Consequences of early life stress on the structure and function of the adult mouse retina

Early-life stress(ELS)refers to a period of environmental/social deprivation,physica l,sexual or emotional abuse,neglect,severe and/or chronic trauma in the prenatal/early postnatal stage,which is closely related to many adverse psychiatric disorders later in life,such as depressive disorder,substance abuse,dysthymia,panic,anxiety,and suicidal behavior in adulthood(Waters and Gould,2022).

Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability,migration and proliferation in vitro

AIM： To analyze the concentration-dependent effects of autologous serum （AS） and fetal bovine serum （FBS） on human corneal epithelial cell （HCEC） viability, migration and proliferation. METHODS： AS was prepared from 13 patients with non- healing epithelial defects Dulbecco＇s modified eagle medium/ Ham＇s F12 （DMEM/F12） with 5% FBS, 0.5% dimethyl sulphoxide （DMSO）, 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media： DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTI＇, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay （ELISA） BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. RESULTS： HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse （P=0.001, P=0.023） compared to baseline and significantly better at 15% FBS （P=0.003） concentrations. HCEC migration was significantly worse （P〈0.007） and HCEC proliferation significantly better （P〈0.001） in all concentration groups compared to baseline. CONCLUSION： For the best viability of HCEC 30% AS or 15% FBS, for HCEC migration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.

Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic reti- nopathy have focused either on highly specific therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resis- tance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging isch- emia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.

Impact of crosslinking/riboflavin-UVA-photodynamic inactivation on viability,apoptosis and activation of human keratocytes in vitro

Riboflavin-UVA photodynamic inactivation is a potential treatment altemative in therapy resistant infectious keratitis. The purpose of our study was to determine the impact of riboflavin-UVA photodynamic inactivation on viability, apop- tosis and activation of human keratocytes in vitro. Primary human keratocytes were isolated from human corneal buttons and cultured in DMEM/Ham＇s F12 medium supplemented with 10% fetal calf serum. Keratocytes underwent UVA light illumination （375 nm） for 4.10 minutes （2 J/cm2） during exposure to different concentrations of riboflavin. Twenty-four hours after treatment, cell viability was evaluated photometrically, whereas apoptosis, CD34 and alpha-smooth muscle actin （α-SMA） expression were assessed using flow cytometry. We did not detect significant changes in cell viability, apoptosis, CD34 and α-SMA expression in groups only treated with riboflavin or UVA light. In the group treated with riboflavin-UVA-photodynamic inactivation, viability of keratocytes decreased significantly at 0.1% riboflavin （P〈0.01） while the percentage of CD34 （P〈0.01 for both 0.05% and 0.1% riboflavin） and alpha-SMA positive keratocytes （P〈0.01 and P〈0.05 for 0.05% and 0.1% riboflavin, respectively） increased significantly compared to the controls. There was no significant change in the percentage of apoptotic keratocytes compared to controls at any of the used ribo- flavin concentrations （P=0.09 and P=0.13）. We concluded that riboflavin-UVA-photodynamic-inactivation decreases viability of myofibroblastic transformation and multipotent haematopoietic stem cell transformation; however, it does not have an impact on apoptosis of human keratocytes in vitro.

A novel viewpoint in glaucoma therapeutics: enriched environment

Glaucoma is one of the world’s most frequent visual impairment causes and leads to selective damage to retinal ganglion cells and their axons.Despite glaucoma’s most accepted risk factor is increased intraocular pressure(IOP),the mechanisms behind the disease have not been fully elucidated.To date,IOP lowering remains the gold standard;however,glaucoma patients may still lose vision regardless of effective IOP management.Therefore,the exclusive IOP control apparently is not enough to stop the disease progression,and developing new resources to protect the retina and optic nerve against glaucoma is a goal of vast clinical importance.Besides pharmacological treatments,environmental conditions have been shown to prevent neurodegeneration in the central nervous system.In this review,we discuss current concepts on key pathogenic mechanisms involved in glaucoma,the effect of enriched environment on these mechanisms in different experimental models,as well as recent evidence supporting the preventive and therapeutic effect of enriched environment exposure against experimental glaucomatous damage.Finally,we postulate that stimulating vision may become a non-invasive and rehabilitative therapy that could be eventually translated to the human disease,preventing glaucoma-induced terrible sequelae resulting in permanent visual disability.

