CXL (Compute Express Link) technology is a relatively new high-speed interconnect standard that was developed to enable faster communication between CPUs, GPUs, and other high-performance components in data center sys...CXL (Compute Express Link) technology is a relatively new high-speed interconnect standard that was developed to enable faster communication between CPUs, GPUs, and other high-performance components in data center systems. This paper aims to provide a comprehensive technical overview of CXL technology, including its features, advantages, and potential applications in the modern data center environment. CXL Technology Research: CXL technology is based on Peripheral Component Interconnect Express (PCIe) and its extensions. CXL 1.0 is a switch-based interconnect architecture that operates on PCIe Gen5 electrical signaling, achieving data speeds of up to 32 Giga transfers per second (GT/s) per lane. CXL technology provides hardware-based support for cache coherency and memory semantics. CXL technology architecture consists of three main components: 1) CXL Devices: Devices that are compatible with the CXL interface can include processors, accelerators such as Graphics Processing Units (GPUs), and Smart Storage Devices;2) CXL Switch: The switch enables communication between devices that support CXL. The switch can be external or embedded, allowing for more complex topologies;3) CXL Memory: CXL memory devices support the CXL protocol for the efficient sharing of System memory.展开更多
Corneal collagen crosslinking(CXL)has revolutionized the treatment of keratoconus in the past decade.In order to evaluate the 3-month effects of CXL on corneal fibroblasts,a longitudinal study at the tissue and cellul...Corneal collagen crosslinking(CXL)has revolutionized the treatment of keratoconus in the past decade.In order to evaluate the 3-month effects of CXL on corneal fibroblasts,a longitudinal study at the tissue and cellular level was carried out with a total of 16 rabbits that underwent CXL,deepithelialization(DEP),or non-treatment(control)and kept for 1 to 3 months.The duration of corneal stromal remodeling after CXL was determined by examining the differentiation,apoptosis,and number changes of keratocytes in tissue sections from animals 1,2,or 3 months post-treatment.Upon the finish of tissue remodeling,separate rabbits were used to extract keratocytes and set up cell culture for vimentin immunofluorescence staining.The same cell culture was used for(1)migration measurement through the wound-healing assay;(2)elastic modulus measurement by atomic force microscope(AFM);(3)the proliferation,apoptosis,cytoskeleton andα-SMA expression tests through EdU(5-ethynyl-2’-deoxyuridine)assay,TUNEL(TdT-mediated dUTP Nick-End Labeling)assay,phalloidin andα-SMA(alpha-smooth muscle actin)immunofluorescence analysis,respectively.Results showed that the migratory activity,elastic modulus,andα-SMA expression of the corneal fibroblasts increased after CXL treatment,while apoptosis,proliferation,and morphology of F-actin cytoskeleton of the fibroblasts had no significant change after 3 months.In contrast,measured cellular parameters(migratory,elastic moduli,α-SMA expression,apoptosis,proliferation,and morphology of F-actin cytoskeleton of fibroblasts)did not change significantly after DEP.In conclusion,the dynamic changes of keratocytes were nearly stable 3 months after CXL treatment.CXL has an impact on corneal fibroblasts,including migration,elastic modulus andα-SMA expression,while epithelialization may not alter the biological behavior of cells significantly.展开更多
Corneal collagen-crosslinking(CXL)has been widely investigated in the adult population.There is still little available in the literature,however,on the effects of CXL in children.A review of the literature on CXL in t...Corneal collagen-crosslinking(CXL)has been widely investigated in the adult population.There is still little available in the literature,however,on the effects of CXL in children.A review of the literature on CXL in the pediatric population is presented here,with a particular emphasis on the refractive effects.Although several studies demonstrate promising results,most studies have small sample sizes with relatively short follow-up periods.Further investigation on the effects of CXL in the pediatric population is required to better understand long-term effects.展开更多
