Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retin...Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.展开更多
The cornea is a transparent tissue that serves as the main refractive element of the eye ball.Limbal epithelial stem cells(LESCs),residing in the basal epithelial layer of the Palisades of Vogt located in the corneal ...The cornea is a transparent tissue that serves as the main refractive element of the eye ball.Limbal epithelial stem cells(LESCs),residing in the basal epithelial layer of the Palisades of Vogt located in the corneal limbus between cornea and scleral,are believed to be crucial for the continuous turnover of the corneal epithelium.The proliferation,migration,and differentiation of the LESCs are modulated by unique physical and chemical futures contained within the microenvironment known as the limbal niche.This niche,composed of nerve terminals,cells,extracellular matrix,vasculature,and signaling molecules,is the home for processes such as proliferation,migration and differentiation.Corneal nerve terminals possess special anatomical structures in the limbal region and basal epithelial cells,and they demonstrate pivotal biological effects in the regulation of the LESC function and corneal epithelium homeostasis.Biological molecules such as neuropeptides,neurotransmitters,and neurotrophic factors play a crucial role in modulating the LESCs phenotype responsible for corneal epithelium homeostasis.This paper will review recent studies on how these nerve derived molecules function in this process and provide clear orientations for future research.展开更多
AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retr...AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retrospective study was conducted on 30 phakic eyes from patients diagnosed with FECD but without clinical edema,and 59 phakic eyes from a control group without corneal alterations.Comprehensive ophthalmic examinations were conducted,including slitlamp biomicroscopy,corneal specular microscopy(CSM),and Scheimpflug tomography.RESULTS:The study encompassed 30 phakic eyes with FECD(mean age 59.8±13.1y)and 59 control eyes(mean age 61.3±7.7y).The best-corrected visual acuity was higher in the control group compared to the FECD group[0(0,0.08)vs 0.05(0,0.15)logMAR;P=0.042].CSM revealed significant differences between the FECD and control groups in several parameters:number of analyzed cells(26±13 vs 135±42,P<0.001),cell density(2049±376 vs 2479±225 cells/mm2,P<0.001),mean cell area[463(434,544)vs 397(383,431)μm2;P<0.001],coefficient of variation(54.8%±18.7%vs 41.0%±7.2%,P<0.001),and hexagonal cells[0(0,47%)vs 47%(40%,53%),P<0.001].Although often used as a clinical parameter for detecting edema,central corneal thickness measured by CSM showed no significant difference between the FECD and control groups(530±57 vs 546±30μm,P=0.179).Significant differences were noted in various Pentacam measurements between the groups.Specifically,parameters like loss of parallel isopachs(13 vs 0 eyes,P<0.001),displacement of the thinnest point(11 vs 0 eyes,P<0.001),posterior focal depression(25 vs 7 eyes,P<0.001),and increased light scatter[21.4(17.6;23.9)vs 18.0(16.8,21.8),P=0.01]were significantly more prevalent in FECD eyes,reflecting the presence of subclinical edema and loss of corneal transparency.CONCLUSION:Scheimpflug tomography allows for an objective assessment of FECD,offering the capability to detect subclinical edema at an early stage,monitor disease progression,and serve as a predictor of corneal decompensation following cataract surgery.展开更多
AIM:To investigate the changes in posterior corneal elevation within 6mo after small incision lenticule extraction(SMILE)surgery for myopia and myopic astigmatism in patients with thin corneas.METHODS:A prospective st...AIM:To investigate the changes in posterior corneal elevation within 6mo after small incision lenticule extraction(SMILE)surgery for myopia and myopic astigmatism in patients with thin corneas.METHODS:A prospective study included patients with thin corneas(preoperative thinnest corneal thickness ranging from 480 to 520μm)who underwent SMILE for myopia or myopic astigmatism.Corneal topography and posterior corneal elevation were assessed using Pentacam HR at three time points:preoperatively,1mo,and 6mo postoperatively.The measured parameters included thinnest point elevation(PTE),posterior maximal elevation(PME),posterior central elevation(PCE),and 24 additional reference points.RESULTS:A total of 106 eyes from 106 patients(age range:18-34)were included in the study.Uncorrected distance visual acuity(UDVA)improved significantly,with a mean logMAR value of-0.07±0.06 at the final follow-up visit.Measurements of posterior corneal elevation showed no significant changes in most points,hemispheres,and meridians at 6mo postoperatively.Notably,only two points,ΔE_(2mm-45°)andΔE_(2mm-90°),exhibited statistically significant elevation changes:the elevation ofΔE_(2mm-45°)increased from-2.3±4.99 to-1.0±5.9μm(P=0.0037),and that ofΔE_(2mm-90°)increased from-16±7.53 to-15±7.4μm(P=0.016).However,these changes were within the measurement error range of the Pentacam HR(±5μm in a 5 mm area).CONCLUSION:SMILE surgery is a safe and stable procedure for correcting myopia or myopic astigmatism in patients with thin corneas,as evidenced by the stability of posterior corneal elevation.展开更多
AIM:To assess early visual outcomes and corneal stability following small incision lenticule extraction(SMILE)in eyes with a pre-planned residual stromal thickness(RST)ranging from 280 to 300μm.METHODS:This retrospec...AIM:To assess early visual outcomes and corneal stability following small incision lenticule extraction(SMILE)in eyes with a pre-planned residual stromal thickness(RST)ranging from 280 to 300μm.METHODS:This retrospective study was designed to evaluate 82 eyes from 82 patients,all of whom had a pre-planned RST of 280 to 300μm and normal corneal topography prior to undergoing SMILE surgery.The mean preoperative spherical equivalent(SE)was-4.82±1.30 D.A standard follow-up protocol was conducted between 1 to 6mo postoperatively.Visual outcomes were recorded using uncorrected visual acuity(UCVA)and subjective refraction.The curvature of the anterior and posterior corneal surfaces,as well as the posterior elevation at the thinnest point(PTE)were derived from the Pentacam system.RESULTS:At the final follow-up,the efficacy index was 1.14±0.15,the safety index was 1.20±0.13.The mean preoperative UDVA was 0.78±0.16 logMAR,which improved significantly to-0.07±0.06 logMAR postoperatively(P<0.001).The preoperative mean SE was-4.82±1.30 D,which decreased to-0.14±0.30 D by the last visit.The curvature of the anterior cornea at the flat meridian(AK1)were 42.62±1.02 D preoperatively,38.56±1.37 D and 38.59±1.39 D at 1 and 6mo after operation,respectively.Corresponding measurements at the steep meridian(AK2)were 43.55±1.14 D preoperatively,39.18±1.46 D and 39.22±1.50 D at 1 and 6mo after operation,respectively.Both AK1 and AK2 remained stable at 1 and 6-mo postoperative intervals(P=0.126 and 0.082,respectively).There were no observed changes in the curvature of the posterior cornea at the flat meridian or at the steep meridian,or the PTE before and after surgery.CONCLUSION:SMILE represents a safe and effective procedure for the correction of myopia and astigmatism in eyes featuring a pre-planned RST ranging from 280 to 300μm accompanied by normal corneal topography,on the premise of strict control of surgical indications.展开更多
