Experimental study on the treatment of rabbit corneal melting after alkali burn with Collagen cross-linking

AIM: To evaluate the effect of Collagen cross-linking on the prevention of melting in rabbit corneas after alkali burn. METHODS: Twenty New Zealand white rabbits were randomly divided into model control group and collagen cross-linking treatment group. The second group of rabbits received collagen cross linked treatment. Both groups were applied with antibiotic eye drops to prevent infection. The corneas were evaluated for melting, opacity, pathological and immunohistochemistry, record the changes when 28 days after the animals were killed. RESULTS: In the control group, 6 out of 8 rabbits showed corneal melting after injury (14 +/- 4) days, while two corneal perforated. In collagen cross-linking treatment group, one rabbit showed corneal melting after injury 23 days, without corneal perforation; corneal dissolution rate between the two groups was significantly different (P <0.05). Pathological examination suggested that in the treatment group, mild corneal edema, mild damage to collagen fibers, inflammatory cell infiltration was significantly less than the control group. Immunohistochemistry showed that corneal collagen fibers arranged in neat rows in the control group. CONCLUSION: Collagen cross-linking treatment not only can prevent and delay the corneal melting after alkali burn, but also can reduce the destruction of corneal collagen fibers and infiltration of inflammatory cells in the corneal tissue.

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.

Scheimpflug imaged corneal changes on anterior and posterior surfaces after collagen cross-linking

AIM:To compare the anterior and posterior corneal parameters before and after collagen cross-linking therapy for keratoconus.METHODS:Collagen cross-linking was performed in31 eyes of 31 keratoconus patients(mean age 30.6±8.9y).Prior to treatment and an average 7mo after therapy,Scheimpflug analysis was performed using Pentacam HR.In addition to corneal thickness assessments,corneal radius,elevation,and aberrometric measurements were performed both on anterior and posterior corneal surfaces.Data obtained before and after surgery were statistically analyzed.RESULTS:In terms of horizontal and vertical corneal radius,and central corneal thickness no deviations were observed an average 7mo after operation.Corneal higher order aberration showed no difference neither on anterior nor on posterior corneal surfaces.During follow-up period,no significant deviation was detected regarding elevation values obtained by measurement in mm units between the 3.0-8.0 mm-zones.CONCLUSION:Corneal stabilization could be observed in terms of anterior and posterior corneal surfaces,elevation and higher order aberration values 7mo after collagen cross-linking therapy for keratoconus.

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.

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 crosslinking in keratoconus and other eye disease

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.

5-year follow-up of combined non-topography guided photorefractive keratectomy and corneal collagen cross linking for keratoconus

AIM： To evaluate the visual outcomes of simultaneous non-topography guided photorefractive keratectomy（PRK） and corneal collagen cross-linking（CXL） in eyes with keratoconus 5 y after the procedure.METHODS： Prospective, interventional, non-randomized, and non-controlled case series design was used. Sixty eyes of 30 patients（16 males and 14 females; age： 21-41 y） with mild, non-progressive（stages 1-2） keratoconus were enrolled. Refraction, uncorrected distance visual acuity（UDVA） and corrected distance visual acuity（CDVA）, flat and steep keratometry readings, and adverse events were evaluated preoperatively and postoperatively. Data were collected preoperatively and postoperatively at 3 mo, 1, 2, 3, 4, and 5 y follow-up visits after combined non-topography-guided PRK with CXL was performed. All patients had at least 5 y of follow-up.RESULTS： All study parameters showed a statistically significant improvement at 5 y over baseline values. The mean follow-up time was 68.20±4.71 mo（range： 60-106 mo）. Patients showed a significant improvement in UDVA from 1.24±0.79 log MAR prior to combined non-TG-PRK＋CXL to 0.06±0.15 log MAR postoperatively at the time of their last follow-up visit. CDVA significantly increased from 0.06±0.19 log MAR preoperatively to 0.03±0.12 log MAR postoperatively. A significant decrease in the mean spherical equivalent（SE） refraction was observed from-2.28±1.8 to-0.79±0.93 diopters（D）（P〈0.05）, and the manifest sphere decreased from-1.62±1.23 to-0.27±0.21 D（P=0.001）. The manifest cylinder significantly decreased from-1.73±0.86 to-0.29±0.34 D postoperatively（P=0.001）. The mean steep keratometry was 45.13±1.32 vs 47.28±2.12 D preoperatively（P〈0.05）, and the preoperative mean steepest keratometry（Kmax） 48.6±3.1 was reduced significantly to 46.8±2.9 postoperatively（P〈0.05）. CONCLUSION： Combined non-TG-PRK with 15 min CXL is an effective and safe option for correcting mild refractive error and improving visual acuity in patients with mild stable keratoconus.

