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Aim: To characterize the N 6 -methyladenosine (m 6 A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC)., Methods: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m 6 A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m 6 A-lncRNAs., Results: Large amount of m 6 A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair., Conclusion: Our results for the first time present an overview of the m 6 A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC., Competing Interests: Conflicts of Interest: Ye HF, None; Zhang X, None; Zhao ZN, None; Zheng C, None; Fei P, None; Xu Y, None; Lyu J, None; Chen JL, None; Guo XX, None; Zhu H, None; Zhao PQ, None., (International Journal of Ophthalmology Press.)

The fluorosulfonyldifluoromethylation of unactivated alkenes and (hetero)arenes with iododifluoromethanesulfonyl fluoride (ICF 2 SO 2 F) under visible light photoredox catalysis was successfully developed. Key to the successful fluorosulfonyldifluoromethylation of aromatic compounds was the usage of AgOTf as an additive to promote the formation of the CF 2 SO 2 F radical. The protocol provided a straightforward way to introduce the interesting and useful CF 2 SO 2 F group on sp 3 and sp 2 carbons.

Aim: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress., Methods: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro . Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca 2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data., Results: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca 2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca 2+ -dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress., Conclusion: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis., Competing Interests: Conflicts of Interest: Huang LH, None; Lyu J, None; Chen S, None; Liang TY, None; Rao YQ, None; Fei P, None; Li J, None; Jin HY, None; Zhao PQ, None., (International Journal of Ophthalmology Press.)

Objective: To analyze the clinical and genetic features of patients with mitochondrial pyruvate carrier deficiency (MPYCD). Methods: This was a case series research. The clinical data, genetic characteristics, and glutamine treatment efficacy of 3 patients diagnosed with MPYCD at the Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, Guizhou Provincial People's Hospital, from August 2019 to June 2023 were retrospectively collected. A literature search with "MPC1 gene" "MPC2 gene and" "mitochondrial pyruvate carrier deficiency" as keywords was conducted at the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure (CNKI) and PubMed (up to June 2023). Clinical and genetic characteristics of patients with MPYCD were summarized. Results: Case 1 was a 3 years and 11 months old boy, while case 2 was a 4 years and 10 months old boy and case 3 was an 8 years and 9 months old girl. Case 2 and case 3 were siblings from one consanguineous family. All 3 patients presented with general developmental delay, growth failure and elevated serum lactate. Cranial magnetic resonance imaging (MRI) showed subtle bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus in case 1, but normal in case 2 and 3. Trio-WES revealed case 1 harboring compound heterozygous missense variants c.208G>A (p.Ala70Thr) and c.290G>A (p.Arg97Gln) in MPC1 gene, while case 2 and 3 revealed a homozygous variant c.290G>A (p.Arg97Gln) in the same gene. All 3 cases were diagnosecl as MPYCD. Clinical symptoms including motor ability, cognition and activity endurance were improved in these 3 patients after taking glutamine for 2 years. A total of 5 articles published in English were reviewed, and no Chinese literature was found. Including these 3 cases, 15 cases were enrolled for analysis. Eleven patients carried MPC1 gene variants and 4 cases carried MPC2 gene variants. Except for 3 cases died during prenatal period, 9 of 12 enrolled born cases were onset before 6 months old. The most common clinical symptoms were mental and motor general developmental delay, microcephaly, growth failure and hypotonia. All patients had elevated blood lactate and pyruvate, but the ratio of lactate/pyruvate was normal. Seven patients performed cranial MRI, 3 exhibited non-specific changes, 2 showed bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus, and 3 were normal. A total of 5 MPC1 gene missense variants and 2 MPC2 gene variants were identified in 15 cases. Conclusions: Onset age of patients with MPYCD is usually within 6 months. The main clinical characteristics are developmental delay, microcephaly and growth failure, accompanied by increased serum lactate and pyruvate. Glutamine supplement could lead to clinical improvements.

Purpose: To explore the clinical and molecular characteristics, diagnosis, and treatment of early-onset autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) in Chinese patients., Methods: A retrospective, interventional case series was assembled from three ADNIV patients., Results: The three ADNIV cases harbored de novo CAPN5 mutations (p.Arg289Trp and p.Leu73Val). The ages of onset ranged from 11 months to 2 years. All the cases presented with vitreous opacity and subretinal inflammatory exudations. During the postoperative follow-up, all the patients manifested with exaggerated postoperative inflammatory responses. An intravitreal Ozurdex injection could not effectively control ocular inflammation in ADNIV. Laser spots after panretinal photocoagulation were partly visible., Conclusions: Two de novo CAPN5 mutations (p.Leu73Val and p.Arg289Trp) could cause early-onset ADNIV. Panretinal photocoagulation during vitrectomy and an intravitreal Ozurdex injection could not significantly stop the progression of subretinal exudations and ocular inflammation in early-onset ADNIV patients.