AIM：To investigate the feasibility of corneal anterior lamellar reconstruction with human corneal epithelial cells and fibroblasts,and an acellular porcine cornea matrix（APCM） in vitro.·METHODS：The scaffold w...AIM：To investigate the feasibility of corneal anterior lamellar reconstruction with human corneal epithelial cells and fibroblasts,and an acellular porcine cornea matrix（APCM） in vitro.·METHODS：The scaffold was prepared from fresh porcine corneas which were treated with 0.5%sodium dodecyl sulfate（SDS）solution and the complete removal of corneal cells was confirmed by hematoxylin-eosin（HE）staining and 4’,6-diamidino-2-phenylindole（DAPI）staining.Human corneal fibroblasts and epithelial cells were cultured with leaching liquid extracted from APCM,and then cell proliferative ability was evaluated by MTT assay.To construct a human corneal anterior lamellar replacement,corneal fibroblasts were injected into the APCM and cultured for 3d,followed by culturing corneal epithelial cells on the stroma construction surface for another 10d.The corneal replacement was analyzed by HE staining,and immunofluorescence staining.·R ESULTS：Histological examination indicated that there were no cells in the APCM by HE staining,and DAPI staining did not detect any residual DNA.The leaching liquid from APCM had little influence on the proliferation ability of human corneal fibroblasts and epithelial cells.At 10d,a continuous 3 to 5 layers of human corneal epithelial cells covering the surface of the APCM was observed,and the injected corneal fibroblasts distributed within the scaffold.The phenotype of the construction was similar to normal human corneas,with high expression of cytokeratin 12 in the epithelial cell layer and high expression of Vimentin in the stroma.·CONCLUSION：Corneal anterior lamellar replacement can be reconstructed in vitro by cultivating human corneal epithelial cells and fibroblasts with an acellular porcine cornea matrix.This laid the foundation for the further transplantation in vitro.展开更多
Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropath...Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.展开更多
BACKGROUND An in vitro injury model mimicking a corneal surface injury was optimised using human corneal epithelial cells(hCEC).AIM To investigate whether corneal-stroma derived stem cells(CSSC) seeded on an amniotic ...BACKGROUND An in vitro injury model mimicking a corneal surface injury was optimised using human corneal epithelial cells(hCEC).AIM To investigate whether corneal-stroma derived stem cells(CSSC) seeded on an amniotic membrane(AM) construct manifests an anti-inflammatory, healing response.METHODS Treatment of hCEC with ethanol and pro-inflammatory cytokines were compared in terms of viability loss, cytotoxicity, and pro-inflammatory cytokine release, in order to generate the in vitro injury. This resulted in an optimal injury of 20%(v/v) ethanol for 30 s with 1 ng/mL interleukin-1(IL-1) beta. Co-culture experiments were performed with CSSC alone and with CSSC-AM constructs.The effect of injury and co-culture on viability, cytotoxicity, IL-6 and IL-8 production, and IL1 B, TNF, IL6, and CXCL8 mRNA expression were assessed.RESULTS Co-culture with CSSC inhibited loss of hCEC viability caused by injury. Enzyme linked immunosorbent assay and polymerase chain reaction showed a significant reduction in the production of IL-6 and IL-8 pro-inflammatory cytokines, and reduction in pro-inflammatory cytokine mRNA expression during co-culture with CSSC alone and with the AM construct. These results confirmed the therapeutic potential of the CSSC and the possible use of AM as a cell carrier for application to the ocular surface.CONCLUSION CSSC were shown to have a potentially therapeutic anti-inflammatory effectwhen treating injured hCEC, demonstrating an important role in corneal regeneration and wound healing, leading to an improved knowledge of their potential use for research and therapeutic purposes.展开更多
A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithel...A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithelialstromal defects.Currently,the etiology and pathogenesis of these defects remain inadequately understood,necessitating further investigation through experimental research.Various modeling methods exist both domestically and internationally,each with distinct adaptive conditions,advantages,and disadvantages.This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury,including mechanical modeling,chemical alkali burns,post-refractive surgery infections,and genetic engineering.The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.展开更多
Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidire...Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.展开更多
Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from dam...Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.展开更多
Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to ass...Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to assess the effect of the widely used fluorescein dye on human corneal endothelial cells(HCEnCs)in vitro at different concentrations and exposure times.Methods:B4G12,an immortalized human corneal endothelium cell line was cultured on pre-coated tissue culture flask with human endothelial-serum free medium(SFM)supplemented with 10 ng/mL basic fibroblast growth factor(bFGF).The fully confluent B4G12 cell monolayers in 96 well plates were treated with water as control,or fluorescein at various concentrations and exposure times.Cell viability was assessed using two techniques:Alamar Blue assay and cell morphology assessment with an inverted phase-contrast microscopy.Results:Short-term exposure to fluorescein(0.01-0.2%)for up to 30 minutes did not affect cell viability.Continuous fluorescein exposure however significantly reduced the viability of the cells with a notable reduction in cell metabolic activity with fluorescein treatments of 0.001%,0.01% and 0.05% for 1 day(and up to 4 days).Conclusions:Short-term exposure to fluorescein for up to 30 minutes in concentrations commonly used in clinical practice did not affect HCEnC viability.However,fluorescein exposure for longer durations can be detrimental to corneal endothelial cell health.Future studies should evaluate the effects of longer-term fluorescein exposure on endothelial function especially in susceptible patients including the elderly and patients with epithelial defects that enable diffusion of fluorescein towards the endothelium.展开更多