Clinical outcomes at one year following keratoconus treatment with accelerated transepithelial cross-linking

This study evaluated the clinical outcomes in keratoconus corneas following accelerated transepithelial corneal collagen cross-linking（CXL）（Avedro KXL system,Waltham,MA,USA） over one year of follow-up.The mean depth of the demarcation line measured by optical coherence tomography（OCT） was 205.19 μm.One month after surgery,a non-statistically significant change was noted in sphere（P= 0.18） and in spherical equivalent（P= 0.17）,whereas a significant improvement was observed in corrected distance visual acuity（P=0.04）.A significant change was observed in topographic astigmatism（P= 0.03） and posterior corneal a sphericity（P= 0.04）.Accelerated transepithelial CXL may be a useful technique for the management of progressive keratoconus.

Combined corneal CXL and photorefractive keratectomy for treatment of keratoconus: a review

Keratoconus and iatrogenic keratectasia are the corneal ectatic disorders occurring due to biomechanical weakening of the cornea resulting in distorted images,myopia, and irregular astigmatism. Corneal collagen cross-linking(CXL) is performed to arrest keratoconus successfully. The main aim of this review is to discuss the safety and efficacy of the adjuvant therapies, such as the combination of CXL and photorefractive keratectomy(PRK) for the treatment of corneal ectatic disorders. A comprehensive literature search was performed using PubM ed, MEDLINE, and Scopus using keywords ‘collagen’‘keratoconus’,‘keratectasia’,‘collagen cross-linking’,and ‘photorefractive keratectomy’. Search results were restricted to clinical studies published in English. Corneal CXL effectively arrests the progression of keratoconus by enhancing corneal rigidity. However, functional vision is not improved by cross-linking. Combining CXL to refractive surgeries such as topography-guided PRK or transepithelial PRK is found to be a safe and effective method in providing corneal stability as well as significantly improving functional visual acuity with few minor complications. This combined technique also prevents regression of keratoconus and reduce the risk of keratectasia. CXL combined with PRK is a promising therapeutic approach in ophthalmology that can be successfully used to treat progressive keratoconus and other corneal ectatic disorders and to enhance visual acuity.

Corneal collagen cross-linking epithelium-on vs. epithelium-off: a systematic review and meta-analysis

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.

FSLASIK联合快速角膜交联术后角膜透明度的临床观察

目的研究飞秒激光辅助准分子激光原位角膜磨镶术(FSLASIK)联合快速角膜交联手术(CXL)矫正近视手术术后患者早期的角膜光密度(CD)、视力、屈光度的变化特点。方法回顾性临床研究。本研究筛选了2019年至2021年在本院行FSLASIK联合快速角膜交联手术矫正近视和散光的30例(60只眼)患者,进行回顾性的分析,分别于术前、术后1个月、术后3个月进行常规检查,检查项目包括屈光度、裸眼视力(UCVA)、裂隙灯检查和Pentacam眼前节分析仪。观察记录手术前后角膜光密度的变化;观察记录等效球镜度数(SE)的变化,数据统计完成后,采用IBM SPSS 24.0统计软件进行分析,通过KolmogorovSmirnov测试对各组数据进行正态性检验。对符合正态分布的数据进行重复方差检验,进一步两两比较采用LSDt检验,对于不符合正态分布的采用Friedman检验分析。结果(1)术后1个月UCVA与术前最佳矫正视力(BCVA)相比,略微降低(P<0.05)。术后3个月UCVA与术后1个月UCVA相比差异无统计学意义(P>0.05)。术后3个月UCVA与术前BCVA相比,差异无统计学意义(P>0.05)。(2)术后等效球镜度明显降低,较术前差异有统计学意义(P<0.05),术后1个月与术后3个月的SE之间差异无统计学意义(P>0.05)。(3)从整体光密度上看,术后1个月的角膜光密度与术前相比差异无统计学意义。术后3个月的角膜光密度与术前相比略微降低(P<0.05),术后3个月与术后1月相比略微降低(P<0.05)。(4)从不同直径范围的角膜光密度上看,术后1个月,角膜直径0~2 mm、2~6 mm区域内的角膜光密度与术前相比略微提高(均P<0.05),角膜直径6~10 mm内的角膜光密度与术前相比略降低(P<0.05);术后3个月,在角膜直径0~2 mm、2~6 mm区域内的角膜光密度与术前比差异均无统计学意义;角膜直径6~10 mm区域内的角膜光密度与术前相比略微降低(P<0.05)。(5)从不同分层的角膜光密度上看,术后1个月,角膜前层(前120μm)和角膜后层(后60μm)的角膜光密度与术前相比差异无统计学意义(P>0.05);角膜中央层的角膜光密度与术前相比略微降低(P<0.05)。术后3个月,角膜前层、中央层、后层角膜光密度与术前相比均略微降低(均P<0.05)。结论FSLASIK Xtra术后早期可以维持较好的角膜透明度,具有较好的安全性、有效性与准确性。

