contained a mix of gene segments from different viruses, indicating that multiple reassortment occurred. The well-known mammalian adaptive substitution (E627K and D701N) in PB2 was not detected in any of these isolates. The detection of multiple reassortant H7Nx AIVs in wild birds highlights the need for intensive surveillance in both wild birds and poultry in Eurasia.