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PACK-CXL: Corneal cross-linking in infectious keratitis

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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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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Long term results of accelerated 9mW corneal crosslinking for early progressive keratoconus:the Siena Eye-Cross Study 2

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Eye and Vision 2021年第1期8卷 154-165页

作者： Cosimo Mazzotta Frederik Raiskup farhad hafezi Emilio A Torres-Netto Ashraf Armia Balamoun Giuseppe Giannaccare Simone Alex Bagaglia Departmental Ophthalmology Unit USL Toscana Sud-EstCampostaggiaSienaItaly Siena Crosslinking Center 53035MonteriggioniSienaItaly Department of Ophthalmology C.G.Carus University HospitalDresdenGermany ELZA Institute DietikonSwitzerland Medical Faculty University of GenevaGenevaSwitzerland Roski Eye Institute University of Southern CaliforniaLos AngelesCAUSA Department of Ophthalmology University of WenzhouWenzhouChina Department of Ophthalmology Federal University of Sao PauloSao PauloBrazil Ashraf Armia Eye Clinic and Al Watany Eye Hospital Watany Research and Development CentreCairoEgypt Department of Ophthalmology University Magna Graecia of CatanzaroCatanzaroItaly

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 ***: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,*** mean age was 18.05±5.6 *** 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 *** 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 ***: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 *** improved at the 6th postoperative month(P=0.03),Δ−1.49 diopters from the baseline ***,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 *** OCT revealed a mean demarcation line depth at 332.6±33.6μ***: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 *** 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.

关键词： Crosslinking Keratoconus Accelerated crosslinking Epi-off Dresden accelerated protocol 9mW crosslinking CXL ACXL

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PACK-CXL *** therapy for bacterial,fungal,and mixed infectious keratitis:a prospective randomized phase 3 trial

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Eye and Vision 2024年第1期10卷 10-20页

作者： farhad hafezi Mohammed Hosny Rohit Shetty Boris Knyazer Shihao Chen Qinmei Wang Hassan Hashemi Emilio A.Torres‑Netto 无 Center for Applied Biotechnology and Molecular Medicine(CABMM) University of ZurichZurichSwitzerland ELZA Institute DietikonSwitzerland. Faculty of Medicine University of GenevaGenevaSwitzerland Department of Ophthalmology Medical University of WenzhouWenzhouChina USC Roski Eye Institute University of Southern California Los AngelesLos AngelesUSA Department of Ophthalmology University of CairoCairoEgypt Narayana Nethralaya Eye Hospital and the Postgraduate Institute of Ophthal‑mology BangaloreIndia Department of Ophthalmology Soroka University Medical CenterBen-Gurion University of the NegevBeershebaIsrael Noor Ophthalmology Research Center Noor Eye HospitalTehranIran University Hospital Zurich ZurichSwitzerland. the PACK-CXL Working Group

Background:Infectious keratitis is a major cause of global *** tested whether standalone photoactivated chromophore corneal cross-linking(PACK-CXL)may be an efective frst-line treatment in early to moderate infectious keratitis,compared with standard antimicrobial ***:This is a randomized,controlled,multinational phase 3 clinical *** in fve centers in Egypt,India,Iran,Israel,and China,aged≥18 years,with infectious keratitis of presumed bacterial,fungal,or mixed origin,were randomly assigned(1:1)to PACK-CXL,or antimicrobial *** measures included healing,defned as time to re-epithelialization of the corneal epithelial defect in the absence of infammatory activity in the anterior chamber and clearance of stromal *** success was defned as the complete resolution of signs of ***:Between July 21,2016,and March 4,2020,participants were randomly assigned to receive PACK-CXL(n=18)or antimicrobial therapy per American Academy of Ophthalmology(AAO)guidelines(n=21).No participants were lost to *** eyes were excluded from the epithelialization time analysis due to treatment failure:two in the antimicrobial therapy group,and two in the PACK-CXL *** rates were 88.9%(16/18 patients)in the PACK-CXL group and 90.5%(19/21 patients)in the medication *** was no signifcant diference in time to complete corneal re-epithelialization(P=0.828)between both treatment ***:PACK-CXL may be an alternative to antimicrobial drugs for frst-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin.

关键词： Photoactivated chromophore Corneal cross-linking Infectious keratitis Corneal melting PACK-CXL

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5-year efficacy of all surface laser ablation with cross-linking(ASLA-XTRA)for the treatment of myopia

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Eye and Vision 2020年第1期7卷 294-299页

作者： Ioannis M.Aslanides farhad hafezi Shihao Chen Hatch Mukherjee Vasileios Selimis Ilias Maragkos Nanji Lu George Kymionis Emmetropia Mediterranean Eye Institute Plateia Eleftherias 44Heraklion71201 CreteGreece Eye Hospital Wenzhou Medical UniversityWenzhouChina Center for Applied Biotechnology and Molecular Medicine University of ZurichDietikon/ZurichSwitzerland ELZA Institute Dietikon/ZurichSwitzerland USC Roski Eye Institute University of Southern CaliforniaCaliforniaLos AngelesUSA Faculty of Medicine University of GenevaGenevaSwitzerland Essex County Hospital EssexUK Athens Medical School University of AthensAthensGreece Faculty of Biology and Medicine Jules Gonin Eye HospitalUniversity of LausanneLausanneSwitzerland

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 ***: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 *** mean spherical equivalent(SEq)refractive error changed from−6.41±2.41 D preoperatively to−0.02±0.53 D at 5 years *** haze score was 0.18,0.25 and 0.28 at 1,3 and 6 months *** 12 months after the treatment,no eyes had significant corneal haze and in all the following postoperative time intervals the haze traces were ***:ASLA combined with accelerated CXL(ASLA-XTRA)appears to be safe,efficacious and offering very good refractive *** 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.

关键词： Refractive surgery Transepithelial PRK ASLA Cross-linking CXL ASLA-XTRA

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