Electro-Chemo-Mechanically Stable and Sodiophilic Interface for Na Metal Anode in Liquid-based and Solid-State Batteries.

Na metal batteries (NMBs) are attracting increasing attention because of their high energy density. However, the widespread application of NMBs is hindered by the growth of Na dendrites and interface instability. The design of artificial solid electrolyte interphase (SEI) with tuned chemical/electrochemical/mechanical properties is the key to achieving high-performance NMBs. This work develops a metal-doped nanoscale polymeric film with tunable composition, sodiophilic sites and improved stiffness. The incorporation of metal crosslinkers in the polymer chains results in exceptional electrochemical stability for Na metal anodes, leading to a significantly prolonged lifespan even at high current densities, which is at the top of the reported literature. The mechanical properties measurements and electro-chemo-mechanical phase-field model are performed to interpret the impact of the ionic transportation capability (decoupled mechanical) and mechanic property in the metal-doped polymer interface. In addition, this approach provides a promising strategy for the rational design of electrode interfaces, providing enhanced mechanical stability and improved sodiophilicity, which can open up opportunities for the fabrication of next-generation energy storage.

Vitrectomy with sulfur hexafluoride versus air tamponade for idiopathic macular hole: a retrospective study.

BACKGROUND: To evaluate the effect of room air and sulfur hexafluoride (SF6) gas in idiopathic macular hole(MH)surgery. METHODS: Retrospective, interventional, and comparative study. 238 eyes with the idiopathic macular hole that underwent pars plana vitrectomy, internal limiting membrane peeling, fluid-air exchange, and 20% SF6 (SF6 group:125 eyes) or room air tamponade (air group: 113 eyes) were reviewed. The primary outcome measure was the closure rate of primary surgery. RESULTS: The baseline characteristics of the SF6 group and air group were comparable except for the hole size (479.90 ± 204.48 vs. 429.38 ± 174.63 µm, P = 0.043). The anatomical closure rate was 92.8% (116 / 125) with the SF6 group and 76.1% (86 / 113) with the air group (P < 0.001). A cut-off value of MH size to predict primary anatomical closure was 520 µm, which is based on the lower limit of 95% confidential interval of the MH size among the unclosed patients in the air group. There was no significant difference in anatomical closure rates between SF6 and air group (98.7% vs. 91.9%, P = 0.051) for MH ≤ 520 µm, whereas a significantly lower anatomical closure rate was shown in the air group than SF6 group (46.2% vs. 84.0%, P < 0.001) for MH > 520 µm. CONCLUSION: SF6 exhibited more effectiveness than air to achieve a good anatomical outcome for its longer tamponade when MH > 520 µm.

From Nanoalloy to Nano-Laminated Interfaces for Highly Stable Alkali-Metal Anodes.

Metal anodes are considered the holy grail for next-generation batteries because of their high gravimetric/volumetric specific capacity and low electrochemical potential. However, several unsolved challenges have impeded their practical applications, such as dendrite growth, interfacial side reactions, dead layer formation, and volume change. An electrochemically, chemically, and mechanically stable artificial solid electrolyte interphase is key to addressing the aforementioned issue with metal anodes. This study demonstrates a new concept of organic and inorganic hybrid interfaces for both Li- and Na-metal anodes. Through tailoring the compositions of the hybrid interfaces, a nanoalloy structure to nano-laminated structure is realized. As a result, the nanoalloy interface (1Al2 O3 -1alucone or 2Al2 O3 -2alucone) presents the most stable electrochemical performances for both Li-and Na-metal anodes. The optimized thicknesses required for the nanoalloy interfaces for Li- and Na-metal anodes are different. A cohesive zone model is applied to interpret the underlying mechanism. Furthermore, the influence of the mechanical stabilities of the different interfaces on the electrochemical performances is investigated experimentally and theoretically. This approach provides a fundamental understanding and establishes the bridge between mechanical properties and electrochemical performance for alkali-metal anodes.

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema.

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.

Semaphorin 3A Inhibits Endoplasmic Reticulum Stress Induced by High Glucose in Müller Cells.

