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Min Seok Kim,1 Jasmine Choi,2 Hyeong Du Lee,3 Se Joon Woo1 On behalf of the Korea Ozurdex Post-Marketing Surveillance Study Group1Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Allergan, an AbbVie Company, Irvine, CA, USA; 3Allergan, an AbbVie Company, Seoul, KoreaCorrespondence: Se Joon WooDepartment of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of KoreaTel +82-31-787-7377Fax +82-31-787-4057Email sejoon1@snu.ac.krPurpose: To supplement established efficacy and safety data, this analysis evaluated the real-world use of dexamethasone (DEX) intravitreal implant 700 μg for retinal vein occlusion (RVO)-related macular edema in an Asian population and baseline factors potentially associated with DEX implant efficacy.Patients and Methods: A prospective, observational, post-marketing surveillance study was conducted at 38 sites in South Korea in patients consecutively presenting with macular edema following branch or central RVO (BRVO, CRVO), and administered a first DEX implant. Follow-up visits and subsequent DEX or other therapies conformed with local practice. Outcome measures included best-corrected visual acuity (BCVA), change in BCVA from baseline, responder rates, and adverse events. Associations between baseline characteristics and BCVA gains were evaluated. Month-1, -2, -4, and -6 visit analysis windows were established.Results: In all, 700 patients (79.1% BRVO, 20.9% CRVO) received 1.12 DEX implants (mean) and were followed for 101.5 days (standard deviation, 51.7); 90% received a single implant. Among patients with analyzable data, mean BCVA improved from baseline with peak changes in Month 2 of − 0.193 and − 0.212 LogMAR, (P < 0.0001) and remained significant in the BRVO subgroup at the Month 4 and 6 windows (P < 0.0001 and P = 0.0039, respectively). Treatment-naïve patients experienced greater BCVA increases. The proportion of patients with stable/improved BCVA tended to decrease after Month 2 through Month 6 and the decline was greater in the CRVO subgroup. At the Month-2 window, ≥ 1-, 2- and 3-line increases were positively associated with younger age, worse baseline BCVA, and treatment naivety. The most common adverse event was increased intraocular pressure.Conclusion: In the real-world clinical setting in South Korea, DEX implant improved visual acuity and had a favorable safety profile similar to that reported in randomized controlled trials and observational European and North American studies. These data further support the value of DEX implant as a treatment option for RVO.ClinicalTrials.gov Identifier: NCT01976650. Date of registration: November 6, 2013.Keywords: retinal vein occlusion, dexamethasone, intravitreal, implant, post-marketing, real world

Min Sagong,1 Se Joon Woo,2 Youkyung Lee3 On behalf of the LUMINOUS™ study investigators from South Korea1Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea; 2Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea; 3Novartis Korea Ltd., Seoul, KoreaCorrespondence: Se Joon WooDepartment of Ophthalmology, Seoul National University Bundang Hospital, 173– 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, South KoreaTel +82-31-787-7377Fax +82-31-787-4057Email sejoon1@snu.ac.krPurpose: To evaluate the real-world effectiveness, treatment patterns, and safety of ranibizumab in Korean patients with neovascular age-related macular degeneration (nAMD).Methods: LUMINOUS™ is a 5-year, global, prospective, observational, open-label study. Adults aged ≥ 18 years who were either treatment-naïve or prior-treated were enrolled and treated with ranibizumab 0.5 mg as per the local label. Outcome measures included mean (± standard deviation [SD]) changes from baseline in visual acuity (VA) and central retinal thickness (CRT), and rate of ocular and non-ocular adverse events (AEs).Results: Overall, 367 Korean patients with nAMD (152 treatment-naïve and 215 prior-treated) were enrolled. The mean (SD) VA changes from baseline at 1-year were +10.1 (± 21.77; P=0.0005) and +1.4 (± 15.17; P=0.2142) Early Treatment Diabetic Retinopathy Study letters, with mean numbers of injections of 5.2 and 3.4 in the treatment-naïve and prior-treated groups, respectively. VA gains were greater in patients with lower baseline VA, who received a loading dose, and with polypoidal choroidal vasculopathy (PCV). Multivariate logistic regression analyses demonstrated younger age, worse baseline VA, and those who received loading dose being associated with higher odds of any gain in VA at 1 year (P< 0.05). Mean (SD) CRT changes from baseline were – 126.7 (± 174.90) μm (P< 0.0001) and +10.8 (± 89.62) μm (P=0.5833) in the treatment-naïve and prior-treated groups, respectively, with greater reductions observed in patients with PCV. Ocular and non-ocular AEs were reported in 8.4% (n=31) and 10.1% (n=37) of patients, respectively.Conclusion: The LUMINOUS study confirms real-world effectiveness and safety of ranibizumab in Korean patients with nAMD; factors including age, baseline VA, and loading-dose were associated with VA gain at one-year post-treatment.Keywords: neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, ranibizumab, real-world

Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.Keywords: TiO2, reactive oxygen species, apoptotic cell death, Fas upregulation, Bax activation, mitochondrial membrane potential loss, caspase activation

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes. [ABSTRACT FROM AUTHOR]

Background: The choice of the deep inferior epigastric perforator (DIEP) flap for breast reconstruction has increased. Three-dimensional (3D) models of DIEP flaps have been introduced with advances in 3D technology to assist the tedious intramuscular dissection of the pedicle. This study presents the process of creating an ideal 3D model for a DIEP flap., Methods: Collaboration among various professionals, including surgeons, radiologists, and 3D-printing model makers, is essential for manufacturing suitable 3D-printing DIEP models. Our team facilitated the collaboration process by sharing the virtual 3D model via a uniform resource locator (URL) using an online platform accessible on mobile devices., Results: During collaboration in 3D DIEP model-making, we continuously upgraded the model to a better version. The model was modified according to the surgeon's preference from a 1:1 ratio size to a handheld size. Additionally, we achieved significant advancements over conventional methods, including improved visualization of detailed vessel pathways with separation of arteries and veins, tissue transparency, and superficial inferior epigastric vein (SIEV)., Conclusions: Through 3D model-making collaborations, our team successfully developed a 3D DIEP model with translucency and visualized arteries and veins separately with accentuation of the perforators, including SIEV tracing, which is more accurate. This ideal 3D model for the DIEP flap enables the selection of a perforator vessel that is safe and easy to dissect to lower complications and procedure time and will be of great help to less experienced surgeons., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

