Epi-LASIK术的研究进展

角膜屈光手术种类繁多,而机械法-准分子激光角膜上皮瓣下磨镶术(epipolis laser in situ keratomileusis,Epi-LASIK)作为新进发展的一种表面角膜屈光手术已引起愈来愈多的角膜屈光手术医师的关注。本文就Epi-LASIK术的基本原理、操作过程、有效性、并发症等方面的进展进行综述。     

去除上皮瓣的微型角膜刀法准分子激光角膜上皮瓣下磨镶术后早期兔角膜的修复方式研究

目的 通过对兔微型角膜刀法准分子激光角膜上皮瓣下磨镶术(Epi-LASIK)和去除上皮瓣的(Flap-free)Epi-LASIK术后早期角膜组织的研究,探讨两种手术方式各自在角膜愈合方式方面的特点.方法 实验研究.27只实验兔,24只按不同取材时间1、2、4、7 d采用随机数字表法分为4组,每组6只兔,一只眼行Epi-LASIK,另一只眼行Flap-free Epi-LASIK手术.另3只兔作为空白对照组.用VISX20/20准分子激光仪作-10.00 D切削,另3只兔作为空白对照,通过观察术后1、2、47 d角膜上皮愈合方式、检测角膜基质细胞数量、碱性成纤维细胞生长因子(bFGF)、角膜基质细胞凋亡的表达来探讨Flap-free Epi-LASIK、Epi-LASIK两种术式术后早期角膜创伤愈合方式的差别.对Epi-LASIK和Flap-free Epi-LASIK术后角膜基质bFGF表达、细胞数量变化和细胞凋亡情况的数据采用t检验进行统计学处理.结果 通过光镜和透射电镜观察发现,Flap-free Epi-LASIK术后第1天有1层新生角膜上皮覆盖切削区域,以后逐层愈合.Epi-LASIK术后第1天角膜上皮基底膜与基质贴附较为紧密,但是在第2天可以看到有角膜上皮瓣水肿发生.术后4 d Flap-free Epi-LASIK角膜基质细胞数量分别为(33.85±3.39)个,多于Epi-LASIK组(t=-2.315,P<0.05).术后2 d、4 d组Flap-free Epi-LASIK角膜基质bFGF表达量分别为101.75±8.07和110.56±9.00,高于Epi-LASIK(t=-2.339,-2.396;P<0.05).术后2 d、4 d组Flap-free Epi-LASIK基质细胞凋亡数量也少于Epi-LASIK(t=3.332,2.989;P<0.05).结论 由于Flap-free Epi-LASIK特定的上皮去除方式导致了特定的上皮愈合方式,有利于减少术后刺激症状及角膜组织的正常修复.     

LASEK与Epi-LASIK角膜上皮瓣细胞培养及增生能力检测

目的 探讨准分子激光上皮下角膜磨镶术(LASEK)与上皮角膜切割激光矫视术(Epi-LASIK)后角膜上皮的愈合方式.方法 取行LASEK及Epi-LASIK的人角膜上皮瓣各20例,兔角膜上皮瓣12例,兔角膜缘组织12例,采用细胞法和组织块法进行上皮瓣细胞及角膜缘细胞培养,并采用WST-8(可溶性噻唑盐)法检测和比较细胞增生能力.结果 人和兔上皮瓣细胞连续观察2周仅见少量细胞生长或未见细胞生长,人LASEK组细胞增生能力较Epi-LASIK组低,差异有统计学意义(P<0.05).兔LASEK组细胞增生能力较Epi-LASIK组低,但差异无统计学意义(P=0.06),兔LASEK、Epi-LASIK组细胞增生能力均低于角膜缘组,差异均有统计学意义(P<0.05).结论 离体角膜上皮瓣细胞增生能力低下,且LASEK术后上皮瓣细胞增生能力低于Epi-LASIK,分析显示LASEK和Epi-LASIK术后角膜创伤愈合过程并非依靠角膜上皮瓣的原位生长,而是以角膜缘干细胞的分裂增生为主导.     