Background: Capillary dysfunction has been implicated in a series of life- threatening vascular diseases characterized by pericyte and endothelial cell (EC) degeneration. However, the molecular profiles that govern the heterogeneity of pericytes have not been fully elucidated. Methods: Single-cell RNA sequencing was conducted on oxygen-induced proliferative retinopathy (OIR) model. Bioinformatics analysis was conducted to identify specific pericytes involved in capillary dysfunction. qRT-PCRs and western blots were conducted to detect Col1a1 expression pattern during capillary dysfunction. Matrigel co-culture assays, PI staining, and JC-1 staining was conducted to determine the role of Col1a1 in pericyte biology. IB4 and NG2 staining was conducted to determine the role of Col1a1 in capillary dysfunction. Results: We constructed an atlas of > 76,000 single-cell transcriptomes from 4 mouse retinas, which could be annotated to 10 distinct retinal cell types. Using the sub-clustering analysis, we further characterized retinal pericytes into 3 different subpopulations. Notably, GO and KEGG pathway analysis demonstrated that pericyte sub-population 2 was identified to be vulnerable to retinal capillary dysfunction. Based on the single-cell sequencing results, Col1a1 was identified as a marker gene of pericyte sub-population 2 and a promising therapeutic target for capillary dysfunction. Col1a1 was abundantly expressed in pericytes and its expression was obviously upregulated in OIR retinas. Col1a1 silencing could retard the recruitment of pericytes toward endothelial cells and aggravated hypoxia-induced pericyte apoptosis in vitro . Col1a1 silencing could reduce the size of neovascular area and avascular area in OIR retinas and suppressed pericyte-myofibroblast transition and endothelial-mesenchymal transition. Moreover, Col1a1 expression was up-regulated in the aqueous humor of the patients with proliferative diabetic retinopathy (PDR) or retinopathy of prematurity (ROP) and up-regulated in the proliferative membranes of PDR patients. Conclusions: These findings enhance the understanding of the complexity and heterogeneity of retinal cells and have important implications for future treatment of capillary dysfunction., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In the present study, a novel and green temperature-responsive deep eutectic solvent (TRDES) system was developed and applied for the simultaneous extraction and separation of different polar active phytochemicals from Schisandra chinensis (Turcz.) Baill. The TRDES, consisting of amino alcohols and phenolic compounds, was chosen as the switching medium, and an upper critical solution temperature (UCST) type switchable solvent was obtained by adding an inorganic salt solution. The switchable phase diagram was plotted based on the relationship between the phase change temperature, the concentration and the amount of sodium chloride solution. Under optimal parameters, the yields with TRDES for different polar active phytochemicals (lignanoids and polysaccharides) from the dried fruit of Schisandra chinensis (DFSC) were 1.62 ∼ 1.17-fold and 1.39-fold to those with conventional solvents. Also, the TRDES system was still effective on extraction of DFSC lignanoids and polysaccharides after four cycles of extraction. The separated polysaccharides and lignanoids both had strong antioxidant activities with IC 50 values of 1.92 mg/ mL and 0.10 mg/ mL against 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), respectively. The extraction mechanism of TRDES was postulated by Density functional theory (DFT) calculations the hydrogen bonding in TRDES was the main factor to the higher extraction yield. This temperature-responsive deep eutectic solvent could be widely used for the efficient extraction and separation of multi-polar components. As a green and recyclable solvents, TRDES has great potential for the lower cost production from plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may suffer from cytomegalovirus retinitis (CMVR) which can cause vision loss. This study is to report the progression and prognosis of patients with WAS and CMVR., Methods: A retrospective case series of ten patients with WAS and CMVR before and after HSCT who were referred to the Ophthalmology Department of Xinhua Hospital from June 2018 to February 2021. Progression and prognosis were recorded., Results: Five patients were diagnosed with CMVR before receiving HSCT at a median age of 10.5 months (range: 4-23 months). Eight patients developed CMVR post-transplantation with a median interval from HSCT of 3.5 months (range: 1-9 months)., Conclusion: Regular fundus examinations and prompt treatments in patients with WAS are therefore crucial before they receiving HSCT or approximately 3.5 months after HSCT until complete reconstitution of immune function.

Aim: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification., Methods: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit., Results: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion., Conclusion: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is., (International Journal of Ophthalmology Press.)

Aim: To investigate the role of procollagen C-proteinase enhancer 1 (PCPE1) in retinal angiogenesis and relevant mechanisms., Methods: The Pcolce1 -knockout (KO) mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo . Pcolce1 siRNA were designed, cell count kit 8 (CCK8) assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells (hRMECs) in vitro . Mouse embryo fibroblasts (MEF) cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage., Results: In vivo studies showed that the retinal vascular density of Pcolce1 -/- mice was significantly lower than that of the control group. Furthermore, silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of hRMECs in vitro . Additionally, much more pro-collagen was found in Pcolce1 -/- MEF cells, compared to wild type MEF cells., Conclusion: PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen, which may provide a potential therapeutic target of retinal vascular disease., (International Journal of Ophthalmology Press.)

Aim: To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment (RD) in a cohort of pediatric patients diagnosed with morning glory syndrome (MGS)., Methods: A total of 24 eyes of 22 consecutive patients aged 0-15y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed. Data including demographics, ocular examination, anatomic and visual outcomes, following treatment and complications were collected., Results: Two patients had bilateral laser treatment and 20 had monocular laser treatment. The age at treatment of 13 (59.1%) patients was less than 12mo. The presenting symptoms included strabismus (6/22, 27.3%), decreased vision (2/22, 9.1%), and routine fundus screening (14/22, 63.6%). Fifteen (68.2%) patients underwent cranial magnetic resonance imaging (MRI) examinations, and 3 of those 15 (20.0%) had abnormal findings in the nervous system. Based on preoperative wide-field fundus photography and B-scan echography, all (100.0%) eyes had no obvious RD. On postoperative 1mo and 6mo and the following follow-ups, the anatomic outcomes of all eyes remained stable. The mean follow-up duration was 27.7±17.5mo. No severe complications were found. Preoperative visual acuity acquired from 2 (9.1%) patients ranged from light perception to 20/200. Postoperative acuity acquired from 11 (50.0%) patients ranged from light perception to 20/125., Conclusion: The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up. Further long-term clinical observation will be needed to confirm its efficacy and safety., (International Journal of Ophthalmology Press.)

Purpose: Familial exudative vitreoretinopathy (FEVR) is an inherited retinal vascular disease genetically heterogeneous with multiple causative genes. The aim of this study is to report five novel copy number variation (CNV) regions in FEVR patients and to investigate the possible contributions of novel CNVs to FEVR., Methods: In this study, 824 FEVR families were collected. All cases were performed using the targeted next generation sequencing (NGS) assay, and families with no definite pathogenic mutations in FEVR genes were screened for CNVs according to the NGS results. Droplet digital polymerase chain reaction (ddPCR) testing was introduced to validate the screened CNV regions. We also reviewed the clinical presentations of the probands and affected family members associated with the novel CNVs and conducted segregation analysis., Results: Five CNVs in five patients were detected in this study: heterozygous deletions of kinesin family member 11 ( KIF11 ) exons 2-4, KIF11 exon 11, KIF11 exons 1-10, tetraspanin-12 ( TSPAN12 ) exons 1-3, and low-density lipoprotein receptor-related protein 5 ( LRP5 ) exons 19-21. Among the five affected families, TSPAN12 exons 1-3 heterozygous deletion and LRP5 exons 19-21 heterozygous deletion originate from the mother and the father of the proband, respectively. No other family members manifested as FEVR except for the probands. The correlation between disease severity and CNV loci seems uncertain., Conclusions: Five novel CNV loci in FEVR patients were uncovered in this study, including one maternally-inherited and one paternally-inherited CNV region. Though there is no evidence of co-segregation between these CNVs and FEVR, our findings suggest novel genetic risk factors for FEVR., (Copyright © 2021 Molecular Vision.)