Purpose: To investigate the risk of retinal vascular occlusion in patients with Moyamoya disease (MMD)., Design: Retrospective, longitudinal cohort study using the Korean National Health Insurance Service database., Participants: Newly diagnosed MMD patients (n=34,627), who were diagnosed between 2004 and 2022, and their propensity score matched controls (n=136,945) were included., Methods: We identified retinal vascular occlusion events using diagnostic codes for central retinal artery occlusion, other retinal artery occlusion, and retinal vein occlusion. After a washout-period from 2002 to 2003, information on the diagnosis of retinal vascular occlusion was extracted in both MMD and control group during the follow up period. The association between MMD and the risk of subsequent retinal vascular occlusion was investigated using a time-dependent Cox proportional hazard model and Kaplan-Meier survival analysis with log-rank test adjusted for age, sex, and comorbidities., Main Outcome Measures: Hazard ratios (HRs) and 95% confidence intervals (CIs) for retinal vascular occlusion development according to the MMD., Results: MMD was associated with an increased risk of subsequent retinal vascular occlusion even after adjusting for confounding variables (HR, 1.22; 95% CI, 1.09-1.36). Among the subtypes of retinal vascular occlusion, central retinal artery occlusion showed a highest HR (2.23; 95% CI, 1.35-3.7). Incidence probability of retinal vascular occlusion was significantly higher among MMD patients than controls (P < 0.001, log-rank test)., Conclusion: In this nationwide population-based cohort study, patients with MMD in Korea had an elevated risk of retinal vascular occlusion, suggesting that the MMD is one of the risk factors for retinal vascular occlusion., (Copyright © 2024. Published by Elsevier Inc.)

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10 -4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 μm (AA, 73.8%) and 31.1 μm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 μm (AA, 74.2%) and 28.2 μm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration., (© 2024. The Author(s).)

Background: Diabetic macular edema (DME), a leading cause of blindness, requires treatment with costly drugs, such as anti-vascular endothelial growth factor (VEGF) agents. The prolonged use of these effective but expensive drugs results in an incremental economic burden for patients with DME compared with those with diabetes mellitus (DM) without DME. However, there are no studies on the long-term patient-centered economic burden of DME after reimbursement for anti-VEGFs., Objective: This retrospective cohort study aims to estimate the 3-year patient-centered economic burden of DME compared with DM without DME, using the Common Data Model., Methods: We used medical data from 1,903,603 patients (2003-2020), transformed and validated using the Observational Medical Outcomes Partnership Common Data Model from Seoul National University Bundang Hospital. We defined the group with DME as patients aged >18 years with nonproliferative diabetic retinopathy and intravitreal anti-VEGF or steroid prescriptions. As control, we defined the group with DM without DME as patients aged >18 years with DM or diabetic retinopathy without intravitreal anti-VEGF or steroid prescriptions. Propensity score matching, performed using a regularized logistic regression with a Laplace prior, addressed selection bias. We estimated direct medical costs over 3 years categorized into total costs, reimbursement costs, nonreimbursement costs, out-of-pocket costs, and costs covered by insurance, as well as healthcare resource utilization. An exponential conditional model and a count model estimated unbiased incremental patient-centered economic burden using generalized linear models and a zero-inflation model., Results: In a cohort of 454 patients with DME matched with 1640 patients with DM, the economic burden of DME was significantly higher than that of DM, with total costs over 3 years being 2.09 (95% CI 1.78-2.47) times higher. Reimbursement costs were 1.89 (95% CI 1.57-2.28) times higher in the group with DME than with the group with DM, while nonreimbursement costs were 2.54 (95% CI 2.12-3.06) times higher. Out-of-pocket costs and costs covered by insurance were also higher by a factor of 2.11 (95% CI 1.58-2.59) and a factor of 2.01 (95% CI 1.85-2.42), respectively. Patients with DME had a significantly higher number of outpatient (1.87-fold) and inpatient (1.99-fold) visits compared with those with DM (P<.001 in all cases)., Conclusions: Patients with DME experience a heightened economic burden compared with diabetic patients without DME. The substantial and enduring economic impact observed in real-world settings underscores the need to alleviate patients' burden through preventive measures, effective management, appropriate reimbursement policies, and the development of innovative treatments. Strategies to mitigate the economic impact of DME should include proactive approaches such as expanding anti-VEGF reimbursement criteria, approving and reimbursing cost-effective drugs such as bevacizumab, advocating for proactive eye examinations, and embracing early diagnosis by ophthalmologists facilitated by cutting-edge methodologies such as artificial intelligence for patients with DM., (©Kyungseon Choi, Sang Jun Park, Hyuna Yoon, Seoyoon Choi, Yongseok Mun, Seok Kim, Sooyoung Yoo, Se Joon Woo, Kyu Hyung Park, Junghyun Na, Hae Sun Suh. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 08.10.2024.)