The Use of the Anterior Chamber Maintainer in Special Cataract Cases

Purpose: To point out the indications for the use of the Anterior Chamber Maintainer (ACM) in order to facilitate cataract surgery in selective cases. Materials and Methods: In a time interval of 4 years the ACM was used in 28 special cataract cases 17 patients had high myopia (12 - 25 dpt, axial length 28 - 34 mm), 3 patients had vitreo-retinal pathology known pre-operatively and 8 cases were previously vitrectomized with silicon oil. In these cases the ACM was introduced either from the beginning or during the surgical procedure when excessive fluctuations of the Anterior Chamber (AC) were observed. Results: Though the new generation phaco machines tend to maintain the stability of the AC, the use of the ACM contributed to even greater stability during the insertion and the removal of probes and during the whole procedure, eliminating the risk of complications. All these risky cases were accomplished without intraoperative complications. The surgeons experienced a sense of increased safety during the procedure. Conclusions: The use of the ACM in cataract cases with high risk for complications offers a much greater stability of the AC, by eliminating the fluctuations of the posterior capsule and consequently prevents intraoperative and potentially postoperative complications.

Changing trends in penetrating keratoplasty indications at a tertiary eye care center in Budapest,Hungary between 2006 and 2017

AIM:To analyze the changing trends in penetrating keratoplasty(PKP)indications.METHODS:This retrospective study included all patients with PKP between 2006 and 2017.Patients were classified using histological diagnoses.Our groups were as the following:pseudophakic or aphakic bullous keratopathy,regraft,acute necrotizing and ulcerative keratitis,keratoconus,Fuchs'dystrophy,corneal dystrophy other than Fuchs',corneal scar,other diagnoses and failed endothelial keratoplasty graft.Additionally,two different time-periods(2006-2012 and 2013-2017)were analysed.RESULTS:Totally 1721 histological analyses of 1214 patients were available for review.The diagnoses were pseudophakic or aphakic bullous keratopathy in 487(28.3%),regraft in 443(25.7%),acute necrotizing and ulcerative keratitis in 313(18.2%),corneal scar in 153(8.9%),keratoconus in 140(8.1%).Fuchs'dystrophy in 61(3.5%),corneal dystrophy other than Fuchs'in 46(2.7%),other diagnoses in 44(2.6%)and failed endothelial keratoplasty graft in 34(2.0%)cases.From the first to the second analysed time-period,incidence of acute necrotizing and ulcerative keratitis,corneal scar,Fuchs'dystrophy increased(P<0.032 for all)and incidence of keratoconus significantly decreased(P=0.015).CONCLUSION:Pseudophakic or aphakic bullous keratopathy is the leading indication for PKP,followed by regraft and acute necrotizing and ulcerative keratitis.

Effect of biometric characteristics on biomechanical properties of the cornea in cataract patient

