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.

Iontophoresis-assisted corneal crosslinking using 0.1% riboflavin for progressive keratoconus

AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity（BCVA）, Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24 mo after I-CXL.RESULTS：After 24 mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07（P=0.010）; mean keratometry signifi cantly decreased 0.72±1.97（P=0.021）; maximum keratometry significantly reduced 2.30±5.01（P=0.014）; central keratoconus index significantly reduced 0.04±0.08（P=0.007）. The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 μm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change significantly.CONCLUSION：I-CXL using 0.1% riboflavin halts keratoconus progression within 24 mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.

Iontophoresis-assisted versus standard corneal crosslinking for progressive keratoconus

Background:To compare the safety and efficacy of iontophoresis-assisted epithelial-on corneal crosslinking(I-CXL)using 0.1%riboflavin-distilled water solution with standard epithelium-off corneal crosslinking(S-CXL)for progressive keratoconus.Methods:In a retrospective analysis,progressive keratoconus patients treated with I-CXL(17 eyes of 17 patients)or S-CXL(13 eyes of 13 patients)were included.All patients were followed up at least 12 months.All patients underwent detailed ophthalmologic examinations involving pre-and postoperative visual acuity,topographic parameters and pachymetry.Intra-and postoperative complications were recorded.Results:No statistically significant differences were observed between the two groups at baseline with respect to visual acuity,age and thinnest corneal thickness(TCT).The postoperative decreases of K1 and Kmean in the S-CXL group represented statistically significantly better results than in the I-CXL group(t=2.093 and 2.123,P=0.046 and 0.043,respectively).Alterations of other parameters showed no significant differences between the two groups.There were no failure cases in the two groups.Conclusions:I-CXL using 0.1%riboflavin-distilled water solution provided effective treatment for progressive keratoconus at 12-month follow-up.However,the decreases of K1 and Kmean caused by I-CXL were less than those by S-CXL.Although treatment time,postoperative patient pain and risk of infection in I-CXL are all less than those in S-CXL,I-CXL is unable to completely replace S-CXL for progressive keratoconus temporarily.

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.

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.

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.

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.

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.

圆锥角膜不同交联方法术后基质分界线发生特点及其对交联效果的影响

目的比较早期圆锥角膜接受核黄素/紫外线A角膜胶原交联术(CXL)不同手术方式术后基质分界线的特点,并分析基质分界线对交联效果的影响。方法采用非随机对照临床研究方法,选取2019年5月至2021年2月于山东第一医科大学附属眼科医院就诊的圆锥角膜患者69例69眼,所有患者均行CXL治疗,其中经上皮交联组21眼,去上皮交联组48眼;5.4 J能量组25眼,7.2 J能量组44眼。分别于术后2周、1个月、3个月、4个月进行随访,观察角膜基质交联反应(基质分界线)的形态及变化特点;记录角膜最薄处厚度(TCT)、裸眼视力(UCVA,LogMAR)、最佳矫正视力(BCVA,LogMAR)和角膜最大曲率(Kmax)等的变化。结果术后出现基质分界线占63.77%(44/69),未出现基质分界线占36.23%(25/69)。去上皮交联组出现基质分界线占79.17%(38/48),明显高于经上皮交联组的28.57%(6/21),差异有统计学意义(χ^(2)=16.186,P<0.01);5.4 J能量组出现基质分界线占72.00%(18/25),7.2 J能量组占56.80%(25/44),差异无统计学意义(χ^(2)=1.565,P=0.302)。裂隙灯显微镜及眼前节光学相干断层扫描显示基质分界线于术后1~2周时出现,1个月时逐渐汇聚、增强;2~3个月后基质分界线开始变得弥散、边界模糊,并逐渐变淡;4个月时基质分界线基本消失。基质分界线深度可达141~423μm,平均(263.44±84.22)μm。激光扫描共聚焦显微镜观察结果显示,交联术后角膜基质细胞激活,反光增强,胶原纤维纵横伸展并相互交错,纤维排列呈网状。术后4个月,TCT由术前的(458.69±38.28)μm降至(443.86±36.54)μm,差异有统计学意义(t=6.705,P<0.001);有基质分界线组与无基质分界线组术后TCT下降幅度比较,差异无统计学意义(t=1.684,P=0.100)。术后4个月所有术眼UCVA由术前的0.74±0.37提高至0.69±0.38,差异有统计学意义(t=2.109,P=0.039);手术前后BCVA比较,差异无统计学意义(t=1.006,P=0.319)。有基质分界线组与无基质分界线组术后UCVA和BCVA变化量比较,差异均无统计学意义(t=0.065,P=0.949;t=0.346,P=0.730)。手术前后所有患者Kmax比较,差异无统计学意义(t=0.050,P=0.950);有基质分界线组和无基质分界线组术后Kmax变化量比较,差异无统计学意义(t=-0.739,P=0.464)。去上皮交联组术后TCT变化量明显大于经上皮交联组,差异有统计学意义(t=2.815,P=0.008),2个组间术眼术后UCVA、BCVA和Kmax变化量比较,差异均无统计学意义(均P>0.05)。所有患者术后无明显角膜瘢痕、感染性角膜炎、角膜内皮失代偿等并发症。结论圆锥角膜CXL术后出现基质分界线可能是交联反应深度的标志;去上皮手术方式术后更容易出现基质分界线;2种角膜胶原交联模式有相似的治疗效果;圆锥角膜不同交联方法术后基质分界线的发生与否对交联效果无明显影响。

