离子导入辅助角膜交联治疗青少年圆锥角膜

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 mA电流)辅助跨上皮给药5min,紫外线A(370 nm,3 mW/cm2)照射30min。记录术前、术后3mo和1a的裸眼视力、最佳矫正视力、K1、K2、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、K1、K2、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,1 a内能够阻止病情恶化,但是长期效果有待于进一步观察。     

跨上皮快速角膜胶原交联术治疗进展期圆锥角膜

目的:研究跨上皮快速角膜胶原交联术(CXL)治疗进展期圆锥角膜的临床效果和安全性。方法:前瞻性自身前后对照研究。收集自2016-08/2019-11在我院进行跨上皮快速CXL的进展期圆锥角膜患者37例47眼,分析患者术前,术后1、3、6、12mo的裸眼视力(UCVA)和最佳矫正视力(BCVA)、屈光状态、角膜透明度、角膜前表面最大K值(Kmax)、角膜最薄点厚度、角膜内皮细胞计数、眼压。结果:术后1、3、6、12mo患者UCVA较术前提高,但总体比较无差异(F=1.372,P=0.261)。患者术后1、3、6、12mo的BCVA均较术前提高,总体比较有差异(F=3.308,P=0.019),进一步比较发现术后3、6、12mo的BCVA与术前比较有差异(P=0.04、0.01、0.007)。患者术后1、3、6、12mo的球镜度数、柱镜度数、Kmax、角膜最薄点厚度与术前总体比较无差异(F=0.293、1.378、2.448、1.970,P=0.881、0.258、0.061、0.116)。术后1mo患者角膜内皮细胞计数与术前比较无差异(t=1.156,P=0.25)。患者术后各时间点眼压与术前比较无差异(F=1.221,P=0.321)。术后7眼出现角膜Haze(1级~2级),术后3~6mo有5眼Haze消退,角膜恢复透明,1眼遗留角膜云翳,1眼角膜中央基质线状混浊,但均未对视力造成影响。结论:跨上皮快速CXL可以显著提高圆锥角膜患者BCVA,稳定患者屈光状态、角膜形态和厚度,阻止或延缓圆锥角膜进展,使患者获得更好的视功能,同时手术时间短,术后并发症少,具有较好的安全性。     

跨上皮角膜胶原交联术治疗进展期圆锥角膜

目的 观察跨上皮紫外线核黄素角膜胶原交联治疗进展期圆锥角膜的临床效果。方法 前瞻性病例研究。对36例（54眼）的进展期圆锥角膜患者行跨上皮角膜胶原交联手术治疗。表面麻醉下采用意大利SOOFT跨上皮角膜胶原交联仪将0.25%的核黄素导入角膜10 min（电流1.0 mA）,370 nm的紫外线照射9 min（能量10 mW/cm2）。平均随诊（14.1±2.3）个月。术后1 d观察角膜上皮愈合情况,术后1、3、6、12个月复诊。检查指标包括UCVA、BCVA、眼压、角膜曲率、角膜厚度、角膜地形图、角膜内皮细胞计数、角膜生物力学、角膜活体激光共聚焦显微镜检查。对手术前后的各项指标行配对t检验。结果 术后1 d裂隙灯显微镜下发现角膜上皮点状混浊、水肿,次日好转。未出现角膜溃疡、角膜溶解、haze、剧烈眼痛等并发症。术后12个月,患者UCVA从4.27±0.23提高到4.41±0.20（t=3.962,P<0.01）,BCVA从4.69±0.23提高到4.82±0.14（t=3.507,P<0.01）;Kmax下降（1.25±0.68）D（t=9.351,P<0.01）;散光值下降（0.30±0.21）D（t=7.227,P<0.01）。角膜最大压陷深度从（1.21±0.11）mm下降为（1.16±0.12）mm（t=4.131,P<0.01）。眼压、角膜内皮细胞密度、角膜厚度治疗前后差异无统计学意义。结论 跨上皮角膜胶原交联法可以有效控制进展期圆锥角膜的发展且未出现类似传统去上皮法导致的多种并发症。跨上皮角膜胶原交联方法是安全、有效的,有望取代去上皮法成为进展期圆锥角膜首选的治疗方式     

角膜胶原交联治疗进展期圆锥角膜

圆锥角膜是一种以角膜扩张为特征,原因不明的双侧进行性角膜病变,可严重影响患者的视力.目前,使用角膜胶原交联治疗,已经成为可以有效阻止圆锥角膜进展的新方法,本文就角膜胶原交联治疗进展期圆锥角膜的原理、方法、并发症及展望进行综述.     

