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.

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.

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.

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.

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.

角膜基质透镜联合跨上皮快速角膜胶原交联术治疗重度圆锥角膜

目的:评估角膜基质透镜联合跨上皮快速角膜胶原交联术(SC-A-TE-CXL)治疗重度圆锥角膜的临床疗效。方法:前瞻性自身前后对照研究。收集2019-03/2022-07于南京医科大学附属眼科医院确诊为重度圆锥角膜且最薄点角膜厚度(含上皮)<400μm的患者10例14眼,其中男8例12眼,女2例2眼,予以SC-A-TE-CXL进行治疗。观察并记录术前和术后1、3、6、12 mo的角膜曲率、裸眼视力(UCVA)、最佳矫正视力(BCVA)、角膜最薄点厚度(TCT)、角膜中心厚度(CCT)、非接触式眼压、内皮细胞密度(ECD)和前后表面最薄点高度以及术后1 mo角膜交联深度。结果:患者行SC-A-TE-CXL术后1、3、6、12 mo UCVA和BCVA较术前提高,但总体无差异(F=0.793,P=0.535;F=0.783,P=0.542)。术后各时间点K1、K2、Km和Kmax较术前下降,但总体无差异(F=0.627,P=0.574;F=1.264,P=0.296;F=0.727,P=0.520;F=1.115,P=0.359)。术后各时间点前后表面最薄点高度较术前均下降,但总体无差异(F=1.046,P=0.359;F=1.164,P=0.337)。术后各时间点非接触式眼压较术前提高,但总体无差异(F=0.814,P=0.522)。术后各时间点CCT、TCT和术前相比总体无差异(F=0.931,P=0.453;F=0.782,P=0.542)。术后12 mo ECD与术前相比无差异(t=1.266,P=0.228)。术后1 mo,前节光学相干层析成像术(AS-OCT)显示角膜浅层基质密度增高,前后基质间存在“分界线”,平均深度为124.07±25.13μm。结论:SC-A-TE-CXL能延缓重度圆锥角膜患者的病情进展,安全性高,其远期疗效有待进一步观察,可以作为一种治疗重度圆锥角膜的手术方式。

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。

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.

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.

保留上皮角膜胶原交联术治疗青少年圆锥角膜的疗效分析

背景圆锥角膜是一种角膜进行性膨隆和变薄的疾病，常于青少年时期发病，伴随不同程度的视觉质量下降。角膜胶原交联术（CXL）是利用维生素B2和紫外线A（UVA）之间的光氧化反应来增加角膜硬度，延缓甚至阻止圆锥角膜膨隆的进展。 目的评估保留上皮CXL治疗青少年圆锥角膜的安全性和有效性。 方法纳入2010年2月至2013年3月于温州医科大学附属眼视光医院拟行保留上皮CXL的原发性圆锥角膜患者9例10眼，年龄13～17岁，平均（15±1）岁。术中使用质量分数0.1%丁卡因滴眼液作为促渗剂点眼，再使用质量分数0.5%核黄素液点眼至前房饱和状态，最后使用强度为3 mW/cm2的紫外线A照射30 min。术后7 d、1个月、3个月、6个月及12个月测量远距裸眼视力（UDVA）、远距矫正视力（CDVA）、球镜度、柱镜度、等效球镜度（SE）、角膜前表面最大角膜曲率值（Kmax）、角膜前后表面高度值、角膜最薄点厚度。术后7 d测量角膜内皮细胞密度（ECD）。记录术后角膜上皮愈合时间。 结果保留上皮CXL术后角膜上皮平均愈合时间为（1.4±0.8）d。术后12个月时，平均UDVA、CDVA分别从术前的1.02±0.16和0.34±0.20改善至0.77±0.18和0.25±0.15，平均球镜度和SE分别从（－7.15±3.00）D和（－9.26±3.23）D改善为（－5.28±2.05）D和（－7.05±2.08）D，平均Kmax从（64.1±11.9）D降低至（61.8±10.4）D，差异均有统计学意义（t＝4.251、3.750、－2.515、－2.597、2.304，均P〈0.05）。术前与术后12个月平均柱镜度、角膜最薄点厚度比较差异均无统计学意义（t＝－1.331、0.328，均P〉0.05）。术前与术后7 d ECD的比较差异无统计学意义（t＝1.205，P〉0.05）。有2眼分别在术后3个月和术后6个月开始出现持续的角膜基质混浊。 结论保留上皮CXL能够安全、有效地延缓或阻止青少年圆锥角膜的进展。