AIM:To assess the corneal high-order aberration(HOA)and its correlation with corneal morphological parameters in patients with bilateral keratoconus(KCN)and unilateral Vogt’s striae.METHODS:A total of 168 eyes of 84 ...AIM:To assess the corneal high-order aberration(HOA)and its correlation with corneal morphological parameters in patients with bilateral keratoconus(KCN)and unilateral Vogt’s striae.METHODS:A total of 168 eyes of 84 patients with KCN,whose corneas had definite signs of unilateral Vogt’s striae,were enrolled.Corneal HOA and morphological parameters were measured using Pentacam HR.RESULTS:The corneal morphological parameters between KCN eyes with and without Vogt’s striae were evidently different(P<0.001).The 3rd coma 90°,4th spherical aberration,5th coma 90°,root-mean-square(RMS)(total),and RMS(HOA)in the front,back surfaces and total cornea in KCN eyes with Vogt’s striae were significantly higher than those in KCN eyes without Vogt’s striae(P<0.001).In KCN eyes with Vogt’s striae,the 3rd coma 90°and 4th spherical aberration in the front surface and total cornea were negatively correlated with flat keratometry value(K1),steep keratometry value(K2),mean keratometry value(Km),maximum keratometry value(Kmax),anterior corneal elevation(ACE),and posterior corneal elevation(PCE;P<0.05).The 3rd coma 90°,4th spherical aberration in back surface and RMS(total),RMS(HOA)in the front,back surfaces,total cornea were positively correlated with K1,K2,Km,Kmax,ACE,and PCE(P<0.05).CONCLUSION:Corneal HOA especially vertical coma and spherical aberration may increase when Vogt’s striae appeared in KCN eyes.The scale of increase is significantly related with changes in corneal shapes.展开更多
AIM:To construct a competent corneal lamellar substitute in order to alleviate the shortage of human corneal donor.METHODS:Rabbit mesenchymal stem cells(MSCs)were isolated from bone marrow and identified by flow cytom...AIM:To construct a competent corneal lamellar substitute in order to alleviate the shortage of human corneal donor.METHODS:Rabbit mesenchymal stem cells(MSCs)were isolated from bone marrow and identified by flow cytometric,osteogenic and adipogenic induction.Xenogenic decellularized corneal matrix(XDCM)was generated from dog corneas.MSCs were seeded and cultured on XDCM to construct the tissueengineered cornea.Post-transplantation biocompatibility of engineered corneal graft were tested by animal experiment.Rabbits were divided into two groups then underwent lamellar keratoplasty(LK)with different corneal grafts:1)XDCM group(n=5):XDCM;2)XDCM-MSCs groups(n=4):tissue-engineered cornea made up with XDCM and MSCs.The ocular surface recovery procedure was observed while corneal transparency,neovascularization and epithelium defection were measured and compared.In vivo on focal exam was performed 3 mo postoperatively.RESULTS:Rabbit MSCs were isolated and identified.Flow cytometry demonstrated isolated cells were CD90 positive and CD34,CD45 negative.Osteogenic and adipogenic induction verified their multipotent abilities.MSC-XDCM grafts were constructed and observed.In vivo transplantation showed the neovascularization in XDCMMSC group was much less than that in XDCM group postoperatively.Post-transplant 3-month confocal test showed less nerve regeneration and bigger cell-absent area in XDCM-MSC group.CONCLUSION:This study present a novel corneal tissue-engineered graft that could reduce post-operatively neovascularization and remain transparency,meanwhile shows that co-transplantation of MSCs may help increase corneal transplantation successful rate and enlarge the source range of corneal substitute to overcome cornea donor shortage.展开更多
Background and Objective:Corneal neurotization is a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy.Neurotrophic keratopathy is a disorder characterized by dysfunct...Background and Objective:Corneal neurotization is a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy.Neurotrophic keratopathy is a disorder characterized by dysfunction of the ophthalmic division of the trigeminal nerve,which provides sensory innervation to the cornea.Without sensation,the cornea is at risk of infection,ulceration,perforation,and ultimately,vision loss.Corneal neurotization has emerged as an innovative technique to reinnervate anesthetized corneas by transferring a healthy donor nerve to the affected eye around the corneoscleral limbus.As the field of corneal neurotization rapidly grows,there is a need to synthesize the existing body of literature on corneal neurotization and identify important areas for further research.In this review,we will discuss neurotrophic keratopathy and its current management strategies,followed by an overview of corneal neurotization techniques,outcomes,surgical considerations,and future directions.Methods:PubMed and Google Scholar searches were conducted to retrieve and analyze relevant original papers and reviews on neurotrophic keratopathy and corneal neurotization up until April 2022.Key Content and Findings:Currently,numerous techniques for corneal neurotization exist,including direct nerve transfers,as well as indirect neurotization via interposition nerve grafts.So far,corneal neurotization has been shown to be highly successful in restoring corneal sensation,improving visual acuity,and improving corneal epithelial health.To date,there have been no significant differences in outcomes between direct versus indirect neurotization techniques,different donor nerves,or autologous versus allogeneic interposition grafts.However,there is some evidence that corneal neurotization procedures may be more successful in pediatric patients.Conclusions:Corneal neurotization shows great promise in treating neurotrophic corneas and represents the first management option to date that addresses the underlying pathophysiological mechanism of neurotrophic keratopathy by restoring corneal sensation.As the use of corneal neurotization continues to broaden,additional studies will become important to compare techniques in a systematic manner,with larger sample sizes,as well as standardized outcome measures and follow-up time.展开更多
Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Method...Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Methods and Results: This case study presents a 24-year-old Lithuanian man, with no previous ocular history, who had experienced slowly progressive visual impairment since his childhood. He was examined at the Department of Ophthalmology at Vejle Hospital and Aarhus University Hospital, where he was diagnosed with bilateral Thiel-Behnke corneal dystrophy. Histology confirmed the diagnosis. A lamellar corneal transplantation was performed in the right eye;however, due to epithelial growth under the corneal graft, it was later decided to redo the operation. Following the operations, the patient experienced a visual improvement in best corrected visual acuity (BCVA) from 0.1 (20/25 Snellen equivalent) to 0.3 (20/40 Snellen equivalent) in his right eye. Conclusions: This case of Thiel-Behnke corneal dystrophy is to our knowledge the first reported case in Denmark.展开更多
Background:The goal of this project was to analyze the relationship between cell morphology and proteases/proteases inhibitors(PIs)secretion profile in fuchs endothelial corneal dystrophy(FECD)corneal endothelial cell...Background:The goal of this project was to analyze the relationship between cell morphology and proteases/proteases inhibitors(PIs)secretion profile in fuchs endothelial corneal dystrophy(FECD)corneal endothelial cells(CECs).Methods:Cell morphology was determined using a circularity index(4π×area/perimeter2)for each CECs population extracted from surgical FECD specimens(N=2)and healthy Eye bank corneas(N=3).CECs were cultured 28 days post-confluency.Supernatant was collected and analysed using Proteome Profiler Array detecting 35 proteases and 32 PIs(R&D Systems).Proteome signal was analyzed using Image Studio Lite and correlated with the population’s circularity index.Results:Calculation of circularity index reported different morphologies among FECD populations(0.59±0.18 and 0.64±0.17)and healthy populations(0.44±0.18,0.66±0.13 and 0.71±0.11).Proteome arrays revealed the presence of 10 proteases(ADAMTS1,Cathepsin A,B,D,and X/Z/P,DPPIV/CD26,MMP-2,3 and 12,uPA/Urokinase)and 10 PIs(Protease Nexin II,Cystatin B and C,EMMPRIN/CD147,Latexin,Lipocalin-1,Serpin E1,TFPI,TFPI-2,TIMP-1,2 and 4).Healthy and FECD specimens showed similar variation patterns according to morphology for secretion of ADAMTS1,MMP-3 and 12.However,opposing patterns between healthy and FECD populations were observed for Cathepsin B and D.Moreover,some proteins did not show variation according to phenotype in healthy CECs,but did in FECD CECs:Cathepsin A,Cystatin C,TFPI-2 and total TIMPs.For the other proteins,secretion did not vary according to morphology or no specific pattern was distinguishable.Conclusions:To conclude,our results suggest that cell phenotype is linked to the secretion of certain proteases/PIs in both groups.However,there seems to be differences in secretion of particular proteases and PIs between FECD and healthy specimens as morphology did not have a similar influence.These differences might initiate an imbalance between proteases and PIs explaining the irregular thickening of the Descemet membrane seen in FECD.展开更多
The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain visio...The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain vision.The main problems of artificial cornea are the biocompatibility and stability of the tissue particularly in penetrating keratoplasty.The current studies of tissue-engineered scaffold materials through comprising composites of natural and synthetic biopolymers together have developed a new way to artificial cornea.Although a wide agreement that the long-term stability of these devices would be greatly improved by the presence of cornea cells,modification of keratoprosthesis to support cornea cells remains elusive.Most of the studies on corneal substrate materials and surface modification of composites have tried to improve the growth and biocompatibility of cornea cells which can not only reduce the stimulus of heterogeneous materials,but also more importantly continuous and stable cornea cells can prevent the destruction of collagenase.The necrosis of stroma and spontaneous extrusion of the device,allow for maintenance of a precorneal tear layer,and play the role of ensuring a good optical surface and resisting bacterial infection.As a result,improvement in corneal cells has been the main aim of several recent investigations;some effort has focused on biomaterial for its well biological properties such as promoting the growth of cornea cells.The purpose of this review is to summary the growth status of the corneal cells after the implantation of several artificial corneas.展开更多
In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell(LESC)hypothesis is most widely accepted. This proposes that ste...In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell(LESC)hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient(or transit) amplifying cells(TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell(CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis.展开更多
AIM： To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS： A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea...AIM： To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS： A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy （TEM） and hematoxylin and eosin （H＆E） staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype, RESULTS： The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process, in vitro, the methyl thiazolyl tetrazoUum results revealed that extracts of the acellular ostrich corneas （AOCs） had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes, The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea （APC） transplantation, The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer, CONCLUSION： We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft.展开更多
文摘Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
文摘The cornea is a transparent tissue that serves as the main refractive element of the eye ball.Limbal epithelial stem cells(LESCs),residing in the basal epithelial layer of the Palisades of Vogt located in the corneal limbus between cornea and scleral,are believed to be crucial for the continuous turnover of the corneal epithelium.The proliferation,migration,and differentiation of the LESCs are modulated by unique physical and chemical futures contained within the microenvironment known as the limbal niche.This niche,composed of nerve terminals,cells,extracellular matrix,vasculature,and signaling molecules,is the home for processes such as proliferation,migration and differentiation.Corneal nerve terminals possess special anatomical structures in the limbal region and basal epithelial cells,and they demonstrate pivotal biological effects in the regulation of the LESC function and corneal epithelium homeostasis.Biological molecules such as neuropeptides,neurotransmitters,and neurotrophic factors play a crucial role in modulating the LESCs phenotype responsible for corneal epithelium homeostasis.This paper will review recent studies on how these nerve derived molecules function in this process and provide clear orientations for future research.