Retinal vascular disease is the leading cause of visual impairment. Although intravitreal drug injections are the most suitable approach for addressing retinal disorders, existing clinical treatments necessitate repeated administration, imposing a substantial burden on patients with various intraocular complications. This study introduces an injectable and biodegradable hyaluronan microgel (Hm)-embedded gelatin-poly(ethylene glycol)-tyramine hydrogel (HmGh) designed for sustained intravitreal ranibizumab (RBZ) delivery to reduce patient burden and minimize the side effects associated with frequent injections. Hm exhibited a controlled RBZ loading capacity and release profile. HmGh effectively controlled the initial burst release and overall release profile. Cytocompatibility and cellular drug efficacy were also demonstrated. In an animal study, HmGh maintained RBZ concentrations in the vitreous and retina for >120 d. Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm, respectively, and 9.58 and 38.46 times longer than that of RBZ solution, respectively. Importantly, the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from the Hm and RBZ solutions. Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses. In conclusion, this injectable microgel-embedded hydrogel formulation is a promising prolonged drug delivery system for treating various posterior segment eye diseases., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

Purpose: To investigate the retinal vascular abnormalities in both affected and fellow eyes of presumed unilateral Coats disease patients using ultra-widefield fluorescein angiography (UWF-FA) and their association with visual prognosis., Methods: A retrospective review of medical records was conducted on 30 patients diagnosed with presumed unilateral Coats disease, who were evaluated with UWF-FA from March 2003 to May 2024 at a tertiary referral hospital. Clinical features and multimodal imaging findings were evaluated, and factors related to final visual outcomes were analyzed., Results: All 30 patients were diagnosed with presumed unilateral Coats disease at presentation, comprising 11 childhood-onset (36.7%) and 19 adult-onset patients (63.3%). Retinal vascular telangiectasia was observed in 51.7% of the fellow eyes. The extent of telangiectasia and exudate in the affected eyes did not significantly correlate with the extent of telangiectasia in the fellow eyes. In the more affected eyes, the childhood-onset group had a significantly greater extent of capillary dropout compared to the adult-onset group (5.0 clock hours vs. 2.8 clock hours, p = 0.023). In the fellow eyes, telangiectasia tended to be more frequent in the childhood-onset group, without statistical significance (63.6% vs. 44.4%, p = 0.160). In the multivariable regression analysis, the final best-corrected visual acuity (BCVA) in the more affected eyes was significantly associated with initial BCVA. The mean extent of telangiectasia in the temporal and nasal quadrants (odds ratio, 12.759; p = 0.043) and the initial BCVA of the more affected eyes (odds ratio, 11.841; p = 0.024) were identified as prognostic factors for final moderate to severe visual loss (Snellen BCVA <20 / 66)., Conclusions: About half of the presumed unilateral Coats disease cases exhibited features of the bilateral disease. Visual prognosis is associated with the peripheral retinal telangiectasia in the temporal and nasal quadrants as well as initial BCVA in the affected eyes while it is not associated with retinal vascular abnormalities in the fellow eyes.

Nerve transfer surgery utilizes the redundant and synergistic innervation of intact muscle groups to rehabilitate motor function. This is achieved by transferring functional nerves or fascicles to damaged nerves near the target area, thereby reducing the reinnervation distance and time. The techniques encompass both proximal and distal nerve transfers, customized according to the specific injury. Successful nerve transfer hinges on accurate diagnosis, innovative surgical approaches, and the judicious choice of donor nerves to maximize functional restoration. This study explores nerve transfer strategies and their integration with other procedures, emphasizing their importance in enhancing outcomes in brachial plexus injury management., Competing Interests: Disclosure The authors declare that there are no conflicts of interest, financial or otherwise, that could influence or bias the content of this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of switching from adalimumab originator (Humira, AbbVie) to SB5, adalimumab biosimilar (Adalloce, Samsung Bioepis) in patients with noninfectious uveitis (NIU)., Methods: Fifteen patients (29 eyes) with NIU who were switched from adalimumab originator to SB5 and followed up for 6 months or longer were retrospectively included. Data consisted of best-corrected visual acuity (BCVA, logMAR), intraocular pressure (IOP, mmHg), anterior chamber (AC) cell grade, anterior vitreous (AV) cell grade, vitreous haze grade, central macular thickness (CMT, μm), and macular volume (MV, mm 3 ) at pre-switching, 2, 4, and 6 months post-switching., Results: There were no significant differences in BCVA, AC and AV cell grades, and vitreous haze grades at 2, 4, and 6 months post- compared with pre-switching, and no significant differences in CMT and MV at 2 and 6 months post-switching. CMT and MV decreased from 260.55 ± 67.44 μm and 8.37 ± 1.14 mm 3 at pre-switching to 244.14 ± 60.31 μm ( p  = 0.032) and 8.11 ± 1.20 mm 3 ( p  = 0.027) at 4 months post-switching, respectively. There was no recurrence of uveitis, as defined by AC cell grade, vitreous haze, or BCVA. Four patients (27%) were switched back to adalimumab originator after a mean of 9 weeks, due to discomfort during the injection (three patients) and technical difficulty with the new injection device (one patient). No other adverse events occurred after switching to SB5., Conclusion: Switching from adalimumab originator to SB5 for NIU does not result in clinically significant differences in treatment efficacy and safety.

In dynamic environments, animals make behavioural decisions on the basis of the innate valences of sensory cues and information learnt about these cues across multiple timescales 1-3 . However, it remains unclear how the innate valence of a sensory stimulus affects the acquisition of learnt valence information and subsequent memory dynamics. Here we show that in the Drosophila brain, interconnected short- and long-term memory units of the mushroom body jointly regulate memory through dopamine signals that encode innate and learnt sensory valences. By performing time-lapse in vivo voltage-imaging studies of neural spiking in more than 500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs) 4 heterogeneously and bidirectionally encode innate and learnt valences of punishment, reward and odour cues. During learning, these valence signals regulate memory storage and extinction in mushroom body output neurons (MBONs) 5 . During initial conditioning bouts, PPL1-γ1pedc and PPL1-γ2α'1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-γ1pedc>α/β to PPL1-α'2α2 and PPL1-α3. During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odour cue, which gates long-term memory formation. A computational model constrained by the fly connectome 6,7 and our spiking data explains how dopamine signals mediate the circuit interactions between short- and long-term memory traces, yielding predictions that our experiments confirmed. Overall, the mushroom body achieves flexible learning through the integration of innate and learnt valences in parallel learning units sharing feedback interconnections. This hybrid physiological-anatomical mechanism may be a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia., (© 2024. The Author(s).)