Collagen cross-linking:when and how?A review of the state of the art of the technique and new perspectives

Since the late 1990s corneal crosslinking(CXL)has been proposed as a new possibility to stop progression of keratoconus or secondary corneal ectasia,with the promising aim to prevent progressive visual loss due to the evolution of the pathology and to delay or avoid invasive surgical procedures such as corneal transplantation.The possibility of strengthening corneal tissue by means of a photochemical reaction of corneal collagen by the combined action of Riboflavin and ultraviolet A irradiation(UVA),radically modified the conservative management of progressive corneal ectasia.This is a review of the state of the art of CXL,reporting basic and clinical evidence.The paper describes basic principles,advantages and limits of different CXL techniques and possible future evolution of the procedure.

跨上皮快速角膜胶原交联术治疗进展期圆锥角膜患者的效果

目的探讨跨上皮快速角膜胶原交联术(CXL)治疗进展期圆锥角膜患者的效果。方法选取2017年10月至2021年3月于哈尔滨爱尔眼科医院诊治的60例(65眼)进展期圆锥角膜患者,均行跨上皮快速CXL,比较患者治疗前后裸眼视力(UCVA)、最佳矫正视力(BCVA)、屈光状态、角膜透明及眼压。结果术后3、6个月,患者UCVA均高于术前及术后1、12个月,且术后12个月高于术后1个月,差异有统计学意义(P<0.05)。术后3、6个月,患者BCVA高于术前及术后1、12个月,且术后6个月高于术后3个月,术后12个月高于术后1个月,差异有统计学意义(P<0.05)。术前及术后不同时间点的球镜度比较差异无统计学意义;术后1个月柱镜度低于术前,术后12个月柱镜度高于术后1、3、6个月,差异有统计学意义(P<0.05)。术前及术后1、3、6、12个月,患者眼压比较差异无统计学意义。随访期间,所有患者未出现角膜感染,晶状体保持透明。结论跨上皮快速CXL治疗进展期圆锥角膜效果显著,可有效改善患者视力水平,具有较高应用价值。

角膜基质透镜移植联合角膜胶原交联术在治疗圆锥角膜中的研究进展

圆锥角膜是一种以角膜扩张为特征的进行性的角膜病变。目前cxl手术是常用的控制圆锥角膜发展的方法,但对角膜薄的患者有局限性。而随着smile的广泛开展,术中大量的角膜基质透镜被取出,角膜基质透镜移植联合cxl手术可使角膜加厚加固,控制圆锥角膜发展。本文主要是针对角膜基质微透镜移植联合cxl手术控制圆锥角膜的研究做一综述。