文摘AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retrospective study was conducted on 30 phakic eyes from patients diagnosed with FECD but without clinical edema,and 59 phakic eyes from a control group without corneal alterations.Comprehensive ophthalmic examinations were conducted,including slitlamp biomicroscopy,corneal specular microscopy(CSM),and Scheimpflug tomography.RESULTS:The study encompassed 30 phakic eyes with FECD(mean age 59.8±13.1y)and 59 control eyes(mean age 61.3±7.7y).The best-corrected visual acuity was higher in the control group compared to the FECD group[0(0,0.08)vs 0.05(0,0.15)logMAR;P=0.042].CSM revealed significant differences between the FECD and control groups in several parameters:number of analyzed cells(26±13 vs 135±42,P<0.001),cell density(2049±376 vs 2479±225 cells/mm2,P<0.001),mean cell area[463(434,544)vs 397(383,431)μm2;P<0.001],coefficient of variation(54.8%±18.7%vs 41.0%±7.2%,P<0.001),and hexagonal cells[0(0,47%)vs 47%(40%,53%),P<0.001].Although often used as a clinical parameter for detecting edema,central corneal thickness measured by CSM showed no significant difference between the FECD and control groups(530±57 vs 546±30μm,P=0.179).Significant differences were noted in various Pentacam measurements between the groups.Specifically,parameters like loss of parallel isopachs(13 vs 0 eyes,P<0.001),displacement of the thinnest point(11 vs 0 eyes,P<0.001),posterior focal depression(25 vs 7 eyes,P<0.001),and increased light scatter[21.4(17.6;23.9)vs 18.0(16.8,21.8),P=0.01]were significantly more prevalent in FECD eyes,reflecting the presence of subclinical edema and loss of corneal transparency.CONCLUSION:Scheimpflug tomography allows for an objective assessment of FECD,offering the capability to detect subclinical edema at an early stage,monitor disease progression,and serve as a predictor of corneal decompensation following cataract surgery.
文摘AIM:To investigate the changes in posterior corneal elevation within 6mo after small incision lenticule extraction(SMILE)surgery for myopia and myopic astigmatism in patients with thin corneas.METHODS:A prospective study included patients with thin corneas(preoperative thinnest corneal thickness ranging from 480 to 520μm)who underwent SMILE for myopia or myopic astigmatism.Corneal topography and posterior corneal elevation were assessed using Pentacam HR at three time points:preoperatively,1mo,and 6mo postoperatively.The measured parameters included thinnest point elevation(PTE),posterior maximal elevation(PME),posterior central elevation(PCE),and 24 additional reference points.RESULTS:A total of 106 eyes from 106 patients(age range:18-34)were included in the study.Uncorrected distance visual acuity(UDVA)improved significantly,with a mean logMAR value of-0.07±0.06 at the final follow-up visit.Measurements of posterior corneal elevation showed no significant changes in most points,hemispheres,and meridians at 6mo postoperatively.Notably,only two points,ΔE_(2mm-45°)andΔE_(2mm-90°),exhibited statistically significant elevation changes:the elevation ofΔE_(2mm-45°)increased from-2.3±4.99 to-1.0±5.9μm(P=0.0037),and that ofΔE_(2mm-90°)increased from-16±7.53 to-15±7.4μm(P=0.016).However,these changes were within the measurement error range of the Pentacam HR(±5μm in a 5 mm area).CONCLUSION:SMILE surgery is a safe and stable procedure for correcting myopia or myopic astigmatism in patients with thin corneas,as evidenced by the stability of posterior corneal elevation.