Purpose: To investigate the intraocular concentration profiles of stem cell factor (SCF)/c-KIT, galectin-1 (GAL-1), and vascular endothelial growth factor (VEGF)-A with regard to retinal disease and treatment response., Methods: The study group included 13 patients with dry age-related macular degeneration (AMD), 196 with neovascular AMD (nAMD), 21 with diabetic macular edema (DME), 10 with retinal vein occlusion (RVO), and 34 normal subjects with cataracts. Aqueous humor levels of SCF, c-KIT, GAL-1, and VEGF-A were analyzed by immunoassay according to disease group and treatment response., Results: Increased aqueous levels of SCF, c-KIT, and GAL-1 were observed in eyes with nAMD (2.67 ± 3.66, 296.84 ± 359.56, and 3945.61 ± 5976.2 pg/mL, respectively), DME (1.64 ± 0.89, 238.80 ± 265.54, and 3701.23 ± 4340.54 pg/mL, respectively), and RVO (4.62 ± 8.76, 509.63 ± 647.58, and 9079.60 ± 11909.20 pg/mL, respectively) compared with controls (1.13 ± 0.24, 60.00 ± 0.00, and 613.27 ± 1595.12 pg/mL, respectively). In the eyes of nAMD, the levels of all three cytokines correlated positively with VEGF-A levels. After intravitreal injections of anti-VEGF agents, the levels of GAL-1 and VEGF-A decreased significantly, whereas those of SCF and c-Kit showed no significant change. Eyes of nAMD patients with improved vision after treatment had significantly lower levels of c-KIT, GAL-1, and VEGF-A at baseline., Conclusions: The intraocular levels of cytokines were significantly elevated in eyes with nAMD, DME, and RVO compared to the controls and they showed different response to anti-VEGF treatment. With this result and their known association with angiogenesis, these cytokines may be potential therapeutic targets for future research.

Purpose: The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region., Methods: The 62-item questionnaire was distributed electronically via email. The questions covered five domains: (1) structure of the IRD service and registry/database; (2) genotyping practices; (3) genetic counselling; (4) deep phenotyping practices; (5) low-vision rehabilitation services., Results: The survey was completed by 36 of 45 centres in twelve countries and regions in APAC. Among these centres, 42 % reported managing more than 1000 patients. Notably, 39 % of centres lack an IRD database or registry, and 44 % of centres have tested less than one-quarter of their IRD patients. The majority of centres (67 %) do not have genetic counsellors. While there was consistency in the imaging-based investigations, there was marked heterogeneity for functional testing using electrophysiology and formal perimetry. Only 34 % of centres confirmed the availability of access to low-vision assistive devices., Conclusions: This study reveals several critical gaps in managing IRDs in the APAC region. These include the lack of IRD database/registry in one-third of centres, a substantial proportion of patients remaining genetically undiagnosed, and limited availability of genetic counsellors. The findings also underscore a need to harmonise investigations for evaluating retinal function and identify areas for improvement in the provision of low-vision rehabilitation services., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery., Methods: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure., Results: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%)., Conclusion: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metal halide perovskite light-emitting diodes (PeLEDs) have exceptional color purity but designs that emit deep-blue color with high efficiency have not been fully achieved and become more difficult in the thin film of confined perovskite colloidal quantum dots (PeQDs) due to particle interaction. Here it is demonstrated that electronic coupling and energy transfer in PeQDs induce redshift in the emission by PeQD film, and consequently hinder deep-blue emission. To achieve deep-blue emission by avoiding electronic coupling and energy transfer, a QD-in-organic solid solution is introduced to physically separate the QDs in the film. This physical separation of QDs reduces the interaction between them yielding a blueshift of ≈7 nm in the emission spectrum. Moreover, using a hole-transporting organic molecule with a deep-lying highest occupied molecular orbital (≈6.0 eV) as the organic matrix, the formation of exciplex emission is suppressed. As a result, an unprecedently high maximum external quantum efficiency of 6.2% at 462 nm from QD-in-organic solid solution film in PeLEDs is achieved, which satisfies the deep-blue color coordinates of CIEy < 0.06. This work suggests an important material strategy to deepen blue emission without reducing the particle size to <≈4 nm., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Purpose: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity., Methods: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not., Results: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group., Conclusion: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