Objective:to study the effect of coixenolide (CXL) on irradiation of human nasophyaryngeal carcinoma cell line CNE-2Z in the absence of oxygen,Methods: Microcolony formation assay was used for determining the sensitiv...Objective:to study the effect of coixenolide (CXL) on irradiation of human nasophyaryngeal carcinoma cell line CNE-2Z in the absence of oxygen,Methods: Microcolony formation assay was used for determining the sensitivity of CNE-2Z to γ-ray in vitro,Results:When CNE-2Z was treated with 10^-7--10^-6 mol/L of CXL,CXL shifted the radiation dose-survival curve to the left,with the decrease of D0,Dq and N values,Radiation dose reduced 10.07%-35.69% at D37 level,the sensitizing enhancement ratios(SER) were 1.07-1.43 and 1.16-1.72 at D0 and Dq levels respectively.Conclusion:CXL increase susceptibility of CNE-2Z to ray under hypoxic condition by the mechanism of inhibiting its sublethal damgae repair.Subject words Nasopharyngeal neoplasm;Coixenolide;Radiosensitzation;Hypoxic irradiation.展开更多
Background:Corneal cross-linking(CXL)using ultraviolet light-A(UV-A)and riboflavin is a technique developed in the 1990’s to treat corneal ectatic disorders such as keratoconus.It soon became the new gold standard in...Background:Corneal cross-linking(CXL)using ultraviolet light-A(UV-A)and riboflavin is a technique developed in the 1990’s to treat corneal ectatic disorders such as keratoconus.It soon became the new gold standard in multiple countries around the world to halt the progression of this disorder,with good long-term outcomes in keratometry reading and visual acuity.The original Dresden treatment protocol was also later on used to stabilize iatrogenic corneal ectasia appearing after laser-assisted in situ keratomileusis(LASIK)and photorefractive keratectomy(PRK).CXL efficiently strengthened the cornea but was also shown to kill most of the keratocytes within the corneal stroma,later on repopulated by those cells.Review:Ultraviolet-light has long been known for its microbicidal effect,and thus CXL postulated to be able to sterilize the cornea from infectious pathogens.This cytotoxic effect led to the first clinical trials using CXL to treat advanced infectious melting corneal keratitis.Patients treated with this technique showed,in the majority of cases,a stabilization of the melting process and were able to avoid emergentàchaud keratoplasty.Following those primary favorable results,CXL was used to treat beginning bacterial keratitis as a first-line treatment without any adjunctive antibiotics with positive results for most patients.In order to distinguish the use of CXL for infectious keratitis treatment from its use for corneal ectatic disorders,a new term was proposed at the 9th CXL congress in Dublin to rename its use in infections as photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL).Conclusion:PACK-CXL is now more frequently used to treat infections from various infectious origins.The original Dresden protocol is still used for this purpose.Careful modifications of this protocol could improve the efficiency of this technique in specific clinical situations regarding certain types of pathogens.展开更多
Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transpa...Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transparency”and“Epithelium&Stroma generation”,as well as“Suturelessness”and“Toughness”.To simultaneously meet the“T.E.S.T.”requirements,a light-curable hydrogel is designed based on methacryloylated gelatin(GelMA),Pluronic F127 diacrylate(F127DA)&Aldehyded Pluronic F127(AF127)co-assembled bi-functional micelles and collagen type I(COL I),combined with clinically applied corneal cross-linking(CXL)technology for repairing damaged cornea.The patch formed after 5 min of ultraviolet irradiation possesses transparent,highly tough,and strongly bio-adhesive performance.Multiple cross-linking makes the patch withstand deformation near 600%and exhibit a burst pressure larger than 400 mmHg,significantly higher than normal intraocular pressure(10-21 mmHg).Besides,the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo,supporting the regrowth of corneal epithelium and stroma.The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks,showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.展开更多
Background The purpose of the study was to determine the advantages and disadvantages of epi-on corneal cross-linking(CXL)techniques compared with standard epi-off CXL.Methods We searched MEDLINE and EMBASE for random...Background The purpose of the study was to determine the advantages and disadvantages of epi-on corneal cross-linking(CXL)techniques compared with standard epi-off CXL.Methods We searched MEDLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias tool.We considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UDVA and CDVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECD).We also investigated adverse events related to the treatments and treatment failure.Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference(MD)with 95%confidence interval(CI)as the effect size.Results A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this meta-analysis.Our analysis revealed significant postoperative differences in CDVA(MD=0.07;95%CI 0.04 to 0.10;P<0.001),and no significative differences in UDVA,Kmax,central corneal thickness(CCT)and ECD(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion Epi-on CXL is as effective as epi-off CXL.Except for a higher significant improvement in CDVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial parameters.Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.展开更多
