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Changes in higher order aberrations after central corneal regularization-a comparative two-year analysis of a semiautomated topography-guided photorefractive keratectomy combined with corneal cross-linking

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Eye and Vision 2020年第1期7卷 99-108页

作者： Katja C.Iselin Philipp B.Baenninger Lucas M.Bachmann Frank Bochmann Michael A.Thiel Claude Kaufmann Department of Ophthalmology Lucerne Cantonal HospitalLucerneSwitzerland Medignition Healthcare Innovations ZurichSwitzerland

Background:The optical quality in progressive keratoconus deteriorates due to ectasia and distortion of the corneal shape and *** corneal cross-linking(CXL)aims at stopping disease progression,“CXL-Plus”combines CXL with excimer laser ablation to improve visual *** corneal Regularization(CCR)represents a therapeutic excimer laser modality specifically designed to smoothen the ectatic corneal shape and to reduce higher order aberrations(HOA).We set out to compare CXL-Plus,consisting of CXL combined with CCR,with CXL by itself for patients with progressive ***:Retrospective 2-year matched group analysis of patients who either underwent CXL-Plus(n=28)or CXL as a sole procedure(n=28)for progressive *** outcome parameters were HOA,visual function and tomographic results 12 and 24 months ***:After 12 months,the total HOA root mean square wavefront error was reduced from 0.79±0.30 to 0.40±0.19μm(CXL-Plus;p<0.0001)and changed from 0.71±0.28 to 0.73±0.36μm(CXL;p=0.814).Uncorrected distance visual acuity improved from 0.70±0.35 to 0.36±0.29 logMAR(CXL-Plus;p=0.0002)and from 0.65±0.39 to 0.46±0.37 logMAR(CXL;p=0.067),translating to gains of three or more lines in 50%(CXL-Plus)and 36%(CXL)of *** steepest keratometry value(Kmax)regressed by 5.84 D(CXL-Plus;p<0.0001)and 0.66 D(CXL;p=0.752).For none of the investigated parameters a statistically significant change could be shown between 12 and 24 ***:CXL-Plus in the form of a CCR reduces HOA and Kmax more effectively than CXL as a sole procedure.

关键词： Keratoconus corneal cross-linking CXL-plus Photorefractive keratectomy Central corneal regularization Higher order aberrations Coma-like aberrations

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Impact of hypothermia on the biomechanical effect of epithelium-off corneal cross-linking

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Eye and Vision 2021年第3期8卷 31-35页

作者： Hormoz Abdshahzadeh Reyhaneh Abrishamchi Emilio A.Torres-Netto Sabine Kling Nikki L.Hafezi Mark Hillen Farhad Hafezi Ocular Cell Biology Group Center for Applied Biotechnology and Molecular MedicineUniversity of ZurichWinterthurerstrasse 1908057 ZurichSwitzerland ELZA Institute Dietikon/ZurichSwitzerland Department of Ophthalmology Paulista School of MedicineFederal University of Sao PauloSao PauloBrazil Faculty of Medicine University of GenevaGenevaSwitzerland OPTIC-team Computer Vision LaboratoryETH ZurichZurichSwitzerland Department of Ophthalmology University of WenzhouWenzhouChina USC Roski Eye Institute USC Los AngelesLos AngelesCAUSA

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 ***,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 ***:One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1%hypo-osmolaric *** corneas were equally assigned to one of four *** 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 *** a stress-strain extensometer,the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal ***: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.

关键词： corneal cross-linking CXL Keratoconus Temperature Oxygen diffusion Hypothermia

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A novel analysis of Scheimpflug total corneal refractive power following corneal cross-linking in mild to moderate keratoconus

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International Journal of Ophthalmology(English edition) 2022年第5期15卷 728-735页

作者： Chao Pan Wei-Na Tan Dan Chen Yu Liu Hao-Yu Wang Deng-Feng Liang Yan-Jun Hua Xiao-Hua Lei Qing-Yan Zeng Shao-Zhen Zhao Tianjin Key Laboratory of Retinal Functions and Diseases Tianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjinChina Hankou Aier Eye Hospital WuhanHubei ProvinceChina School of Ophthalmology Central South UniversityChangshaHunan ProvinceChina Department of Ophthalmology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