AIM： To determine the impact of biometric characteristics on the biomechanical properties of the human cornea using the ocular response analyzer （ORA） and standard comprehensive ophthalmic examinations before and after standard phacoemulsificaUon. METHODS： This study comprised 54 eyes with cataract with significant lens opacification in stages I or II that underwent phacoemulsification （2.8 mm incision）. Corneal hysteresis （CH）, corneal resistance factor （CRF）, Goldmann-correlated intraocular pressure （IOPg）, and corneal-compensated intraocular pressure （IOPcc） were measured by ORA preoperatively and at lmo postoperatively. Biometric characteristics were derived from corneal topography [TMS-5, anterior equivalent （EQTMS） and cylindric （CYLTMS） power], corneal tomography [Casia, anterior and posterior equivalent （EQaCASC, EQpCASIA） and cylindric （CYLaCASIA, CYLpCASIA） power], keratometry [IOLMaster, anterior equivalent （EQIOL） and cylindric （CYL,oL） power] and autorefractor [anterior equivalent （EQAR）]. Results from ORA were analyzed and correlated with those from all other examinations taken at the same time point. RESULTS： Preoperatively, CH correlated with EQpCASIA and CYLpCASIA only （P=0.001, P=0.002）. Postoperatively, IOPg and IOPcc correlated with all equivalent powers （EQTMS, EQIOL, EQAR, EQaCASIA, and EQpCASIA）（P=0.001, P=0.007, P=0.001, P= 0.015, P=0.03 for IOPg and P〈0.001, ,0=0.003, P〈0.001, P= 0.009, P=0.014 for IOPcc）. CH correlated postoperatively with EQaCASIA and EQpCASIA only （P=0.021, P=0.022）. CONCLUSION： Biometric characteristics may significantly affect biomechanical properties of the cornea in terms of CH, IOPcc and IOPg before, but even more after cataract surgery.

Ocular stem cells:a narrative review of current clinical trials

·Stem cells are undifferentiated cells showcasing a remarkable capacity of self-replenishing and differentiating into mature cells.Their ability to proliferate connotes that a designated stem cell source is capable of generating an unrestricted number of mature cells.The ever-increasing comprehension of position,activity,and function of ocular stem cells has led to rapid progress and incessant improvement of possible procedures and therapies.A narrative review was conducted to summarize the current evidence on clinical trials and respective literature,regarding current evolution in the field of ocular regenerative medicine.We tried to ascertain the safety of experimental and clinical procedures,their effectiveness,and the ethical repercussion of their use.

Visual Allesthesia in a Patient with Glioblastoma Multiforme

Purpose: To report a rare case of visual allesthesia in a patient with glioblastoma multiforme. Material - Methods : A 46 – year old male presented in emergency ophthalmologic department complaining for difficulties in performing tasks related to color discrimination in his occupation (PC technician). The patient underwent a thorough ophthalmological examination and then he was referred to the neurological department for further evaluation. Results: The patient presented an atypical pattern of color perception disturbance. His best corrected visual acuity decreased progressively during hospitalization. He also experienced visual allesthesia paroxysmally (illusory left homonymous transpositions of subjects viewed in the right homonymous visual field). The visual field evaluation revealed homonymous left hemianopsia. Magnetic resonance imaging revealed glioblastoma multiforme confirmed by biopsy. Conclusions: A thorough ophthalmological and neuro-imaging control is suggested in patients with sudden color perception disturbance. Patients with temporal or occipital cortex damage may experience visual allesthesia.

Contrast Sensitivity and Eye Drops

Purpose: To evaluate the influence of commonly used eye drops on contrast sensitivity (CS). Design: Prospective study. Participants: One hundred twenty volunteers (120) were enrolled. Methods: The CS of ophthalmologically healthy individuals was evaluated at baseline examination before the instillation, 20 and 40 minutes after the instillation of diclofenac sodium and commonly used antiglaucoma eye drops (latanoprost, brimonidine tartrate, combination of dorzolamide hydrochloride and timolol maleate). CS was assessed at 7 spatial frequencies varying from 1.5 c/d to 20 c/d by the use of Mentor B-VAT II-SG video acuity tester. Results: Diclofenac sodium induced a mild, however statistically significant decrease on the CS in 4 out of 30 subjects 20 minutes after instillation at the spatial frequency of 1.5 c/d and 3 c/d (p p > 0.05). Brimonidine tartrate decreased CS in 4 out of 30 subjects 20 minutes after the instillation at a high spatial frequency (20 c/d) yet this decrease was marginally statistically significant (p = 0.057). CS returned to baseline scores 40 minutes after the instillation for all drugs. Conclusions: Diclofenac sodium eye drops had a mild temporal effect on the low spatial frequencies of 1.5 c/d and 3 c/d in some individuals. Latanoprost and dorzolamide/timolol had a non-statistically significant effect on the same spatial frequencies. Brimonidine eye drops had a temporal effect on the high spatial frequency of 20 c/d with marginal statistical significance. The CS scores returned to normal, in all cases, within the next 40 minutes after the instillation. Ophthalmologists should be aware of the fact that some eye drops may have an influence on CS.