文摘AIM:To assess early visual outcomes and corneal stability following small incision lenticule extraction(SMILE)in eyes with a pre-planned residual stromal thickness(RST)ranging from 280 to 300μm.METHODS:This retrospective study was designed to evaluate 82 eyes from 82 patients,all of whom had a pre-planned RST of 280 to 300μm and normal corneal topography prior to undergoing SMILE surgery.The mean preoperative spherical equivalent(SE)was-4.82±1.30 D.A standard follow-up protocol was conducted between 1 to 6mo postoperatively.Visual outcomes were recorded using uncorrected visual acuity(UCVA)and subjective refraction.The curvature of the anterior and posterior corneal surfaces,as well as the posterior elevation at the thinnest point(PTE)were derived from the Pentacam system.RESULTS:At the final follow-up,the efficacy index was 1.14±0.15,the safety index was 1.20±0.13.The mean preoperative UDVA was 0.78±0.16 logMAR,which improved significantly to-0.07±0.06 logMAR postoperatively(P<0.001).The preoperative mean SE was-4.82±1.30 D,which decreased to-0.14±0.30 D by the last visit.The curvature of the anterior cornea at the flat meridian(AK1)were 42.62±1.02 D preoperatively,38.56±1.37 D and 38.59±1.39 D at 1 and 6mo after operation,respectively.Corresponding measurements at the steep meridian(AK2)were 43.55±1.14 D preoperatively,39.18±1.46 D and 39.22±1.50 D at 1 and 6mo after operation,respectively.Both AK1 and AK2 remained stable at 1 and 6-mo postoperative intervals(P=0.126 and 0.082,respectively).There were no observed changes in the curvature of the posterior cornea at the flat meridian or at the steep meridian,or the PTE before and after surgery.CONCLUSION:SMILE represents a safe and effective procedure for the correction of myopia and astigmatism in eyes featuring a pre-planned RST ranging from 280 to 300μm accompanied by normal corneal topography,on the premise of strict control of surgical indications.
基金Supported by the National Natural Science Foundation of China(No.81271716)
文摘AIM：To investigate the feasibility of corneal anterior lamellar reconstruction with human corneal epithelial cells and fibroblasts,and an acellular porcine cornea matrix（APCM） in vitro.·METHODS：The scaffold was prepared from fresh porcine corneas which were treated with 0.5%sodium dodecyl sulfate（SDS）solution and the complete removal of corneal cells was confirmed by hematoxylin-eosin（HE）staining and 4’,6-diamidino-2-phenylindole（DAPI）staining.Human corneal fibroblasts and epithelial cells were cultured with leaching liquid extracted from APCM,and then cell proliferative ability was evaluated by MTT assay.To construct a human corneal anterior lamellar replacement,corneal fibroblasts were injected into the APCM and cultured for 3d,followed by culturing corneal epithelial cells on the stroma construction surface for another 10d.The corneal replacement was analyzed by HE staining,and immunofluorescence staining.·R ESULTS：Histological examination indicated that there were no cells in the APCM by HE staining,and DAPI staining did not detect any residual DNA.The leaching liquid from APCM had little influence on the proliferation ability of human corneal fibroblasts and epithelial cells.At 10d,a continuous 3 to 5 layers of human corneal epithelial cells covering the surface of the APCM was observed,and the injected corneal fibroblasts distributed within the scaffold.The phenotype of the construction was similar to normal human corneas,with high expression of cytokeratin 12 in the epithelial cell layer and high expression of Vimentin in the stroma.·CONCLUSION：Corneal anterior lamellar replacement can be reconstructed in vitro by cultivating human corneal epithelial cells and fibroblasts with an acellular porcine cornea matrix.This laid the foundation for the further transplantation in vitro.
文摘Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.
文摘BACKGROUND An in vitro injury model mimicking a corneal surface injury was optimised using human corneal epithelial cells(hCEC).AIM To investigate whether corneal-stroma derived stem cells(CSSC) seeded on an amniotic membrane(AM) construct manifests an anti-inflammatory, healing response.METHODS Treatment of hCEC with ethanol and pro-inflammatory cytokines were compared in terms of viability loss, cytotoxicity, and pro-inflammatory cytokine release, in order to generate the in vitro injury. This resulted in an optimal injury of 20%(v/v) ethanol for 30 s with 1 ng/mL interleukin-1(IL-1) beta. Co-culture experiments were performed with CSSC alone and with CSSC-AM constructs.The effect of injury and co-culture on viability, cytotoxicity, IL-6 and IL-8 production, and IL1 B, TNF, IL6, and CXCL8 mRNA expression were assessed.RESULTS Co-culture with CSSC inhibited loss of hCEC viability caused by injury. Enzyme linked immunosorbent assay and polymerase chain reaction showed a significant reduction in the production of IL-6 and IL-8 pro-inflammatory cytokines, and reduction in pro-inflammatory cytokine mRNA expression during co-culture with CSSC alone and with the AM construct. These results confirmed the therapeutic potential of the CSSC and the possible use of AM as a cell carrier for application to the ocular surface.CONCLUSION CSSC were shown to have a potentially therapeutic anti-inflammatory effectwhen treating injured hCEC, demonstrating an important role in corneal regeneration and wound healing, leading to an improved knowledge of their potential use for research and therapeutic purposes.
基金Supported by the National Key Research and Development Program of China(No.2020YFE0204400)the National Natural Science Foundation of China(No.82271042)the Zhejiang Province Key Research and Development Program(No.2023C03090).
文摘A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithelialstromal defects.Currently,the etiology and pathogenesis of these defects remain inadequately understood,necessitating further investigation through experimental research.Various modeling methods exist both domestically and internationally,each with distinct adaptive conditions,advantages,and disadvantages.This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury,including mechanical modeling,chemical alkali burns,post-refractive surgery infections,and genetic engineering.The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.
基金Supported by the National Key R&D Program of China (No.2016YFC1100100)the Key R&D Program of Shaanxi Province (No.2018ZDXM-SF-056)+2 种基金the Health and Family Planning Research Fund Project of Shaanxi Province (No.2016C004)the Key Research and Development Program of Shaanxi Province (No.2019SF-196)the Research Talent Project of Xi’an Municipal Health Commission (No.J201902037)。
文摘Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.