Chicken embryos serve as an important model for investigating germ cells due to their ease of accessibility and manipulation within the egg. Understanding the development of germ cells is particularly crucial, as they are the only cell types capable of transmitting genetic information to the next generation. Therefore, gene expression regulation in germ cells is important for genomic function. Epigenetic programming is a crucial biological process for the regulation of gene expression without altering the genome sequence. Although epigenetic programming is evolutionarily conserved, several differences between chickens and mammals have been revealed. In this review, we compared the epigenetic regulation of germ cells in chickens and mammals (mainly mice as a representative species). In mammals, migrating primordial germ cells (precursors for germ cells [PGCs]) undergo global DNA demethylation and persist until sexual differentiation, while in chickens, DNA is demethylated until reaching the gonad but remethylated when sexually differentiated. Prospermatogonia is methylated at the onset of mitotic arrest in mammals, while DNA is demethylated at mitotic arrest in chickens. Furthermore, genomic imprinting and inactivation of sex chromosomes are differentially regulated through DNA methylation in chickens and mammals. Chickens and mammals exhibit different patterns of histone modifications during germ cell development, and non-coding RNA, which is not involved in PGC differentiation in mice, plays an important role in chicken PGC development. Additionally, several chicken-specific non-coding RNAs have been identified. In conclusion, we summarized current knowledge of epigenetic gene regulation of chicken germ cells, comparing that of mammals, and highlighted notable differences between them., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify longitudinal retinal layer thickness changes in normal eyes of cognitively healthy elderly people., Methods: Post hoc analysis was performed on 57 cognitively healthy elderly participants from the population-based Korean Longitudinal Study on Health and Aging and Korean Longitudinal Study on Cognitive Aging and Dementia cohort studies who underwent baseline and final optical coherence tomography scans. The peripapillary retinal nerve fiber layer, subfoveal choroid, and average retinal layer thickness at four quadrant (nasal, temporal, superior, and inferior) points 1 mm, 2 mm, and 3 mm from the center of the fovea were measured., Results: The mean age of subjects was 75.1 years and the mean follow-up period was 55.9 months. Among the analyzed retinal layers, both the ganglion cell-inner plexiform layer and the outer nuclear layer at all 1 mm, 2 mm, and 3 mm points showed a statistically significant decrease in thickness at the final visit compared with baseline. The annual decrease rates were -1.2 µm/year at 1 mm (total -6.6%), -1.3 µm/year at 2 mm (total -8.4%), and -1.1 µm/year at 3 mm (total -9.7%) for ganglion cell-inner plexiform layer and -0.6 µm/year at 1 mm (total -4.2%), -0.5 µm/year at 2 mm (total -3.9%), and -0.4 µm/year at 3 mm (total -4.1%) for outer nuclear layer., Conclusion: Aging plays a significant role in the reduction of ganglion cell-inner plexiform layer and outer nuclear layer thicknesses in cognitively healthy elderly individuals., Competing Interests: None of the authors has any conflict of interest or financial interests to declare.

Purpose: Homozygous hypomorphic variants of the RP1 gene, including c.5797C>T, p.Arg1933Ter, have traditionally been considered non-pathogenic. This study aimed to elucidate the clinical manifestations of late-onset, slowly progressive cone/macular dystrophy in patients homozygous for p.Arg1933Ter in the RP1 gene., Methods: Five patients with biallelic p.Arg1933Ter in RP1 were retrospectively recruited, and their clinical profiles were analyzed. Copy number variation analysis and Alu insertion assessment of genes associated with inherited retinal diseases were conducted. The results of comprehensive ophthalmological examinations, multimodal imaging, and full-field electroretinogram tests were analyzed., Results: No specific sequencing errors or structural variations associated with the clinical phenotypes were identified. Alu element insertion in RP1 was not detected. The mean ± SD age at the first visit was 62.2 ± 9.8 years, with symptoms typically starting between 45 and 50 years of age. Two patients exhibited a mild form of cone/macular dystrophy, characterized by a relatively preserved fundus appearance and blurring of the ellipsoid zone on optical coherence tomography. Three patients had late-onset cone/macular dystrophy with significant atrophy., Conclusions: To our knowledge, this study is the first to report that a homozygous hypomorphic variant of RP1, previously considered non-pathogenic, leads to cone/macular dystrophy., Translational Relevance: The study introduces novel possibilities suggesting that the homozygous hypomorphic variant of RP1 may be linked to variant pathogenicity.

Purpose: To determine the association between pentosan polysulfate (PPS) use and the subsequent development of maculopathy in an Asian population., Design: A nationwide, population-based retrospective cohort study using the Health Insurance Review and Assessment Service database., Participants: A total of 103 553 individuals in the PPS user group and 205 792 individuals in the PPS nonuser group, all newly diagnosed with cystitis between 2009 and 2020., Methods: The association between PPS use and maculopathy was evaluated using a time-dependent Cox proportional hazard model. Additionally, 2 sensitivity analyses were conducted by defining PPS users as individuals with an observation period over 6 months from the initial prescription or those with a cumulative dose exceeding 9 g, using the same analysis., Main Outcome Measures: The outcome measures included the hazard ratios (HRs) representing the association between PPS use and maculopathy., Results: Use of PPS was associated with an increased risk of subsequent maculopathy in univariate (HR, 1.7; 95% confidence interval [CI], 1.66-1.75) and multivariate analysis (HR, 1.34; 95% CI, 1.31-1.38). These results were also confirmed in 2 sensitivity analyses. The mean cumulative dose of PPS for the cohort was 37.2 ± 76.7 g., Conclusions: In this nationwide cohort study involving an Asian population, individuals with cystitis using PPS exhibit an increased risk of developing subsequent maculopathy., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024. Published by Elsevier Inc.)

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin ( RS1 ) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Reducing the size of perovskite crystals to confine excitons and passivating surface defects has fueled a significant advance in the luminescence efficiency of perovskite light-emitting diodes (LEDs). However, the persistent gap between the optical limit of electroluminescence efficiency and the photoluminescence efficiency of colloidal perovskite nanocrystals (PeNCs) suggests that defect passivation alone is not sufficient to achieve highly efficient colloidal PeNC-LEDs. Here, we present a materials approach to controlling the dynamic nature of the perovskite surface. Our experimental and theoretical studies reveal that conjugated molecular multipods (CMMs) adsorb onto the perovskite surface by multipodal hydrogen bonding and van der Waals interactions, strengthening the near-surface perovskite lattice and reducing ionic fluctuations which are related to nonradiative recombination. The CMM treatment strengthens the perovskite lattice and suppresses its dynamic disorder, resulting in a near-unity photoluminescence quantum yield of PeNC films and a high external quantum efficiency (26.1%) of PeNC-LED with pure green emission that matches the Rec.2020 color standard for next-generation vivid displays., (© 2024. The Author(s).)

