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

Therapeutic effect and safety of accelarated transepithelial riboflavin-ultraviolet corneal collagen crosslinking for keratoconus

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。

Background Researches showed that classic corneal collagen crosslinking （CXL） can effectively control the progression of keratoconus and corneal eetasia,but its adverse responses and complications arc common due to the de-epithelial procedure. A transepithelial riboflavin-ultraviolet CXL surgery has applied in ophthalmology,but its effectiveness and safety evaluation is less. Objective This study was to evaluate the effectiveness and safety of rapid transepithelial riboflavin-ultraviolet CXL for keratoconus. Methods A prospective self-controlled study was designed. Forty-six eyes of 28 keratoconus patients scheduled to receive the rapid transepithelial riboflavin-ultraviolet CXL in Beijing Tongren Hospital from March to October in 2014 under the approval of this hospital and informed consent with a follow-up duration for one year. The spherical equivalent （SE） , astigmatic power, central corneal thickness （CCT）, endothelial cell count, corneal topography parameters, the parameters from the anterior segment optical coherence tomography （AS-OCT） and corneal biomechanical parameters were examined before surgery and 1 week,1 month,3 months,6 months and 12 months after surgery, and the results were compared among different time points to assess the effectiveness of transepithelial riboflavin-ultraviolet CXL for keratoconus. The postoperative irritation symptoms and adverse response were observed to evaluate the safety of surgery. Results No intraoperative complication and serious adverse postoperative infection were found in all the operated eyes. Slight irritation symptoms occurred in operated eyes 1 day after surgery and disappeared 3 days after surgery. A little reducing was seen in the spherical equivalent 1 month later, without significant difference among various time points （F = 0. 722, P = 0. 614 ）. However, a significant reducing was found in astigmatic power in 12 months after surgery compared with before surgery （t = 3. 242 ,P= 0. 004）. No considerably differences were seen in corneal endothelial cell （CEC） density, variation coefficient of CEC area and hexagonal CEC ratio among different time points （F= 0. 246,0. 465,0. 981 ;all at P〉0. 05 ）. The corneal thickness values in postoperative 3 and 6 months were （467.86±52.92）μm and （468.51±52.96） μm,which were insignificantly higher than （453.91±45.78）μm in preoperation （ t = 0. 236,0. 469 ; both at P〉 0.05 ） , however, the corneal thickness value in postoperative 12 months （ [488.67±51.44] μm） was significantly increased in comparison with preoperation （ t = 3. 681, P = 0. 002）. The maximal corneal curvature value （Ks）, minimal corneal curvature value （Kf） and average corneal curvature value （Avek） were not significantly lower 3,6 and 12 months after surgery than those before surgery （ F= 0. 592,0. 897, 1. 029 ,all at P〉0. 05）. High reflective light band of corneal stroma was found in OCT images in 39 eyes （84.78%） with the mean depth of （214.38±31.92）μm. No significant differences were found in corneal hysteresis （CH） and corneal resistance factor （CRF） before and after surgery （ F = 1. 268,0. 894, both at P 〉 0. 05 ）. Conclusions Rapid transepithelial riboflavin-ultraviolet CXL for keratoconus can increase corneal thickness, flatten corneal curvature and therefore arrest the development of keratoconus corneas. In addition, this therapy does not alter the shape and function of corneal epithelial and endothelial cells with mild irritation to eyes.