| Purpose Keratoconus(KCN)is a degenerative ectatic condition of the cornea that is bilateral,asymmetric and progressive development.The corneal biomechanics of keratoconus is weakened,which causes the thinning of the corneal stroma and the increasing of the corneal curvature.UVA/Riboflavin corneal collagen cross-linking(CXL)is a new method to halt the progress of keratoconus by creating new chemical bond between protein molecules and collagen fibers,thus stabilizing the structure of corneal,improving patients uncorrected distant visual acuity(UDVA),the best distant visual acuity(BDVA),and maximum K values.Traditional corneal collagen crosslinking requires the removal of corneal epithelium because it is difficult for the hydrophilic riboflavin to penetrate through the corneal epithelium and reach the corneal stromal.The removal of the epithelium may lead to a series of postoperative complications,including haze,permanent scarring,sterile infiltration,and herpes recurrence.Transepithelial corneal collagen cross-linking(T-CXL)can avoid the removal of the corneal epithelium and effectively reduce crosslinking related complications.The riboflavin solution of T-CXL contains penetration enhancers such as benzalkonium chloride(BAC)、ethylene diamine tetraacetic acid(EDTA).The efficacy of the transepithelial corneal collagen cross-linking is still under controversial,different selection and application of riboflavin solution in a study results in the different conclusion.This study used two stage application of initial ParaCel containing BAC followed by BAC and dextran free ViberX Xtra combined with accelerated and pulsed UVA irradiance protocols(total energy dose of 5.4J/cm2),reduced riboflavin soak time and promoted epithelial integrity.As to different options of riboflavin solution acting time,it may reported conflicting outcomes after T-CXL.With the hypothesis,we design the study to compare the therapy of T-CXL for three options of Penetration Enhancers acting time,short-term treatment group:4 minutes ParaCel and subsequently 6 minutes ViberX Xtra;mid-term treatment group:6minutes ParaCel and subsequently 4 minutes ViberX Xtra;long-term treatment group:8 minutes ParaCel and subsequently 2 minutes ViberX Xtra.Methods:Twenty eight progressive keratoconus patients(48 eyes)underwent TCXL from January 2015 to march 2019 were included in the study.Patients were randomly divided into three different penetration enhancers action time groups:4minute ParaCel plus 6-minute ViberX Xtra(short-term treatment group);6-minute ParaCel plus 4-minute ViberX Xtra(mid-term treatment group);8-minute ParaCel plus 2-minute ViberX Xtra(long-term treatment group).Slit-lamp bioscopy,UDVA,BDVA,topography(mainly Kmax value,astigmatism,thickness of corneal thinnest point),anterior OCT(optical coherence tomography),corneal confocal microscope were observed before and 1 year after treatment.Statistical analysis was performed using SPSS 19.0.One-way ANOVA was used to compare the difference in the parameters among the three groups,and the differences of pre-and postoperative parameters are compared by paired samples T test.The test level of statistical analysis was 0.05,and P<0.05 was considered to be statistically significant.Results:1.The therapy of combined group:Preoperative UDVA and BDVA were 0.89±0.35 and 0.27±0.34(logMAR)respectively.One year after T-CXL,UDVA and BDVA improved to 0.86±0.35 and 0.24±0.38(logMAR),and the difference in BDVA was not statistically significant(P>0.05).Preoperative Kmax value and corneal astigmatism values was 58.78±11.52 and 3.99±2.64 D respectively,One year after T-CXL,Kmax value and corneal astigmatism values decreased to 58.46± 11.17 and 3.71±2.61 D,and the difference in Kmax value was not statistically significant(P>0.05).2.The comparison of short-term treatment group,mid-term treatment group and longterm treatment group:2.1 The changes of UDVA and BDVA:Short-term treatment group.Preoperative UDVA and BDVA were 0.97±0.36 and 0.50±0.48(logMAR)respectively.One year after T-CXL,UDVA and BDVA improved to 0.93±0.30 and 0.49±0.53(logMAR).The difference was not statistically significant(P>0.05).Mid-term treatment group.Preoperative UDVA and BDVA were 0.93±0.31and 0.19±0.18(logMAR)respectively.One year after T-CXL,UDVA and BDVA improved to 0.92±0.38 and 0.16±0.15(logMAR).