Aim: To determine the etiologies, treatment modalities and visual outcomes of vitreous hemorrhage (VH; range from birth to 18y)., Methods: A total of 262 eyes from 210 patients between January 2010 and September 2016 were included. All children underwent an appropriate ocular and systemic examination. Data collected included demographics, clinical manifestations, details of the ocular and systemic examination, management details, final fundus anatomy and visual acuity (VA)., Results: The most common etiologies were non-traumatic VH (64.89%), most of which were due to retinopathy of prematurity (ROP; 37.10%); while traffic accidents, including 16 (21.00%) eyes, was the most common ocular traumas. Surgery, performed in 143 (54.58%) eyes, was the most common management modality. The initial mean baseline visual acuity was 2.77±0.21 logarithm of the minimal angle of resolution (logMAR) in children and adolescent with traumatic VH, which was significantly improved to 2.15±1.31 logMAR ( P <0.05)., Conclusion: VH in children and adolescent has a complicated and diverse etiology. ROP is the primary cause of non-traumatic VH, which is the most common etiology. Appropriate treatment of traumatic VH is associated with obvious improvement in visual acuity. The initial VA is one of most important predictors of outcome., (International Journal of Ophthalmology Press.)

Earlier electroencephalographic studies have compared attractive and unattractive faces and between faces with other objects, such as flowers, without revealing if a recognition memory bias toward faces and flowers exists or whether humans exhibit enhanced specific components toward all attractive objects or only toward attractive faces. For objects with similar degrees of attractiveness, we sought to determine if the N170, P1, and N250 reflect upon the attractiveness of faces and flowers and demonstrated by comparing event-related potentials of humans' different perceptual mechanisms recognizing high attractive faces and high attractive flowers. The repeated high attractive faces tended to elicit a larger N170. Simultaneously, the P1 was preferentially associated with the repeated high attractive flowers, but both indicated that the repetitive enhancement effect only occurred on repeated attractive faces. Thus, differences existed in the perceptual mechanisms for processing repeated high attractive faces and repeated high attractive flowers. However, there was no significant difference in N250 between repeated faces and repeated flowers or between high attractive faces and high attractive flowers. Consequently, high attractive faces and high attractive flowers capture the beholder's memory bias in different processing stages. The N170 and P1 components are affected by attractiveness, thereby demonstrating the differences between human perceptual mechanisms in recognizing high attractive faces and objects., Competing Interests: The authors declare no conflict of interest., (© 2020 Zhang et al. Published by IMR Press.)

Aim: To describe and compare pathologic findings in eyes enucleated after superselective ophthalmic arterial chemotherapy (SOAC) or SOAC with intravenous chemotherapy (IVC) for retinoblastoma., Methods: Medical records between January 1 st , 2014 and June 30 th , 2017 were retrospectively analyzed, and pathologic findings were recorded. This study included 36 eyes from 22 (61.1%) male and 14 (38.9%) female patients. Nineteen of 36 (52.8%) eyes received SOAC (mean=3, range=1-7) as primary treatment, and 17 of 36 (47.2%) eyes received SOAC (mean=3.7, range=1-10) after IVC (mean=6.1, range=2-11). Tumor extension including choroidal invasion ( n =9, 25%), optic nerve invasion ( n =5, 13.9%) and anterior segment invasion ( n =5, 13.9%) were recorded., Results: Histopathologic evidence of ischemic damage in the retina and choroid was found in 28 (77.8%) eyes. Thrombosed blood vessels were identified in 9 (25%) eyes, including orbital artery in the retrobulbar orbit ( n =1), intrascleral vessels ( n =4), and chorioretinal vessels ( n =6). Fibrotic changes were found in extraocular muscles ( n =5, 13.9%) and optic nerve ( n =5, 13.9%). Varying degrees of scleral degeneration were found in all eyes. In statistical analysis, there was no significant difference in clinical and pathologic changes between SOAC group and SOAC with IVC group except for optic nerve invasion ( P =0.047)., Conclusion: SOAC for retinoblastoma can result in ocular toxicity, and SOAC with IVC do not increase the toxicity but reduced the incidence of optic nerve invasion., (International Journal of Ophthalmology Press.)

Aim: To demonstrate local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade for the treatment of partial rhegmatogenous retinal detachment (RRD) with local vitreous traction in patients at high-risk for proliferative vitreoretinopathy (PVR)., Methods: Eleven eyes of 11 patients were retrospectively studied, including 5 retinal dialysis and 6 retinal detachment (RD; 5 eyes with peripheral retinal hole and 1 eye with giant tear). All patients exhibited partial RD and local vitreous traction. Combined local dry vitrectomy without conventional infusion and segmental scleral buckling was performed. Viscoelastic fluid was injected into the vitreous cavity if needed. Demographic information, preoperative and post-operative complications, and outcomes were recorded., Results: The mean age of the patients at presentation was 26.55±13.52y. All 11 patients obtained retinal reattachment after a single surgical intervention. Postoperative visual acuities were improved or remained stable in all patients. None of them developed complications, except for temporary mildly increased intraocular pressure in 3 cases., Conclusion: Combined local dry vitrectomy and segmental scleral buckling are effective for patients of RRD with local vitreous traction. The technique avoids many complications associated with regular surgery and was minimally invasive to both the external and internal eye., (International Journal of Ophthalmology Press.)

