The Short-Term Efficacy and Safety of Faricimab in Refractory Neovascular Age-Related Macular Degeneration: The Real-World Experience in Taiwan.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) treatment stands as the primary approach for neovascular age-related macular degeneration (nAMD). Faricimab has recently emerged as a novel anti-VEGF option for nAMD. This study aimed to assess the efficacy of faricimab in patients with refractory nAMD. METHOD: This retrospective study focused on refractory nAMD patients treated with faricimab at Taipei Veterans General Hospital from March 2023 to December 2023. Primary outcomes assessed the change in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over the first 4 months. Secondary outcomes included the presence of subretinal and intraretinal fluid (SRF and IRF) and changes in pigment epithelial detachment (PED). Subgroup analysis for the successful and unsuccessful treatment groups was conducted to identify potential confounding factors influencing treatment response. RESULT: This study included 42 eyes with refractory nAMD treated with faricimab. During a 6-month follow-up, no significant improvement in BCVA was observed, while CRT significantly decreased at all time points, except during the 5-month follow-up. Height PED showed significant reduction up to 5 months. The prevalence of SRF decreased significantly, while IRF remained lower but not significant. According to the treatment criteria, 67.4% successfully met the treatment goals. Subgroup analysis between successful and unsuccessful groups showed no significant differences in baseline characteristics, except a higher predominantly serous PED percentage in the successful group. CONCLUSION: Faricimab showed favorable outcomes in refractory nAMD patients. Further investigations are needed to understand the factors contributing to its efficacy.

Unveiling novel LRP5 pathogenic variant in familial exudative vitreoretinopathy: Diverse phenotypic expressions in a mother-daughter duo.

PURPOSE: This report aims to delineate distinct phenotypes of Familial Exudative Vitreoretinopathy (FEVR) observed in a mother and her daughter, both harboring a novel LRP5 pathogenic variation. METHODS: The investigation involves a retrospective review of medical records accompanied by multimodal imaging. Molecular characterization was performed using whole exon sequencing, and the pathogenic variant was subsequently confirmed through Sanger sequencing. RESULT: A 6-year-old girl diagnosed with anisometropic amblyopia exhibited macular dragging and peripheral avascular retina in her right eye. Whole exon sequencing identified a previously unreported heterozygous missense LRP5 pathogenic variation, Glu528Lys. Simultaneously, her 43-year-old mother also carried the same mutation, manifesting peripheral exudations, avascular areas, and multiple microaneurysms. Notably, both cases presented distinctive phenotypes of FEVR. CONCLUSION: Our findings underscore the diversity in clinical presentations associated with FEVR, emphasizing the pivotal role of genetic evaluation. Despite variations in severity between the eyes of the same patient, it is crucial to remain vigilant for potential progression to a pathological status in the seemingly normal eye. Additionally, this study contributes to expanding the genetic spectrum of FEVR.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Elevated serum levels of T-cell immunoglobulin and mucin-domain containing molecule 3 in patients with systemic inflammation following COVID-19 vaccination.

BACKGROUND: ChAdOx1 nCoV-19 vaccine has been widely used. Some unexpected adverse effects such as the development of systemic hyper inflammation with multiorgan involvement after vaccination, in rare cases, have been reported. However, its pathogenesis remains unclear. METHODS: This study recruited two cases who suffered from systemic inflammation following ChAdOx1 nCoV-19 vaccine and two 30-year-old male volunteers without underlying disease who have received ChAdOx1 nCoV-19 vaccine as control group. Blood samples were collected from our patients and healthy subjects before and after treatment with anti-inflammatory agent such as glucocorticoid and tocilizumab. The immune profile from our patients and healthy controls were measured using a human XL cytokine Proteome Profiler array (ARY022b, R&D Systems). RESULTS: Biochemical parameters revealed leukocytosis with segmented neutrophil dominance and elevated serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate, and ferritin in these two patients. The cytokine array revealed that mean levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3) (3640.3 vs 1580.5 pixels per inch [ppi]), B-cell activating factor (BAFF) (3036.8 vs 1471.0 ppi), urokinase plasminogen activator surface receptor (uPAR) (1043.1 vs 516.8 ppi), Resistin (1783.7 vs 711.3 ppi), platelet-derived growth factor (PDGF)-AB/BB (1980.7 vs 939.7 ppi), macrophage inflammatory protein-3-beta (MIP-3ß) (911.9 vs 346.2 ppi), and interferon-inducible T-cell alpha chemoattractant (I-TAC) (1026.3 vs 419.7 ppi) were 2-fold higher in the patients than in normal subjects who received ChAdOx1 nCoV-19 vaccine. CONCLUSION: We demonstrated that systemic inflammation may occur in subjects who have received the ChAdOx1 nCoV-19 vaccination. Moreover, we proposed immune markers, which may be implicated in the pathogenesis of systemic inflammation following COVID-19 vaccination as potential diagnostic biomarkers.

Polygenic Risk Score Improves Cataract Prediction in East Asian Population.