兔Epi-LASIK术后早期角膜创伤愈合反应的研究

目的 通过比较Epi-LASlK、PRK两种术式,探讨上皮瓣保留对早期角膜创伤愈合反应的影响.方法建立兔上皮瓣下角膜磨镶术(Epi-LASIK)、PRK模型,检测术后角膜基质炎性细胞数量、角膜基质细胞数量、白细胞介素1(IL-1β)、转化生长因子(TGF-β2)的表达来探讨角膜创伤愈合反应.结果 Epi-LASIK术后1 d、3 d角膜基质炎性细胞数量明显比PRK少,差异有统计学意义(P<0.05);Epi-LASIK术后1 d、3 d角膜基质细胞数量与正常对照比较差异无统计学意义(P>0.05);Epi-LASIK、PRK角膜上皮层TGF-β2、IL-1β表达差异均无统计学意义(P>0.05);Epi-LASIK术后1d、3 d角膜基质TGF-β2、IL-1β表达明显比PRK弱,差异有统计学意义(P<0.05).结论 Epi-LASIK由于上皮瓣的物理屏障作用,减轻了Epi-LASIK术后早期角膜创伤的过度反应,有利于其正常修复.     

机械法准分子激光上皮瓣下角膜磨镶术与去瓣Epi-LASIK术后兔角膜基质细胞凋亡的研究

目的观察机械法准分子激光上皮瓣下角膜磨镶术（Epi-LASIK）与去瓣Epi-LASIK术后不同时间点角膜基质细胞的凋亡,探讨2种手术方式对角膜创伤修复过程的影响。方法 42只新西兰大白兔随机编号,其中40只兔各取一侧眼行Epi-LASIK,对侧眼行去瓣Epi-LASIK,剩余2只兔4只眼作为正常对照组。分别于术后4h,1、3、7d共4个时间点取出角膜组织,透射电镜下观察各组兔角膜组织的超微结构改变,采用TUNEL法检测2组兔手术后不同时间点角膜基质细胞的凋亡情况,应用免疫组织化学法检测2组兔手术后不同时间点白细胞介素-1β（IL-1β）在角膜基质细胞中的表达。结果 Epi-LASIK组术后1d及3d角膜基质细胞凋亡细胞数明显高于去瓣Epi-LASIK组,差异均有统计学意义（t=2.42,P〈0.05;t=4.04,P〈0.05）;Epi-LASI组术后1、3、7d角膜基质中IL-1β表达的阳性细胞数明显高于去瓣Epi-LASIK组,差异均有统计学意义（t=2.13,P〈0.05;t=3.71,P〈0.05;t=3.06,P〈0.05）。Epi-LASIK组术后透射电镜下可见兔角膜基质细胞核固缩,染色质边集并可见凋亡小体。免疫组织化学染色显示Epi-LASIK组术后角膜基质中IL-1β的表达强于去瓣Epi-LASIK组。结论去瓣Epi-LASIK对角膜基质细胞的损害较Epi-LASIK轻,提示去瓣Epi-LASIK术后早期角膜创伤愈合反应的程度较轻,有利于角膜组织的快速修复。     

丝裂霉素C在Epi—LASIK治疗高度近视术中的应用

微型角膜刀准分子激光上皮瓣下原位角膜磨镶术（epipolis laser in situ keratomoleusis,Epi-LASIK）是近几年开展的一种新的屈光手术,术中保留了尚存活性的角膜上皮层,使术后haze得到了部分抑制,但对于高度近视患者,术后haze仍是主要并发症,是导致屈光回退的主要原因。我院从2007年以来在高度近视患者Epi-LASIK术中应用丝裂霉素C（mitomyein C,MMC）预防术后haze形成,取得满意效果,现报告如下。     

微型角膜刀法准分子激光上皮下角膜磨镶术后兔角膜愈合的实验研究

目的探讨微型角膜刀法准分子激光上皮下角膜磨镶术（Epi-LASIK）术后角膜的愈合规律,并与准分子激光屈光性角膜切削术（PRK）比较。方法建立兔近视性Epi-LASIK及近视性改良PRK动物模型,用锥虫蓝-茜素红活性染色法观察Epi-LASIK术后角膜上皮细胞活性,裂隙灯显微镜下观察角膜瓣变化、上皮修复过程和上皮下雾状混浊（haze）形成情况,通过角膜组织病理学观察角膜上皮及基质的愈合反应。结果 Epi-LASIK术后角膜上皮愈合时间为（4.67±0.41）d,而PRK术后为（2.75±0.27）d,差异有统计学意义（t=9.550,P=0.000）。PRK术后即刻和3d、5d角膜上皮瓣细胞活性率分别为（85.83±2.07）%、（48.67±3.41）%、（91.33±3.10）%,差异有统计学意义（F=215.060,P=0.000）。Epi-LASIK术后角膜瓣逐渐融解并被新生上皮取代,上皮愈合过程较改良PRK缓慢。PRK术后haze分级高于Epi-LASIK,差异有统计学意义（Z=2.27,P=0.02）。角膜组织病理学检查显示,术后1个月时2组上皮均明显增厚,3个月时上皮细胞排列仍不规则,6个月时上皮细胞形态基本恢复正常,术后3～6个月时Epi-LASIK组角膜上皮厚度已基本接近正常,与PRK组比较差异有统计学意义（P〈0.05）。术后3～6个月时Epi-LASIK组角膜前基质细胞数明显低于PRK组（P〈0.05）。结论 Epi-LASIK术后上皮瓣活性随时间的推移而降低,上皮修复较慢。与改良PRK比较,Epi-LASIK术后上皮细胞形态变化和上皮增厚程度较轻,角膜基质细胞恢复快,haze程度明显减轻。     