Background:The corneal cross-linking(CXL)photochemical reaction is essentially dependent on oxygen and hypothermia,which usually leads to higher dissolved oxygen levels in tissues,with potentially greater oxygen avail...Background:The corneal cross-linking(CXL)photochemical reaction is essentially dependent on oxygen and hypothermia,which usually leads to higher dissolved oxygen levels in tissues,with potentially greater oxygen availability for treatment.Here,we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas.Methods:One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1%hypo-osmolaric riboflavin.These corneas were equally assigned to one of four groups.Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm^(2) irradiance for 10 min,performed either in a cold room temperature(group 2,4℃)or at standard room temperature(group 4,24℃).Groups 1 and 3 served as non-cross-linked,temperature-matched controls.Using a stress-strain extensometer,the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness.Results:Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1%and 5%of strain when compared to non-cross-linked controls(P<0.05),both at 4℃(1.40±0.22 vs.1.23±0.18 N/mm)and 24 C(1.42±0.15 vs.1.19±0.11 N/mm).However,no significant difference was found between control groups(P=0.846)or between groups in which CXL was performed at low or standard room temperature(P=0.969).Conclusions:Although initial oxygen availability should be increased under hypothermic conditions,it does not appear to play a significant role in the biomechanical strengthening effect of accelerated epithelium-off CXL protocols in ex vivo porcine corneas.展开更多
Background:To compare the outcomes of two different protocols of accelerated corneal crosslinking(CXL)on visual,corneal high order aberrations(HOA)and topographic parameters in patients with progressive keratoconus.Me...Background:To compare the outcomes of two different protocols of accelerated corneal crosslinking(CXL)on visual,corneal high order aberrations(HOA)and topographic parameters in patients with progressive keratoconus.Methods:In this prospective comparative study,sixty-six eyes of 66 patients with progressive keratoconus were divided into two groups;37 eyes in Group 1 received 18 mW/cm^(2) for five minutes,and 29 eyes in Group 2 were treated with 9 mW/cm^(2) for 10 min.The uncorrected distant visual acuity(UCVA),best-corrected distant visual acuity(BCVA),corneal HOAs and topography parameters were measured preoperatively and postoperatively at the end of 12 months.The data for the two groups were compared statistically.Results:The mean UCVA and BCVA were significantly improved at the postoperative 12 months compared with the preoperative values in both groups(P<0.05 for all).A significant improvement in corneal HOAs was observed in both groups(P<0.05 for all).The change in corneal coma value was significantly higher in Group 2(P<0.05).The change in keratometric values K1,K2,AvgK and maximum keratometry(AKf)were significantly higher in Group 2(P<0.05 for all).The regression model showed that the most important factor predicting the change in AKf was the type of CXL(β=−0.482,P=0.005).Conclusions:Accelerated CXL using 10 min of UVA irradiance at 9 mW/cm^(2) showed better topographic improvements and coma values than five minutes of UVA irradiance at 18 mW/cm^(2) independent of keratoconus severity.展开更多
Background:The purpose of the study was to determine the advantages and disadvantages of epi-on corneal crosslinking(CXL)techniques compared with standard epi-off CXL.Methods:We searched MEDLINE and EMBASE for randomi...Background:The purpose of the study was to determine the advantages and disadvantages of epi-on corneal crosslinking(CXL)techniques compared with standard epi-off CXL.Methods:We searched MEDLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias tool.We considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UDVA and CDVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECD).We also investigated adverse events related to the treatments and treatment failure.Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference(MD)with 95%confidence interval(CI)as the effect size.Results:A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this meta-analysis.Our analysis revealed significant postoperative differences in CDVA(MD=0.07;95%CI 0.04 to 0.10;P<0.001),and no significative differences in UDVA,Kmax,central corneal thickness(CCT)and ECD(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion:Epi-on CXL is as effective as epi-off CXL.Except for a higher significant improvement in CDVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial parameters.Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.展开更多