PURPOSE: This study aimed to explore the effect of the Semaphorin3A (Sema3A)/Neuropilin-1 (Nrp-1) pathway on Müller cell activities and endoplasmic reticulum (ER) stress induced by high glucose (HG) in vitro. METHODS: The primary Müller cells of C57BL/6J mice were isolated and cultured in normal or high glucose medium. The expression of endogenous Sema3A and its coreceptor Nrp-1 was measured by Western blot. Müller cells were incubated with exogenous recombinant Sema3A protein or transfected with lentiviral vectors expressing small hairpin RNA (shRNA) to knock down the expression of endogenous Sema3A. The proliferation of Müller cells was detected by CCK-8 assay and EdU staining. The migratory ability was detected by the Transwell migration assay. The level of endoplasmic reticulum (ER) stress was analyzed through the detection of GRP78/BiP, IRE1α, phosphorylated IRE1αS724 (p-IRE1αS724), and the splicing rate of XBP1 (XBP1s/XBP1) by using immunofluorescence, Western blot or quantitative polymerase chain reaction (qPCR). RESULTS: HG induced the upregulation of endogenous Sema3A and Nrp-1 receptors in Müller cells. The expression of GRP78/BiP and IRE1α was upregulated by HG, with an increased splicing rate of XBP1. Exogenous Sema3A inhibited HG-induced Müller cell proliferation, migration, and GRP78/BiP-IRE1α-XBP1 axis activation. Knockdown of Sema3A promoted proliferation, migration, and ER stress induced by high glucose in Müller cells. CONCLUSION: Sema3A inhibited the increased proliferative and migratory activities induced by high glucose by attenuating ER stress in Müller cells.

Comparison of 24×20 mm2 swept-source OCTA and fluorescein angiography for the evaluation of lesions in diabetic retinopathy.

AIM: To compare ultra-widefield (24×20 mm2) swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA) in the evaluation of diabetic retinopathy (DR) lesions. METHODS: Forty-six eyes of 23 patients with treatment-naïve DR were included at Peking University People's Hospital from September 1, 2021, until December 31, 2021, as well as 23 age and gender matched healthy controls. Quantitative assessments of DR lesions on FA and SS-OCTA (superficial capillary plexus, SCP, 24×20 mm2) were performed. RESULTS: Area of fovea avascular zone (FAZ) was larger in DR cases than controls (0.34±0.069 mm2 vs 0.287±0.108 mm2, P=0.006). In DR eyes, the mean FAZ area was 0.34±0.069 and 0.334±0.087 mm2 on SS-OCTA and FA, respectively (P=0.428), while the median FAZ perimeter was 2.382 (IQR, 2.201-2.59) and 2.333 (IQR, 2.138-2.6) mm on SS-OCTA and FA images (P=0.733). There was no significant difference in the size of the non-perfusion area (NPA) between the images on SS-OCTA and FA (12.389, IQR 4.96-28.3 and 11.125, IQR 5-28.31 mm2, P=0.197). The median total microaneurysm (MA) count was 35 (IQR, 19-46) and 73 (IQR, 43-93) on SS-OCTA and FA (P<0.001), respectively. No significant difference in intra-retinal microvascular abnormality (IRMA) and neovascularization (NV) count was found between the two techniques. The intraclass coefficient (ICCs) of all the parameters above indicated stable repeatability. CONCLUSION: Ultra-widefield SS-OCTA represents a reliable, noninvasive, and quantitative imaging technique in the assessment of microvasculature in DR, which offers a potential substitute for FA in DR evaluation.

Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes.

Purpose: To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application. Methods: This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups. Result: Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA. Conclusion: This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.

An Insertion Variant in CRH Confers an Increased Risk of Central Serous Chorioretinopathy.

Purpose: To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC). Methods: We performed a genetic study of CSC in families and sporadic cases with controls. Using whole-exome sequencing and linkage analysis, we identified a heterozygous insertion variant, Gln52insPro, in the CRH gene that cosegregated in two Chinese families with CSC. This variant was evaluated among an additional 1307 patients with CSC and 1438 ethnicity-matched control individuals from three independent Chinese cohorts. Results: The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (Pmeta = 1.24 × 10-11; odds ratio, 3.01; 95% confidence interval, 2.15-4.21). The risk variant Gln52insPro decreased CRH gene expression. Conclusions: Our results implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.