Epi-LASIK术后应用不同透氧性角膜接触镜对角膜上皮愈合的影响

Pallikaris等提小了机械法准分子激光上皮下角膜磨镶术（epipolis laser in situ keratomiteusis,Epi—LASIK）。Epi-LASIK制作完整而保持活力的角膜上皮瓣十分简便,避免了乙醇的刺激作用和制作上皮瓣带来的一些并发症,术后haze程度轻,但无法避免术后角膜上皮愈合慢及轻微疼痛的缺点,术后需用绷带式角膜接触镜保护角膜上皮瓣。     

Epi-LASIK、PRK术后角膜上皮下雾状混浊的实验研究

目的通过对兔Epi-LASIK、PRK术后研究,探讨Epi-LAsIK手术在角膜上皮下雾状混浊(Haze)减轻方面是否具有优越性及其机制.方法 18只新西兰白兔,双眼分别建立Epi-LASIK和PRK模型,观察术后1周、4周、8周角膜Haze的变化、角膜组织形态学结构的变化、转化生长因子β2(transforming growth factor β2,TGF-β2)的表达.结果术后1周、4周Epi-LASIK组Hazc(1.07±0.49、3.38±1.26)比PRK组(2.38±1.04、5.00±1.95)轻,差异均有统计学意义(Z,=-2,57、Z4=-2.41,P均<0.05),8周时差异无统计学意义(Z8=-0.96,P0.05);组织形态学:Epi-LASIK组角膜上皮细胞的紧密性,角膜上皮基底膜的完整性、上皮与基质黏合程度,胶原排列规则性比同时间段PRK组都具有优越性;Epi-LASIK、PRK角膜上皮TGF-β2表达:1周、4周差异无统计学意义(P均0.05),8周Epi-LASIK组表达比PRK弱,差异有统计学意义(t=-4.19,P<0.05);1周、8周Epi-LASIK、PRK角膜基质TGF-β2表达差异无统计学意义(P均0.05),4周Epi-LASIK表达比PRK弱,差异有统计学意义(t=-2.53,P<0.05).结论Epi-LASIK手术在减轻Haze方面较PRK具有优越性,其上皮瓣的保留对减少Haze的形成具有重要意义.     

上皮瓣弃留对兔Epi-LASIK术后haze影响的研究

目的观察角膜上皮下雾状混浊(haze)形成过程中转化生长因子β2(transfor-ming growth factor β2,TGF-β2)在兔机械法准分子激光上皮瓣下角膜磨镶术(epipo lislaser insitu keratomileusis,Epi-LASIK)和去瓣Epi-LASIK术后的表达差异,并探讨上皮瓣弃留对Epi-LASIK术后haze形成的影响。方法 24只新西兰白兔,双眼分别建立Epi-LASIK和去瓣Epi-LASIK模型。裂隙灯显微镜下观察术后1个月、2个月、3个月角膜haze的情况,免疫组织化学SABC法检测角膜组织TGF-β2的表达。结果 Epi-LASIK组和去瓣Epi-LASIK组haze分级情况在术后1个月、2个月、3个月差异均无统计学意义(χ2=0.08、0.58、0.25,均为P>0.05)。Epi-LASIK组术后1个月、2个月、3个月TGF-β2的表达分别为8546.42±2013.25、7831.62±1560.27、6253.21±1962.35,去瓣Epi-LASIK组术后1个月、2个月、3个月TGF-β2的表达分别为8037.21±1634.29、6994.56±2013.58、6042.58±1862.24,2组术后各时间点角膜组织TGF-β2的表达差异均无统计学意义(t=0.96、1.31、0.38,均为P>0.05);组内比较,随时间延长,TGF-β2的表达呈逐渐降低的趋势。结论上皮瓣弃留对Epi-LASIK术后各时间点角膜组织TGF-β2的表达及haze发生程度均无明显影响。     