文摘Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
文摘Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to assess the effect of the widely used fluorescein dye on human corneal endothelial cells(HCEnCs)in vitro at different concentrations and exposure times.Methods:B4G12,an immortalized human corneal endothelium cell line was cultured on pre-coated tissue culture flask with human endothelial-serum free medium(SFM)supplemented with 10 ng/mL basic fibroblast growth factor(bFGF).The fully confluent B4G12 cell monolayers in 96 well plates were treated with water as control,or fluorescein at various concentrations and exposure times.Cell viability was assessed using two techniques:Alamar Blue assay and cell morphology assessment with an inverted phase-contrast microscopy.Results:Short-term exposure to fluorescein(0.01-0.2%)for up to 30 minutes did not affect cell viability.Continuous fluorescein exposure however significantly reduced the viability of the cells with a notable reduction in cell metabolic activity with fluorescein treatments of 0.001%,0.01% and 0.05% for 1 day(and up to 4 days).Conclusions:Short-term exposure to fluorescein for up to 30 minutes in concentrations commonly used in clinical practice did not affect HCEnC viability.However,fluorescein exposure for longer durations can be detrimental to corneal endothelial cell health.Future studies should evaluate the effects of longer-term fluorescein exposure on endothelial function especially in susceptible patients including the elderly and patients with epithelial defects that enable diffusion of fluorescein towards the endothelium.
基金Supported by Xi’an Health Committee Research Projects(No.2023yb14)Shaanxi Province Natural Science Basic Research Project(No.2024JC-YBMS-623)Shaanxi Province Science and Technology Plan Project(No.2024SFYBXM-331).
文摘AIM:To assess the corneal high-order aberration(HOA)and its correlation with corneal morphological parameters in patients with bilateral keratoconus(KCN)and unilateral Vogt’s striae.METHODS:A total of 168 eyes of 84 patients with KCN,whose corneas had definite signs of unilateral Vogt’s striae,were enrolled.Corneal HOA and morphological parameters were measured using Pentacam HR.RESULTS:The corneal morphological parameters between KCN eyes with and without Vogt’s striae were evidently different(P<0.001).The 3rd coma 90°,4th spherical aberration,5th coma 90°,root-mean-square(RMS)(total),and RMS(HOA)in the front,back surfaces and total cornea in KCN eyes with Vogt’s striae were significantly higher than those in KCN eyes without Vogt’s striae(P<0.001).In KCN eyes with Vogt’s striae,the 3rd coma 90°and 4th spherical aberration in the front surface and total cornea were negatively correlated with flat keratometry value(K1),steep keratometry value(K2),mean keratometry value(Km),maximum keratometry value(Kmax),anterior corneal elevation(ACE),and posterior corneal elevation(PCE;P<0.05).The 3rd coma 90°,4th spherical aberration in back surface and RMS(total),RMS(HOA)in the front,back surfaces,total cornea were positively correlated with K1,K2,Km,Kmax,ACE,and PCE(P<0.05).CONCLUSION:Corneal HOA especially vertical coma and spherical aberration may increase when Vogt’s striae appeared in KCN eyes.The scale of increase is significantly related with changes in corneal shapes.
基金Supported by National Natural Science Foundation of China(No.81700799)Clinical Medicine Plus X-Young Scholar Project,Peking University。
文摘AIM:To construct a competent corneal lamellar substitute in order to alleviate the shortage of human corneal donor.METHODS:Rabbit mesenchymal stem cells(MSCs)were isolated from bone marrow and identified by flow cytometric,osteogenic and adipogenic induction.Xenogenic decellularized corneal matrix(XDCM)was generated from dog corneas.MSCs were seeded and cultured on XDCM to construct the tissueengineered cornea.Post-transplantation biocompatibility of engineered corneal graft were tested by animal experiment.Rabbits were divided into two groups then underwent lamellar keratoplasty(LK)with different corneal grafts:1)XDCM group(n=5):XDCM;2)XDCM-MSCs groups(n=4):tissue-engineered cornea made up with XDCM and MSCs.The ocular surface recovery procedure was observed while corneal transparency,neovascularization and epithelium defection were measured and compared.In vivo on focal exam was performed 3 mo postoperatively.RESULTS:Rabbit MSCs were isolated and identified.Flow cytometry demonstrated isolated cells were CD90 positive and CD34,CD45 negative.Osteogenic and adipogenic induction verified their multipotent abilities.MSC-XDCM grafts were constructed and observed.In vivo transplantation showed the neovascularization in XDCMMSC group was much less than that in XDCM group postoperatively.Post-transplant 3-month confocal test showed less nerve regeneration and bigger cell-absent area in XDCM-MSC group.CONCLUSION:This study present a novel corneal tissue-engineered graft that could reduce post-operatively neovascularization and remain transparency,meanwhile shows that co-transplantation of MSCs may help increase corneal transplantation successful rate and enlarge the source range of corneal substitute to overcome cornea donor shortage.
文摘Background and Objective:Corneal neurotization is a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy.Neurotrophic keratopathy is a disorder characterized by dysfunction of the ophthalmic division of the trigeminal nerve,which provides sensory innervation to the cornea.Without sensation,the cornea is at risk of infection,ulceration,perforation,and ultimately,vision loss.Corneal neurotization has emerged as an innovative technique to reinnervate anesthetized corneas by transferring a healthy donor nerve to the affected eye around the corneoscleral limbus.As the field of corneal neurotization rapidly grows,there is a need to synthesize the existing body of literature on corneal neurotization and identify important areas for further research.In this review,we will discuss neurotrophic keratopathy and its current management strategies,followed by an overview of corneal neurotization techniques,outcomes,surgical considerations,and future directions.Methods:PubMed and Google Scholar searches were conducted to retrieve and analyze relevant original papers and reviews on neurotrophic keratopathy and corneal neurotization up until April 2022.Key Content and Findings:Currently,numerous techniques for corneal neurotization exist,including direct nerve transfers,as well as indirect neurotization via interposition nerve grafts.So far,corneal neurotization has been shown to be highly successful in restoring corneal sensation,improving visual acuity,and improving corneal epithelial health.To date,there have been no significant differences in outcomes between direct versus indirect neurotization techniques,different donor nerves,or autologous versus allogeneic interposition grafts.However,there is some evidence that corneal neurotization procedures may be more successful in pediatric patients.Conclusions:Corneal neurotization shows great promise in treating neurotrophic corneas and represents the first management option to date that addresses the underlying pathophysiological mechanism of neurotrophic keratopathy by restoring corneal sensation.As the use of corneal neurotization continues to broaden,additional studies will become important to compare techniques in a systematic manner,with larger sample sizes,as well as standardized outcome measures and follow-up time.