FS-LASIK联合胶原交联术后的早期临床观察

目的:探讨飞秒激光辅助准分子激光原位角膜磨镶术(femtosecond laser-assisted excimer laser in situ keratomileusis,FS-LASIK)联合胶原交联术后的早期安全性和有效性。方法:选取2016-07/2017-08我院接受飞秒辅助LASIK联合胶原交联术近视患者30例60眼,分别于术前、术后1、3mo检查裸眼视力。应用角膜地形图(TMS)测量陡峭K值(Ks)、平坦K值(Kf)、角膜规则指数(SRI)、角膜非对称指数(SAI)。眼反应分析仪(ocular response analyzer,ORA)检测角膜补偿眼压(corneal compensated intraocular pressure,IOPcc)、模拟Goldmann眼压(Goldmann correlated IOP value,IOPg)、角膜阻力因子(corneal resistance factor,CRF)、角膜滞后量(corneal hysteresis,CH)。伽利略眼前节分析值包括前后表面屈光度和角膜厚度分布。角膜内皮细胞计数仪器进行内皮计数检查,比较手术前后各指标的差异。结果:术后1d 26眼(43%)、1mo 55眼(92%)、3mo 50眼(83%)裸眼视力保持0.8以上。术后1mo与术前比较,IOPcc、IOPg、CRF、CH较术前显著降低,差异均有统计学意义(P<0.01)。术后3mo与1mo比较,IOPcc、IOPg、CRF、CH值无统计学差异(P>0.05)。角膜地形图参数:术后1mo与术前比较,Ks、Kf显著下降(P<0.01),SRI、SAI显著上升(P<0.01);术后3mo与1mo比较,Ks有显著升高(P<0.05),Kf变化无统计学差异(P>0.05),SRI、SAI有显著下降(P<0.05)。伽利略眼前节分析中:模拟角膜曲率计陡峭K值(Sim Ks)、模拟角膜曲率计平坦K值(Sim Kf)在3mo较1mo有0.94D和0.95D的增长。另外,前后表面Kf值3mo较1mo明显增加,差异有统计学意义(P<0.01);而Ks值差异无统计学意义(P>0.05)。同时,中心点、厚度最薄点,术后3mo与1mo角膜厚度差异无统计学意义(P>0.05)。角膜内皮计数检查:术前(3059.95±247.87/mm^2)与术后1mo(3052.87±267.71/mm^2)比较,差异无统计学意义(t=0.279,P>0.05)。结论:屈光角膜手术联合胶原交联术对于度数高和角膜薄、角膜厚度分布不均、地形图异常(除外圆锥角膜)的患者治疗安全有效。

Corneal collagen cross‑linking epithelium‑on vs.epithelium‑off:a systematic review and meta‑analysis

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.

FS-LASIK与FS-LASIK Xtra矫正近视术后角膜上皮重塑状态及角膜像差变化比较

目的探讨飞秒激光辅助准分子激光角膜原位磨镶术(FS-LASIK)与FS-LASIK联合角膜胶原交联(FS-LASIK Xtra)术后角膜上皮重塑状态和角膜像差,分析角膜上皮厚度(CET)与角膜像差的关系。方法采用队列研究方法,纳入2021年6月至2022年2月于成都中医大银海眼科医院接受FS-LASIK的近视患者172例172眼,按手术方式不同分为FS-LASIK组94眼和FS-LASIK Xtra组78眼,共随访6个月。以角膜中央为基点将角膜分为中央2 mm环区和2~5 mm环区,分别于术前及术后1、3和6个月采用眼前节光学相干断层扫描测量角膜中央0~5 mm范围内9个区域的CET,采用iTrace视觉功能分析系统测量角膜高阶像差(HOA),研究主要结局为术后6个月CET增加量(ΔCET)及角膜HOA,分析角膜中央ΔCET与角膜像差的关系。结果FS-LASIK Xtra组术眼术后1、3和6个月角膜中央、上方、鼻上、鼻侧、鼻下、下方、颞下、颞侧、颞上ΔCET均明显低于FS-LASIK组,差异均有统计学意义(均P<0.05)。FS-LASIK Xtra组术眼术后6个月角膜中央、上方、鼻上、下方、颞下ΔCET明显高于术后1个月,术后3个月和6个月颞侧ΔCET均明显高于术后1个月,术后6个月颞上ΔCET均明显高于术后1个月和3个月,差异均有统计学意义(均P<0.05)。FS-LASIK组术眼术后3个月和6个月角膜中央、上方、下方、颞下ΔCET均明显高于术后1个月,术后6个月鼻上ΔCET明显高于术后3个月,术后6个月鼻侧、鼻下、颞侧、颞上ΔCET均明显高于术后1个月和3个月,差异均有统计学意义(均P<0.05)。FS-LASIK Xtra组和FS-LASIK组术眼术后不同时间点垂直三叶草、垂直彗差、水平彗差变化量总体比较差异均无统计学意义(垂直三叶草:χ^(2)_(分组)=4.27,P=0.118;χ^(2)_(时间)=0.01,P>0.05.垂直彗差:χ^(2)_(分组)=5.74,P=0.057;χ^(2)_(时间)=0.08,P=0.957.水平彗差:χ^(2)_(分组)=3.97,P=0.137;χ^(2)_(时间)=0.51,P=0.773)。FS-LASIK Xtra组术眼术后1、3和6个月倾斜三叶草变化量均明显高于FS-LASIK组,差异均有统计学意义(均P<0.05)。FS-LASIK Xtra组术眼术后6个月球差变化量明显高于术后1个月,FS-LASIK组术眼术后6个月明显高于术后1个月和3个月,差异均有统计学意义(均P<0.05)。FS-LASIK组术眼术后6个月总HOA变化量明显低于术后1个月和3个月,差异均有统计学意义(均P<0.05)。FS-LASIK组术后1个月和6个月,角膜中央ΔCET与球差均呈弱正相关(r_(s)=0.257,P=0.008;r_(s)=0.244,P=0.012),与总HOA均呈弱正相关(r_(s)=0.253,P=0.009;r_(s)=0.279,P=0.004)。结论与FS-LASIK相比,FS-LASIK Xtra术后ΔCET明显较小,但2个组各区域CET增加的均一性相似。2种手术方法术后角膜HOA变化趋势接近,上皮整体分布与角膜像差有一定联系。