准分子激光角膜表层切削术后的止痛措施

准分子激光角膜表层切削术因降低角膜膨隆的风险和避免准分子激光原位角膜磨镶术(LASIK)角膜瓣相关的并发症而受到青睐。但术后严重疼痛不适为表层切削的主要缺陷,因此表层切削术后疼痛不适的控制显得尤其重要。我们总结了表层切削术后疼痛的机制以及降低术后疼痛的措施的进展。     

Causes of spherical aberration induced by laser refractive surgery

PURPOSE: To develop a corneal model to better explain how refractive surgery procedures induce spherical aberration. SETTING: Department of Ophthalmology and Center for Visual Science, University of Rochester, Rochester, New York, USA. METHODS: The preoperative cornea was modeled as a rotationally symmetric surface with various radii of curvature and asphericities. The postoperative cornea was defined as the difference between the preoperative cornea and an ablation thickness profile computed based on the Munnerlyn equation. A ray-tracing program and Zernike polynomial fitting were used to calculate the induced amount of spherical aberration assuming a fixed ablation depth per pulse or a variable ablation depth depending on the incidence angle of each pulse on the cornea. A biological eye model of the corneal surface change after laser refractive surgery was also developed to explain the induced spherical aberrations after myopic and hyperopic treatments. RESULTS: The clinical data showed that positive spherical aberration was induced after myopic correction and negative spherical aberration increased after hyperopic correction. In contrast, assuming a fixed ablation depth per pulse, the theoretical prediction was that negative spherical aberration with myopic treatment and positive spherical aberration with hyperopic treatment would increase. However, when assuming a variable ablation depth per pulse caused by non-normal incidence of laser spot on the cornea, the theoretically predicted induction of spherical aberration tends to fit better with the myopic and hyperopic clinical data. The effect of a variable ablation depth accounted for approximately half the clinically observed amount of spherical aberration. The biological model of the corneal surface change used to explain this remaining discrepancy showed the magnitude of the biological response in myopic correction is 3 times smaller than in hyperopic correction and that the direction of the biological response in hyperopic treatment is opposite that in myopic treatment. CONCLUSIONS: This nontoric eye model, which separates the effects of differences in ablation efficiency and biological corneal surface change quantitatively, explains how spherical aberration is induced after myopic and hyperopic laser refractive surgery. With the corneal topographic data, this model can be incorporated into the ablation algorithm to decrease induced spherical aberrations, improving the outcomes of conventional and customized treatments.     

角膜表层屈光手术后疼痛控制的研究进展

准分子激光角膜表层屈光手术因其可保留较多的角膜基质组织,术后角膜生物力学相对稳定,且有一些特殊的手术适应证（角膜偏薄、角膜瘢痕及角膜移植术后等）,目前仍是屈光矫正手术中较为主要的方法之一.然而,因其手术后特殊的愈合反应所导致的术后疼痛是困扰医生和患者的主要问题,影响了此术式在临床上更为广泛的应用,因此手术后如何缓解疼痛亟待解决.现就角膜表层屈光手术后疼痛的控制做一综述.     

Biomechanics and wound healing in the cornea

The biomechanical and wound healing properties of the cornea undermine the predictability and stability of refractive surgery and contribute to discrepancies between attempted and achieved visual outcomes after LASIK, surface ablation and other keratorefractive procedures. Furthermore, patients predisposed to biomechanical failure or abnormal wound healing can experience serious complications such as keratectasia or clinically significant corneal haze, and more effective means for the identification of such patients prior to surgery are needed. In this review, we describe the cornea as a complex structural composite material with pronounced anisotropy and heterogeneity, summarize current understanding of major biomechanical and reparative pathways that contribute to the corneal response to laser vision correction, and review the role of these processes in ectasia, intraocular pressure measurement artifact, diffuse lamellar keratitis (DLK) and corneal haze. The current understanding of differences in the corneal response after photorefractive keratectomy (PRK), LASIK and femtosecond-assisted LASIK are reviewed. Surgical and disease models that integrate corneal geometric data, substructural anatomy, elastic and viscoelastic material properties and wound healing behavior have the potential to improve clinical outcomes and minimize complications but depend on the identification of preoperative predictors of biomechanical and wound healing responses in individual patients.     