AIM:To detect an earlier improvement in mild to moderate keratoconus following corneal cross-linking(CXL)with total corneal refractive power(TCRP)using ray tracing ***:A total of 40 eyes of 30 consecutive patients who underwent CXL for progressive keratoconus were retrospectively *** following keratometric parameters provided by Pentacam HR,including maximum keratometry(Kmax),steepest keratometry(Ksteep),3 mm zonal TCRP centered over corneal apex(TCRPapex,zone 3 mm),zonal mean keratometry and TCRP centered over corneal cone(Kmcone,zone and TCRPcone,zone 1,2,3 mm)were evaluated preoperatively and 1,3,6,and 12 mo *** 1 and 2 were defined based on Kmax at postoperative 1 mo as improved(the initial improvement group)or worsen(the initial deterioration group)compared to the preoperative ***:In the overall group,only keratometric parameters based on ray tracing method displayed significant improvement early at 3 mo postoperatively,in which TCRPcone,zone 1 mm and 2 mm exhibited the largest flattening(0.57 D and 0.53 D,respectively).In Group 1,only Kmax,Kmcone,zone 2 mm and TCRPcone,zone 2 mm showed significant improvement initially at 1 mo postoperatively,in which Kmax exhibited the largest improvement(1.05 D),followed by TCRPcone,zone 2 mm(0.82 D).In Group 2,only keratometric parameters based on ray tracing method and Kmcone,zone 3 mm showed slight but not significant improvement early at 3 mo,in which TCRPcone,zone 3 mm displayed the most improvement(0.19 D),followed by TCRPcone,zone 2 mm(0.15 D).CONCLUSION:The findings indicate that a 2 mm zonal TCRP centered over Kmax could earlier detect keratometric improvement by CXL compared to other commonly used parameters in mild to moderate keratoconic eyes.

关键词： keratoconus corneal cross-linking keratometry total corneal refractive power ray tracing

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Comparison of corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus

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International Journal of Ophthalmology(English edition) 2021年第7期14卷 998-1005页

作者： Bo-Wen Ouyang Hui Ding Han Wang Zhen-Duo Yang Tan Zhong Hong-Ming Fan Xing-Wu Zhong Zhongshan Ophthalmic Center State Key Laboratory of OphthalmologySun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Hainan Eye Hospital Zhongshan Ophthalmic CenterSun Yat-sen UniversityHaikou 570311Hainan ProvinceChina

AIM:To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in ***:In our prospective clinical trial,40 patients(60 eyes)with progressive keratoconus were randomized to undergo corneal cross-linking with transepithelial(TE group,n=30)or epithelium-off(EO group,n=30)*** comprised topography,corneal biomechanical analysis and specular microscopy at 6 mo ***:The keratometer values were not significantly different between the TE and EO corneal cross-linked groups in different periods(each P>0.05).The corneal thickness of the EO group was greater than that of the TE group at 1 wk after the operation(each Pcorneal biomechanical responses,the EO group showed a longer second applanation length than TE group(P=0.003).Regarding the corneal endothelial function,standard deviation of the endothelial cell size,and coefficient of variation in the cell area,the values of EO group were larger than those of TE group at 1 wk(P=0.011,0.026),and the percentage of hexagonal cells in EO group was lower than that in TE group at 1 and 6 mo(P=0.018,0.019).CONCLUSION:Epithelium-off corneal cross-linking may strengthen corneal biomechanics better than TE procedure ***,the TE procedure with a lower ultraviolet-A irradiation intensity would be safer for corneal endothelial function.

关键词： keratoconus corneal cross-linking transepithelial epithelium-off corneal biomechanics corneal topography

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Trans-epithelial accelerated corneal cross-linking for keratoconus in children

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International Journal of Ophthalmology(English edition) 2017年第12期10卷 1919-1921页

作者： Andrew Olivo-Payne Juan Carlos Serna-Ojeda Erick Hernandez-Bogantes Alexandra Abdala-Figuerola Lucero Pedro-Aguilar Alejandro Lichtinger Arturo Ramirez-Miranda Alejandro Navas Enrique O.Graue-Hernandez Department of Cornea and Refractive Surgery Institute of Ophthalmology ＂Conde de Valenciana＂ department of cornea and refractive surgery institute of ophthalmology"conde de valenciana"Cuauhtemoc 06800Mexico CityMexico

The aim of the study is to evaluate the safety and effi cacy of trans-epithelial accelerated corneal cross-linking（TE-ACXL） in children with progressive ***,case-series of 23 eyes of 14 children who underwent *** were performed at baseline and 1,3,6,12 and 18 mo *** follow-up time of 23.82±3.15 mo and mean age was 13.7±1.4 y（range 11 to 16 y）.Mean preoperative uncorrected distance visual acuity changed from 0.92±0.45 log MAR（20/160） to 0.71±0.40 log MAR（20/100）（P=0.001）.Mean keratometry（Km） changed from 53.87± 6.03 to 53.00±5.81（P=0.001）.Pachymetry did not have significant changes at last follow-up（P=0.30）.The mean preoperative sphere was-5.58±2.48 and-4.89±4.66 D（P=0.11） at last follow-up;refractive cylinder from-5.58±2.48 to-5.02±2.23（P=0.046）.In conclusion,tomographic and refractive stability are shown in over 91% of eyes with pediatric progressive keratoconus who underwent TE-ACXL.