Background:The purpose of our study is to examine the long(5-year)efficacy of the all surface laser ablation(ASLA)combined with accelerated cross-linking(CXL)for the treatment of myopia without the use of mitomycin-C(...Background:The purpose of our study is to examine the long(5-year)efficacy of the all surface laser ablation(ASLA)combined with accelerated cross-linking(CXL)for the treatment of myopia without the use of mitomycin-C(MMC).Methods:This retrospective study consisted of 202 eyes of 118 myopic(SD:2.41,range:−1.50 to−12.75 D)patients(44 males,74 females).Mean age was 28.50 years(SD:6.45,range:18 to 51 years)that underwent ASLA with accelerated CXL for the treatment of their myopia.Results:The patients underwent routine postoperative assessment on the 1st,3rd,7th day and in the 1st,3rd,6th and 12th month,30th month(±6 months),4th and 5th year.The mean spherical equivalent(SEq)refractive error changed from−6.41±2.41 D preoperatively to−0.02±0.53 D at 5 years postoperatively.The haze score was 0.18,0.25 and 0.28 at 1,3 and 6 months postoperatively.At 12 months after the treatment,no eyes had significant corneal haze and in all the following postoperative time intervals the haze traces were gone.Conclusion:ASLA combined with accelerated CXL(ASLA-XTRA)appears to be safe,efficacious and offering very good refractive results.The potential additional benefits of this modality are the stabilizing effect of the refraction and its sterilization effect on the treated cornea without the potential side effects of MMC.展开更多
Background:The corneal cross-linking(CXL)photochemical reaction is essentially dependent on oxygen and hypothermia,which usually leads to higher dissolved oxygen levels in tissues,with potentially greater oxygen avail...Background:The corneal cross-linking(CXL)photochemical reaction is essentially dependent on oxygen and hypothermia,which usually leads to higher dissolved oxygen levels in tissues,with potentially greater oxygen availability for treatment.Here,we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas.Methods:One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1%hypo-osmolaric riboflavin.These corneas were equally assigned to one of four groups.Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm^(2) irradiance for 10 min,performed either in a cold room temperature(group 2,4℃)or at standard room temperature(group 4,24℃).Groups 1 and 3 served as non-crosslinked,temperature-matched controls.Using a stress-strain extensometer,the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness.Results:Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5%of strain when compared to non-cross-linked controls(P<0.05),both at 4℃(1.40±0.22 vs 1.23±0.18 N/mm)and 24℃(1.42±0.15 vs 1.19±0.11 N/mm).However,no significant difference was found between control groups(P=0.846)or between groups in which CXL was performed at low or standard room temperature(P=0.969).Conclusions:Although initial oxygen availability should be increased under hypothermic conditions,it does not appear to play a significant role in the biomechanical strengthening effect of epithelium-off CXL accelerated protocols in ex vivo porcine corneas.展开更多
Purpose:To assess clinical results of the 9 mW/5.4 J/cm^(2) accelerated crosslinking(ACXL)in the treatment of progressive keratoconus(KC)over a span of 5 years.Methods:The prospective open non-randomized interventiona...Purpose:To assess clinical results of the 9 mW/5.4 J/cm^(2) accelerated crosslinking(ACXL)in the treatment of progressive keratoconus(KC)over a span of 5 years.Methods:The prospective open non-randomized interventional study(Siena Eye-Cross Study 2)included 156 eyes of 112 patients with early progressive KC undergoing the Epi-Off 9 mW/5.4 J/cm^(2) ACXL at the Siena Crosslinking Centre,Italy.The mean age was 18.05±5.6 years.The 20-min treatments were performed using the New KXL I(Avedro,Waltham,USA),10 min of 0.1%HPMC Riboflavin soaking(VibeX Rapid,Avedro,Waltham,USA)and 10 min of continuous-light UV-A irradiation.Uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),Kmax,coma,minimum corneal thickness(MCT),surface asymmetry index(SAI),endothelial cell count(ECC)were measured,and corneal OCT performed.Results:UDVA and CDVA improved significantly at the 3rd(P=0.028),Δ+0.17 Snellen lines and 6th postoperative month,respectively(P<0.001),Δ+0.23 Snellen lines.Kmax improved at the 6th postoperative month(P=0.03),Δ−1.49 diopters from the baseline value.Also,coma aberration value improved significantly(P=0.004).A mild temporary haze was recorded in 14.77%of patients without affecting visual acuity and without persistent complications.Corneal OCT revealed a mean demarcation line depth at 332.6±33.6μm.Conclusion:The 5-year results of Epi-Off 9 mW/5.4 J/cm^(2) ACXL demonstrated statistically significant improvements in UCVA and CDVA,corneal curvature and corneal higher-order aberrations which confers a long-term stability for progressive ectasia.Based on the results of the Siena Eye-Cross Study 2,the 9 mW/5.4 J/cm^(2) ACXL is a candidate to be the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia,and thus optimize clinic workflow.展开更多
文摘CXL (Compute Express Link) technology is a relatively new high-speed interconnect standard that was developed to enable faster communication between CPUs, GPUs, and other high-performance components in data center systems. This paper aims to provide a comprehensive technical overview of CXL technology, including its features, advantages, and potential applications in the modern data center environment. CXL Technology Research: CXL technology is based on Peripheral Component Interconnect Express (PCIe) and its extensions. CXL 1.0 is a switch-based interconnect architecture that operates on PCIe Gen5 electrical signaling, achieving data speeds of up to 32 Giga transfers per second (GT/s) per lane. CXL technology provides hardware-based support for cache coherency and memory semantics. CXL technology architecture consists of three main components: 1) CXL Devices: Devices that are compatible with the CXL interface can include processors, accelerators such as Graphics Processing Units (GPUs), and Smart Storage Devices;2) CXL Switch: The switch enables communication between devices that support CXL. The switch can be external or embedded, allowing for more complex topologies;3) CXL Memory: CXL memory devices support the CXL protocol for the efficient sharing of System memory.
基金supported by the National natural science foundation of China(Nos.31370952,31470914).
文摘Corneal collagen crosslinking(CXL)has revolutionized the treatment of keratoconus in the past decade.In order to evaluate the 3-month effects of CXL on corneal fibroblasts,a longitudinal study at the tissue and cellular level was carried out with a total of 16 rabbits that underwent CXL,deepithelialization(DEP),or non-treatment(control)and kept for 1 to 3 months.The duration of corneal stromal remodeling after CXL was determined by examining the differentiation,apoptosis,and number changes of keratocytes in tissue sections from animals 1,2,or 3 months post-treatment.Upon the finish of tissue remodeling,separate rabbits were used to extract keratocytes and set up cell culture for vimentin immunofluorescence staining.The same cell culture was used for(1)migration measurement through the wound-healing assay;(2)elastic modulus measurement by atomic force microscope(AFM);(3)the proliferation,apoptosis,cytoskeleton andα-SMA expression tests through EdU(5-ethynyl-2’-deoxyuridine)assay,TUNEL(TdT-mediated dUTP Nick-End Labeling)assay,phalloidin andα-SMA(alpha-smooth muscle actin)immunofluorescence analysis,respectively.Results showed that the migratory activity,elastic modulus,andα-SMA expression of the corneal fibroblasts increased after CXL treatment,while apoptosis,proliferation,and morphology of F-actin cytoskeleton of the fibroblasts had no significant change after 3 months.In contrast,measured cellular parameters(migratory,elastic moduli,α-SMA expression,apoptosis,proliferation,and morphology of F-actin cytoskeleton of fibroblasts)did not change significantly after DEP.In conclusion,the dynamic changes of keratocytes were nearly stable 3 months after CXL treatment.CXL has an impact on corneal fibroblasts,including migration,elastic modulus andα-SMA expression,while epithelialization may not alter the biological behavior of cells significantly.
文摘Corneal collagen-crosslinking(CXL)has been widely investigated in the adult population.There is still little available in the literature,however,on the effects of CXL in children.A review of the literature on CXL in the pediatric population is presented here,with a particular emphasis on the refractive effects.Although several studies demonstrate promising results,most studies have small sample sizes with relatively short follow-up periods.Further investigation on the effects of CXL in the pediatric population is required to better understand long-term effects.