(P>0.05).Long-term treatment group.Preoperative UDVA and BDVA were 0.77±0.37 and 0.23±0.33(logMAR)respectively.One year after T-CXL,UDVA and BDVA improved to 0.72±0.35 and 0.18±0.27(logMAR).(P>0.05).The changes of UDVA of short-term treatment group,mid-term treatment group and long-term treatment group were-0.04±0.11,-0.02±0.20,-0.03±0.15(logMAR),The changes of BDVA of the three groups were-0.01 ±0.23,-0.04±0.13,-0.05±0.16(logMAR),Again,the difference was not statistically significant(P>0.05).2.2 The changes of Kmax value and corneal astigmatism values:Short-term treatment group.Preoperative Kmax and astigmatism were 60.03±11.60 and 3.72±2.28D,respectively.One year after T-CXL,Kmax and astigmatism decreased to 59.78±11.42 and 2.96± 1.80D.(P>0.05).Short-term treatment group.Preoperative Kmax and astigmatism were 60.49±13.64 and 4.14±2.85 D,respectively.One year after T-CXL,Kmax and astigmatism decreased to 60.04±13.12 and 4.16±2.85D.(P>0.05).Mid-term treatment group.Preoperative Kmax and astigmatism were 55.58±8.43 and 4.58±2.98D,respectively.One year after T-CXL,Kmax and astigmatism decreased to 55.3 8±8.21D and 4.40±3.17D.(P>0.05).The changes of Kmax of short-term treatment group,mid-term treatment group and long-term treatment group were-0.25±3.26,-0.45±1.42,-0.21 ± 1.28 D,The changes of corneal astigmatism of the three group were-0.76±1.1D、-0.05±1.33D、0.18±0.49D.The difference was not statistically significant(P>0.05).2.3 The changes of the minimal corneal thickness:Short-term treatment group.The mean value of the minimal corneal thickness was 455.9±45.2μm before surgery and increased to 459.7±50.6μm one year after surgery,with a statistically significant difference(P>0.05).Mid-term treatment group.The mean value of the minimal corneal thickness was 477.8±47.9μm before surgery and 472.7±50.5μm one year after surgery,with no significant difference(P<0.05).Long-term treatment group.The mean value of the minimal corneal thickness was 491.4±58.4μm before surgery and decreased to 488.0±56.6μm one year after surgery.(P>0.05).The changes of the minimal corneal thickness of short-term treatment group,midterm treatment group and long-term treatment group were 3.8±13.9μm、-5.0±8.0μm-3.4±9.7μm.The difference between the short-term treatment group and the mid-term treatment group,long-term treatment group was statistically significant(P=0.00),while the difference between the mid-term treatment group and the long-term treatment group was not statistically significant(P=1.00).3、The recovery of corneal:At 1st day after operation,the initial slit-lamp examination showed diffuse punctate epithelial keratopathy among three groups,which healed on 2th day after operation.And the extent of punctate epithelial defects in mid-term treatment group and long-term treatment group were more extensive.No recurrence epithelia corneal defects were observed in 1 year follow-up.In AS-OCT,the corneal demarcation line is invisible one year after surgery.Confocal microscopy showed the transition zone from acellular(treated)to cellular(untreated)corneal stroma 1 year after operation,which can be seen as the depth of cross-linking reaction.The cross-linking depth of short-term treatment group were less than 100μm.The cross-linking depth of mid-term treatment group and long-term treatment group were exceed 100μm,about 100-130μm.Conclusion:The transepithelial accelerate corneal collagen cross-linking could not provide improvements in CDVA、BDVA、Kmax、astigmatism,but is safe and effective in halting the progressive keratoconus.Different action time of ParaCel and ViberX Xtra riboflavin solution shows no significance difference in vision and corneal topography parameters outcomes at one year postoperative.The group of mid-term treatment and long-term treatment have the same change trend in the corneal thickness,and the confocal microscopy are similar in these two groups,we speculated that application of 6 minutes ParaCel plus 4 minutes ViberX Xtra and and 8 minutes ParaCel plus 2 minutes ViberX Xtra may have the same and better effect in keratoconus. |
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