Cataracts, characterized by crystalline lens opacities in human eyes, is the leading cause of blindness globally. Due to its multifactorial complexity, the molecular mechanisms remain poorly understood. Larger cohorts of genome-wide association studies (GWAS) are needed to investigate cataracts' genetic basis. In this study, a GWAS was performed on the largest Han population to date, analyzing a total of 7079 patients and 13,256 controls from the Taiwan Biobank (TWB) 2.0 cohort. Two cataract-associated SNPs with an adjustment of p < 1 × 10−7 in the older groups and nine SNPs with an adjustment of p < 1 × 10−6 in the younger group were identified. Except for the reported AGMO in animal models, most variations, including rs74774546 in GJA1 and rs237885 in OXTR, were not identified before this study. Furthermore, a polygenic risk score (PRS) was created for the young and old populations to identify high-risk cataract individuals, with areas under the receiver operating curve (AUROCs) of 0.829 and 0.785, respectively, after covariate adjustments. Younger individuals had 17.45 times the risk while older people had 10.97 times the risk when comparing individuals in the highest and lowest PRS quantiles. Validation analysis on an independent TWB1.0 cohort revealed AUROCs of 0.744 and 0.659.

Clinical manifestation and current therapeutics in X-juvenile retinoschisis.

X-linked juvenile retinoschisis (XLRS) is one of the common early-onset hereditary retinal degenerative diseases in men. The common symptoms of XLRS range from mild to severe central vision loss and radial stripes created by the fovea, the division of the inner layer of the retina in the peripheral retina and the significant decrease in b-wave amplitude (ERG). Retinoschisin, the 224-amino-acid protein product of the retinoschisis 1 (RS1) gene, contains a discoid domain as the primary structural unit, an N-terminal cleavable signal sequence, and an oligomerization-area component. Retinoschisin is a homo-octamer complex with disulfide links that are released by retinal cells. It helps preserve the retina's integrity by binding to the surface of photoreceptors and bipolar cells. As a recessive genetic disease, XLRS was usually treated by prescribing low vision aids in most clinical cases. A gene replacement therapy based on adeno-associated virus vectors was initiated and showed a breakthrough in treating XLRS in 2014. Understanding the revolution of gene therapy for treating XLRS may accelerate its development and make this gene therapy the template for developing therapeutics against other inherited retinal diseases.

Retinal Circular RNA hsa_circ_0087207 Expression Promotes Apoptotic Cell Death in Induced Pluripotent Stem Cell-Derived Leber's Hereditary Optic Neuropathy-like Models.

Backgrounds: Leber's hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON.

Modifications of intravitreal injections in response to the COVID-19 pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruption to the normal operation of the healthcare system. On a worldwide scale, hospitals suspended nonurgent surgeries and outpatient visits to downsize clinical loadings to redistribute manpower to counteract the pandemic's impact. So far, there is no evidence-based guideline defining a clear line between urgent and nonurgent indications of intravitreal injections (IVI). Herein, we aimed to summarize IVI algorithm modifications and discuss the patient prioritization according to medical needs in the hostile environment in the COVID crisis. Assessing current literature, we found that neovascular age-related macular degeneration is considered the utmost priority among conditions that require IVI. Other conditions assigned with a high priority include monocular or quasi-monocular patients (only one eye > 20/40), neovascular glaucoma, and new patients with significant vision loss. Although patients with central retinal vein occlusion and proliferative diabetic retinopathy are not advised to delay treatments, we found no consistent evidence that correlated with a worse outcome. Diabetic macular edema and branch retinal vein occlusion patients undertaking treatment delay should be regularly followed up every 2 to 3 months. Serving as the principle of management behind the algorithm modifications, the reduction of both patient visit and IVI therapy counts should be reckoned together with the risk of permanent visual loss and COVID infection.

Repeatability of the amplitude of accommodation measured by a new generation autorefractor.

SIGNIFICANCE: This is the first study to validate the repeatability of objective measurements of amplitude of accommodation (AA) using the TONOREF III (NIDEK Co., Ltd., Japan), which can measure the AA in 30 seconds. PURPOSE: To evaluate the repeatability of objective measurements of AA using the TONOREF III and explored the association between objectively measured AA and factors, including age, sex, spherical equivalent, baseline pupil size and pupil size change during accommodation. METHODS: This cross-sectional study recruited 35 healthy subjects aged 26 to 52 years. The Bland-Altman method and intraclass correlation coefficients (ICCs) were used to assess the repeatability of TONOREF III measurements. The relationships between AA and age, sex, baseline pupil size, changes in pupil size (ΔPS) during accommodation were analyzed using linear regression for univariate and multivariate analysis. RESULTS: The mean difference in AA (ΔAA) between two sessions of TONOREF III measurements was 0.23 D (95% CI: -1.07 to +1.53 D), while no significant correlation was found between the mean and ΔAA (p = .14). The ICCs of the TONOREF III was 0.96. Age, sex, and ΔPS during accommodation were significant factors affecting the AA in multivariate analysis. CONCLUSIONS: The repeatability of objective AA measurements using the TONOREF III was good. Measuring AA using the TONOREFTM III in clinical practice is feasible.