Introduction: Japanese quail are of significant economic value, providing protein nutrition to humans through their reproductive activity; however, sexual dimorphism in this species remains relatively unexplored compared with other model species., Method: A total of 114 RNA sequencing datasets (18 and 96 samples for quail and chicken, respectively) were collected from existing studies to gain a comprehensive understanding of sexual dimorphism in quail. Cross-species integrated analyses were performed with transcriptome data from evolutionarily close chickens to identify sex-biased genes in the embryonic, adult brain, and gonadal tissues., Results: Our findings indicate that the expression patterns of genes involved in sex-determination mechanisms during embryonic development, as well as those of most sex-biased genes in the adult brain and gonads, are identical between quails and chickens. Similar to most birds with a ZW sex determination system, quails lacked global dosage compensation for the Z chromosome, resulting in directional outcomes that supported the hypothesis that sex is determined by the individual dosage of Z-chromosomal genes, including long non-coding RNAs located in the male hypermethylated region. Furthermore, genes, such as WNT4 and VIP, reversed their sex-biased patterns at different points in embryonic development and/or in different adult tissues, suggesting a potential hurdle in breeding and transgenic experiments involving avian sex-related traits., Discussion: The findings of this study are expected to enhance our understanding of sexual dimorphism in birds and subsequently facilitate insights into the field of breeding and transgenesis of sex-related traits that economically benefit humans., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Park, Kim, Lee, Jung, Pack, Lee, Yoon, Woo, Han and Seo.)

Background: The prevalence of diabetes is increasing globally, highlighting the importance of preventive healthcare. This study aimed to identify the diabetic retinopathy (DR) screening rates and risk factors linked to DR screening nonadherence in the Korean population through a nationally representative sample survey., Methods: Among the Korea National Health and Nutrition Examination Survey database from 2016 to 2021, participants aged ≥ 40 years with diabetes were included. The weighted estimate for nonadherence to DR screening within a year was calculated. Risk factor analyses were conducted using univariate and multivariate logistic regression., Results: Among the 3,717 participants, 1,109 (29.5%) underwent DR screening within the past year, and this national estimate exhibited no statistically significant difference from 2016 to 2021 ( P = 0.809). Nonadherence to annual DR screening was associated with residing in rural areas, age ≥ 80 years, low educational level, self-reported good health, absence of ocular disease, current smoking, lack of exercise and dietary diabetes treatment, and no activity limitation (all P < 0.05)., Conclusion: The recent DR screening rate in Korea was relatively low. Factors associated with apathy and complacency towards personal health were associated with the nonadherence to DR screening. Educational interventions have the potential to enhance the annual screening rate for diabetic patients., (© 2024 The Korean Academy of Medical Sciences.)

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis., (© 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.)

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: To investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye., Methods: We searched the RAO registry at Seoul National University Bundang Hospital and included patients with recurrent RAO in the present study. Ophthalmic and systemic features were analysed to identify risk factors and visual outcomes., Results: Of the 850 patients in the non-arteritic RAO cohort, 11 (1.3%) experienced a second RAO recurrence, either in the same (5 patients; 0.6%) or opposite (6 patients; 0.7%) eye. The same eye group experienced an earlier recurrence (1-2 months, median 1 month) than the opposite eye group, where the time to recurrence was notably longer (8-66 months, median 22 months). Best corrected visual acuity (BCVA) in the same eye group decreased after the recurrence of RAO. In the same eye group, initial BCVA ranged from 20/200 to counting fingers (CF), while BCVA during RAO recurrence ranged from CF to hand motion. When RAO recurred in the opposite eye, the reduction in visual acuity was less severe than the reduction of the initial episode: initial episode ranged from 20/400 to light perception and recurrent episode ranged from 20/25 to 20/400. Patients exhibited varying degrees of carotid (81.8%) and cerebral (9.1%) artery occlusions. Additionally, one patient in each group (total 2 patients, 18.2%) experienced a stroke 6 months after RAO recurrence., Conclusions: Since the RAO recurrences could lead to devastating visual impairment, it is essential to emphasise the importance of risk factor screening to patients while collaborating with neurologists and cardiologists., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1 + MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo., Methods: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1 + MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion., Results: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1 + MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1 + MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1 + MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression., Conclusion: Tuberculous pleural fibrosis induces M2 Arg-1 + polarization, and M2 Arg-1 + MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1 + tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression., (© 2024. The Author(s).)

In hand and upper extremity replantation surgery, simultaneous free flap reconstruction restores the physiologic circulation to the amputated part, ensuring its survival, and promotes wound healing through anatomic restoration. Especially in digit replantation, an arterialized venous flap serves to reconstruct both vessel and soft tissue defects simultaneously. Delayed free flap reconstruction aims to enhance both functional improvement and cosmetic acceptance in a successfully replanted part using flaps that include functioning muscle, bone, joint, nerve, and soft tissue., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.

Purpose: To investigate the efficacy, safety, and indications for additional pneumatic retinopexy (PR) in patients with persistent retinal detachment after scleral buckling., Methods: This retrospective study included patients who underwent additional PR after scleral buckling for primary rhegmatogenous retinal detachment (n = 78). We defined "inadequate buckle" as retinal detachment persistence because of low buckle height despite accurate buckle placement and "buckle misplacement" as an uncovered tear because of incorrect buckle placement., Results: The anatomical success rate after additional PR was 52.6%. Development of proliferative vitreoretinopathy Grade B (hazard ratio, 5.73; P < 0.001) and inferior retinal tears (hazard ratio, 2.12; P = 0.040) were significant risk factors for anatomical failure. The most common cause of anatomical failure was proliferative vitreoretinopathy (19 of 37; 51.4%), and epiretinal membrane formation was a common complication after additional PR (22 of 78; 28.2%). The anatomical success rate with additional PR was significantly higher in the inadequate buckle group than in the misplacement group (8 of 9 [88.9%] vs. 1228 [42.9%]; P = 0.023)., Conclusion: Development of proliferative vitreoretinopathy Grade B and inferior retinal tears were significantly associated with anatomical failure after additional PR. Additional PR may benefit patients with superior retinal tears or low buckle height and those without proliferative vitreoretinopathy.