Atypical Adams-Oliver syndrome with typical ocular signs of familial exudative vitreoretinopathy.

AIM: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR). METHODS: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family. RESULTS: Two novel mutations of DOCK6 (c.1396C>T and c.4796G>A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents. CONCLUSION: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist.

Ionic Conductive and Highly-Stable Interface for Alkali Metal Anodes.

Alkali metals are regarded as the most promising candidates for advanced anode for the next-generation batteries due to their high specific capacity, low electrochemical potential, and lightweight. However, critical problems of the alkali metal anodes, especially dendrite formation and interface stabilization, remain challenging to overcome. The solid electrolyte interphase (SEI) is a key factor affecting Li and Na deposition behavior and electrochemical performances. Herein, a facile and universal approach is successfully developed to fabricate ionic conductive interfaces for Li and Na metal anodes by modified atomic layer deposition (ALD). In this process, the Li metal (or Na metal) plays the role of Li (or Na) source without any additional Li (or Na) precursor during ALD. Moreover, the key questions about the influence of ALD deposition temperature on the compositions and structure of the coatings are addressed. The optimized ionic conductive coatings have significantly improved the electrochemical performances. In addition, the electrochemical phase-field model is performed to prove that the ionic conductive coating is very effective in promoting uniform electrodeposition. This approach is universal and can be potentially applied to other different metal anodes. At the same time, it can be extended to other types of coatings or other deposition techniques.

Treatment for Retinopathy of Prematurity in Twins: The Small Twin without High Birth Weight Discordant Is Not at Increased Risk.

Purpose: As common retinopathy is observed in low-birth infants, the characteristics of ROP in twins are worth exploring. The present study tried to demonstrate the risk factors of treatment for retinopathy of prematurity (ROP) in twins both diagnosed with ROP. Methods: A retrospective, institution-based cohort study of 62 premature ROP twin pairs with a mean gestational age (GA) younger than 35 weeks and a birth weight (BW) lower than 2500 g. Only infants with a follow-up period longer than 6 months and complete treatment records were included. The demographic data, treatment requirements and further rescue treatments were all collected and analyzed for all infants according to whether they accepted treatments. Moreover, all twin infants were divided into small and large twin groups according to birth weight, and they were also categorized as three groups according to the treatment requirement including both twins receiving treatment (BT group), one of the twins receiving treatment (ST group) and none of the twins receiving treatment (NT group). Comparisons of demographic data, treatment requirements and further rescue treatments were all conducted according to the different grouping methods. Results: The mean GA of the enrolled infants was (29.29 ± 2.45) weeks with a mean BW of (1335.77 ± 390.36) grams. Among them, 110 infants were mechanically ventilated. Fifty-one of the infants did not receive any treatment and 73 infants received laser or intravitreal injection of anti-VEGF agents. In total, 64 infants only underwent intravitreal injection of anti-VEGF agents or laser treatment, while the other nine infants received scleral buckling or vitrectomy as a necessary treatment when the retinal detachment was observed. No significantly different mechanical ventilation or treatment requirements could be observed between the small twin group and the large twin group (p = 0.73, 0.94). The twins in the BT groups showed the lowest BW, while the NT group infants had the highest BW. The GA for the BT, ST and NT groups were (27.86 ± 1.87) weeks, (29.60 ± 1.52) weeks and (31.33 ± 2.39) weeks, respectively, and showed significant differences as well (p < 0.001). Conclusion: Being a small twin in twin-paired ROP without a high BW discordant will not increase the risk for treatment requirement or additional surgery necessity with a much more severe stage of ROP.

Serum Untargeted Metabolomics Reveal Potential Biomarkers of Progression of Diabetic Retinopathy in Asians.

Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients. Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models. Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways. Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

Risk factors of persistent subretinal fluid after half-dose photodynamic therapy for treatment-naïve central serous chorioretinopathy.