基金This project was supported by Guangdong provincial natural science foundation (No.970839) and Guangdong provincial administrati
文摘Objective:to study the effect of coixenolide (CXL) on irradiation of human nasophyaryngeal carcinoma cell line CNE-2Z in the absence of oxygen,Methods: Microcolony formation assay was used for determining the sensitivity of CNE-2Z to γ-ray in vitro,Results:When CNE-2Z was treated with 10^-7--10^-6 mol/L of CXL,CXL shifted the radiation dose-survival curve to the left,with the decrease of D0,Dq and N values,Radiation dose reduced 10.07%-35.69% at D37 level,the sensitizing enhancement ratios(SER) were 1.07-1.43 and 1.16-1.72 at D0 and Dq levels respectively.Conclusion:CXL increase susceptibility of CNE-2Z to ray under hypoxic condition by the mechanism of inhibiting its sublethal damgae repair.Subject words Nasopharyngeal neoplasm;Coixenolide;Radiosensitzation;Hypoxic irradiation.
文摘Background:Corneal cross-linking(CXL)using ultraviolet light-A(UV-A)and riboflavin is a technique developed in the 1990’s to treat corneal ectatic disorders such as keratoconus.It soon became the new gold standard in multiple countries around the world to halt the progression of this disorder,with good long-term outcomes in keratometry reading and visual acuity.The original Dresden treatment protocol was also later on used to stabilize iatrogenic corneal ectasia appearing after laser-assisted in situ keratomileusis(LASIK)and photorefractive keratectomy(PRK).CXL efficiently strengthened the cornea but was also shown to kill most of the keratocytes within the corneal stroma,later on repopulated by those cells.Review:Ultraviolet-light has long been known for its microbicidal effect,and thus CXL postulated to be able to sterilize the cornea from infectious pathogens.This cytotoxic effect led to the first clinical trials using CXL to treat advanced infectious melting corneal keratitis.Patients treated with this technique showed,in the majority of cases,a stabilization of the melting process and were able to avoid emergentàchaud keratoplasty.Following those primary favorable results,CXL was used to treat beginning bacterial keratitis as a first-line treatment without any adjunctive antibiotics with positive results for most patients.In order to distinguish the use of CXL for infectious keratitis treatment from its use for corneal ectatic disorders,a new term was proposed at the 9th CXL congress in Dublin to rename its use in infections as photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL).Conclusion:PACK-CXL is now more frequently used to treat infections from various infectious origins.The original Dresden protocol is still used for this purpose.Careful modifications of this protocol could improve the efficiency of this technique in specific clinical situations regarding certain types of pathogens.
基金This work was supported by the Shanghai Rising-Star Program(Grants No.21QA1401500)Clinical Research Plan of SHDC(Grants No.SHDC2020CR1043B).
文摘Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transparency”and“Epithelium&Stroma generation”,as well as“Suturelessness”and“Toughness”.To simultaneously meet the“T.E.S.T.”requirements,a light-curable hydrogel is designed based on methacryloylated gelatin(GelMA),Pluronic F127 diacrylate(F127DA)&Aldehyded Pluronic F127(AF127)co-assembled bi-functional micelles and collagen type I(COL I),combined with clinically applied corneal cross-linking(CXL)technology for repairing damaged cornea.The patch formed after 5 min of ultraviolet irradiation possesses transparent,highly tough,and strongly bio-adhesive performance.Multiple cross-linking makes the patch withstand deformation near 600%and exhibit a burst pressure larger than 400 mmHg,significantly higher than normal intraocular pressure(10-21 mmHg).Besides,the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo,supporting the regrowth of corneal epithelium and stroma.The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks,showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.
基金This study has been financed in part by the Network for Cooperative Research in Health“OFTARED”—Reference:RD16/0008/0012.Funded by Instituto de Salud Carlos III and co-funded by the European Regional Development Fund(ERDF),Project“A way to make Europe”.
文摘Background The purpose of the study was to determine the advantages and disadvantages of epi-on corneal cross-linking(CXL)techniques compared with standard epi-off CXL.Methods We searched MEDLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias tool.We considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UDVA and CDVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECD).We also investigated adverse events related to the treatments and treatment failure.Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference(MD)with 95%confidence interval(CI)as the effect size.Results A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this meta-analysis.Our analysis revealed significant postoperative differences in CDVA(MD=0.07;95%CI 0.04 to 0.10;P<0.001),and no significative differences in UDVA,Kmax,central corneal thickness(CCT)and ECD(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion Epi-on CXL is as effective as epi-off CXL.Except for a higher significant improvement in CDVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial parameters.Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.