文摘Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Methods and Results: This case study presents a 24-year-old Lithuanian man, with no previous ocular history, who had experienced slowly progressive visual impairment since his childhood. He was examined at the Department of Ophthalmology at Vejle Hospital and Aarhus University Hospital, where he was diagnosed with bilateral Thiel-Behnke corneal dystrophy. Histology confirmed the diagnosis. A lamellar corneal transplantation was performed in the right eye;however, due to epithelial growth under the corneal graft, it was later decided to redo the operation. Following the operations, the patient experienced a visual improvement in best corrected visual acuity (BCVA) from 0.1 (20/25 Snellen equivalent) to 0.3 (20/40 Snellen equivalent) in his right eye. Conclusions: This case of Thiel-Behnke corneal dystrophy is to our knowledge the first reported case in Denmark.
文摘Background:The goal of this project was to analyze the relationship between cell morphology and proteases/proteases inhibitors(PIs)secretion profile in fuchs endothelial corneal dystrophy(FECD)corneal endothelial cells(CECs).Methods:Cell morphology was determined using a circularity index(4π×area/perimeter2)for each CECs population extracted from surgical FECD specimens(N=2)and healthy Eye bank corneas(N=3).CECs were cultured 28 days post-confluency.Supernatant was collected and analysed using Proteome Profiler Array detecting 35 proteases and 32 PIs(R&D Systems).Proteome signal was analyzed using Image Studio Lite and correlated with the population’s circularity index.Results:Calculation of circularity index reported different morphologies among FECD populations(0.59±0.18 and 0.64±0.17)and healthy populations(0.44±0.18,0.66±0.13 and 0.71±0.11).Proteome arrays revealed the presence of 10 proteases(ADAMTS1,Cathepsin A,B,D,and X/Z/P,DPPIV/CD26,MMP-2,3 and 12,uPA/Urokinase)and 10 PIs(Protease Nexin II,Cystatin B and C,EMMPRIN/CD147,Latexin,Lipocalin-1,Serpin E1,TFPI,TFPI-2,TIMP-1,2 and 4).Healthy and FECD specimens showed similar variation patterns according to morphology for secretion of ADAMTS1,MMP-3 and 12.However,opposing patterns between healthy and FECD populations were observed for Cathepsin B and D.Moreover,some proteins did not show variation according to phenotype in healthy CECs,but did in FECD CECs:Cathepsin A,Cystatin C,TFPI-2 and total TIMPs.For the other proteins,secretion did not vary according to morphology or no specific pattern was distinguishable.Conclusions:To conclude,our results suggest that cell phenotype is linked to the secretion of certain proteases/PIs in both groups.However,there seems to be differences in secretion of particular proteases and PIs between FECD and healthy specimens as morphology did not have a similar influence.These differences might initiate an imbalance between proteases and PIs explaining the irregular thickening of the Descemet membrane seen in FECD.
基金National Natural Science Foundation of China(No.50973082)
文摘The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain vision.The main problems of artificial cornea are the biocompatibility and stability of the tissue particularly in penetrating keratoplasty.The current studies of tissue-engineered scaffold materials through comprising composites of natural and synthetic biopolymers together have developed a new way to artificial cornea.Although a wide agreement that the long-term stability of these devices would be greatly improved by the presence of cornea cells,modification of keratoprosthesis to support cornea cells remains elusive.Most of the studies on corneal substrate materials and surface modification of composites have tried to improve the growth and biocompatibility of cornea cells which can not only reduce the stimulus of heterogeneous materials,but also more importantly continuous and stable cornea cells can prevent the destruction of collagenase.The necrosis of stroma and spontaneous extrusion of the device,allow for maintenance of a precorneal tear layer,and play the role of ensuring a good optical surface and resisting bacterial infection.As a result,improvement in corneal cells has been the main aim of several recent investigations;some effort has focused on biomaterial for its well biological properties such as promoting the growth of cornea cells.The purpose of this review is to summary the growth status of the corneal cells after the implantation of several artificial corneas.
基金Supported by Grants from the Wellcome Trust,No.088876/Z/09/Zthe UK Biotechnology and Biological Sciences Research Council,No.BB/J015172/1 and No.BB/J015237/1
文摘In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell(LESC)hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient(or transit) amplifying cells(TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell(CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis.
基金Supported by National Natural Science Foundation of China(No.31200724)Key Innovation Project of Shaanxi Science and Technology Plan(No. 2012KTCQ03-11)+1 种基金Shenzhen Peacock Plan(No. KQCX20130628155525051)Projects of Basic Research of Shenzhen(No.JCYJ20120614193611639,No.JCYJ 20140509172959988)
文摘AIM： To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS： A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy （TEM） and hematoxylin and eosin （H＆E） staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype, RESULTS： The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process, in vitro, the methyl thiazolyl tetrazoUum results revealed that extracts of the acellular ostrich corneas （AOCs） had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes, The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea （APC） transplantation, The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer, CONCLUSION： We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft.