Aim: To introduce a modified technique of internal limiting membrane (ILM) centripetal dragging and peeling to treat idiopathic macular hole (IMH) and to observe the ILM-retina adhesive forces., Methods: Twenty-six consecutive patients with stage 3 to 4 IMH and followed up at least six months were enrolled. All patients underwent complete par plana vitrectomy, ILM dragging and peeling, fluid and gas exchange, 15% C 3 F 8 tamponade and 2-week prone position. The best corrected visual acuity, macular hole evaluation by optical coherence tomography, and complications were evaluated., Results: The mean diameter of IMH was 524±148 µm (range: 201-683 µm), with 21 cases (80.8%) greater than 400 µm. ILM dragging and peeling were successfully performed in all cases. Most of the ILM-retina adhesive forces are severe (42.3%, 11/26), followed by mild (38.5%, 10/26), and moderate (19.2%, 5/26). The mean follow-up duration was 21.2±6.1mo. The IMH was closed in 25 (96.3%) eyes. Visual acuity (logMAR) improved significantly from 1.2±0.6 preoperatively to 0.7±0.5 postoperatively ( P <0.001)., Conclusion: Preexisting ILM-retina adhesive force is found in IMH patients. With assistance of this force, this modified technique may help to release the IMH edges and improve the closure rate of large IMH., (International Journal of Ophthalmology Press.)

Aim: To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma., Methods: This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM. The clinical status and complications were recorded at each visit., Results: The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes. All eyes showed severe cloud vitreous seeds at the first visit. The mean number of IAC cycles and intravitreal injections was 3.2 (range, 3-4) and 6 (range, 1-14), respectively. The median follow-up time was 29mo (range, 7-36mo). Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes (96.7%). Globe salvage was attained in 93.3% (28/30) eyes, and enucleation ( n =2) was performed due to neovascular glaucoma and persistent vitreous hemorrhage. Complications included retinal pigment epithelium (RPE) atrophy ( n =13; 43%), mild lens opacity ( n =7; 23%), vitreous hemorrhage ( n =5; 17%) and rhegmatogenous retinal detachment ( n =1; 3%). No extraocular tumor extension or metastasis occurred., Conclusion: Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma., (International Journal of Ophthalmology Press.)

Background: Superior oblique weakening is a common method to treat A-pattern strabismus. This study aims to evaluate the surgical results of the bilateral superior oblique posterior tenectomy procedure to treat A-pattern strabismus patients who had bilateral superior oblique overaction without objective ocular intorsion., Methods: The records of 18 consecutive patients who underwent surgery of superior oblique posterior tenectomy close to its insertion with superior oblique overaction (SOOA)-associated A-pattern strabismus between September 1, 2015 and August 31, 2018 were retrospectively reviewed. Ocular alignment, objective torsion, A-pattern and ocular motility were assessed. Ocular alignment was measured in the primary position, 25° upgaze, and 25° downgaze using the prism bar cover test, and torsion was measured using fundus photographs., Results: A total of 18 patients (mean age: 15 years; 6 female, 12 male) underwent bilateral superior oblique posterior tenectomy and simultaneous horizontal rectus muscle surgery were included. The mean preoperative A-pattern deviation was 15 PD and the mean postoperative A-pattern deviation was 2.25 PD with a mean reduction of 12.75 PD. The mean preoperative superior oblique overaction was 2.28 and the mean postoperative superior oblique overaction was 0.43 with a mean reduction of 1.85. There was no significant correlation between the ocular torsional, vertical alignment change and the superior oblique posterior tenectomy procedure., Conclusions: Superior oblique posterior tenectomy surgery selectively improved the A-pattern and superior oblique overaction but not affect the primary position vertical deviation, as well as the ocular torsion. It is an effective procedure to treat the mild to moderate superior oblique overaction associated A pattern strabismus without ocular intorsion.

TIPE1, which acts as a cell death regulator, has emerged as a tumor suppressor in the process of carcinogenesis. However, our recent research demonstrated that it serves as an oncogene in the pathogenesis of cervical cancer, indicating that the role of TIPE1 in carcinogenesis needs to be further evaluated. In this study, we show that TIPE1 is able to inhibit breast cancer cell growth both in vivo and in vitro . Functionally, TIPE1 inhibits cancer cell proliferation preferentially by downregulating ERK phosphorylation. Furthermore, the expression of TIPE1 is decreased in breast cancer tissues compared to matched adjacent tissues, and its expression is positively correlated with patients' lifespan. These data indicate that TIPE1 suppresses breast cancer proliferation by inhibiting the ERK signaling pathway. This study also suggests that TIPE1 could serve as a potential therapeutic target and a diagnostic biomarker for breast cancer.

Magnolol is the active component of the traditional Chinese medicine Magnolia officinalis, and has antioxidant, anti‑inflammatory and anticancer activities, as well as an effect on bone metabolism in vitro. In the present study, it is reported that magnolol suppresses osteoclastogenesis in vivo and in vitro. Magnolol prevented ovariectomy‑induced bone loss and osteoclastogenesis in vivo, and decreased the serum levels of C‑terminal telopeptide of type 1 collagen, interleukin‑6, tumor necrosis factor (TNF)‑α and tartrate‑resistant acid phosphatase 5B. In vitro, magnolol inhibited the osteoclastogenesis induced by the receptor activator for nuclear factor‑κB ligand, and impaired the osteoclast function in bone marrow monocytes and RAW264.7 cells in a dose‑dependent manner. Furthermore, magnolol suppressed the expression levels of the osteoclastogenesis markers cathepsin K, calcitonin receptor, matrix metalloproteinase 9, TNF receptor‑associated factor 6 and tartrate‑resistant acid phosphatase by inhibiting the nuclear factor‑κB and mitogen‑activated protein kinase pathways. Therefore, magnolol is a promising agent for the treatment of osteoporosis and associated disorders.

Aim: To clinically differentiate nanophthalmos (NO) and posterior microphthalmos (PM) and to explore the mechanisms related to papillomacular folds (PMF)., Methods: Medical records of 34 unrelated patients with microphthalmos (54 eyes) from April 2009 to October 2017 were retrospectively reviewed., Results: Fourteen eyes of 7 unrelated patients with NO and PM were included in the study. The presenting age of the NO cohort was significantly higher compared with the PM cohort (NO: 27±16y; PM: 3.7±0.6y). PMF was more likely to occur in cases with PM than in NO (25% in NO, 100% in PM). The anatomic features of PMF from optical coherence tomography (OCT) included: ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and outer nuclear layer. In eyes without an apparent PMF (these were all NO eyes), rudimentary fovea without a foveal pit was noted. Four eyes that were NO developed angle closure glaucoma. Three NO eyes developed exudative retinal detachment and were successfully treated with lamellar sclerectomy., Conclusion: Posterior segment changes are pervasive both in PM and NO. Complications like angle closure glaucoma and exudative retinal detachment are likely to occur in eyes with NO but not with PM. Detailed OCT analysis found that PMF was partially a neural retinal issue, suggesting that redundancy of retinal issues involved only inner retinal layers.

