Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia

AIM:To observe the effects of femtosecond laserassisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking(FS-LASIK Xtra)on corneal densitometry after correcting for high myopia.METHODS:In this prospectively study,130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia.Their right eyes were selected for inclusion in the study,of which 65 cases of 65 eyes in the FS-LASIK group,65 patients with 65 eyes in the FS-LASIK Xtra group.Patients were evaluated for corneal densitometry at 1,3,and 6mo postoperatively using Pentacam Scheimpflug imaging.RESULTS:Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant(P>0.05).Layer-by-layer analysis revealed statistically significant differences in the anterior(120μm),central,and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively(all P<0.05),the FS-LASIK Xtra group is higher than that of the FS-LASIK group.Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0–2,2–6,and 6–10 mm(both P<0.05);At 3mo postoperatively,the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0–2 and 2–6 mm(P<0.05).At 6mo postoperatively,there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges(all P>0.05).CONCLUSION:There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia.However,the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery,with the most significant changes observed in the superficial central zone.

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

AIM:To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus.METHODS: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)keratoconus.Examinations comprised topography,corneal biomechanical analysis and specular microscopy at 6 mo postoperatively.RESULTS: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 P<0.05).Regarding corneal 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 can.However,the TE procedure with a lower ultraviolet-A irradiation intensity would be safer for corneal endothelial function.

Efficacy of iontophoresis-assisted epithelium-on corneal cross-linking for keratoconus

Corneal cross-linking（CXL） is a noninvasive therapeutic procedure for keratoconus that is aimed at improving corneal biomechanical properties by induction of covalent cross-links between stromal proteins. It is accomplished by ultraviolet A（UVA） radiation of the cornea, which is first saturated with photosensitizing riboflavin. It has been shown that standard epithelium-off CXL（S-CXL） is efficacious, and it has been recommended as the standard of care procedure for keratoconus. However, epithelial removal leads to pain, transient vision loss, and a higher risk of corneal infection. To avoid these disadvantages, transepithelial CXL was developed. Recently, iontophoresis has been adopted to increase riboflavin penetration through the epithelium. Several clinical observations have demonstrated the safety and efficacy of iontophoresisassisted epithelium-on CXL（I-CXL） for keratoconus. This review aimed to provide a comprehensive summary of the published studies regarding I-CXL and a comparison between I-CXL and S-CXL. All articles used in this review were mainly retrieved from the Pub Med database. Original articles and reviews were selected if they were related to the I-CXL technique or related to the comparison between I-CXL and S-CXL.

Analysis of the effective dose of ultraviolet light in corneal cross-linking

AIM: To analyze the efficacy of ultraviolet (UV) light initiating corneal cross-linking (CXL). METHODS: The time-dependent absorption of UV light due to the depletion of the initiator (riboflavin) was calculated. The effective dose of CXL with corneal surface covered by a thin layer of riboflavin was derived analytically. The cross linking time was calculated by the depletion level of the riboflavin concentration. A comprehensive method was used to derive analytic formulas. RESULTS: The effective dose of CXL was reduced by a factor (R) which was proportional to the thickness (d) and concentrations (C-0) of the riboflavin surface layer. Our calculations showed that the conventional dose of 5.4 J/cm(2) had a reduced effective dose of 4.3 and 3.45 J/cm(2), for d was 100 and 200 pm, respectively, and C-0=0.1%. The surface cross linking time was calculated to be T*=10.75s, for a depletion level of 0.135 and UV initial intensity of 30 mW/cm(2). The volume T* was exponentially increasing and proportional to exp (bdC(0)), with b being the steady state absorption coefficient. CONCLUSION: The effective dose of CXL is reduced by a factor proportional to the thickness and concentrations of the riboflavin surface layer. The wasted dose should be avoided by washing out the extra riboflavin surface layer prior to the UV light exposure.

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

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 keratoconus.Retrospective,case-series of 23 eyes of 14 children who underwent TE-ACXL.Evaluations were performed at baseline and 1,3,6,12 and 18 mo postoperatively.Mean 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.

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

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 CXL.METHODS:Forty-two rabbits(42 eyes)were randomly divided into seven groups.One group served as the control group,while the other six groups were treated with CXL.The concentrations of MMPs in corneal stroma were evaluated through parallel reaction monitoring at baseline and 3,7,15,30,90,and 180 d after treatment.RESULTS: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,respectively.The 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),respectively.The 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,respectively.After CXL,the expression of MMP-2 and TIMP-1 in the rabbit corneal stroma was initially increased and subsequently decreased.The levels of MMP-2 remained higher than those recorded at baseline 180 d after treatment,but it was not statistically significant.The levels of TIMP-1 returned to baseline levels at 90 d after treatment.The ratio of MMP-2/TIMP-1 started to rise from 7 d after CXL.It was significantly higher than that calculated at baseline 30-180 d after CXL.The results for MMP-1,-3,-7,-9,-13,and TIMP-2 were negative.CONCLUSION:CXL can lead to changes in the content of MMP-2 and TIMP-1 in the rabbit corneal stroma.The ratio of MMP-2/TIMP-1 remains higher versus baseline,indicating that MMP-2 is involved in the corneal pathophysiological process after CXL.