Ocular Manifestations in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common autoimmune disease. Ocular manifestations of this autoimmune disease vary and are mainly keratoconjunctivitis sicca, episcleritis, scleritis and keratitis. Their appearance, as well as their severity are related to RA chronicity and resistance to therapy. The treatment consists of corticosteroids, NSAIDs and cytotoxic drugs, depending on the type of ocular manifestations and the patient’s response to treatment.

青光眼患者血清抗视网膜抗原的抗体轮廓质谱分析

目的比较原发性开角型青光眼（POAG）患者与正常对照（CTRL）者间的抗体轮廓差异。方法病例对照研究。将44例POAG患者与48例CTRL者的血清分别加入到含有预洗Dyna珠-G蛋白的反应管中，以捕获人免疫球蛋白G（IgG）抗体，形成的IgG—G蛋白复合体用来捕获目标抗原（匀质化牛视网膜组织）。经洗提后获得的抗原蛋白通过“表面增强激光解吸附-电离-飞行时间-质谱”仪进行检测。采用Proteomic software project统计学软件，对两组质谱数据连同受检者年龄和性别等参数，自动进行t检验和初步多变量判别分析；随后采用Statistica version8．0统计学软件，进行包括抗原蛋白质谱数据、蛋白质芯片类型和激光解吸附-电离能量等的多变量判别分析。结果CTRL组的平均质谱强度为4244．427±4721．115，POAG组为4049．864±4083．819，两组间差异有统计学意义（F=1．340，P〈0．01）；在POAG患者中，出现了部分高调节免疫反应，但主要表现为低调节免疫反应。结论在POAG患者与CTRL者之间存在明显的抗体轮廓差异，在POAG组中出现的低调节免疫反应表明部分患者可能与“异常免疫”有关。

A deep learning model for generating fundus autofluorescence images from color fundus photography

Background:Fundus Autofluorescence(FAF)is a valuable imaging technique used to assess metabolic alterations in the retinal pigment epithelium(RPE)associated with various age-related and disease-related changes.The practical uses of FAF are ever-growing.This study aimed to evaluate the effectiveness of a generative deep learning(DL)model in translating color fundus(CF)images into synthetic FAF images and explore its potential for enhancing screening of age-related macular degeneration(AMD).Methods:A generative adversarial network(GAN)model was trained on pairs of CF and FAF images to generate synthetic FAF images.The quality of synthesized FAF images was assessed objectively by common generation metrics.Additionally,the clinical effectiveness of the generated FAF images in AMD classification was evaluated by measuring the area under the curve(AUC),using the LabelMe dataset.Results:A total of 8410 FAF images from 2586 patients were analyzed.The synthesized FAF images exhibited an impressive objectively assessed quality,achieving a multi-scale structural similarity index(MS-SSIM)of 0.67.When evaluated on the LabelMe dataset,the combination of generated FAF images and CF images resulted in a noteworthy improvement in AMD classification accuracy,with the AUC increasing from 0.931 to 0.968.Conclusions:This study presents the first attempt to use a generative deep learning model to create authentic and high-quality FAF images from CF images.The incorporation of the translated FAF images on top of CF images improved the accuracy of AMD classification.Overall,this study presents a promising approach to enhance largescale AMD screening.

The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm

The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells,which can elicit acute respiratory distress syndrome(ARDS)characterized by the rapid onset of widespread inflammation,the so-called cytokine storm.In response to viral infections,monocytes are recruited into the lung and subsequently differentiate into dendritic cells(DCs).DCs are critical players in the development of acute lung inflammation that causes ARDS.Here,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with DCs.We show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these cells.In addition,we identified DC-SIGN as a possible interaction partner of ORF8 on DCs.Blockade of ORF8 leads to reduced production of IL-1β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by DCs.Therefore,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.