PURPOSE: To investigate the prognostic factors on spectral domain optical coherence tomography (SD-OCT) associated with incomplete subretinal fluid (SRF) absorption in treated-naïve eyes with central serous chorioretinopathy (CSC) after the half-dose verteporfin photodynamic therapy (vPDT). METHODS: Patients with CSC who underwent half-dose vPDT with a follow-up period of more than 3 months were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with the SRF persistence at 3 months after the treatment. RESULTS: A total of 143 patients with 150 eyes were enrolled in this study (102 male and 41 female patients). The rate of complete SRF resolution was 82.7% at 3 months for all cases. The duration of symptoms > 6 months (odds ratio [OR] = 3.135, 95% confidence interval [95% CI] (1.147-8.573), p = 0.026), larger SRF area with base diameter > 3 mm (odds ratio (OR) = 4.051, 95% CI: 1.336-12.284, p = 0.013), and larger flat irregular pigment epithelium detachment (FI-PED) area with base diameter > 1 mm (OR = 3.311, 95% CI: 1.249-8.780, p = 0.016) on OCT B-scans were risk factors for incomplete SRF absorption after half-dose vPDT, while outer nuclear layer (ONL) thickness was not significantly associated with the anatomical outcome (OR = 1.015, 95% CI: 0.995-1.036, p = 0.145). CONCLUSION: The duration of symptoms, baseline SRF, and FI-PED base diameter on SD-OCT were important predictors for the anatomical outcome at 3 months after half-dose vPDT. Further studies are needed to establish a better therapeutic strategy for patients with poor response to half-dose vPDT.

Proteomics of Vitreous Humor Reveals PPARA, RXR, and LXR Are Possible Upstream Regulators of Proliferative Diabetic Retinopathy.

Purpose: To investigate the key regulators of the disease by comparing the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and the controls with idiopathic epiretinal membrane (iERM). Methods: Vitreous humor (VH) samples were derived from patients with PDR or iERM through the pars plana vitrectomy. The VH proteins were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. MaxQuant software and Metascape were applied to explore the enrichment of differentially expressed proteins in biological processes, cellular components, and molecular functions. Enrichr online tool and Gene Set Enrichment Analysis (GSEA) were performed to detect upstream transcriptional regulators of the highly expressed proteins. Results: The present study collected 8 vitreous humor samples from 5 PDR eyes and 3 iERM eyes and identified 88 highly expressed proteins in PDR patients. We validated our highly expressed proteome was able to distinguish the PDR patients from the non-PDR patients by using the VH proteomics data from a previous study. The majority of highly expressed proteins were involved in complement and coagulation cascades, regulating exocytosis, and hemostasis. Using the Gene Set Enrichment Analysis (GSEA), we identified that transcription factors (TFs) PPAR-α, RXR, LXR regulate these proteins. Conclusions: In this study, we identified a highly expressed proteome in VH of PDR patients. The role of the complement and coagulation system, regulating exocytosis, and hemostasis has been of great significance to PDR. Nuclear receptors PPARA, RXR, LXR were possible upstream regulators of disease progression and required further study.

Plasma metabolomic profiling of central serous chorioretinopathy.

Our study aimed to investigate metabolites alterations in the blood plasma of central serous chorioretinopathy (CSC) patients and to identify the key biomarkers to increase the understanding of the mechanism of CSC at the molecular level. Quantitative and targeted metabolomics using liquid chromatography tandem-mass spectrometry (LCMS, Biocrates P500) assays were performed on plasma samples from the 42 subjects(CSC patients = 30, control = 12) enrolled at the Department of Ophthalmology of People's Hospital Peking University. A total of 61 altered metabolites were distinguished between CSC patients and controls. Taurine was selected as a candidate biomarker for CSC among 6 potential metobolites: taurine, glutamic acid, sarcosine, lactic acid, glutamine and C18_1. The P values of these potential metabolites were 1.01E-06, 7.35E-08, 1.27E-24, and 1.85E-10, 1.02E-05 and 8.59E-08, and the areas under the curve for them were 0.926, 0.991, 1.000, 0.900, 0.897 and 0.841, respectively. This study is the first to identify that taurine may be a biologically relevant biomarker for CSC and to provide a novel understanding of CSC.

Comparison of the outcomes of photodynamic therapy for central serous chorioretinopathy with or without subfoveal fibrin.