Purpose: To identify baseline factors associated with 1-year outcomes when treating neovascular age-related macular degeneration (nAMD) with ranibizumab biosimilar SB11 or reference ranibizumab (rRBZ), and to compare efficacy of the two products within subgroups judged to be clinically relevant., Design: Post hoc analysis of a prospective, equivalence phase 3 randomized clinical trial (RCT) METHODS: 705 patients with nAMD were randomized 1:1 to receive SB11 or rRBZ for 48 weeks. Pooled and randomized groups were used to identify baseline factors associated with clinical outcomes at Week 52 using multiple linear regression models. Significant factors identified in regression analyses were confirmed in analyses of variance. Subgroup analyses comparing best-corrected visual acuity (BCVA) changes between SB11 and rRBZ were conducted., Results: 634 (89.9%) participants completed the 52-week visit. Regression analyses showed that younger age, lower BCVA, and smaller total lesion area at baseline were associated with greater BCVA gain at Week 52, while older age, lower BCVA, and thicker central subfield thickness (CST) at baseline were predictors of greater CST reduction in the pooled group. Subgroup analyses demonstrated that BCVA outcomes appeared comparable for the SB11 and rRBZ groups., Conclusion: Post hoc analyses of the SB11-rRBZ equivalence study showed that baseline age, BCVA, CST, and total lesion area were prognostic factors for visual or anatomical outcomes of nAMD, while subgroup analyses demonstrated comparable results for SB11 and rRBZ. Collectively, the results appear comparable to similar RCTs of anti-vascular endothelial growth factor reference products for nAMD and strengthen confidence in the biosimilarity of SB11., Competing Interests: Declaration of Competing Interest Se Joon Woo: Samsung Bioepis (consultant, study grant), Allergan-Abbvie (consultant, lecture fee), Alcon (lecture fee, study grant), Alteogen (consultant, study grant), Bayer (lecture fee, study grant), Curacle (consultant, study grant), Genentech (study grant), Janssen (consultant), Novartis (consultant, lecture fee, study grant), Novelty Nobility (consultant, study grant), Panolos Bioscience (stock owner), Pharmabcine (consultant, study grant), Rznomics (consultant), Retimark (stock owner), Sometech (consultant). Jin Ah Jung: Samsung Bioepis (employee). Taehyung Kim: Samsung Bioepis (employee). Inkyung Oh: Samsung Bioepis (employee). Mercy Yeeun Kim: Samsung Bioepis (employee). Neil M. Bressler: Samsung Bioepis (Grant to my employer, Johns Hopkins University), Bayer (Grant to my employer, Johns Hopkins University), Biogen (Grant to my employer, Johns Hopkins University), Boehringer-Ingelheim (Grant to my employer, Johns Hopkins University), Genentech (Roche) (Grant to my employer, Johns Hopkins University), Regeneron (Grant to my employer, Johns Hopkins University), Editor in Chief, JAMA Ophthalmology (Contract), Chair, Data and Safety Monitoring Committee for intramural trials of the National Eye Institute, National Institutes of Health (Honoraria), Chair, Ophthalmic Devices Panel of the U.S. FDA (Honoraria), Acting Chair, Epidemiology of Diabetes Interventions and Complications (EDIC) Oversight Safety Monitoring Board (OSMB) for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Honoraria)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Perovskite light-emitting diodes (PeLEDs) have emerged as a promising new light source for displays. The development roadmap for commercializing PeLEDs should include a tandem device structure, specifically by stacking a thin nanocrystal PeLED unit and an organic light-emitting diode unit, which can achieve a vivid and efficient tandem display; however, simply combining light-emitting diodes with different characteristics does not guarantee both narrowband emission and high efficiency, as it may cause a broadened electroluminescence spectra and a charge imbalance. Here, by conducting optical simulations of the hybrid tandem (h-tandem) PeLED, we have discovered a crucial optical microcavity structure known as the h-tandem valley, which enables the h-tandem PeLED to emit light with a narrow bandwidth. Specifically, the centre structure of the h-tandem valley (we call it valley-centre tandem) demonstrates near-perfect charge balance and optimal microcavity effects. As a result, the h-tandem PeLED achieves a high external quantum efficiency of 37.0% and high colour purity with a narrow full-width at half-maximum of 27.3 nm (versus 64.5 nm in organic light-emitting diodes) along with a fast on-off response. These findings offer a new strategy to overcome the limitations of nanocrystal-based PeLEDs, providing valuable optical and electrical guidelines for integrating different types of light-emitting device into practical display applications., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Traditional skin grafts for syndactyly often cause color mismatches and unsightly donor sites, whereas no-skin-graft methods leave noticeable dorsal hand scars. This study presents plantar full-thickness skin graft (FTSG) from the weight-bearing midline area for syndactyly repair, a novel approach not previously reported in the literature., Methods: The study included three groups of patients with congenital syndactyly of the hand who underwent primary operations with plantar FTSG (n=70), groin FTSG (n=20), and no-skin-graft techniques (n=22). Postoperative outcomes were evaluated by an assessment panel, and guardians' satisfaction scores were measured. Color similarity between the graft and surrounding skin was assessed using a three-dimensional color space., Results: The plantar FTSG group demonstrated a significantly higher likelihood of receiving an 'excellent' rating compared to the groin FTSG group, with an odds ratio of 6.30 (p<0.001). Color difference analysis showed that plantar FTSG more closely matched surrounding skin color than groin FTSG (6.33 vs. 22.57, p<0.001). Guardians reported greater satisfaction with outcomes on the hand in the plantar FTSG group compared to the groin FTSG and no-skin-graft groups (7.16 vs. 5.05 and 4.36, p<0.001). Satisfaction with donor sites was also significantly higher in the plantar FTSG group than in the groin FTSG group (8.23 vs. 6.30, p<0.001)., Conclusion: Correction of congenital hand syndactyly using midline plantar FTSG from the weight-bearing area can reduce scarring on the hand dorsum, ensure superior color similarity with surrounding skin, and offer inconspicuous donor sites compared to no-skin-graft or groin FTSG techniques., Competing Interests: Statement of Financial Disclosures, Conflicts of Interest, and Products: The authors declare that they have no financial disclosures or conflicts of interest related to this research., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Purpose: To compare the posterior capsule rupture (PCR) rates of cataract surgery using a traditional ophthalmic surgical microscope (OSM) and a 3D heads-up visualization system (HUVS)., Setting: Single tertiary referral center., Design: Retrospective study., Methods: This study included 10 101 eyes that underwent phacoemulsification cataract surgery. Surgeries were performed using either 3D HUVS (1964 eyes, performed by 2 surgeons, HUVS group) or traditional OSM (8137 eyes, performed by 6 surgeons, OSM group) from February 2018 to June 2022. Data were collected based on the diagnosis-related group system, and the rate of PCR requiring vitrectomy and the surgical time were evaluated., Results: The PCR rates were not significantly different between the OSM (n = 63; 0.7%) and HUVS (n = 19; 0.9%, P = .392) groups. The mean surgical time was significantly longer in the HUVS group (14.7 ± 10.6 minutes) than in the OSM group (12.9 ± 9.9 minutes, P < .001). In the 3D HUVS group, there were no PCR cases among the initial 100 patients. In both groups, no significant difference was observed in the PCR rates over time. Although the difference was not statistically significant, the PCR rate decreased over time in the HUVS group., Conclusions: The results indicate that 3D HUVS-based cataract surgery performed by experienced cataract surgeons had a PCR rate similar to that of traditional OSM-based surgery during the 4-year study period. Although the surgical time was slightly longer with 3D HUVS, cataract surgery using 3D HUVS can be performed safely by experienced surgeons., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: This study aimed to analyze the genetic results of inherited retinal diseases (IRDs) and evaluate the diagnostic usefulness of whole genome sequencing (WGS) in the Korean National Project of Bio Big Data., Methods: As part of the Korean National Project of Bio Big Data, WGS was performed on 32 individuals with IRDs with no identified pathogenic variants through whole or targeted exome sequencing., Results: Individuals with retinitis pigmentosa (n = 23), cone dystrophy (n = 2), cone-rod dystrophy (n = 2), familial exudative vitreoretinopathy (n = 2), pigmented paravenous chorioretinal atrophy (n = 1), North Carolina macular dystrophy (n = 1), and bull's-eye macular dystrophy (n = 1) were included. WGS revealed genetic mutations in the IQCB1, PRPF31, USH2A, and GUCY2D genes in five cases (15.6%). Two large structural variations and an intronic variant were newly detected in three cases. Two individuals had biallelic missense mutations that were not identified in previous exome sequencing., Conclusion: With WGS, the causative variants in 15.6% of unsolved IRDs from the Korean National Project of Bio Big Data were identified. Further research with a larger cohort might unveil the diagnostic usefulness of WGS in IRDs and other diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Monolayer transition metal dichalcogenides (TMDs) have drawn significant attention for their potential in optoelectronic applications due to their direct band gap and exceptional quantum yield. However, TMD-based light-emitting devices have shown low external quantum efficiencies as imbalanced free carrier injection often leads to the formation of non-radiative charged excitons, limiting practical applications. Here, electrically confined electroluminescence (EL) of neutral excitons in tungsten diselenide (WSe 2 ) light-emitting transistors (LETs) based on the van der Waals heterostructure is demonstrated. The WSe 2 channel is locally doped to simultaneously inject electrons and holes to the 1D region by a local graphene gate. At balanced concentrations of injected electrons and holes, the WSe 2 LETs exhibit strong EL with a high external quantum efficiency (EQE) of ≈8.2 % at room temperature. These experimental and theoretical results consistently show that the enhanced EQE could be attributed to dominant exciton emission confined at the 1D region while expelling charged excitons from the active area by precise control of external electric fields. This work shows a promising approach to enhancing the EQE of 2D light-emitting transistors and modulating the recombination of exciton complexes for excitonic devices., (© 2024 Wiley‐VCH GmbH.)