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

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 method.METHODS:A total of 40 eyes of 30 consecutive patients who underwent CXL for progressive keratoconus were retrospectively enrolled.The 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 postoperatively.Groups 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 level.RESULTS: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.

Clinical and microstructural changes with different iontophoresis-assisted corneal cross-linking methods for keratoconus

AIM: To compare the clinical and microstructural changes induced by different transepithelial iontophoresis-assisted corneal cross-linking(I-CXL) methods for keratoconus. METHODS: A total of 42 eyes of 42 patients with progressive keratoconus were divided into two groups. Group A received I-CXL for 5 min, while group B received I-CXL for 10 min. Visual acuity, optical coherence tomography(OCT), specular microscopy and confocal microscopy were evaluated preoperatively and at 1, 3, 6, and 12 mo postoperatively. RESULTS: Twelve months after the operation, uncorrected visual acuity(UCVA) and corrected distance visual acuity(CDVA) were improved in both groups, with a better outcome in the I-CXL 10 min group(P=0.025, 0.021, respectively). Kmax values decreased by 0.94±3.00 D in the I-CXL 10 min group(P=0.033) but increased by 1.87±3.29 D in the I-CXL 5 min group(P=0.012). OCT scans showed that the demarcation line was most visible and substantially deeper in the I-CXL 10 min group. Confocal microscopy showed greater anterior stromal keratocyte decreases in the I-CXL 10 min group than in the I-CXL 5 min group at 3 and 6 mo postoperatively(P<0.001); however, anterior stromal keratocytes and subbasal nerve density were not significantly different between the two groups at 12 mo postoperatively. CONCLUSION: I-CXL for 10 min more effectively halts the progression of keratoconus than I-CXL for 5 min after 12 mo of follow-up. However, long-term studies are needed to evaluate the efficacy and safety of I-CXL.

Clinical Evaluation of Pranoprofen Combined with Fluorometholone Eye Drops on Postoperative Reaction of Corneal Cross-linking

Purpose:To evaluate the efficacy and safety of pranoprofen eye drops for reducing postoperative ocular pain and inflammation after corneal cross-linking (CXL). Methods:Twenty-seven patients (38 eyes) with keratoconus undergoing CXL were examined and randomly divided into control (12 cases; 18 eyes) and experimental groups (15 cases;20 eyes).The patients in the control group were given fluorometholone eye drops,and those in the experimental group were administered with fluorometholone combined with pranoprofen eye drops.Corneal irritation and haze were compared between the two groups at 1 month postoperatively. Results:At 1 to 3 days after surgery,the corneal irritation in the experimental group was significantly reduced compared with that in the control group (P<0.05), but there was no significant difference on 5 to 7 days postoperatively (P>0.05). The average degree of haze in the experimental group was significantly lower than that in the control group 1 month after surgery (P<0.05), but there was no significant difference in the best-corrected vision acuity and intraocular pressure between the two groups. There were 2 cases with >20 mmHg intraocular pressure in the control group. Conclusion:The combined use of fluorometholone and pranoprofen can significantly reduce inflammatory response,alleviate corneal irritation at early stage after CXL,effectively prevent and control the average of haze,and reduce the incidence of steroid-induced ocular hypertension after surgery.

Topography versus non-topography-guided photorefractive keratectomy with corneal cross-linking variations in keratoconus

AIM:To compare the visual results of non-topographyguided and topography-guided photorefractive keratectomy(PRK)applying sequential and simultaneous corneal crosslinking(CXL)treatment for keratoconus.METHODS:Interventional and comparative prospective study.Sixty-nine eyes(36 patients)suffering from keratoconus(stages 1 Amsler-Krumeich classification)were divided into four groups:sequential topography-guided photorefractive keratectomy with CXL,simultaneous topography-guided photorefractive keratectomy with CXL,simultaneous nontopography guided photorefractive keratectomy with CXL,and sequential non-topography guided photorefractive keratectomy with CXL.The main outcome measures were pre-and postoperative uncorrected distance visual acuity(UDVA),best corrected distance visual acuity(CDVA),manifest refraction,contrast sensitivity,and keratometry.RESULTS:All analyzed visual,contrast sensitivity,and refractive parameters showed a significant improvement in the four groups(all P<0.05).A noticeable improvement was seen in keratometry in all the groups,and a remarkable difference was observed between topography-guided groups in comparison to non-topography-guided groups(P<0.05).Interestingly,the improvement in all parameters showed a degree of stability to the end of the follow-up.CONCLUSION:The treatment priorities in all four groups are safety,efficacy,and predictability in the correction of the sphero-cylindrical errors in mild and moderate keratoconus.No significant differences among groups in the recorded objective outcomes were found.