BACKGROUND: To compare the outcomes of half-dose verteporfin photodynamic therapy (vPDT) for central serous chorioretinopathy (CSCR) with or without subfoveal fibrin. METHODS: One hundred seventy-three cases of CSCR treated with half-dose vPDT between September 2008 and February 2018 were retrospectively reviewed and classified into two groups: CSCR with subfoveal fibrin (fibrin group) and without subfoveal fibrin (no-fibrin group). The changes in best-corrected visual acuity (BCVA) from baseline and in central macular thickness (CMT) were recorded at 1, 3, and 6 months after the treatment. RESULTS: Forty-eight eyes were included in the fibrin group and 125 eyes in the no fibrin group. There were no statistical differences in the baseline characteristics including age, gender, duration of symptoms, and CMT between the groups. The baseline mean BCVA of the fibrin group was significantly worse than that of the no fibrin group (0.47 ± 0.32 versus 0.32 ± 0.31 in logMAR; p = 0.003). There was no statistically significant difference between the two groups in the improvement of BCVA at each follow-up point (1 month: p = 0.069; 3 months: p = 0.111; 6 months: p = 0.172, respectively) and in the reduction of CMT (1 month: p = 0.367; 3 months: p = 0.767; 6 months: p = 0.496, respectively). In the fibrin group, the rates of complete resolution of the subretinal fibrin at 1, 3, and 6 months after vPDT were 72.9%, 95.8%, 95.8%, respectively. The SRF resolution rate at 1, 3, and 6 months was 72.9%, 89.6% and 91.7% respectively in the fibrin group and was 62.4%, 83.2% and 84.0% in the no fibrin group. There was no significant difference of SRF resolution rate between the two groups at 1 month (p = 0.216), 3 months (p = 0.350), and 6 months (p = 0.228). No ocular adverse event was encountered in both groups. CONCLUSION: Half-dose vPDT was effective and safe for CSCR patients with subfoveal fibrin.

Long-term follow-up of primary silicone oil tamponade for retinal detachment secondary to macular hole in highly myopic eyes: a prognostic factor analysis.

PURPOSE: To investigate the risk factors associated with retinal detachment recurrence after first vitrectomy in high myopic eyes with macular hole retinal detachment (MHRD). METHODS: Patients with high myopic eyes with MHRD who underwent pars plana vitrectomy and silicone oil (SO) tamponade with a follow-up period more than 12 months and more than 3 months after SO removal were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with retinal re-detachment. RESULTS: A total of 45 eyes from 43 patients were included in this study (11 male and 34 female patients). The retinal re-detachment rate after the first removal of silicon oil was 35.5% (16/45) in a mean postoperative follow-up time of 35.64 ± 32.94 months. Complete macular atrophy on fundus photography (odds ratio (OR) = 17.021, 95% confidence interval (95% CI): 2.218-130.609, p = 0.006) was a risk factor for MHRD after SO removal, while internal limiting membrane (ILM) peeling (OR = 0.091, 95% CI: 0.013-0.633, p = 0.015) and duration of SO tamponade (OR = 0.667, 95% CI: 0.454-0.980, p = 0.039) were protective factors. CONCLUSION: For high myopic eyes with MHRD, complete macular atrophy was a significant risk factor for retinal re-detachment after silicon oil removal. ILM peeling and the duration of silicon oil tamponade were protective factors.

Different Types of Hyperfluorescence Observed in Post Anti-VEGF Fluorescein Angiographic Patterns in Retinopathy of Prematurity Patients.

PURPOSE: To demonstrate that the demographic and treatment characteristics of retinopathy of prematurity (ROP) eyes showed different types of hyperfluorescence in fluorescein angiography (FA) initially treated with anti-vascular endothelial growth factor (VEGF) agents. METHODS: A consecutive case series of ROP treated with anti-VEGF agents was retrospectively studied. All the patients underwent FA examinations at least 6 months later after treatment. The demographic and treatment characteristics of eyes with or without hyperfluorescence in FA were analyzed. The different types of hyperfluorescence were divided into three groups, including vascular leakage, fibrous membrane, and vascular abnormality. RESULTS: Two hundred and forty-two eyes of 123 patients with treatment-required ROP were included. Hyperfluorescence was defined in 51/242 eyes, and 2.08 ± 1.11 injections were performed for them, while the eyes without hyperfluorescence received 1.65 ± 0.80 injections (P = 0.013). Vascular leakage was defined in 26/51 hyperfluorescence eyes. The postmenstrual age (PMA) of first injection for the hyperfluorescence group was 38.56 ± 3.24 weeks, which is earlier than that of infants without hyperfluorescence (P = 0.011). More additional treatments were performed in eyes with hyperfluorescence (23.53 vs. 3.66%, P = 0.000). Among them, the eyes with vascular leakage required more additional treatment than eyes without vascular leakage (42.31 vs. 4.00%, P = 0.004). For the 26 eyes with vascular leakage, 11 eyes of 8 patients received further treatments during further follow-up. No significant difference of refractive errors can be defined between different groups. CONCLUSION: Eyes with persistent hyperfluorescencein FA after treatment required more anti-VEGF and additional treatments, including laser and PPV. Not all hyperfluorescences were vascular leakage and required additional treatment.