基金supported in part by the Light for Sight Foundation,Zurich,Switzerland(FH),Velux Stiftung(FH)and International Council of Ophthalmology Award(ETN).
文摘Background:The corneal cross-linking(CXL)photochemical reaction is essentially dependent on oxygen and hypothermia,which usually leads to higher dissolved oxygen levels in tissues,with potentially greater oxygen availability for treatment.Here,we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas.Methods:One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1%hypo-osmolaric riboflavin.These corneas were equally assigned to one of four groups.Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm^(2) irradiance for 10 min,performed either in a cold room temperature(group 2,4℃)or at standard room temperature(group 4,24℃).Groups 1 and 3 served as non-cross-linked,temperature-matched controls.Using a stress-strain extensometer,the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness.Results:Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1%and 5%of strain when compared to non-cross-linked controls(P<0.05),both at 4℃(1.40±0.22 vs.1.23±0.18 N/mm)and 24 C(1.42±0.15 vs.1.19±0.11 N/mm).However,no significant difference was found between control groups(P=0.846)or between groups in which CXL was performed at low or standard room temperature(P=0.969).Conclusions:Although initial oxygen availability should be increased under hypothermic conditions,it does not appear to play a significant role in the biomechanical strengthening effect of accelerated epithelium-off CXL protocols in ex vivo porcine corneas.
文摘Background:To compare the outcomes of two different protocols of accelerated corneal crosslinking(CXL)on visual,corneal high order aberrations(HOA)and topographic parameters in patients with progressive keratoconus.Methods:In this prospective comparative study,sixty-six eyes of 66 patients with progressive keratoconus were divided into two groups;37 eyes in Group 1 received 18 mW/cm^(2) for five minutes,and 29 eyes in Group 2 were treated with 9 mW/cm^(2) for 10 min.The uncorrected distant visual acuity(UCVA),best-corrected distant visual acuity(BCVA),corneal HOAs and topography parameters were measured preoperatively and postoperatively at the end of 12 months.The data for the two groups were compared statistically.Results:The mean UCVA and BCVA were significantly improved at the postoperative 12 months compared with the preoperative values in both groups(P<0.05 for all).A significant improvement in corneal HOAs was observed in both groups(P<0.05 for all).The change in corneal coma value was significantly higher in Group 2(P<0.05).The change in keratometric values K1,K2,AvgK and maximum keratometry(AKf)were significantly higher in Group 2(P<0.05 for all).The regression model showed that the most important factor predicting the change in AKf was the type of CXL(β=−0.482,P=0.005).Conclusions:Accelerated CXL using 10 min of UVA irradiance at 9 mW/cm^(2) showed better topographic improvements and coma values than five minutes of UVA irradiance at 18 mW/cm^(2) independent of keratoconus severity.
基金financed in part by the Network for Cooperative Research in Health“OFTARED”—Reference:RD16/0008/0012Funded by Instituto de Salud Carlos IIIco-funded by the European Regional Development Fund(ERDF),Project"A way to make Europe".
文摘Background:The purpose of the study was to determine the advantages and disadvantages of epi-on corneal crosslinking(CXL)techniques compared with standard epi-off CXL.Methods:We searched MEDLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias tool.We considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UDVA and CDVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECD).We also investigated adverse events related to the treatments and treatment failure.Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference(MD)with 95%confidence interval(CI)as the effect size.Results:A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this meta-analysis.Our analysis revealed significant postoperative differences in CDVA(MD=0.07;95%CI 0.04 to 0.10;P<0.001),and no significative differences in UDVA,Kmax,central corneal thickness(CCT)and ECD(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion:Epi-on CXL is as effective as epi-off CXL.Except for a higher significant improvement in CDVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial parameters.Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.