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.

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。

应用两种不同核黄素溶液的离子导入交联治疗进展期圆锥角膜后基质分界线深度比较

目的比较应用0.1%核黄素蒸馏水溶液的离子导入交联与应用0.1%核黄素乳酸钠林格液的离子导入交联治疗进展期圆锥角膜后基质分界线的深度。方法选取2013年1月-2013年7月行0.1%核黄素乳酸钠林格液离子导入交联治疗进展期圆锥角膜11例患者16眼和2013年8月-2015年11月行0.1%核黄素蒸馏水溶液离子导入交联治疗进展期圆锥角膜62例患者78眼的眼科资料。比较治疗1个月后两组前节OCT检查的基质分界线深度。结果 0.1%核黄素乳酸钠林格液离子导入角膜交联组分界线深度为(268.25±18.06)μm,0.1%核黄素蒸馏水溶液离子导入角膜交联组分界线深度为(298.95±51.97)μm,差异有统计学意义(t=3.594,P=0.001)。两组分界线发生数量分别为9眼(9/16)和65眼(65/78),差异有统计学意义(χ~2=5.514,P=0.019)。结论 0.1%核黄素蒸馏水溶液离子导入角膜交联治疗进展期圆锥角膜效果可能优于0.1%核黄素乳酸钠林格液离子导入角膜交联。

离子导入辅助角膜交联治疗青少年圆锥角膜（英文）

目的:评估离子导入辅助的跨上皮角膜交联治疗青少年圆锥角膜的安全性和有效性。方法:搜集12例(年龄12!18岁,平均15.8±2.08岁)进展期圆锥角膜患者,共15眼,采用0.1%核黄素蒸馏水溶液,离子导入(1 m A电流)辅助跨上皮给药5min,紫外线A(370 nm,3 m W/cm^2)照射30min。记录术前、术后3mo和1a的裸眼视力、最佳矫正视力、K_1、K_2、最大K值、平均K值、角膜散光度数、角膜内皮细胞密度、眼内压、最薄角膜厚度、角膜顶点厚度。角膜参数应用角膜地形图评估,角膜内皮细胞密度应用非接触角膜内皮镜检查。结果:角膜交联1a后,裸眼视力、最佳矫正视力、K_1、K_2、最大K值、平均K值、角膜散光度数、角膜内皮细胞密度和眼内压均无显著变化。最薄角膜厚度从468.08±33.40μm下降到447.46±40.20μm(t=4.379,P=0.001),差异有统计学意义。角膜顶点厚度从476.07±35.96μm下降到454.60±49.32μm(t=4.270,P=0.001),差异有统计学意义。结论:采用0.1%核黄素蒸馏水溶液的离子导入辅助的角膜交联治疗青少年圆锥角膜是安全、有效的,1a内能够阻止病情恶化,但是长期效果有待于进一步观察。