紫外光/核黄素-维生素E聚乙二醇琥珀酸酯交联方案对兔眼角膜基质超微结构和胶原纤维的影响

目的探讨紫外光/核黄素-维生素E聚乙二醇琥珀酸酯交联方案(也称个性化快速角膜胶原交联手术,CF-CXL)对兔眼角膜基质超微结构和胶原纤维的影响。方法选取15只10~15周龄SPF级新西兰大白兔进行实验,所有动物右眼作为实验眼,均行CF-CXL,左眼作为对照眼。术后1周、1个月和3个月,注射过量戊巴比妥钠处死实验动物,取中央区角膜进行透射电镜检查。采用裂隙灯显微镜和眼前节OCT观察兔眼角膜的透明度、角膜厚度以及角膜胶原交联反应发生的深度。采用透射电镜对中央区角膜基质胶原纤维进行评估,以角膜胶原纤维横截面面积来评估胶原纤维的变化,使用ImageJ图像处理软件测量胶原纤维横截面面积。结果裂隙灯显微镜下观察可见,实验眼术后1周组、1个月组和3个月组角膜均保持透明,无角膜上皮损伤、角膜上皮下雾状混浊以及角膜瘢痕发生。与术前相比,实验眼术后1周组兔眼中央角膜厚度变薄,术后1个月组和3个月组变化不大。透射电镜检查结果显示,实验眼术后不同时间组均可见角膜基质中横行、纵行、斜行的胶原纤维板层分布,胶原纤维板层之间角膜基质细胞填充;角膜基质细胞内可见到散在分布的胶原原纤维;在胶原纤维的纵切面中,纤维周边可见错综分布的蛋白多糖装饰;胶原纤维的横切面可用于计算纤维的横截面面积。与对照眼相比,实验眼术后1周组、1个月组和3个月组胶原纤维横截面面积均明显增大,差异均有统计学意义(均为P<0.001),并且术后1个月组兔眼角膜胶原纤维横截面面积大于术后1周组和3个月组,差异均有统计学意义(均为P<0.001)。与对照眼相比,实验眼1个月组胶原纤维横截面面积增加21.37%。结论CF-CXL可以有效增加兔眼角膜基质胶原纤维的直径,对较薄的圆锥角膜是一种安全、有效的交联方式。

Consideration of corneal biomechanics in the diagnosis and management of keratoconus: is it important?

Keratoconus is a bilateral,non-inflammatory,degenerative corneal disease.The occurrence and development of keratoconus is associated with corneal thinning and conical protrusion,which causes irregular astigmatism.With the disruption of the collagen organization,the cornea loses its shape and function resulting in progressive visual degradation.Currently,corneal topography is the most important tool for the diagnosis of keratoconus,which may lead to false negatives among the patient population in the subclinical phase.However,it is now hypothesised that biomechanical destabilisation of the cornea may take place ahead of the topographic evidence of keratoconus,hence possibly assisting with disease diagnosis and management.This article provides a review of the definition,diagnosis,and management strategies for keratoconus based on corneal biomechanics.