Aim: To evaluate the outcomes of vitreoretinal surgery for four different phenotypes of X-linked retinoschisis (XLRS)., Methods: This study included thirty-one eyes of 25 patients who developed XLRS with severe complications. Among the 31 eyes, there were 7 eyes with vitreous hemorrhage, 8 eyes with retinal detachment and vitreous hemorrhage, and 16 eyes with rhegmatogenous retinal detachment. All of the patients underwent standard three-port pars plana vitrectomy. All of the eyes were divided into 4 groups before surgery according to a modified classification scheme, with the first three groups as follows: group A, with foveal cystic schisis; group B with macular lamellar schisis; and group C with foveolamellar changes. Peripheral schisis was not present in these 3 groups; however, group D was a complex group with both macular and peripheral changes. One year after surgery, we analyzed the best corrected visual acuity and postoperative anatomical and functional outcomes of these 4 groups., Results: There were 7 eyes in group A (22.6%), 1 eye in group B (3.2%), 15 eyes in group C (48.4%) and 8 eyes in group D (25.8%). Postoperative anatomical and functional outcomes were satisfactory at the last visit, while the mean visual acuity was increased to 0.27±0.11, with a significant difference ( t =-1.049, P =0.000) compared with the results before surgery (0.1±0.08). Visual acuity was improved in 23 eyes (74.2%). Complications were found in three eyes: two eyes with proliferative vitreoretinopathy and traction retinal detachment 10 and 12mo after surgery, respectively; and one eye with vitreous hemorrhage 15mo after surgery. These eyes were in groups C and D. The retinas remained attached in these 3 eyes after reoperation., Conclusion: We should pay greater attention to XLRS with foveolamellar changes because it is the most changeable phenotype. Once complications occur, vitreoretinal surgery can significantly improve visual acuity and restore the anatomic structure of the retina.

Purpose: To determine whether internal limiting membrane (ILM) peeling improves anatomical and functional outcomes in idiopathic macular pucker (IMP)/epiretinal membrane (ERM) surgery in this systematic review and meta-analysis., Methods: We searched the PubMed, Medline, Web of Science, Cochrane, Ovid MEDLINE, ClinicalTrials.gov and CNKI databases for studies published before 15 September 2016. The eligibility criteria included studies comparing ILM peeling versus no-peeling for IMP surgery., Results: Thirteen articles (10 retrospective cohort studies, 1 prospective cohort study and 2 randomised controlled trials (RCTs)) were included in the review. Primary outcomes: no differences were observed in the best-corrected visual acuity (BCVA) or central macular thickness (CMT) at 12 months; however, lower ERM recurrence (OR, 0.13; 95% CI 0.04 to 0.41; p=0.0004) and reoperation rates (OR, 0.10; 95% CI 0.02 to 0.49; p=0.004) that favoured ILM peeling were observed at the final follow-up., Secondary Outcomes: no difference was observed in BCVA at 3, 6 months, the final follow-up or in CMT at 3, 6 months, the final follow-up. Significantly increased CMT, which favoured ILM peeling, was observed at the final follow-up (p=0.002) in the RCTs., Conclusions: ILM peeling yielded greater anatomical success, but no improvement in functional outcomes as the treatment of choice for patients undergoing IMP surgery., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To compare the intraoperative and postoperative clinical properties of 1% ropivacaine, 0.75% bupivacaine, 2% lidocaine and a mixture of 0.75% bupivacaine and 2% lidocaine (bupi+lido) administered for peribulbar anaesthesia during vitrectomy., Methods: A total of 140 patients were randomly allocated to four groups. The time of onset of analgesia and akinesia was measured. The efficacy of anaesthesia, degree of postoperative pain and intraoperative and postoperative complications were recorded., Results: The mean times of onset (±SD) of analgesia for the ropivacaine, bupivacaine, lidocaine and lido+bupi groups were 90.46±30.08, 94.83±40.72, 78.31±12.56 and 101.51±56.94 s, respectively (p=0.087). The mean times of onset (±SD) of akinesia for the ropivacaine, bupivacaine, lidocaine and lido+bupi groups were 138.89±62.65, 151.86±84.78, 122.66±49.35 and 141.54±62.69 s, respectively (p=0.323). No significant difference was observed in the number of patients who attained grade-5 anaesthesia in the four groups (p=0.966). The outcome of ordered logit analysis showed that the 1% ropivacaine resulted in a significantly lower degree of postoperative pain compared with the other three groups (p=0.017, p=0.001 and p=0.001, respectively). The incidence of postoperative subconjunctival haemorrhage was decreased in the ropivacaine group compared with the other three groups (p<0.001)., Conclusions: For peribulbar anaesthesia in vitrectomy, 1% ropivacaine alone provides an adequate intraoperative anaesthesia similar to that provided by the bupivacaine, lidocaine and lido+bupi solutions, as well as provides a better quality of postoperative analgesia and decreases postoperative subconjunctival haemorrhage., Trial Registration Number: ChiCTR-IPR-16007876; Results., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aim: To analyze cytokines as biomarkers for evaluation of severity of glaucoma., Methods: This was a prospective case-control study including 29 eyes with glaucoma. Besides, 28 eyes with senile cataract were used as control. Patients were classified into four groups: acute angle closure glaucoma (AACG), chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG) and senile cataract. Undiluted vitreous samples were collected, then vitreous concentrations of 9 types of cytokines were determined by cytometric bead assay system: γ-interferon (IFNg), interleukin (IL)-10, IL-2, IL-4, IL-5, interferon-γ-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF). We also recorded the intraocular pressure (IOP) of patients in each group and Pearson correlated analysis was performed to analysis the correlation between each type of cytokine with IOP., Results: Vitreous levels of IL-2, IL-5, MCP-1, TNF-α and IP-10 were significantly higher ( P <0.05) in AACG group. Patients with AACG, CACG and POAG have higher IOP than senile cataract, but we didn't find any significant correlation between IOP with any type of the cytokines., Conclusion: Inflammation and immune reaction have a strong link with the pathology of glaucoma especially AACG. Some cytokines may act as biomarkers to evaluate the severity of glaucoma. Anti-inflammatory treatments and controlling of IOP are necessary for the therapy of glaucoma.