关键词： corneal cross-linking keratoconus acceleratedcross-linking pediatric keratoconus

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PACK-CXL: corneal cross-linking in infectious keratitis

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Eye and Vision 2016年第1期3卷 84-88页

作者： David Tabibian Cosimo Mazzotta Farhad Hafezi Laboratory for Ocular Cell Biology University of GenevaGenevaSwitzerland Siena crosslinking Center Siena University HospitalSienaItaly Department of Ophthalmology University of Southern CaliforniaLos AngelesCAUSA EyeCare Laboratory Research Zurich Associates(ELZA)Institute Webereistrasse 28953 DietikonSwitzerland Department of Ophthalmology Northampton General HospitalNorthamptonUnited Kingdom

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 *** 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 *** 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 ***:Ultraviolet-light has long been known for its microbicidal effect,and thus CXL postulated to be able to sterilize the cornea from infectious *** cytotoxic effect led to the first clinical trials using CXL to treat advanced infectious melting corneal *** treated with this technique showed,in the majority of cases,a stabilization of the melting process and were able to avoid emergentàchaud *** 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 *** 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 *** original Dresden protocol is still used for this *** modifications of this protocol could improve the efficiency of this technique in specific clinical situations regarding certain types of pathogens.

关键词： Infectious Keratitis corneal cross-linking Keratoconus CXL PACK-CXL corneal ulcer Ultraviolet light A Riboflavin

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Changes of matrix metalloproteinases in the stroma after corneal cross-linking in rabbits

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International Journal of Ophthalmology(English edition) 2021年第1期14卷 26-31页

作者： Hong-Zhen Jia Xu Pang Xiu-Jun Peng Department of Ophthalmology the Sixth Medical Center of Chinese PLA General HospitalBeijing 100048China

AIM:To observe changes in the content of matrix metalloproteinases(MMPs)in the corneal stroma after corneal cross-linking(CXL)in rabbits,and further explore the corneal pathophysiological process after ***:Forty-two rabbits(42 eyes)were randomly divided into seven *** group served as the control group,while the other six groups were treated with *** concentrations of MMPs in corneal stroma were evaluated through parallel reaction monitoring at baseline and 3,7,15,30,90,and 180 d after ***:The levels of MMP-2 in the corneal stroma of rabbits were 0.76±0.07,2.78±1.39,4.12±0.69,2.00±0.29,2.00±0.30,1.22±0.18,and 1.35±0.18(10^(-9)mol/g)at baseline and 3,7,15,30,90,and 180 d after treatment,*** contents of tissue inhibitor of metalloproteinase-1(TIMP-1)were 1.83±0.26,7.94±0.58,6.95±2.64,3.81±0.48,3.07±0.92,1.72±0.19,and 1.69±0.74(10^(-9)mol/g),*** ratios of MMP-2/TIMP-1 were 0.42±0.33,0.36±0.20,0.62±0.10,0.54±0.15,0.68±0.13,0.71±0.10,and 0.68±0.09,*** CXL,the expression of MMP-2 and TIMP-1 in the rabbit corneal stroma was initially increased and subsequently *** levels of MMP-2 remained higher than those recorded at baseline 180 d after treatment,but it was not statistically *** levels of TIMP-1 returned to baseline levels at 90 d after *** ratio of MMP-2/TIMP-1 started to rise from 7 d after *** was significantly higher than that calculated at baseline 30-180 d after *** results for MMP-1,-3,-7,-9,-13,and TIMP-2 were ***:CXL can lead to changes in the content of MMP-2 and TIMP-1 in the rabbit corneal *** ratio of MMP-2/TIMP-1 remains higher versus baseline,indicating that MMP-2 is involved in the corneal pathophysiological process after CXL.