Background: Concerns of intraocular inflammation associated with intravitreal administration of anti-VEGF drugs have been risen and the exact mechanism is not yet elucidated., Objective: To explore the relationship between immunogenicity and intraocular inflammation in intravitreal anti-VEGF drugs., Methods: This review examines the immunogenicity of individual intravitreal anti-VEGF drugs and their potential link to intraocular inflammation., Results: We suggest that the main cause of intraocular inflammation is the presence of pre-existing and treatment-induced antidrug antibodies, along with considerations related to the molecular structure, which includes the drug's format and size., Conclusions: Researchers and clinicians involved in the advancement of new anti-VEGF drugs should take into consideration the factors related to intraocular inflammation that have been discussed., Competing Interests: 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., (© 2024 The Author(s).)

To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair., (© 2024. The Author(s).)

Congenital and infantile (CI) cataract is one of the most important and preventable cause of blindness in children, but the incidence has not been studied in Korea. We collected data from the national claims database of the National Health Insurance Service of Korea from 2002 through 2019. We identified children who underwent cataract surgery within the age of 5 years, and cumulative incidence rates were calculated for each of the three age criteria. 989 patients out of 4,221,459 births underwent surgery with CI cataract during the period. The cumulative incidence rates per 10,000 births were 1.60 (0-1 years), 2.38 (0-3 years), and 2.95 (0-5 years), respectively. The incidence peaked in the 2007 birth cohort, which coincides with the start of the national screening program for infants/children. Primary intraocular lens implantation was performed in 439 patients (44%). Strabismus and glaucoma requiring surgery occurred in 291 patients (29.4%) and 32 patients (3.2%), respectively, within 8 years after cataract surgery. The incidence rates of CI cataract in Korea appear to be comparable to previous studies in other regions. The early screening program for infants may reduce delayed diagnosis and increase the proportion of patients undergoing surgery at a critical time for visual development., (© 2024. The Author(s).)