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease characterized by defects in the development of periphery retinal vessels. However, the clinical phenotypes of FEVR vary widely from asymptomatic to complete blindness. We analyzed patients from three Chinese families and one sporadic patient with FEVR to investigate the clinical features and disease-causing mutations. Ocular phenotypes included increased ramification of the peripheral retinal vessels, a peripheral avascular zone, inferotemporal dragging of the optic disc and macula, and retinal folds. Peripheral blood DNA samples were obtained from patients with FEVR and their family members. Primers were designed to amplify the coding exons and adjacent intronic regions of the FEVR-causing genes FZD4, LRP5, NDP and TSPAN12. By polymerase chain reactions, each amplicon was subjected to direct Sanger sequencing analysis. Potential pathogenic changes of the sequence variants were analyzed by the orthologous protein sequence alignment and computational prediction software. We identified five LRP5 mutations: three novel heterozygous mutations-p.M181R, p.R399S and p.G503R and two known mutations that were never reported in FEVR patients: p.R494Q and p.G876S. All five mutations involved highly conserved residues and were predicted to be damaging by SIFT and PolyPhen-2. None was present in 500 normal individuals. To assess the pathogenesis of these mutations, wild-type and all five mutant LRP5 proteins were assayed for the ability to activate the Norrin/β-catenin pathway by established luciferase reporter assays, and all mutants failed to activate the pathway. This study extends the genetic database of the FEVR disease in China and provides a basis for molecular diagnosis of the disease.

Purpose: To investigate timing and risk factors of recurrent retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) monotherapy., Methods: Fifty eyes (the more severe eye) of 50 infants treated with IVR monotherapy for type 1 ROP were studied retrospectively. The mean follow-up time was 31 weeks after IVR. Recurrent ROP (recurrence of extraretinal fibrovascular proliferation [EFP]) was determined by RetCam wide-angle fundus imaging and binocular indirect ophthalmoscopy. Risk time of recurrence was estimated by Kaplan-Meier survival analysis with recurrence as the endpoint. Time-varying recurrence hazard rate was determined using the hazard function of life-table analysis. The risk factors of recurrence were explored by logistic regression analysis., Results: Recurrence of ROP occurred in 32 (64%) of 50 eyes at 7.9 ± 2.7 weeks after IVR. Most of recurrence (94%) occurred in 2.5 to 12.0 weeks following IVR treatment. The recurrence hazard rate reached its maximum at 8 weeks. Recurrence affecting the initial site of EFP occurred significantly earlier than recurrence only at the new vascular advancing edge (4.5 ± 1.4 weeks versus 9.1 ± 2.0 weeks after IVR, P < 0.001). The independent risk factors of recurrence included extensive retinal neovascularization (P = 0.005) and oxygen requirement after IVR (P = 0.016)., Conclusions: Recurrence of type 1 ROP should be carefully watched in a long-term follow-up after IVR monotherapy, particularly in the first 12 weeks after IVR and for those with extensive retinal neovascularization or prolonged oxygen therapy.

Purpose: This study aims to investigate the ability of the ultra-wide-field scanning laser ophthalmoscope (UWF SLO) in clinically detecting and evaluating asymptomatic early-stage familial exudative vitreoretinopathy (FEVR)., Methods: We retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 patients with FEVR. UWF SLO imaging (Optos® PLC, Scotland, UK) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and the findings were compared with subsequent examinations using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography (FA), fundus autoflourescence, and genetic sequencing., Results: A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, and 17 of the affected 43 family members were also genetically diagnosed. Compared with FA as a standard, the UWF SLO was highly effective in diagnosing FEVR with a sensitivity and specificity of 93.0 % and 97.5 %, respectively. The UWF SLO was able to diagnose early-stage FEVR in 93.0 % of eyes, and guided the selection of therapies in 46.5 % of the eyes studied., Conclusion: UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and this tool can assist in the clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

Exosomes are small vesicles that are released by almost every cell type and play a crucial role in many physiological and pathological processes associated with different diseases. Specifically, they promote angiogenesis in the pathogenesis of some diseases. According to previous research, the proteins of exosomes taken from the aqueous humor (AH) of patients with wet-age related macular degeneration (AMD) may function as a new diagnostic biomarker of AMD, suggesting that exosomes may play an important role in the occurrence and development of choroidal neovascularization (CNV). Moreover, additional research has revealed that the levels of some protein makers of exosomes are up-regulated in aged retinal pigment epithelium (RPE) and that drusen and oxidative stress may promote the secretion of exosomes derived from RPE cells. Consequently, we hypothesize that RPE cell-derived exosomes may be relevant to CNV in wet AMD. If this hypothesis is proven correct, future studies based on this link may also help to elucidate the molecular mechanisms of wet AMD and to find new therapeutic targets for the treatment of AMD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To report a simple approach to actively remove high viscosity silicone oil through a 23-gauge cannula via pars plana., Methods: Forty-eight eyes of 48 patients underwent silicone oil (5700 centistokes) removal (SOR) were enrolled. A section of blood transfusion set was prepared to connect a standard 23-gauge cannula and vitrectomy machine. Silicone oil was removed with suction of 500-mm Hg vacuum through the cannula. Main outcome measures were SOR duration, number of sutured sites, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications., Results: Silicone oil was successfully removed in all cases. The mean SOR time was 5.70±0.85min. Nine eyes (18.75%) needed suture partial sclerotomies. No intraoperative complications were noted. Transient hypotony (≤8 mm Hg) was seen in 3 eyes (6.25%) on postoperative day 1, but all resolved within 1wk. Retinal reattachment was achieved in all cases and no other postoperative complications were noted during 3-month following-up. BCVA at the final visit improved or stabilized in all patients comparing to the preoperative level., Conclusion: Active removal of high viscosity silicone oil through a 23-gauge instrument cannula jointed with blood transfusion set is a practical and reliable technique when considering two sides of efficacy and safety.

