超高度近视准分子激光角膜原位磨镶术前后角膜改变的共聚焦显微镜研究
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摘要
准分子激光原位角膜磨镶术(laser in situ keratomileusis，LASIK)治疗近视在我国开展仅有6～7年的历史，但其发展速度之快、普及面之广令人惊叹。与准分子激光角膜切削术(photorefractive keratectomy，PRK)相比，LASIK保留了角膜上皮及前弹力层和大部分基质，更符合角膜的解剖生理，术后感染少，疼痛轻，视力恢复快，稳定性和预测性好，尤其适合于中高度近视的治疗。自20世纪90年代以来，已成为首选的屈光矫治术式。对于中高度近视的矫治得到了肯定。然而其创伤愈合反应的机制尚未完全明了，研究多局限在动物实验及人工器官培养的角膜上。近年来应用的角膜共聚焦显微镜可以对角膜进行活体、实时、三维和连续的非侵入性扫描检查，在细胞水平观察角膜的动态变化，并可对角膜各层结构进行直接、准确的厚度测量，使LASIK术后在活体、动态观察人眼角膜创伤愈合反应成为可能。
对于屈光度大于-10D的超高度近视而言，一方面手术切削角膜基质时间较长，切削深度较大，其创伤愈合反应可能较中低度近视更重；另一方面超高度近视本身有着复杂的病理改变，术后发生回退机率较高，也时有报道发生医源性角膜扩张的病例，因此应用共聚焦显微镜观察超高度近视患者LASIK术后角膜形态学的改变一方面可以更深入的理解LASIK术后角膜的创伤愈合反应及其发生机制，另一方面可以分析其主要并发症产生的原因及可能的预防方法。本研究应用共聚焦显微镜对超高度近视患者LASIK手术前后角膜的改变进行前瞻性观察，从细胞水平分析LASIK术后角膜各层的形态改变，角膜细胞的数量变化，并对其相关因素进行分析，探讨LASIK术后角膜创伤愈合反应的发生机制及与创伤愈合相关的并发症的可能原因。
天津医科大学硕士学位论文
选择2003年6月至2004年4月于天津医科大学眼科中心准分子激光治疗
中心行LAsIK手术的患者31人54眼，术前屈光度介于一1 0.ooD一18.ooD之间。
31人(54眼)分别于术前、术后l天、l周、l月、3个月，27人(48眼)
于术后6个月行共聚焦显微镜检查，记录患者术前及术后各时间点角膜形态及
各层细胞数量的变化，分析屈光手术前及术后各时间点角膜各层细胞的变化规
律，及其与屈光状态、角膜感觉的恢复、手术的效果及手术并发症之间的关系。
现将研究结果简述如下:
1.超高度近视LASIK术后视力与术前相比明显提高，术后视力逐渐提高，
术后6月视力与术前最佳矫正视力相比提高，其差别具有统计学意义，超高度
近视行LASIK手术效果可靠。
2.术后1天至1周球镜度数变化较大，术后1月、3月、6月球镜度数呈
下降趋势，术后6月球镜度数与术后1周相比差异具有统计学意义，术后6
月球镜度数尚未达到稳定;术后各时间点散光差异不具有统计学意义，术后6
月散光较术前减少，差异具有统计学意义。
3.超高度近视患者角膜厚度较薄，前基质细胞数、后基质细胞数及内皮细
胞数均较中低度近视低，差异具有统计学意义。超高度近视内皮细胞面积变异
系数较中低度近视高，六角形细胞百分比较中低度近视低，差异具有统计学意
义。
4.LAS工K术后部分患者出现神经营养性上皮病变，可影响或不影响视力，
多于术后半年消失，术后10天上皮基底层可见反光增强的小圆形颗粒的沉积，
随访期间，沉积颗粒的大小及范围逐渐增多，对视力无影响。
5.LAS工K术后1天，神经数量和形态与术前相比无明显改变，术后l周16
眼可见1~2支神经纤维，余角膜未见神经纤维图像，术后3月神经纤维略增
多，至术后6月未恢复至术前水平。
6.LASIK术后前弹力层及前基质可出现皱褶，且长期存在，可能是LASIK
天津医科大学硕士学位论文
手术的亚临床并发症，与术后角膜的不规则散光有关。术后在角膜瓣与基质床
的交界处可出现特征性的高反光和较低反光颗粒，颗粒的总体反光强度随访期
间逐渐降低。
7.术后1天界面的上下可出现无细胞区，随访期间无细胞区不随时间推移
改变。无细胞区的下方可见“激活细胞”，多于术后1周左右反光降低，部分
术后1周及1月仍见“激活细胞”及其周围的基质和胶原，激活细胞区深度与
角膜瓣厚度呈负相关。
8.内皮细胞数、内皮细胞面积变异系数、六角形细胞百分比手术前后未见
明显改变。
9.术后各时间点上皮厚度与屈光度的变化呈负相关，术后上皮厚度的改变
可能与术后早期屈光回退有关，术后基质床厚度未见明显改变。
结论:
1.超高度近视患者LASIK术后屈光呈回退趋势，至术后6月尚未达到稳定，
视力呈渐进性增加，术后6月视力高于术前最佳矫正视力。
2.超高度近视患者角膜显微形态学存在改变。
3.超高度近视角膜的创伤愈合反应较小，术后早期可出现上皮、基质等部位
的改变，微皱褶、界面反光颗粒等长期存在，可能为LASIK手术对角膜的亚临
床损伤，对角膜的远期影响不明。
4.上皮的代偿性增厚可能是影响术后早期屈光改变的主要原因，角膜瓣的厚
度是影响创伤愈合反应的因素之一，合适厚度的角膜瓣可能降低创伤愈合反
应，有助于降低回退的发生率，提高手术的效果。
Laser in situ keratomileusis(LASIK) has been adapted to correct myopia in our country for about 6 to 7 years, compared with photorefractive keratectomy(PRK), Laser in situ keratomileusis (LASIK) involves the performing of an anterior cornea! flap (130μm~160μm of thickness) and removal of midstromal tissue by excimer laser photoablation. The preservation of the corneal epithelium, Bowman's layer and the most parts of anterior stroma makes LASIK safe and effective. Since 1990s it became the first choice of myopic correction. Although the good refractive results have been clearly demonstrated, few