文摘Background:The purpose of our study is to examine the long(5-year)efficacy of the all surface laser ablation(ASLA)combined with accelerated cross-linking(CXL)for the treatment of myopia without the use of mitomycin-C(MMC).Methods:This retrospective study consisted of 202 eyes of 118 myopic(SD:2.41,range:−1.50 to−12.75 D)patients(44 males,74 females).Mean age was 28.50 years(SD:6.45,range:18 to 51 years)that underwent ASLA with accelerated CXL for the treatment of their myopia.Results:The patients underwent routine postoperative assessment on the 1st,3rd,7th day and in the 1st,3rd,6th and 12th month,30th month(±6 months),4th and 5th year.The mean spherical equivalent(SEq)refractive error changed from−6.41±2.41 D preoperatively to−0.02±0.53 D at 5 years postoperatively.The haze score was 0.18,0.25 and 0.28 at 1,3 and 6 months postoperatively.At 12 months after the treatment,no eyes had significant corneal haze and in all the following postoperative time intervals the haze traces were gone.Conclusion:ASLA combined with accelerated CXL(ASLA-XTRA)appears to be safe,efficacious and offering very good refractive results.The potential additional benefits of this modality are the stabilizing effect of the refraction and its sterilization effect on the treated cornea without the potential side effects of MMC.
基金supported in part by the Light for Sight Foundation,Zurich,Switzerland(FH),Velux Stiftung(FH)and International Council of Ophthalmology Award(ETN).
文摘Background:The corneal cross-linking(CXL)photochemical reaction is essentially dependent on oxygen and hypothermia,which usually leads to higher dissolved oxygen levels in tissues,with potentially greater oxygen availability for treatment.Here,we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas.Methods:One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1%hypo-osmolaric riboflavin.These corneas were equally assigned to one of four groups.Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm^(2) irradiance for 10 min,performed either in a cold room temperature(group 2,4℃)or at standard room temperature(group 4,24℃).Groups 1 and 3 served as non-crosslinked,temperature-matched controls.Using a stress-strain extensometer,the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness.Results:Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5%of strain when compared to non-cross-linked controls(P<0.05),both at 4℃(1.40±0.22 vs 1.23±0.18 N/mm)and 24℃(1.42±0.15 vs 1.19±0.11 N/mm).However,no significant difference was found between control groups(P=0.846)or between groups in which CXL was performed at low or standard room temperature(P=0.969).Conclusions:Although initial oxygen availability should be increased under hypothermic conditions,it does not appear to play a significant role in the biomechanical strengthening effect of epithelium-off CXL accelerated protocols in ex vivo porcine corneas.
文摘Purpose:To assess clinical results of the 9 mW/5.4 J/cm^(2) accelerated crosslinking(ACXL)in the treatment of progressive keratoconus(KC)over a span of 5 years.Methods:The prospective open non-randomized interventional study(Siena Eye-Cross Study 2)included 156 eyes of 112 patients with early progressive KC undergoing the Epi-Off 9 mW/5.4 J/cm^(2) ACXL at the Siena Crosslinking Centre,Italy.The mean age was 18.05±5.6 years.The 20-min treatments were performed using the New KXL I(Avedro,Waltham,USA),10 min of 0.1%HPMC Riboflavin soaking(VibeX Rapid,Avedro,Waltham,USA)and 10 min of continuous-light UV-A irradiation.Uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),Kmax,coma,minimum corneal thickness(MCT),surface asymmetry index(SAI),endothelial cell count(ECC)were measured,and corneal OCT performed.Results:UDVA and CDVA improved significantly at the 3rd(P=0.028),Δ+0.17 Snellen lines and 6th postoperative month,respectively(P<0.001),Δ+0.23 Snellen lines.Kmax improved at the 6th postoperative month(P=0.03),Δ−1.49 diopters from the baseline value.Also,coma aberration value improved significantly(P=0.004).A mild temporary haze was recorded in 14.77%of patients without affecting visual acuity and without persistent complications.Corneal OCT revealed a mean demarcation line depth at 332.6±33.6μm.Conclusion:The 5-year results of Epi-Off 9 mW/5.4 J/cm^(2) ACXL demonstrated statistically significant improvements in UCVA and CDVA,corneal curvature and corneal higher-order aberrations which confers a long-term stability for progressive ectasia.Based on the results of the Siena Eye-Cross Study 2,the 9 mW/5.4 J/cm^(2) ACXL is a candidate to be the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia,and thus optimize clinic workflow.