快速跨上皮核黄素-紫外光角膜胶原交联治疗圆锥角膜的临床疗效和安全性评价

背景研究证实经典角膜胶原交联法（CXL）可有效控制圆锥角膜的进展及角膜扩张，但由于其需要去上皮，因此引起较多不良反应和并发症。目前跨上皮核黄素-紫外线CXL已开始在临床上使用，但其有效性和安全性评价的研究较少。目的评价快速跨上皮核黄素-紫外线CXL治疗圆锥角膜的安全性及有效性。方法采用前瞻性自身对照系列病例观察研究设计，纳入2014年3—10月在北京同仁医院眼科就诊的圆锥角膜患者28例46眼，采用快速跨上皮核黄素-紫外线CXL治疗，术后随访1年。分别于术前、术后1周及术后1个月、3个月、6个月和12个月测定术眼的视力、屈光度、中央角膜厚度（CCT）、角膜内皮细胞计数、角膜地形图参数、眼前节光学相干断层扫描仪检查结果及角膜生物力学参数，对术眼手术前后的检查指标进行比较，评价快速跨上皮核黄素-紫外线CXL治疗的有效性。对随访期间术眼的刺激症状和不良反应进行观察，评价快速跨上皮核黄素-紫外线CXL治疗的安全性。结果所有手术顺利，未发现术中并发症及术后感染。术眼术后1d出现轻度刺激症状，均于术后3d缓解或消失。术眼术后1个月及以后等效球镜度（SE）较术前降低，但手术前后总体比较差异无统计学意义（F=0．722，P=0．614）；术眼术后12个月术眼柱镜度（CD）明显低于术前，差异有统计学意义（t=3．242，P=0．004）。术眼手术后不同时间点角膜内皮细胞密度、角膜内皮细胞面积的变异系数（CV）及六边形角膜内皮细胞比率值均接近于术前值，总体比较差异均无统计学意义（F=0．246、0．465、0．981，均P〉0．05）。术眼术后3个月和6个月的角膜厚度值分别为（467．86±52．92）和（468．51±52．96）μm，高于术前的（453．91±45．78）μm，但差异均无统计学意义（t=0．236、0．469，均P〉0．05），术眼术后12个月角膜厚度值为（488．67±51．44）μm，明显高于术前值，差异有统计学意义（t=3．681，P=0．002）。术眼术后3、6和12个月角膜曲率最大值（Ks）、角膜曲率最小值（Kf）及角膜平均曲率值（Avek）逐渐下降，但手术前后不同时间点间总体比较差异均无统计学意义（F=0．592、0．897、1．029，均P〉0．05）。术后1个月角膜基质层可见高密度光反射条带者39眼，占84．78％，深度平均为（214．38±31．92）μm。手术前后不同时间点角膜滞后量（CH）及角膜阻力因素（CRF）值的总体比较差异均无统计学意义（F=1．268、0．894，均P〉0．05）。结论快速跨上皮核黄素-紫外线CXL后圆锥角膜的角膜厚度增加，曲率逐渐扁平，角膜应力增强，因此可以有效地阻止圆锥角膜的进展，此外圆锥角膜患者用快速跨上皮核黄素-紫外线CXL治疗后不影响角膜上皮和内皮细胞的形态和功能，治疗后刺激症状轻，安全性较好。

不同经上皮角膜胶原交联方法治疗进展期圆锥角膜的早期疗效观察

目的:观察比较不同经上皮角膜胶原交联方法(transepithelial corneal collagen cross-linking,TE-CXL)治疗进展期圆锥角膜的早期疗效。方法:回顾性研究。将24例34眼进展期圆锥角膜分为三组,低渗CXL组10眼接受低渗胶原交联治疗,I-CXL5min组14眼接受离子导入5min胶原交联治疗,I-CXL10min组10眼接受离子导入10min胶原交联治疗。治疗前,治疗后1wk,1、3、6mo观察视力、Pentacam眼前节分析仪、角膜激光共焦显微镜、光学相关断层扫描结果变化。结果:术后6mo,I-CXL 10min组CDVA(矫正远视力,LogM AR)提高-0.21±0.23(t=2.735,P=0.026);最大角膜屈光力(Kmax)降低2.32±5.21D,但差异无统计学意义(t=1.40,P=0.193),低渗CXL组与I-CXL 5min组的UDVA、CDVA、Kmax稳定,差异均无统计学意义(P>0.05)。术后1wk时,分界线平均深度在各组分别为:低渗CXL组152.7±42.9μm,I-CXL 5min组213.6±42.3μm,I-CXL10min组237.0±46.4μm,组间比较,差异有统计学意义(F=7.111,P=0.006)。术后基质细胞的凋亡-活化-再生现象在I-CXL 10min组最明显。三组角膜最薄点厚度、角膜内皮细胞密度与术前比较,差异无统计学意义(P>0.05)。结论:三种经上皮CXL短期观察均能安全有效控制圆锥角膜病情的发展,其中离子导入10min胶原交联方法组织反应更显著。

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.

跨上皮快速角膜交联术治疗圆锥角膜的1年期疗效观察

目的评估跨上皮快速角膜胶原交联术(ATE-CXL)治疗圆锥角膜的1年期有效性和安全性。方法选取22例(29只眼)术前处于进展状态的圆锥角膜行跨上皮快速角膜胶原交联术,术后随访平均时长为13.2个月;对比分析术前、术后SimK1、SimK2、Kmax、角膜内皮细胞计数和形态、裸眼视力(UCVA)、最佳镜片矫正视力(BSCVA)、角膜及晶状体情况、主觉验光及角膜最薄处厚度等指标的变化。结果所有患者均顺利完成手术,未见术中并发症,术后1~2d术眼有刺激症状。术后1个月、3个月和6个月的散光较术前减少,所有随访节点的球镜度、等效球镜度以及术后1年的散光度数较术前的减少均无统计学意义。UCVA从术前的(1.07±0.43)LogMAR提高到术后6个月的(0.86±0.40)LogMAR,以及术后1年的(0.75±0.41)LogMAR,而BSCVA从术前的(0.38±0.43)LogMAR提高到术后1年的(0.22±0.17)LogMAR。SimK1、SimK2、Kmax、角膜散光、角膜内皮细胞计数和形态及角膜最薄处厚度是稳定的。结论跨上皮快速角膜胶原交联术治疗圆锥角膜是有效、安全的。