articles have been published regarding the wound healing process after LASIK and most of them confined to animal trial and organ cultured cornea. Recently, technological advances led to the development of powerful clinical confocal microscope which allows observation of the living human eye in situ at the cellular level. The confocal microscopy in vivo is an acceptable and reproducible method to detect the changes of
corneal stroma and sublayer thickness. It is especially useful in the area of corneal refractive surgery, where it aids to detect the subtle short and long term changes in cornea.
When correcting high myopia (refractive error>=10D), people have different views, for the corneal pachymetry is more thinner, and laser ablation is more deeper than low and moderate myopia, the complications rate increases after LASIK. This study evaluates the changes before and after LASIK at cellular level prospectively, analyzes the affecting factors, discusses the wound healing process and the probable method to prevent the complications about it.
In this study, 54 eyes of 31 patients (mean preoperative refraction range: -10D to -18.00D) were analyzed. All the patients were examined before LASIK, 1 day, 1
week,l month,3 month after LASIK ,48 eyes were also examined 6 months after LASIK. All the scan were reviewed and analyzed. The visual acuity and refractive changes were also analyzed. Results are as following:
1. Uncorrected visual acuity evidently increased after LASIK, and uncorrected visual acuity 6 months postoperatively increased compared with the best corrected visual acuity before surgery. The differences were statistically significant.
2. spherical refractive diopter changed markedly from 1 day postoperatively to 1 week, decreased gradually afterwards, and didn't reach a steady state till 6 months postoperatively. The change of spherical refractive diopter negatively correlated with thickness of the epithelium. Astigmatism decreased at 6 months after surgery compared with that before surgery. The differences were statistically significant.
3. For high myopia the corneal patchmetry is more thinner, and cell count in anterior stroma, posterior stroma and endothelium is less than that of low and moderate myopia, and the differences were statistically significant. Pleomagthism of endothelium increased and polymagthism decreased compared with low and moderate myopia, The differences were statistically significant.
4. After LASIK some patients may have neurotrophic epitheliopathy which may affect visual acuity or not, and disappeared about 6 months postoperatively. 1 week after LASIK, deposits were seen at the basal cells layer, and its area and reflection intensity increased with tune till 6 months, we didn't find it affect visual acuity.
5. Nerve fiber could be seen 1 day after LASIK the same as that before surgery, but most of them disappeared 1 week later, the number of nerve fiber increased but didn't reach the level before surgery till 6 months postoperatively.
6. Microfolds exiting at the anterior stroma and Bowman's layer. It didn't change with time and correlated with the irregular astigmatism after LASIK. High and low reflection intensity particles were seen at the corneal flap and stromal bed interface, and the total intensity level decreased with tune and became stead at 6 months postoperatively.
7. Acellular area were observed at above and below the interface, and its thickness didn't change w
对于屈光度大于-10D的超高度近视而言，一方面手术切削角膜基质时间较长，切削深度较大，其创伤愈合反应可能较中低度近视更重；另一方面超高度近视本身有着复杂的病理改变，术后发生回退机率较高，也时有报道发生医源性角膜扩张的病例，因此应用共聚焦显微镜观察超高度近视患者LASIK术后角膜形态学的改变一方面可以更深入的理解LASIK术后角膜的创伤愈合反应及其发生机制，另一方面可以分析其主要并发症产生的原因及可能的预防方法。本研究应用共聚焦显微镜对超高度近视患者LASIK手术前后角膜的改变进行前瞻性观察，从细胞水平分析LASIK术后角膜各层的形态改变，角膜细胞的数量变化，并对其相关因素进行分析，探讨LASIK术后角膜创伤愈合反应的发生机制及与创伤愈合相关的并发症的可能原因。
天津医科大学硕士学位论文
选择2003年6月至2004年4月于天津医科大学眼科中心准分子激光治疗
中心行LAsIK手术的患者31人54眼，术前屈光度介于一1 0.ooD一18.ooD之间。
31人(54眼)分别于术前、术后l天、l周、l月、3个月，27人(48眼)
于术后6个月行共聚焦显微镜检查，记录患者术前及术后各时间点角膜形态及
各层细胞数量的变化，分析屈光手术前及术后各时间点角膜各层细胞的变化规
律，及其与屈光状态、角膜感觉的恢复、手术的效果及手术并发症之间的关系。
现将研究结果简述如下:
1.超高度近视LASIK术后视力与术前相比明显提高，术后视力逐渐提高，
术后6月视力与术前最佳矫正视力相比提高，其差别具有统计学意义，超高度
近视行LASIK手术效果可靠。
2.术后1天至1周球镜度数变化较大，术后1月、3月、6月球镜度数呈
下降趋势，术后6月球镜度数与术后1周相比差异具有统计学意义，术后6
月球镜度数尚未达到稳定;术后各时间点散光差异不具有统计学意义，术后6
月散光较术前减少，差异具有统计学意义。
3.超高度近视患者角膜厚度较薄，前基质细胞数、后基质细胞数及内皮细
胞数均较中低度近视低，差异具有统计学意义。超高度近视内皮细胞面积变异
系数较中低度近视高，六角形细胞百分比较中低度近视低，差异具有统计学意
义。
4.LAS工K术后部分患者出现神经营养性上皮病变，可影响或不影响视力，
多于术后半年消失，术后10天上皮基底层可见反光增强的小圆形颗粒的沉积，
随访期间，沉积颗粒的大小及范围逐渐增多，对视力无影响。
5.LAS工K术后1天，神经数量和形态与术前相比无明显改变，术后l周16
眼可见1~2支神经纤维，余角膜未见神经纤维图像，术后3月神经纤维略增
多，至术后6月未恢复至术前水平。
6.LASIK术后前弹力层及前基质可出现皱褶，且长期存在，可能是LASIK
天津医科大学硕士学位论文
手术的亚临床并发症，与术后角膜的不规则散光有关。术后在角膜瓣与基质床
的交界处可出现特征性的高反光和较低反光颗粒，颗粒的总体反光强度随访期
间逐渐降低。
7.术后1天界面的上下可出现无细胞区，随访期间无细胞区不随时间推移
改变。无细胞区的下方可见“激活细胞”，多于术后1周左右反光降低，部分
术后1周及1月仍见“激活细胞”及其周围的基质和胶原，激活细胞区深度与
角膜瓣厚度呈负相关。
8.内皮细胞数、内皮细胞面积变异系数、六角形细胞百分比手术前后未见
明显改变。
9.术后各时间点上皮厚度与屈光度的变化呈负相关，术后上皮厚度的改变
可能与术后早期屈光回退有关，术后基质床厚度未见明显改变。
结论:
1.超高度近视患者LASIK术后屈光呈回退趋势，至术后6月尚未达到稳定，
视力呈渐进性增加，术后6月视力高于术前最佳矫正视力。
2.超高度近视患者角膜显微形态学存在改变。
3.超高度近视角膜的创伤愈合反应较小，术后早期可出现上皮、基质等部位
的改变，微皱褶、界面反光颗粒等长期存在，可能为LASIK手术对角膜的亚临
床损伤，对角膜的远期影响不明。
4.上皮的代偿性增厚可能是影响术后早期屈光改变的主要原因，角膜瓣的厚
度是影响创伤愈合反应的因素之一，合适厚度的角膜瓣可能降低创伤愈合反
应，有助于降低回退的发生率，提高手术的效果。
Laser in situ keratomileusis(LASIK) has been adapted to correct myopia in our country for about 6 to 7 years, compared with photorefractive keratectomy(PRK), Laser in situ keratomileusis (LASIK) involves the performing of an anterior cornea! flap (130μm~160μm of thickness) and removal of midstromal tissue by excimer laser photoablation. The preservation of the corneal epithelium, Bowman's layer and the most parts of anterior stroma makes LASIK safe and effective. Since 1990s it became the first choice of myopic correction. Although the good refractive results have been clearly demonstrated, few articles have been published regarding the wound healing process after LASIK and most of them confined to animal trial and organ cultured cornea. Recently, technological advances led to the development of powerful clinical confocal microscope which allows observation of the living human eye in situ at the cellular level. The confocal microscopy in vivo is an acceptable and reproducible method to detect the changes of
corneal stroma and sublayer thickness. It is especially useful in the area of corneal refractive surgery, where it aids to detect the subtle short and long term changes in cornea.
When correcting high myopia (refractive error>=10D), people have different views, for the corneal pachymetry is more thinner, and laser ablation is more deeper than low and moderate myopia, the complications rate increases after LASIK. This study evaluates the changes before and after LASIK at cellular level prospectively, analyzes the affecting factors, discusses the wound healing process and the probable method to prevent the complications about it.
In this study, 54 eyes of 31 patients (mean preoperative refraction range: -10D to -18.00D) were analyzed. All the patients were examined before LASIK, 1 day, 1
week,l month,3 month after LASIK ,48 eyes were also examined 6 months after LASIK. All the scan were reviewed and analyzed. The visual acuity and refractive changes were also analyzed. Results are as following:
1. Uncorrected visual acuity evidently increased after LASIK, and uncorrected visual acuity 6 months postoperatively increased compared with the best corrected visual acuity before surgery. The differences were statistically significant.
2. spherical refractive diopter changed markedly from 1 day postoperatively to 1 week, decreased gradually afterwards, and didn't reach a steady state till 6 months postoperatively. The change of spherical refractive diopter negatively correlated with thickness of the epithelium. Astigmatism decreased at 6 months after surgery compared with that before surgery. The differences were statistically significant.
3. For high myopia the corneal patchmetry is more thinner, and cell count in anterior stroma, posterior stroma and endothelium is less than that of low and moderate myopia, and the differences were statistically significant. Pleomagthism of endothelium increased and polymagthism decreased compared with low and moderate myopia, The differences were statistically significant.
4. After LASIK some patients may have neurotrophic epitheliopathy which may affect visual acuity or not, and disappeared about 6 months postoperatively. 1 week after LASIK, deposits were seen at the basal cells layer, and its area and reflection intensity increased with tune till 6 months, we didn't find it affect visual acuity.
5. Nerve fiber could be seen 1 day after LASIK the same as that before surgery, but most of them disappeared 1 week later, the number of nerve fiber increased but didn't reach the level before surgery till 6 months postoperatively.
6. Microfolds exiting at the anterior stroma and Bowman's layer. It didn't change with time and correlated with the irregular astigmatism after LASIK. High and low reflection intensity particles were seen at the corneal flap and stromal bed interface, and the total intensity level decreased with tune and became stead at 6 months postoperatively.
7. Acellular area were observed at above and below the interface, and its thickness didn't change w
引文
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11．金学海，刘汉强，马长荣等．单纯近视准分子激光原位角膜磨镶术后散光分析．眼视光学杂志 2002，4(1)：4-7
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13．林文，刘秀珍，张子武等．LASIK治疗高度复性近视散光的疗效分析临床眼科杂志 2001，(5)373-376
14. Huang D, Sur S, Seffo F et al. Surgically-induced astigmatism after laser in situ keratomileusis for spherical myopia. J Refract Surg 2000,16:525-518
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16. Steven E. Wilson, MD, Ambmsio R Laser in situ keratomileusis-induced neurotropic epitheliopathy. Am J Ophthamol 2001,32:405-406
17. Steven E, Wilson M. Laser in situ keratomileusis-induced (presumed) neurotropic epitheliopathy. Ophthamology 2001,108:1082-87
18. linna TU, Vesaluoma MH, Perez-Santomja JJ, et al. Effect of myopic LASIK on corneal sensitivity and morphology of subbasal nerves. Invest Ophthamol Vis Sci 2000;41:393-7
19. Shah SS, et al.photorefractive kemtectomy using the summit SVS Apex laser with or without astigmatic keratectomy. Cornea 1998,17:508-16
20. Breil P, Frisch L, Dick HB. Diagnosis and therapy of LASIK-induced neurotrophic epitheliopathy.Ophthalmologe 2002 Jan;99(1):53-7.
21. Mastropasqua L, et al. Confocal microscopy of the cornea.2001 52-57
22. Linda J, et al. Novel aspect of the ultrastructural organization of human corneal keratocyte. Invest Ophtharnol Vis Sci 1995 36:2557-2567
23. Price FW Jr, Whitson WE, Gonzales JS, Gonzales CR, Smith J. et al. Automated lamellar keratomileusis in situ for myopia. J Refract Surg,1996;2:29-35
24. Holladay JT, Dudeja DR, Chang J. et al. Functional vision and corneal changes
after laser in situ keratomileusis determined by contrast sensitivity, glare testing, and corneal topography. J Cataract Refractive Surg 1999;25:663-668
25．朱志忠等．角膜病学．人民卫生出版社．北京，1986 10
26. Linna TU, Vesaluoma MH, Petroll WM, et al. Confocal microscopy of a patient with irregular astigmatism after LASIK reoperations and relaxation incisions.Cornea 2000; 19(2): 163-169
27. Linna TU, Perez-Santonja JJ, Tervo KM, et al. Recovery of corneal nerve morphology following laser in situ keratomileusis. Exp Eye Res, 1998,66:755-763
28. Latvala T, Barraquer-Coll C, Tervo K, Tervo T. Corneal wound healing and morphology after eximer laser in situ keratomileusis(LASIK)in human eyes. J Refrect Surg, 1996,12:677-683
29. Lee BH, McLaren JW, Erie JC, et al. Reinnervation in the cornea after LASIK. Invest Ophthamol Vis Sci 2002,43(12):3660-3664
30. Patel SV, Erie JC1. Aberrant regeneration of corneal nerves after laser in situ keratomileusis. J Cataract Refract Surg 2003 Feb, 29(2)387-389:
31. Vesaluoma M, Perez-Santonja J, Petroll M, et al. Corneal stromal changes induced by myopic LASIK. Invest Ophthamol Vis Sci 2000,41:369-376
32. Pisella P-J, Auzerie O, Bokobza Y, et al. Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with confocal microscopy. Ophthamol 2001,108:1744-1750
33. Perez-Gomez I, Efron N. Con_focal microscopic evaluation of particles at the corneal flap interface after myopic laser in situ keratomileusis. J Cataract Refract Surg 2003;29:
34. Steven E, Wilson MD. Role of apoptosis in wound healing in the cornea. Cornea
2000 19 (suppl 1):S7-S12
35. Kuo IC, Seitz B, et al. Can zinc prevent apoptosis of anterior keratocyte after superficial keratectomy? Cornea 1997;16:50-55
36．付清，杨亚波．LASIK后角膜的愈合反应及发生机制．国外医学眼科学分册 2003，6：370-373
37. May CA, Priglinger SG, Neubauer AS, et al. Laser in situ keratomileusis in human corneas: new organ culture model. J Cataract Refract Surg 2004,30(1): 179-186
38. Mathers WD. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology. 1993 Mar; 100(3):347-51
39. Kooch JW, Lang GK, Naumann GO. Endothelial reaction to perforating and non-perforating excimer laser excisions in rabbits. Refract corneal Surg 1991 7:214-222
40．杨亚波，姚克，杜新华等．准分子激光原位角膜磨镶术后角膜内皮细胞的观察 中国实用眼科杂志 2000,18：366-367
41. Speada L, et al. Role of the corneal epithelium in refractive changes following laser in situ keratomileusis for high myopia. Ophthamology 2000,16:133-139
42. Erie JC, Patel SV, Mclaren JW, et al. Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness. Ophthamology 2002;109:1447-1452
43. Gauthier CA, Epstein D, Holden BA, et al. Epithelial alterations following photorefractive keratectomy for myopia. J Refract Surg 1995;11:113-118
44. Gauthier CA, Holden BA, Epstein D , et al. Factors affecting epithelial hyperplasia after photorefractive keratectomy. J Cataract Refract Surg 1997,23:1042-1050
45. Cartry DS, Kerr MG, Marshall J, et al. Excimer laser photorefractive keratectomy. 18-month follow up. Ophthamology 1992,99:1209-1219
46. Dillon EC, Missotten L. Compensatory epithelial hyperplasia in human corneal diseases. Ophthamic Surg 1992,23:729-732
47. Dierick HG, Missotten L. Is the corneal contour influenced by a tension in the superficial epithiliul cell? A new hypothesis. Refract Corneal Surg 1992,80:54-59
48. Reinstein DZ, Silverman RH, Sutton HFS, et al. Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery. Anatomic diagnosis in lamellar surgery Ophthamology 1999, 106:474-482
49. Pisella I J, Auzerie O, Bokobza Y, et al. Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with con.focal microscopy. Ophthamology 2001,108:1744-1750
50．李赵霞，谢立信等．准分子激光原位角膜磨镶术后角膜瓣及瓣下角膜厚度对角膜强度影响的实验研究．中华眼科杂志 2003，39(3)：150-155
51. Perez-Gomez I, Efron E. Change to corneal morphology after refractive surgery as viewed with a cofocal microscope. Optom Vis Sci 2003, 80(10):690-697
52. Linna TU, Perez-Santonja JJ, Tervo KM, et al. Recovery of corneal nerve morphology following laser in situ keratomileusis. Exp Eye Res 1998, 66:755-763
53. Vesaluoma M, Perez-Santonja J, Petroll WM, et al. Corneal stromal changes indued by myopic LASIK. Invest Ophthamol Vis Sci 2000, 41:369-376
54. Cierek-Ciaciura S, Mrukwa-Kominek E, Rokita-Wala I, et al. Stromal changes
in the cornea after LASIK during the early postoperative period. Klin Oczna.2000, 102(5):335-338
55．陆文秀．准分子激光屈光性角膜手术学．科学技术文献出版社．北京，2000，17
56．祝丽娜，朱美玲．兔角膜准分子激光切除术皮质类固醇激素治疗后的病理学及超微结构观察．安徽医科大学学报，2002，37(1)：35-38
2. Chang SW, Tsai IL, Hu FR, et al. The cornea in yang myopic adults. Br J Ophthamol 2001,85:521-526
3．黄勇，金玲，唐照福等．LASIK手术前后中央角膜厚度的测量与分析．临床眼科杂志，2001，9(1)：25-27
4．卢奕，楮仁远，李梅等．近视眼多方位角膜厚度测定．中华眼科杂志，1993，29：186
5. Salah T, Waring GO 3rd, el Maghraby A, Moadel K, Grimm SB. Excimer laser in situ keratomileusis under a corneal flap for myopia of 2 to 20 diopters.Am J Ophthalmol 1996 Feb; 121(2): 143-55.
6. McCarty CA,Aldred GF, Taylor HR. Comparison of results of excimer laser correction of all degrees of myopia at 12 months postoperatively. The Melbourne Excimer Laser Group. Am J Ophthamol 1996 121:372-383
7．徐广第．眼科屈光学 军事医学科学出版社 北京 1995 118-120
8．王泽欧，刘华，尚志宏等．超高度近视LASIK后视力分析 中国实用眼科杂志 2000 3：180-181
9．刘华，王泽欧，李红等．超高度近视LASIK后视力及屈光的变化．中国实用眼科杂志．1999，17：669-672
10. Hersh P S, Scherk S, Irani R, et al. Corneal topography of photorefractive keratectomy versus laser in situ keratomileusis. Ophthamology 1998,105:612-619
11．金学海，刘汉强，马长荣等．单纯近视准分子激光原位角膜磨镶术后散光分析．眼视光学杂志 2002，4(1)：4-7
12．毕洪生，王兴荣，王桂敏．LASIK后散光的变化分析中国实用眼科杂志 1999，17(8)：369-371
13．林文，刘秀珍，张子武等．LASIK治疗高度复性近视散光的疗效分析临床眼科杂志 2001，(5)373-376
14. Huang D, Sur S, Seffo F et al. Surgically-induced astigmatism after laser in situ keratomileusis for spherical myopia. J Refract Surg 2000,16:525-518
15．程振英，李镜海，李艳等．角膜瓣蒂部位置对LASIK术后散光的影响 山东医药 2002，42(4)：15-16
16. Steven E. Wilson, MD, Ambmsio R Laser in situ keratomileusis-induced neurotropic epitheliopathy. Am J Ophthamol 2001,32:405-406
17. Steven E, Wilson M. Laser in situ keratomileusis-induced (presumed) neurotropic epitheliopathy. Ophthamology 2001,108:1082-87
18. linna TU, Vesaluoma MH, Perez-Santomja JJ, et al. Effect of myopic LASIK on corneal sensitivity and morphology of subbasal nerves. Invest Ophthamol Vis Sci 2000;41:393-7
19. Shah SS, et al.photorefractive kemtectomy using the summit SVS Apex laser with or without astigmatic keratectomy. Cornea 1998,17:508-16
20. Breil P, Frisch L, Dick HB. Diagnosis and therapy of LASIK-induced neurotrophic epitheliopathy.Ophthalmologe 2002 Jan;99(1):53-7.
21. Mastropasqua L, et al. Confocal microscopy of the cornea.2001 52-57
22. Linda J, et al. Novel aspect of the ultrastructural organization of human corneal keratocyte. Invest Ophtharnol Vis Sci 1995 36:2557-2567
23. Price FW Jr, Whitson WE, Gonzales JS, Gonzales CR, Smith J. et al. Automated lamellar keratomileusis in situ for myopia. J Refract Surg,1996;2:29-35
24. Holladay JT, Dudeja DR, Chang J. et al. Functional vision and corneal changes
after laser in situ keratomileusis determined by contrast sensitivity, glare testing, and corneal topography. J Cataract Refractive Surg 1999;25:663-668
25．朱志忠等．角膜病学．人民卫生出版社．北京，1986 10
26. Linna TU, Vesaluoma MH, Petroll WM, et al. Confocal microscopy of a patient with irregular astigmatism after LASIK reoperations and relaxation incisions.Cornea 2000; 19(2): 163-169
27. Linna TU, Perez-Santonja JJ, Tervo KM, et al. Recovery of corneal nerve morphology following laser in situ keratomileusis. Exp Eye Res, 1998,66:755-763
28. Latvala T, Barraquer-Coll C, Tervo K, Tervo T. Corneal wound healing and morphology after eximer laser in situ keratomileusis(LASIK)in human eyes. J Refrect Surg, 1996,12:677-683
29. Lee BH, McLaren JW, Erie JC, et al. Reinnervation in the cornea after LASIK. Invest Ophthamol Vis Sci 2002,43(12):3660-3664
30. Patel SV, Erie JC1. Aberrant regeneration of corneal nerves after laser in situ keratomileusis. J Cataract Refract Surg 2003 Feb, 29(2)387-389:
31. Vesaluoma M, Perez-Santonja J, Petroll M, et al. Corneal stromal changes induced by myopic LASIK. Invest Ophthamol Vis Sci 2000,41:369-376
32. Pisella P-J, Auzerie O, Bokobza Y, et al. Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with confocal microscopy. Ophthamol 2001,108:1744-1750
33. Perez-Gomez I, Efron N. Con_focal microscopic evaluation of particles at the corneal flap interface after myopic laser in situ keratomileusis. J Cataract Refract Surg 2003;29:
34. Steven E, Wilson MD. Role of apoptosis in wound healing in the cornea. Cornea
2000 19 (suppl 1):S7-S12
35. Kuo IC, Seitz B, et al. Can zinc prevent apoptosis of anterior keratocyte after superficial keratectomy? Cornea 1997;16:50-55
36．付清，杨亚波．LASIK后角膜的愈合反应及发生机制．国外医学眼科学分册 2003，6：370-373
37. May CA, Priglinger SG, Neubauer AS, et al. Laser in situ keratomileusis in human corneas: new organ culture model. J Cataract Refract Surg 2004,30(1): 179-186
38. Mathers WD. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology. 1993 Mar; 100(3):347-51
39. Kooch JW, Lang GK, Naumann GO. Endothelial reaction to perforating and non-perforating excimer laser excisions in rabbits. Refract corneal Surg 1991 7:214-222
40．杨亚波，姚克，杜新华等．准分子激光原位角膜磨镶术后角膜内皮细胞的观察 中国实用眼科杂志 2000,18：366-367
41. Speada L, et al. Role of the corneal epithelium in refractive changes following laser in situ keratomileusis for high myopia. Ophthamology 2000,16:133-139
42. Erie JC, Patel SV, Mclaren JW, et al. Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness. Ophthamology 2002;109:1447-1452
43. Gauthier CA, Epstein D, Holden BA, et al. Epithelial alterations following photorefractive keratectomy for myopia. J Refract Surg 1995;11:113-118
44. Gauthier CA, Holden BA, Epstein D , et al. Factors affecting epithelial hyperplasia after photorefractive keratectomy. J Cataract Refract Surg 1997,23:1042-1050
45. Cartry DS, Kerr MG, Marshall J, et al. Excimer laser photorefractive keratectomy. 18-month follow up. Ophthamology 1992,99:1209-1219
46. Dillon EC, Missotten L. Compensatory epithelial hyperplasia in human corneal diseases. Ophthamic Surg 1992,23:729-732
47. Dierick HG, Missotten L. Is the corneal contour influenced by a tension in the superficial epithiliul cell? A new hypothesis. Refract Corneal Surg 1992,80:54-59
48. Reinstein DZ, Silverman RH, Sutton HFS, et al. Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery. Anatomic diagnosis in lamellar surgery Ophthamology 1999, 106:474-482
49. Pisella I J, Auzerie O, Bokobza Y, et al. Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with con.focal microscopy. Ophthamology 2001,108:1744-1750
50．李赵霞，谢立信等．准分子激光原位角膜磨镶术后角膜瓣及瓣下角膜厚度对角膜强度影响的实验研究．中华眼科杂志 2003，39(3)：150-155
51. Perez-Gomez I, Efron E. Change to corneal morphology after refractive surgery as viewed with a cofocal microscope. Optom Vis Sci 2003, 80(10):690-697
52. Linna TU, Perez-Santonja JJ, Tervo KM, et al. Recovery of corneal nerve morphology following laser in situ keratomileusis. Exp Eye Res 1998, 66:755-763
53. Vesaluoma M, Perez-Santonja J, Petroll WM, et al. Corneal stromal changes indued by myopic LASIK. Invest Ophthamol Vis Sci 2000, 41:369-376
54. Cierek-Ciaciura S, Mrukwa-Kominek E, Rokita-Wala I, et al. Stromal changes
in the cornea after LASIK during the early postoperative period. Klin Oczna.2000, 102(5):335-338
55．陆文秀．准分子激光屈光性角膜手术学．科学技术文献出版社．北京，2000，17
56．祝丽娜，朱美玲．兔角膜准分子激光切除术皮质类固醇激素治疗后的病理学及超微结构观察．安徽医科大学学报，2002，37(1)：35-38