Aim: To compare the results of non-mydriatic ultra-wide field imaging system, mydriatic slit-lamp lens (Volk +90 D) and mydriatic Goldmann three-mirror contact lens examinations in screening fundus lesions among patients after cataract surgery., Methods: Non-mydriatic images were obtained with an Optomap panoramic 200Tx (Optomap 200Tx) 3d after surgery and graded by a blinded ophthalmologist. A mydriatic slit-lamp lens examination was performed by another blinded retinal specialist on the same day. A third blinded retinal specialist examined patients two weeks after surgery using a Goldmann three-mirror contact lens., Results: In total, 160 patients (184 eyes) were examined, and 66, 69, and 75 cases of retinal lesion(s) were identified using the Optomap 200Tx, slit-lamp lens, and Goldmann three-mirror contact lens, respectively. In 13 cases, fundus changes were sight-threatening. The results obtained by Optomap 200Tx examination and by mydriatic slit-lamp lens examination have good consistency (P=0.375, Kappa=0.942). The mydriatic Goldmann three-mirror lens examination revealed more fundus lesions but are consistent with Optomap 200Tx (P=0.004, Kappa=0.897) and mydriatic slit-lamp lens examination (P=0.031, Kappa=0.932)., Conclusion: Early post-operative fundus screening in cataract patients is extremely important and necessary to prevent further vision loss. Wide-field imaging is a feasible and convenient tool for fundus examination that can be used as a primary screening method among patients after cataract surgery.

Aim: To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis (LCA) in Chinese., Methods: LCA subjects and their families were retrospectively collected from 2013 to 2015. Firstly, whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found, and then homozygous sites was selected, candidate sites were annotated, and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant (SIFT), Polyphen-2, Mutation assessor, Condel, and Functional Analysis through Hidden Markov Models (FATHMM). Furthermore, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test. Sanger sequencing was used to validate single-nucleotide variations (SNVs). Expanded verification was performed in the rest patients., Results: Totally 51 LCA families with 53 patients and 24 family members were recruited. A total of 104 SNVs (66 LCA-related genes and 15 co-segregated genes) were submitted for expand verification. The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families. Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion, biological adhesion, retinoid metabolic process, and eye development biological adhesion. Additionally, WFS1 and STAU2 had the highest homozygous frequencies., Conclusion: LCA is a highly heterogeneous disease. Mutations in KRT12, CYP1A1, WFS1, and STAU2 may be involved in the development of LCA.

Optical imaging-guidance of indocyanine green (ICG) for photothermal therapy (PTT) has great latent capacity in cancer therapy. However, the conventional optical image-guidance mode has caused strong tissue autofluorescence of the living tissue, which leads to the accurate infrared light irradiation cannot be conducted. In this article, ICG and persistent luminescence phosphors (PLPs) coloaded mesoporous silica nanocarriers ((ICG+PLPs)@mSiO2) were first designed and prepared for persistent luminescent imaging-guided PTT. The (ICG+PLPs)@mSiO2 nanocarriers could significantly improve signal-to-noise ratio during luminescence imaging-guided PTT, making the PLP promising for improving the accuracy of the tumor site for photothermal therapy in vivo. This paper is likely to develop a new way for accurately regulating cancer cell death based on luminescence imaging-guided PTT selectively triggered by near-infrared (NIR)-remote.

Aim: To compare the effect of anti-vascular endothelial growth factor (VEGF) monotherapy versus photodynamic therapy (PDT) and anti-VEGF combination treatment in age-related macular degeneration (AMD)., Methods: A computerized online search was performed using PubMed, Web of Science and the Cochrane Library. Studies that compared anti-VEGF monotherapy with PDT and anti-VEGF combination treatment of AMD and were designed as randomized controlled trials were included. The means and standard deviations of the best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of treatments and proportions of patients who gained BCVA ≥15, 10, 5, or 0 letters at 12(th) month were extracted. A systematic review and Meta-analysis of the comparison of the two approaches was conducted using Review Manager 5.2. Subgroup. A sensitivity analysis was also performed., Results: Eight studies were included. When the subgroup and sensitivity analysis was conducted, the results indicated that in the findings that included the monotherapy group and PDT (standard fluence, SF) group of Kaiser's study, the patients in the monotherapy group had a better BCVA compared with the combination group at 12(th) month in the PDT (SF) subgroup [weighted mean difference (WMD): 3.54; 95%CI: 0.36 to 6.73; P=0.03], and there were more patients who gained ≥15 letters of BCVA in the monotherapy group compared with the combination group in the total result [odds ratio (OR): 1.41; 95%CI: 1.02 to 1.95; P=0.04]. The same conclusion was obtained in the total result that included the monotherapy group and PDT (reduced fluence, RF) group of Kaiser's study (OR: 1.56; 95%CI: 1.13 to 2.15; P=0.007). However, there were no significant differences in the other indexes between the two therapies., Conclusion: We found that anti-VEGF monotherapy is more effective on the recovery of visual acuity than combination therapy and more researches with lager sample size should be performed to study on the effect of the two therapy approaches on CRT and number of injections.

Purpose: Four-port bimanual vitrectomy is a surgical technique that facilitates removal of epiretinal membranes in severe proliferative diabetic retinopathy (PDR). As the illumination is held by the assistant through the fourth scleral incision, fibrovascular membranes are removed by bimanual manipulation techniques. The objective of this study was to evaluate the safety and efficacy of four-port bimanual 23-gauge vitrectomy for patients with tractional retinal detachment (TRD) in severe PDR., Design: Retrospective, comparative, consecutive, interventional case series., Methods: Sixty-six eyes of 58 consecutive patients who underwent primary vitrectomy for severe diabetic TRD. Thirty-six eyes of 31 cases that were treated with four-port 23-gauge vitrectomy were compared with 30 eyes of 27 cases that were treated with 23-gauge pars plana vitrectomy (PPV). Main outcome measures were best-corrected visual acuity (BCVA), retinal status, intraocular pressure, and incidence of intraoperative and postoperative complications with at least 6 months of follow-up., Results: The primary and ultimate anatomic success rates (94.4% versus 93.3%, and 100% in both groups, respectively) and the mean BCVA changes did not differ significantly between groups. The whole surgical time and the membrane removal time were significantly (p < 0.001, respectively) shorter in the four-port 23-gauge group than in the 23-gauge group. There was no difference in the incidence of intraoperative and postoperative complications in both groups., Conclusions: Four-port bimanual 23-gauge vitrectomy offers comparable anatomic success and shortens the surgical time compared with conventional 23-gauge PPV in patients with TRD resulting from severe PDR., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD(+)) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD(+) administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD(+) administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD(+) administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD(+) against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD(+) administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD(+) administration might be potential value for the treatment of AMD.