关键词： corneal cross-linking keratoconus rabbit riboflavin matrix metalloproteinase

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The potential application of formulation with pimelic acid as eye drops for corneal collagen cross-linking

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Medicine in Novel Technology and Devices 2024年第2期22卷 29-37页

作者： Daishi Chen Di Jiang Zhaoyang Ke Shenzhen People's Hospital Southern University of Science and TechnologyShenzhen518020GuangdongPeople's Republic of China The Tenth Affiliated Hospital of Southern Medical University(Dongguan People's Hospital) DongguanPeople's Republic of China

Background and aim:Keratoconus is a slowly progressive and non-inflammatory disease of eye of unknown etiology characterized by significant structural degeneration,thinning and protrusion of *** cross linking using Riboflavin/ultraviolet A,paraformaldehyde and glutaraldehyde has been widely used to treat keratoconus,but these techniques have several clinical *** study aimed to develop a rapid,safer,less toxic and more effective method to increase the corneal stiffness hence treating keratoconus by using EDC/NHS coupling with pimelic acid(PA)as ***:The viability of corneal epithelial and endothelial cells was examined using Alamar *** corneal collagen and tissue integrity were evaluated with Masson and hematoxylin and eosin stains *** tensile testing was conducted to determine the tissue *** further assessed the effective penetration depth of cross-linking by fluorescence dye and confocal *** assay was performed to detect the damaged DNA fragments in the presence of ***:The effect of PA solution on corneal cross-linking showed a significant increase in corneal rigidity without affecting the epithelium integrity under neutralized pH condition,while DEC/NHS alone did not induce the mechanical *** penetration depth showed consistent results with increased stiffness,which could be affected by the parameters including pH condition,coupling with or without *** addition,PA significantly decreased the percentage of TUNEL-positive cells compared to that of EDC/NHS only *** cytotoxic effect to endothelium was considered minimal and protected in the presence of ***:We demonstrated PA as a potential alternative for cross-linking in the model of whole eye with intact epithelium and its protective role on *** administration of this chemical cross-linker stands as an extremely promising technique for the treatment of corneal keratoconus.

关键词： corneal cross-linking Keratoconus Pimelic acid NHS/EDCI

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corneal collagen crosslinking in keratoconus and other eye disease

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International Journal of Ophthalmology(English edition) 2015年第2期8卷 407-418页

作者： Adel Alhayek Pei-Rong Lu Department of Ophthalmology the First Affiliated Hospital of Soochow University

Keratoconus is a condition characterized by biomechanical instability of the cornea, presenting in a progressive, asymmetric and bilateral way. corneal collagen crosslinking(CXL) with riboflavin and Ultraviolet-A(UVA) is a new technique of corneal tissue strengthening that combines the use of riboflavin as a photo sensitizer and UVA irradiation. Studies showed that CXL was effective in halting the progression of keratoconus over a period of up to four years. The published studies also revealed a reduction of max K readings by more than 2 D, while the postoperative spherical equivalent(SEQ) was reduced by an average of more than 1 D and refractive cylinder decreased by about1 D. The major indication for the use of CXL is to inhibit the progression of corneal ecstasies, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photo ablation. This treatment has been used to treat infectious corneal ulcers with apparent favorable results. Most recent studies demonstrate the beneficial impact of CXL for iatrogenic ecstasies, pellucid marginal degeneration, infectious keratitis, bullous keratopathy and ulcerative keratitis. Several long-term and short-term complications of CXL have been studied and documented. The possibility of a secondary infection after the procedure exists because the patient is subject to epithelial debridement and the application of a soft contact lens. Formation of temporary corneal haze,permanent scars, endothelial damage, treatment failure,sterile infiltrates, bullous keratopathy and herpes reactivation are the other reported complications of this procedure.

关键词： keratoconus collagen corneal cross-linking ultraviolet radiation and riboflavin

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Iontophoresis-assisted corneal crosslinking using 0.1% riboflavin for progressive keratoconus

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International Journal of Ophthalmology(English edition) 2017年第5期10卷 717-722页

作者： Hong-Zhen Jia Xu Pang Zheng-Jun Fan Na Li Gang Li Xiu-Jun Peng Chinese PLA Medical School Beijing 100853 China Department of Ophthalmology Chinese PLA Navy General Hospital Beijing 100048 China

AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity（BCVA）, Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24 mo after ***：After 24 mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07（P=0.010）; mean keratometry signifi cantly decreased 0.72±1.97（P=0.021）; maximum keratometry significantly reduced 2.30±5.01（P=0.014）; central keratoconus index significantly reduced 0.04±0.08（P=0.007）. The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 μm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change ***：I-CXL using 0.1% riboflavin halts keratoconus progression within 24 mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.

关键词： corneal cross-linking iontophoresis keratoconus distilled water riboflavin

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