The critical role of m6A methylation in the pathogenesis of Graves' ophthalmopathy.

PURPOSE: To investigate the role of N6-methyladenosine (m6A) RNA modification in the pathogenesis of Graves' ophthalmopathy (GO). METHODS: Surgically excised extraocular muscles from 7 patients with GO and 5 subjects without GO were used. The global m6A levels in the specimens were determined using an m6A RNA methylation quantification kit. RNA sequencing (RNA-seq) was used to analyze the molecules involved in the regulation of m6A RNA methylation and the differential expression of mRNAs between the two groups (4 eyes, respectively). The expression of m6A RNA modification genes was evaluated by real-time PCR. The functional implications of the gene alterations between the GO and control specimens were determined by Gene Ontology analysis. RESULTS: The m6A level was significantly increased in the specimens of GO patients compared to the control specimens (P < 0.05). The expression of m6A methylation regulators, such as WT1 associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), E74 like ETS transcription factor 3 (ELF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTHDF3 and YTH domain containing 2 (YTHDC2), was significantly upregulated (P < 0.05). Gene Ontology enrichment analysis showed that the most highly upregulated genes and biological pathways were related to the immune response and inflammatory processes such as lymphocyte activation, leukocyte differentiation, cytokine production and cytokine-mediated signaling pathways. CONCLUSIONS: Our results suggest that m6A methylation may play a critical role in the pathogenesis of GO and that targeting genes that regulate m6A methylation may provide a new therapeutic approach for GO.

High-dose ruthenium-106 plaque therapy for circumscribed choroidal hemangioma: a retrospective study of 25 Chinese patients.

AIM: To evaluate the efficacy and safety of ruthenium-106 (106Ru) plaque radiotherapy at a dose (>50 Gy) higher than recommended (29-50 Gy) for treatment of circumscribed choroidal hemangioma (CCH) in Chinese patients. METHODS: This retrospective study included 25 symptomatic CCH patients undergoing 106Ru plaque brachytherapy involving 25 eyes between January 2005 and August 2016. Ophthalmic examination was performed at the baseline and at each post-treatment follow-up visit, using best-corrected visual acuity (BCVA), dilated fundus examination, and B-scan ultrasonography. The primary efficacy outcome measures included the changes in BCVA and hemangioma dimensions at the last followup visit from the baseline. RESULTS: The mean follow-up duration was 28.0±26.6 (range, 12-110)mo. All the hemangiomas were located in the posterior pole except for two involving the fovea. The mean apex dose of 106Ru plaque radiotherapy was 84.4±19.7 Gy. The mean BCVA improved from 41.4±29.3 (0-97) at the baseline to 53.0±33.8 (0-97) ETDRS letters at the last visit (P=0.01). The mean hemangioma height declined from 3.98±0.88 (2.40-5.50) mm to 0.84±1.63 (0-6.47) mm (P≤0.001), and the greatest linear diameter (GLD) reduced from 9.36±2.23 (6.80-15.00) to 7.40±2.45 (0-13.00) mm (P≤0.001). Hemangioma size increased in one (4%) eye with a worsened vision, and subretinal fluid completely resolved in all but one patient (4%). Radiation-related retinopathy was observed in two patients at post-treatment 9 and 11mo, respectively. CONCLUSION: 106Ru plaque brachytherapy at a dose (>50 Gy) higher than recommended (29-50 Gy) is an effective treatment regimen for symptomatic CCH associated with significantly improved visual acuity and a favorable safety profile in Chinese patients.