PurposeWe report a simplified ab externo scleral fixation technique to manage the late dislocation of scleral-sutured polymethyl methacrylate (PMMA) intraocular lenses (IOLs) in the absence of capsule support.Materials and methodsThe technique was performed on five eyes of five patients. Symmetrical scleral pocket tunnels without conjunctival peritomy were created. An anterior vitrectomy via a limbal approach with an anterior chamber infusion or a 3-port pars plana vitrectomy was performed to rescue the dislocated IOL. A long straight suture needle and 23-gauge vitreoretinal forceps were used to conveniently reposition the IOL and loop sutures through the IOL positioning eyelets without externalizing IOL haptics. The outside suture knots were buried under the roof of the scleral tunnels.ResultsThe patients were followed for 5-14 months after surgery. All the operated eyes quickly recovered with negligible corneal endothelial cell loss and mild inflammation. Visual acuity improvement and IOL centration were achieved in all eyes with no major complications.ConclusionThe simplified ab externo scleral fixation technique offers an effective and minimally invasive surgical alternative to salvage dislocated previously scleral-sutured PMMA IOLs.

Objective: T cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) receives much attention as a potentially negative regulator of immune responses. However, its modulation on macrophages has not been fully elucidated so far. This study aimed to identify the role of Tim-4 in nitric oxide (NO) modulation., Methods: Macrophages were stimulated with 100 ng/ml LPS or 100 U/ml IFN-γ. RT-PCR was performed to detect TIM-4 mRNA expression. Tim-4 blocking antibody and NF-κB inhibitory ligand were involved in the study. NO levels were assayed by Griess reaction. Phosphorylation of NF-κB, Jak2 or Stat1 was verified by western blot., Results: Tim-4 was up-regulated in murine macrophages after interferon-gamma (IFN-γ) stimulation. Tim-4 over-expression decreased NO production and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS) or IFN-γ-stimulated macrophages. Consistently, Tim-4 blockade promoted LPS or IFN-γ-induced NO secretion and iNOS expression. Tim-4 over-expression decreased LPS-induced nuclear factor kappa B (NF-κB) p65 phosphorylation in macrophages, which was abrogated by NF-κB inhibitory ligand. On the contrary, Tim-4 blocking increased LPS-induced NF-κB signaling, which was also abrogated by NF-κB inhibition. In addition, Tim-4 blockade promoted Jak2 and Stat1 phosphorylation in IFN-γ stimulated macrophages., Conclusion: These results indicate that Tim-4 is involved in negative regulation of NO production in macrophages, suggesting the critical role of Tim-4 in immune related diseases.

The xylem sap flows of two pioneer tree species, i.e., Acacia mangium and Schima superba, in degraded hill lands of South China, were continually monitored with Granier' s thermal dissipation probes during 2004-2007 and 2008-2012, respectively, and their seasonal transpiration changes at different tree age levels were compared. The results showed that the annual transpiration of both species increased with tree ages, and S. superba demonstrated a higher value than A. mangium. The average annual whole-tree transpiration of S. superba (7014.76 kg) was higher than that of A. mangium (3704.97 kg). A. mangium (511.46-1802.17 kg) had greater seasonal variation than S. superba (1346.48-2349.35 kg). The standard regression coefficients (beta) of transpiration (Eh), photosynthetically active radiation (PAR) and vapor pressure deficit (VPD) for both species increased with soil moisture, suggesting the increase of soil moisture generated a greater sensitivity of plants to environmental factors. Partial correlation analysis revealed that soil moisture played an important role in the seasonal variation of transpiration of both species. The optimum soil moistures of S. superba and A. mangium were 0.22-0.40 and 0.29-0.30 (V/V), respectively, indicating the native pioneer species S. superba better adapted to water deficit compared with exotic pioneer species A. mangium.

Purpose: To investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations., Methods: A comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed., Results: The I62V polymorphism showed a significant summary OR1 for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51-4.04, P<0.00001), the OR2 of heterozygous genotype GA versus AA was 2.29 (95% CI: 1.79-2.94, P<0.00001), the OR3 of homozygous genotype GG versus AA was 4.42 (95% CI: 3.45-5.67, P<0.00001), and the OR4 of allele G versus A was 2.04 (95% CI: 1.85-2.26, P<0.00001). Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Cumulative meta-analysis revealed that the summary ORs were stable. There was no significant difference in every genetic model between PCV and nAMD (n = 5, OR1 = 0.92, OR2 = 0.96, OR3 = 0.90, OR4 = 0.94)., Conclusions: Our analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.

The aim of this study was to investigate the characteristics of fundus autofluorescence (FAF) in patients with wet (exudative) age-related macular degeneration (AMD). Color fundus photographs, fundus fluorescein angiograms, indocyanine green angiograms, and FAF images were obtained from 61 patients (72 eyes) with exudative AMD. The FAF results for different patterns of exudative AMD were compared to those revealed by other fundus images. Of the 72 eyes evaluated, which were classified into three patterns based on the results of fundus fluorescein angiography, 68 had abnormal FAF. Forty-six eyes (63.9%) had classic wet AMD with abnormal FAF. Among these, 10 exhibited a slightly decreased FAF with near-normal or background FAF signal at the center of the lesion area; 36 demonstrated not only decreased FAF at the center of the lesion but also an increased FAF signal toward the lesion edge. Sixteen eyes (22.2%) had occult wet AMD, of which 12 exhibited heterogeneous fluorescence at the lesion site; 4 yielded normal FAF images. Ten eyes (13.9%) had a mixed pattern of wet AMD with abnormal FAF. FAF imaging suggested that the areas of blood and exudates decreased; however, fluorescence angiography revealed that lesions with hyperfluorescence had background or slightly increased FAF. These results showed that various patterns of wet AMD exhibit different autofluorescence characteristics. These represent the functional and metabolic features of retinal pigment epithelial cells. Therefore, FAF can be used to monitor disease development and evaluate the severity and prognosis of AMD.