准分子激光术后超微结构变化与生物组织反应

目的 以超微结构为基础,了解准分子激光表面切削术后角膜生物组织反应特点。方法 透射电镜对38只兔眼4,8,12周角膜组织进行观察和分析,并设对照。结果 角膜基质细胞线粒体和粗面内质网损害;出现功能不良性角膜实质细胞;在各种细胞中有成堆的骶鳞体积聚,提示大量自由基的产生;免疫细胞反应和淋巴细胞的凋亡;气化性碎屑产生;角膜胶原纤维区域性溶解等。结论 准分子激光可使角膜组织产生特异性的生物组织反应,可能是临床合并症的组织病理学基础。     

Residual bed thickness and corneal forward shift after laser in situ keratomileusis

PURPOSE: To prospectively assess the forward shift of the cornea after laser in situ keratomileusis (LASIK) in relation to the residual corneal bed thickness. SETTING: Miyata Eye Hospital, Miyazaki, Japan. METHODS: Laser in situ keratomileusis was performed in 164 eyes of 85 patients with a mean myopic refractive error of -5.6 diopters (D) +/- 2.8 (SD) (range -1.25 to -14.5 D). Corneal topography of the posterior corneal surface was obtained using a scanning-slit topography system before and 1 month after surgery. Similar measurements were performed in 20 eyes of 10 normal subjects at an interval of 1 month. The amount of anteroposterior movement of the posterior corneal surface was determined. Multiple regression analysis was used to assess the factors that affected the forward shift of the corneal back surface. RESULTS: The mean residual corneal bed thickness after laser ablation was 388.0 +/- 35.9 microm (range 308 to 489 microm). After surgery, the posterior corneal surface showed a mean forward shift of 46.4 +/- 27.9 microm, which was significantly larger than the absolute difference of 2 measurements obtained in normal subjects, 2.6 +/- 5.7 microm (P<.0001, Student t test). Variables relevant to the forward shift of the corneal posterior surface were, in order of magnitude of influence, the amount of laser ablation (partial regression coefficient B = 0.736, P<.0001) and the preoperative corneal thickness (B = -0.198, P<.0001). The residual corneal bed thickness was not relevant to the forward shift of the cornea. CONCLUSIONS: Even if a residual corneal bed of 300 microm or thicker is preserved, anterior bulging of the cornea after LASIK can occur. Eyes with thin corneas and high myopia requiring greater laser ablation are more predisposed to an anterior shift of the cornea.     

Evaluation of apparent ectasia of the posterior surface of the cornea after keratorefractive surgery

PURPOSE: To calculate the apparent posterior corneal changes after keratorefractive surgery and reevaluate corneal ectasia displayed by Orbscan (Orbtek). SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan. METHODS: Postoperative:preoperative magnification ratio of the posterior surface of the cornea was calculated in a theoretical eye model. RESULTS: Assuming the preoperative corneal thickness is 600.00 microm, the preoperative refractive power of the anterior corneal surface is 48.0 diopters (D), the refractive power of the cornea is 1.376, the ablation diameter is 6.0 mm, the postoperative corneal thickness is 480.00 microm, the postoperative refractive power of the anterior corneal surface is 38.0 D, and the posterior surface of the cornea does not change postoperatively, the apparent image of the posterior surface of the cornea becomes 0.778% smaller postoperatively. If the posterior radius of curvature of the cornea is 6.2 mm, it becomes smaller by 48.24 microm. If this change directly affects the difference map, the posterior surface of the cornea moves forward by 48.24 microm. CONCLUSION: The results correspond to the amount of ectasia in previous reports. This artifact may explain the apparent ectasia detected by Orbscan.     

角膜前表面非球面性的研究进展

角膜前表面是人眼屈光系统的重要组成部分，占人眼总屈光力的80％以上。正常角膜前表面从中央到周边逐渐变平坦，这种非球面特性和其它屈光成分相互协调，保证视网膜成像的质量。随着角膜屈光手术、个体化切削理论的发展及人们对像差认识的不断提高，角膜非球面性的重要性被重新认识。本文就角膜前表面非球面性的研究做一综述。     

Excimer laser ablation of a corneal protuberance.

The ablation of a post-traumatic superficial corneal nodule with an argon fluoride excimer laser is reported. Three months postoperatively the area had a smooth surface with no distortion of adjacent cornea.     

准分子激光表层切削术新进展——TransPRK

经上皮准分子激光屈光性角膜切削术（TransPRK）是一种新型角膜表层屈光手术,采用治疗屈光性角膜切削术（PTK）模式在角膜表面用激光切削一个预先设定的非球面形状,随后附加一定厚度的激光板层切削,整个切削过程除上皮和屈光切削一步完成,最后戴软性角膜接触镜保护创面.其优点是激光切削更加精确、有效缩短手术时间、无需负压吸引,真正实现了无接触式的角膜表层手术.但目前此手术开展较少,仍需继续研究并完善.