角膜胶原交联术治疗圆锥角膜的研究进展

角膜胶原交联术(corneal collagen cross-linking,CXL)是一种治疗原发或继发性圆锥角膜、感染性角膜炎及大泡性角膜病变等角膜疾病的新疗法。它利用光化学原理来增加角膜强度,阻止角膜病变进展,现已被广泛应用于临床。目前临床上普遍采用的方法多为经典去上皮角膜交联(dresden protocol),但经典方法耗时较长,可能存在角膜上皮愈合不良、感染等术后并发症。近年来多项研究对经典方式进行了改良,例如核黄素液浸入角膜的多种方式选择,增加紫外光照射能量以缩短照射时间的加速交联以及跨上皮角膜交联等。本文就非经典角膜胶原交联术在治疗圆锥角膜的研究作一综述。     

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)<400 μm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±25.13 μm。

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。     

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-CXL 5min组14眼接受离子导入5min胶原交联治疗,I-CXL 10min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,LogMAR)提高-0.21±0.23(t=2.735,P=0.026); 最大角膜屈光力(K_max)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-CXL 10min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。     

跨上皮角膜胶原交联手术治疗进展期圆锥角膜的疗效

目的:分析跨上皮角膜胶原交联手术治疗进展期圆锥角膜后1a的疗效并讨论其临床意义。方法:收集2017-01/2018-12于我院进行快速跨上皮角膜胶原交联手术的进展期圆锥角膜患者45例48眼,术后随访1a,分析手术前后视力、角膜最薄点厚度、角膜内皮细胞计数、角膜交联线深度、角膜前表面曲率Km值及角膜生物力学参数等变化情况。结果:与术前比较,本组患者术后裸眼视力明显改善(P<0.05),但最佳矫正视力、角膜最薄点厚度和角膜内皮细胞计数均无明显变化(P>0.05),术后6mo,1a角膜前表面曲率Km值(48.54±2.57、48.77±2.29D)均显著下降,角膜生物力学参数第1次压平宽度(1.52±0.21、1.57±0.22mm)均显著降低(P<0.05),第2次压平速度绝对值(0.82±0.09、0.82±0.18m/s)均显著增加(P<0.05)。结论:快速跨上皮角膜胶原交联手术治疗进展期圆锥角膜对裸眼视力有明显改善,术后角膜生物力学也有改善,但最佳矫正视力改善不明显。     

【In Press】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) irradiation 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 iontophoresis-assisted 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 PubMed 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. Letters and case reports were excluded.     

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 iontophoresis-assisted 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 PubMed 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 24mo after I-CXL. RESULTS: After 24mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07 (P=0.010); mean keratometry signifi­cantly 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 24mo, 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.     

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 cross-linking (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 to 369.8±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 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 about 1 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.     

角膜胶原交联术及不同交联剂的研究进展

角膜胶原交联术是治疗圆锥角膜的有效手段之一,通过角膜交联剂与光照射提高角膜强度,遏制或延缓圆锥角膜进行性发展。基于传统核黄素紫外光交联的创新术式和基于不同交联剂的交联方式不断涌现,包括跨上皮、快速核黄素紫外光交联,玫瑰红绿光交联、京尼平交联和甘油醛交联等。对于以上交联术式和不同交联剂的研究均致力于增加治疗效果和减少患者不适,研究结果将为临床上选择合适的角膜胶原交联术式治疗圆锥角膜提供理论基础和临床依据。