快速角膜交联治疗进展性圆锥角膜临床疗效评价

目的评价去上皮快速角膜胶原交联术治疗进展性圆锥角膜的临床疗效。方法纳人2016年9月-2017年9月于解放军总医院第一医学中心接受手术治疗的进展性圆锥角膜患者35例(48只眼)。分别于术前、术后1周、1个月、3个月、6个月和12个月进行视力(LogMAR)、屈光状态(球镜和柱镜)、角膜内皮细胞计数、角膜地形图及角膜生物力学检查。术后1个月行眼前节光学相干断层扫描仪(AS-OCT)检查。比较治疗前后各指标变化。结果本研究统计完成全部时间点复查的患者35例(48只眼),其中男性24例,女性11例;年龄(22.83±3.87)岁。患者术前、术后1周、1个月、3个月、6个月和12个月裸眼视力分别为0.70±0.20、0.73±0.20、0.64±0.19、0.63 1±0.21、0.57±0.20和0.56±0.20(P<0.01),最佳矫正视力分别为0.38±0.23、0.34±0.20、0.31±0.18、0.23±0.14、0.21±0.14和0.16±0.09(P<0.01)。术前球镜度数中位数为-5.00 D,术后1周、1个月、3个月、6个月和12个月时,分别为-5.00 D、-5.00 D、-5.13 D、-5.00 D和-5.13 D,总体比较差异均有统计学意义(P<0.01)。术前柱镜度数中位数为-5.63 D。术后1周、1个月、3个月、6和12个月时,分别为-5.00 D、-4.75 D、-5.00 D、-4.87 D和-4.50 D,较术前均明显下降,差异有统计学意义(P<0.01)。治疗前后角膜内皮细胞相关指标未见明显变化,差异均无统计学意义(P>0.05)。术前最薄点角膜厚度(thinnest corneal thickness,TCT)中位数为450.50μm。术后1个月、3个月和6个月分别为444.50μm、445.50μm和447.00μm,均较术前降低,差异有统计学意义(P<0.01)。术前、术后1周、1个月、3个月、6个月和12个月的角膜曲率最大值(maximum keratometry,Kmax)中位数分别为56.70 D、55.70 D、54.95 D、54.70 D、54.65 D和54.75 D,差异均有统计学意义(P<0.01)。角膜生物力学相关的第一次压平期角膜硬度参数(stiffness parameter applanation 1,SP-A1)较术前明显升高(P<0.01),术后不同时间角膜变形幅度比率(deformation amplitude ratio,DA-ratio)及反向内凹半径(inverse concave radius,1/R)均较术前明显下降(P<0.05),其中术后1周的1/R与术前相比差异无统计学意义(P>0.05)。40眼(83.33%)术后第1天有明显刺激症状,5眼(10.42%)发生轻度角膜混浊(Haze),未出现其他术中及术后严重并发症。结论去上皮快速角膜交联术可以改善患者术后视力,增加角膜生物力学稳定性,对进展性圆锥角膜的治疗具有良好的安全性及有效性。远期疗效需要进一步观察。

跨上皮快速交联术联合术后配戴RGPCL治疗圆锥角膜的疗效

目的:探讨跨上皮快速交联术联合术后配戴硬性透气性角膜接触镜(RGPCL)治疗圆锥角膜患者的临床效果。方法:回顾性研究。选取2014-10/2015-10在福建中医药大学附属第二人民医院确诊为进展性圆锥角膜并进行跨上皮快速角膜交联术联合术后配戴RGPCL的患者16例25眼,平均年龄25.31±5.92岁,术前最大角膜曲率为58.96±6.76D,角膜最薄点厚度为439.52±53.24μm。使用核黄素及45mW/cm^(2)紫外光照射进行跨上皮快速交联,总能量7.2J/cm^(2),术后配戴RGPCL。术后随访3~6a,平均52.44±11.39mo,观察患者治疗前后BCVA(配戴RGPCL)、平坦子午线角膜曲率(K1)、陡峭子午线角膜曲率(K2)、最大角膜曲率(Kmax)、角膜屈光力(MPP)、角膜前后表面膨隆状态评价参数包括BCVf、BCVb、前表面曲率不对称指数(SIf)、后表面曲率不对称指数(SIb)、圆锥角膜前表面最高点(KVf)、圆锥角膜后表面最高点(KVb)、角膜最薄处厚度(ThkMin)、晶状体混浊、角膜内皮细胞计数。结果:所有患者手术过程顺利,无术中并发症,术后1d均有轻微刺痛伴异物感,轻微畏光流泪;2例2眼患者术后1d摘绷带镜后角膜上皮小片脱失,重新戴绷带镜3d后上皮愈合;随访期间所有患者均未出现晶状体混浊,角膜内皮细胞计数较术前无差异(P>0.05);术后BCVA(配戴RGPCL)较术前BCVA明显改善,术后Kmax、SIf、KVf、BCVf、BCVb均较术前降低(P<0.05)。结论:跨上皮快速角膜交联术联合RGPCL治疗圆锥角膜能有效且安全控制圆锥角膜进展,长期效果稳定。

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.

离子导入辅助跨上皮角膜胶原交联治疗进展期圆锥角膜2a随访分析

目的:报道离子导入辅助跨上皮角膜胶原交联(iontophoresis-assited transepithelial corneal collagen crosslinking,I-CXL)治疗进展期圆锥角膜的2a观察结果。方法:选取进展期圆锥角膜患者24例34眼,应用1g/L核黄素蒸馏水溶液,离子导入(1m A电流)辅助跨上皮给药5min后,紫外线A(370nm,3m W/cm^2)照射30min。观察术前和术后2a最佳矫正视力(best corrected distance visual acuity,BCVA)、角膜散光度数、K1、K2、Kmean、Kmax、眼压、角膜内皮细胞密度、角膜顶点厚度、角膜最薄厚度变化。结果:术后2a,BCVA(Log MAR)从0.32±0.25提高到0.25±0.19,差异具有统计学意义(t=2.849,P=0.015),K1从47.12±4.33下降到46.06±4.77,差异具有统计学意义(t=2.652,P=0.015),K2从51.36±5.59下降到50.40±6.16,差异具有统计学意义(t=2.121,P=0.047),Kmean从49.12±4.76下降到48.10±5.25,差异具有统计学意义(t=2.663,P=0.015),Kmax从57.57±8.30下降到55.91±8.14,差异具有统计学意义(t=2.398,P=0.026),角膜顶点厚度从476.90±38.71下降到454.43±40.86μm(t=2.853,P=0.010),角膜最薄厚度从464.38±39.92下降到433.86±50.78μm,差异具有统计学意义(t=3.485,P=0.002)。角膜散光度数、眼压和角膜内皮细胞密度无明显变化。结论:I-CXL治疗进展期圆锥角膜安全、有效,2a内能够阻止进展期圆锥角膜病情恶化,但长期效果仍需进一步观察。

去上皮和经上皮快速角膜交联术紫外光脉冲输出模式治疗进展期圆锥角膜患者的临床效果

目的探讨去上皮快速角膜交联术紫外光脉冲输出模式(pl-快速CXL)和经上皮pl-快速CXL治疗进展期圆锥角膜患者的临床效果。方法选取2018年1月至2019年6月在河北省眼科医院行pl-快速CXL治疗的进展期圆锥角膜患者16例31眼;根据术式将患眼分为两组,去上皮pl-快速CXL组7例13眼和经上皮pl-快速CXL组9例18眼。术前及术后3个月和6个月进行随访。记录患眼最佳矫正远视力、散光度、角膜前表面最大曲率、角膜前表面最小曲率、角膜最薄点厚度、角膜内皮细胞计数、交联线深度,对各指标进行统计学分析。结果去上皮pl-快速CXL组和经上皮pl-快速CXL组患者术后3个月和术后6个月最佳矫正远视力、散光度、角膜前表面最大曲率、角膜前表面最小曲率、角膜内皮细胞计数与术前相比,差异均无统计学意义(均为P>0.05);术后3个月和术后6个月时两组角膜最薄点厚度均较术前变薄,差异均有统计学意义(均为P<0.05)。两组患者交联线深度术后3个月与术后6个月相比,差异均无统计学意义(均为P>0.05)。术后3个月和术后6个月时,去上皮pl-快速CXL组患者角膜交联线深度均较经上皮pl-快速CXL组更深,差异均有统计学意义(均为P<0.05)。对于相同时间点的其他参数而言,两组间差异均无统计学意义(均为P>0.05)。结论无论是去上皮pl-快速CXL还是经上皮pl-快速CXL都安全可行,在术后6个月内均能够稳定圆锥角膜病情。

角膜胶原交联术的应用与研究进展

近年来,随着诊疗技术的应用及角膜屈光手术的开展,圆锥角膜、大泡性角膜病变及屈光手术导致的医源性角膜扩张、感染性角膜炎等患病率呈上升趋势,但传统的药物治疗疗效差,手术治疗供体紧张且操作难度高,不能满足临床工作需求。而角膜胶原交联作为交联技术在医学领域中新兴的应用手段,为解决这一临床难题带来了新的希望。现就目前角膜胶原交联术的研究现状展开综述。

角膜交联术的研究进展

角膜交联术是目前治疗圆锥角膜等角膜疾病的重要手术方法,其治疗效果受核黄素浓度、照射能量、照射时间等因素的影响。角膜交联术经历了20余年的发展,通过改变核黄素的导入方式、提高紫外线照射能量、改变光敏剂及照射源等,从经典的去上皮角膜交联术逐渐发展到经上皮角膜交联术、快速角膜交联术、脉冲式角膜交联术,其安全性、有效性不断提高,并逐渐被临床医师认可和应用。相信随着对角膜交联术认识的不断深入及医疗设备的不断发展,角膜交联术将得到进一步发展完善。