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions:theoretical basis

Keratoconus is an ectatic condition characterized by gradual corneal thinning,corneal protrusion,progressive irregular astigmatism,corneal fibrosis,and visual impairment.The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages,gas-permeable rigid contact lenses,scleral lenses,implantation of intrastromal corneal ring or corneal transplants for most advanced stages.In keratoconus cases showing disease progression corneal collagen crosslinking(CXL)has been proven to be an effective,minimally invasive and safe procedure.CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation,resulting in stromal crosslinks formation.The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models,from the original Dresden protocol to the most recent developments in the technique,reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols.Finally,the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

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

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.

A“T.E.S.T.”hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair

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.

PACK-CXL: Corneal cross-linking in infectious keratitis

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.

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

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.

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

Background:The optical quality in progressive keratoconus deteriorates due to ectasia and distortion of the corneal shape and optics.While corneal cross-linking(CXL)aims at stopping disease progression,"CXL-Plus"combines CXL with excimer laser ablation to improve visual function.Central 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 keratoconus.Methods: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 keratoconus.Main outcome parameters were HOA,visual function and tomographic results 12 and 24 months postoperatively.Results:After 12 months,the total HOA root mean square wavefront error was reduced from 0.79±0.30 to 0.40±0.19 pm(CXL-Plus;P<0.0001)and changed from 0.71±0.28 to 0.73±0.36 pm(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 patients.The steepest keratometry value(Kmax)regressed by 5.84 D(CXL-Plus;P<0.0001)and 0.66 D(CXL;P=0752).For none of the investigated parameters a statistically significant change could be shown between 12 and 24 months.Conclusions:CXL-Plus in the form of a CCR reduces HOA and Kmax more effectively than CXL as a sole procedure.

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

Background:The optical quality in progressive keratoconus deteriorates due to ectasia and distortion of the corneal shape and optics.While corneal cross-linking(CXL)aims at stopping disease progression,“CXL-Plus”combines CXL with excimer laser ablation to improve visual function.Central 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 keratoconus.Methods: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 keratoconus.Main outcome parameters were HOA,visual function and tomographic results 12 and 24 months postoperatively.Results: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 patients.The 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 months.Conclusions:CXL-Plus in the form of a CCR reduces HOA and Kmax more effectively than CXL as a sole procedure.

Construction of all-organic low dielectric polyimide hybrids via synergistic effect between covalent organic framework and cross-linking structure

Polyimide(PI)is a promising electronic packaging material,but it remains challenging to obtain an all-organic PI hybrid film with decreased dielectric constant and loss without modifying the monomer.Herein,a series of allorganic PI hybrid films were successfully prepared by introducing the covalent organic framework(COF),which could induce the formation of the cross-linking structure in the PI matrix.Due to the synergistic effects of the COF fillers and the cross-linking structure,the PI/COF hybrid film containing 2 wt%COF exhibited the lowest dielectric constant of 2.72 and the lowest dielectric loss(tanδ)of 0.0077 at 1 MHz.It is attributed to the intrinsic low dielectric constant of COF and a large number of mesopores within the PI.Besides,the cross-linking network of PI prevents the molecular chains from stacking and improves the fraction of free volume(FFV).The molecular dynamics simulation results are well consistent with the dielectric properties data.Furthermore,the PI/COF hybrid film with 5 wt%COF showed a significant enhancement in breakdown strength,which increased to 412.8 kV/mm as compared with pure PI.In addition,the PI/COF hybrid film achieve to reduce the dielectric constant and thermal expansion coefficient(CTE).It also exhibited excellent thermal,hydrophobicity,and mechanical performance.The all-organic PI/COF hybrid films have great commercial potential as next-generation electronic packaging materials.

A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas

AIM: To report the 3mo outcomes of collagen crosslinking(CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium.METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure.RESULTS: The mean thinnest thickness of the cornea was 408.5 ±29.0 μm before treatment and reduced to369.8 ±24.8 μm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0 ±26.5 μm before CXL and recover to 412.5 ±22.7 μm at 3mo after treatment, P =0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6 ±4.0 diopters, and slightly decreased(54.7±4.9 diopters) after surgery(P =0.085). Mean best-corrected visual acuity was 0.55 ±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery(P =0.879).The endothelial cell density was 2706.4 ±201.6 cells/mm2 before treatment, and slightly decreased( 2641. 2 ±218.2 cells/mm2) at last fellow up(P =0.002).CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.

Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

AIM： To observe the therapeutic effect of corneal collagen cross-linking（CXL） in combination with liposomal amphotericin B in fungal corneal ulcers.METHODS： New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B（n =5 each）. The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28 d after treatment. The corneas were examined with transmission electron microscopy（TEM） at 4wk.RESULTS： A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d（P 〈0.05）. The corneal epithelium defect areas of the combined group was smaller than that of the CXL group（P 〈0.05） on 7 and 14 d, but there were no statistical differences on 3, 21 and 28 d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28 d. The diameters of the corneal collagen fiber bundles（42.960 ±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group） were thicker than that of the control group（24.900±1.868 nm）,but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION： CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease.