外伤性角膜散光防治的基础和临床研究
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摘要
背景及意义
眼外伤在临床上极为常见。角膜创伤愈合后，常遗留瘢痕而形成角膜散光，影响视功能的恢复和美观，严重者可形成框架镜或准分子激光手术等亦难以矫正的屈光参差。一个多世纪以来，通过手术矫正散光以获得良好的裸眼视力，一直是眼科医师们不懈努力的方向和屈光手术关注的课题，并对散光手术进行着多样化的尝试，不断地进行着技术改进和创新，虽然都取得了一定的疗效，但也存在有一定的局限性和不足。尤其是对外伤性角膜散光的手术矫治尚未见有关的文献报道。
本研究从基础和临床两部分入手探索外伤性角膜散光的防治措施。基础部分：在角膜损伤后愈合过程的早期，通过药物干预减少瘢痕形成从而降低角膜散光；临床部分：在角膜愈合瘢痕形成稳定后3个月，通过手术矫正将角膜散光降低到可控制的范围，即可以通过框架镜或准分子激光手术等来矫正，以改善患者的裸眼视力，将眼外伤对视功能造成的损害减少至最低限度。
第一部分TGF-β_2反义寡核苷酸对兔角膜损伤修复的影响
目的
研究表明转化生长因子—beta(Transforming growth factor-β_2，TGF-β)在机体伤口愈合过程中起到重要的调节作用，其中TGF-β_2是角膜创伤修复的启动因子，通过调控TGF—β_2的活性可调控角膜创伤的修复过程。本实验采用实验动物兔制作角膜穿孔伤模型，设计应用TGF-β_2的反义寡核苷酸(TGF-β_2antisense oligonucleotide，TGF-β_2 ASON)转染角膜外伤缝合术后的瘢痕组织，然后通过裂隙灯观察、HE染色、免疫组化和荧光定量PCR等检测方法，从大体形态、组织结构、蛋白数量及基因水平等不同层面观察分析TGF-β_2反义寡核苷酸对TGF-β_2的活性的影响，为实现药物干预减少瘢痕形成以控制外伤性角膜散光的设想提供理论依据。
方法
1．TGF-β_2反义寡核苷酸(anti-sense oligodeoxynucleotide，ASON)的制备：根据兔TGF-β_2 mRNA序列(Gene bank号AY429466)，由上海生工生物技术有限公司合成一段21bp的ASON，其序列为5′-AGAAGTTGGCATTATACCCTT-3′，并合成一段错义寡核苷酸(missense oligodeoxynucleotide，MSON)作为对照。
2．选用清洁级健康无眼病的新西兰大白兔24只，雌雄兼用，月龄为3个月。
随机分组：实验组16只，双眼均制备角膜穿孔伤缝合术后模型。左眼术后滴TGF-β_2 ASON，为TGF-β_2 ASON组；右眼滴生理盐水，为生理盐水组；对照组8只，不做手术，同样左眼滴TGF-β_2 ASON，右眼滴生理盐水。两组分别于手术后4、7、14、28天取角膜标本，每次6只，实验组4只，对照组2只。
3．观察指标：应用裂隙灯观察角膜瘢痕组织的形态变化；HE染色观察角膜基质细胞，即成纤维细胞的激活、增生、分化情况；免疫组织化学法(SP法)检测α-SMA及纤维连接蛋白(FN)的染色情况；应用实时荧光定量PCR观察TGF-β_2的mRNA表达情况，评价TGF-β_2反义寡核苷酸对角膜创伤修复过程的影响及毒副作用。
结果
1．裂隙灯观察
TGF-β_2 ASON组：球结膜轻度充血，角膜缝线附近水肿，前房闪辉(0～+)，虹膜纹理清晰，瞳孔圆居中，眼压正常。随着时间的延长，眼前段炎症反应逐渐减轻，至术后1周完全消失。生理盐水组：角膜明显水肿，前房闪辉(+～++)，虹膜纹理不清晰，瞳孔欠圆，眼压正常，角膜缘同时期出现大量新生血管。随着时间的延长，眼前段炎症逐渐减轻，至术后2周完全消失，但角膜缘新生血管未消退。
2．HE染色组织病理学观察
TGF-β_2 ASON组：术后4d上皮细胞生长1～2层，基质层成纤维细胞体积增大，扁平，数量增多，平均每个高倍镜下9个染色细胞；术后7d，上皮增生4～5层，排列不规则，基质层成纤维细胞数目增多，平均每个高倍镜下12个染色细胞；术后14d，上皮基本趋于完整，基质层成纤维细胞数量少；胶原纤维排列疏松。生理盐水组：术后4d上皮细胞生长4～6层，基质层成纤维细胞体积增大，扁平，数量增多，平均每个高倍镜下21个染色细胞；术后7d，上皮增生4～5层，排列不规则，基质层成纤维细胞数目增多，平均每个高倍镜下18个染色细胞；术后14d，上皮层排列稍有些不规则，基质层成纤维细胞数量增生；胶原纤维排列致密紊乱。同时期两组相比较，差异具有统计学意义(P＜0.05)。
对照组：滴TGF-β_2 ASON的和滴生理盐水的兔角膜组织高倍镜下表现一致。表现为上皮4—5层，基质层中偶有细胞，扁平；基质疏松。说明TGF-β_2 ASON对正常角膜无毒副作用。
3．免疫组化观察
(1) TGF-β_2 ASON组：α-SMA染色阳性的成纤维细胞数于术后7d达到高峰，术后14d回到基线水平已检测不到；生理盐水组：α-SMA染色阳性的成纤维细胞数于术后4d达到高峰，以后逐渐减少，术后14d尚有少许α-SMA阳性的成纤维细胞。两组均随着造模时间的延长，α-SMA染色阳性的成纤维细胞数逐渐减少；并且在术后4d和7d TGF-β_2 ASON组的α-SMA阳性的成纤维细胞数均比生理盐水组少，差异具有统计学意义(P＜0.05)。
(2) FN：可见TGF-β_2 ASON组FN染色明显减弱，呈板层散在分布于角膜伤口周围的基质层内；生理盐水组FN呈浓密板层分布于伤口周围的基质层内。
4．实时荧光定量PCR的检测结果
TGF-β_2 ASON组：兔角膜组织中TGF-β_2的mRNA于术后4d、7d、14d、28d相对表达量均明显减少，分别为0.0851±0.0028、0.1389±0.0079、0.0753±0.0026、0.0658±0.0007；与同时期生理盐水组：TGF-β_2的mRNA于术后4d、7d、14d、28d相对表达量分别为0.1943±0.0094、0.1915±0.0101、0.1623±0.0090、0.1318±0.0134比较，差异均具有统计学意义(p＜0.05=。
结论
1．TGF-β_2 ASON可特异性的阻断TGF-β_2的转录和翻译，从基因水平抑制TGF-β_2 mRNA的合成并影响TGF-β_2活性，从而调控角膜损伤修复的愈合过程。即抑制成纤维细胞的活化增生、胶原和纤维连接蛋白等ECM的堆积，从而发挥抗瘢痕化的作用。
2．角膜损伤缝合术后成纤维细胞移行、增生最活跃的时期是术后4 d～7 d，TGF-β_2反义寡核苷酸对α-SMA阳性的成纤维细胞数明显的抑制作用也是在术后的14天以内。在角膜损伤修复这个动态级联过程的早期，即术后14 d内进行干预调控是减少术后瘢痕形成的关键。
3．实时荧光定量RT-PCR对于检测兔角膜这样微量标本的基因表达是一个切实可行的技术，具有特异性高、定量准确、结果可靠及可重复性强等优点。
第二部分外伤性角膜散光规律的及手术矫正的探讨
目的
本研究分两部分，第一部分拟通过对外伤性角膜散光规律的分析，找出角膜瘢痕与散光之间的相关关系；第二部分，对手术矫正散光的方法、术前手术量的设计与计算、手术效果的预测等进行系统研究，为散光的手术矫治提供理论依据。
一、外伤性角膜散光规律的探讨
方法
收集30例外伤性角膜散光患者，接受裂隙灯下角膜摄像、角膜地形图的检测，电脑及检影验光(35岁以下患者麻痹睫状肌)。精确测量并记录瘢痕的形状长度及与角膜缘的位置关系、散光度及其轴向。将上述患者的资料与数据对比列表，进行相关分析和回归分析，探讨角膜瘢痕的长度与散光度之间的相关性。对瘢痕所致的角膜散光进行定性和定量的研究。
结果
1．相关分析结果显示：瘢痕长度(mm)与散光度(D)的相关系数为0.563，P值0.00＜0.01，说瘢痕长度与散光度数之间有相关性。进一步以Y(散光度)为因变量，X(瘢痕长度)为自变量进行线性回归分析，求得直线回归方程为：Y=1.703+0.478X。方程模型的假设检验：F=13.023，P=0.001，有统计学意义，说明瘢痕长度与散光度之间呈正相关关系，即瘢痕每改变1mm，散光度将会增加0.478D。
(2)角膜瘢痕的形状、长度及部位与所引起的散光类型有关：①平行于角膜缘切线方向的横形瘢痕，引起与瘢痕长轴相垂直的角膜经线变陡峭，形成近视散光。②垂直于角膜缘切线方向的纵形瘢痕：引起与瘢痕长轴相平行的角膜经线变平坦，形成远视散光。
二、外伤性角膜散光手术矫正的探讨
方法
随机收集角膜穿孔伤缝线拆除后3个月以上的外伤性角膜散光患者22例(22眼)，其中单纯近视散光6例，复性近视散光4例，复性远视散光2例，混合性散光10例，所有病例角膜散光度数均＞2.5D，瘢痕长度≥4mm。
1．术前检查：常规的裂隙灯眼前节检查和检眼镜眼底检查，测量眼压，电脑和检影验光(35岁以下的患者麻痹睫状肌)：检测裸眼视力、矫正视力、散光度及其轴向。角膜地形图检查：分析角膜陡峭经线和平坦经线。对比敏感度、立体视觉和波阵面像差的相关检查。
2．手术设计及原理
(1)切口位置及形状：为了最大限度保存透明角膜，切口设计做在角膜平坦经线上，角膜缘灰白交线前0.5～1.0mm处，平行于角膜缘做一对对称的弧行楔形切除，长度达90°弧度，深度达3／4角膜厚度。通过楔形切除+牵张缝线使平坦的经线变陡峭，矫正远视散光。同时，还可通过“偶联效应”使与其垂直的陡峭经线变平坦，矫正近视散光。
(2)手术量的计算：据Gullstrand模型眼，将眼球看成一个近似圆球，推导出角膜缘楔形切除宽度的计算公式：D_V=(n′-n)/(r-x/π)-D_A
(3)手术矫正量的设计：根据散光矫正的“偶联效应”，术中楔形切除的宽度应以所需矫正散光量的三分之二来设计，即按拟矫正散光量的2／3来设计楔形切除的宽度。
(4)术后屈光状态的预测：在计算散光矫正手术量时，应预测患眼术后的屈光状态，是否与健眼的屈光状态相一致，力争恢复舒适而满意的视觉效果。
3．手术方法
依据角膜地形图、验光数据及术前设计的手术量标记散光轴向、切口的位置和长度、楔形切除的宽度，用锋利的刀片或单刃金刚石刀沿标记线做一对平行于角膜缘的楔形切除，长90弧度，切口深达3／4角膜厚度。用10～0聚丙稀缝线间断缝合切口并埋藏线结。术中用Placidou氏角膜计适时调整缝线的松紧度。
结果
1．术后屈光状态的改变：
本组术前平均散光度为5.13±1.85D，术后平均散光度为1.42±0.22 D，平均下降3.71D，两者差异有统计学意义(P＜0.001)；残余散光度均在2.0D以内，散光轴变化在5°～10°，随访3个月疗效稳定，散光度波动在0.5 D～1D范围内。
2．术后视功能的改变
(1)术后视力：本组22眼平均裸眼视力术前为0.23±0.12，术后为0.62±0.26，矫正视力术前为0.8±0.25，术后为0.94±0.18，较术前有不同程度的提高，差异具有统计学意义(P＜0.001)。
(2)术后OrbScan-Ⅱ检测：术后3个月复查OrbScan-Ⅱ，模拟角膜镜读数(simulated keratoscope reading，SimK)，由术前的45.03±2.16D改变为43.75±1.98D，接近与正常的43.05±1.20D；术后角膜表面地形情况明显改善，差异均有统计学意义(P＜0.01)。
(3)术后对比敏感度的检查：术后1个月与术前相比无明显差异，术后3个月与术前相比，差异均有统计学意义(P＜0.01)。
(4)术后立体视的检查：与术前400″～200″组有17人(占77.3％)相比，术后3个月时仅剩8人(36.4％)；术后3个月超过60％的患者立体视在100″以内，差异均有统计学意义(P＜0.01)。
(5)术后波阵面相差的检查：因瘢痕造成角膜屈光界面发生较大畸变，大多数患者无法测出结果，故未进行统计学处理。
结论
1．外伤性角膜瘢痕的形状与散光的类型有一定的关系，平行于角膜缘切线方向的横形瘢痕，引起与瘢痕长轴垂直经线的近视散光；垂直于角膜缘切线方向的纵形瘢痕，引起与瘢痕长轴平行经线的远视散光。
2．瘢痕长度与散光度呈正相关关系。即瘢痕每改变1mm，散光度将会增加0.478D。
3．角膜缘对称楔形切除+牵张缝线术，矫正外伤性角膜散光是一种安全有效的、简便易行的手术方法，适用于矫正+4.00D以下的远视散光和混合性散光，及—2.00D以下的近视散光。与透明角膜的松弛性切开术相比，具有保存透明角膜、手术损伤轻、疗效稳定、可预测性强、切口愈合快、并发症少等优点。
4．根据Gullstrand模型眼，将眼球看成一个近似圆球，推导出角膜缘楔形切除量的计算公式，通过计算分析发现：角膜缘楔形切除的量与散光矫正的量之间存在非线性相关关系，增强了手术的安全性和可预测性。但其准确性和应用前景，尚待在今后的研究中进一步加以验证。
Background
Ocular trauma is common clinically. After cornea wound healing, astigmatismemerged and disturbed visual function as scar formed. Sometimes the astigmatism isdifficult to be corrected by spectacles or excimer laser. Oculists have been striving toexplore and improve operation methods to correct corneal astigmatism for a century.These operations are effective in astimagtism treatment, but there are also manydefects and restricts in practice. Up to now, correcting traumatic corneal astimagtismby operation hasn't been reported. Based on the anatomical and physiologicalchataracters of cornea and the pathophysiology procedure of corneal wound healing,this research explored the prevention and treatment measures about traumatic cornealastigmatism from foundational and clinical aspects. The foundational part studieddrugs effects on lessening corneal scars forming in the early healing period of cornealwounds. In the clinical part, operations were designed and performed to correcttraumatic corneal astigmatism 3 months after cornea wounds suture, meanwhileoperations effects were investgated. The results confirmed that the traumatic cornealastagmatism can be corrected effectively by drugs and operations. On the basis of thetreatments mentioned above, spectacles and excimer laser proved practical.
PartⅠThe influence of TGF-β_2ASON to the corneal injuries rehabilition
Objective
Researchs have proved that TGF-βplays an important role in organism wound healing. Among them,TGF-β_2 is the initiator of corneal wounds repair and it isfeasible to controll the repair procedure by regulating the actaviting of TGF-β_2
In this study, rabbit models of corneal perforating injuries were made andTGF-β_2 ASON were designed and applied to transfect the scars tissue of post-suturecorneal perforation. To reveal the influence of TGF-β_2 ASON to TGF-β_2 actaviting incorneal injuries rehabilition, the changes in morphous, histio-structure、cell proteinquantities and gene expression were observed and analysised by slitlamp observation、HE staining、immunohistochemistory and real-time PCR. The results provided atheoretical ground for the presumption of reducing corneal scars forming by drugs.
Methods
1. The preparation of TGF-β_2 anti-sense oligodeoxynucleotide (TGF-β_2ASON)
Reference to the sequence of TGF-β_2 mRNA (Gene bank AY429466),ShanghaiSangon Biotechnology co. synthesized a piece of ASON that is 21 bp.Its sequence is5'-AGAAGTTGGCATTATACCCTT-3'. as a control, a piece of missense oligodeoxy-nucleotide(MSON) were synthesized.
2.A total of 24 clearing, healthy Newzealand rabbits which are three monthsold were used.
Randomization: Experiment group were sixteen, all whose corneas were madecornea perforating injuries and then sutured. After surgery the TGF-β_2 ASON wasgiven to their left eyes as TGF-β_2 ASON group and the normal saline(N.S) was givento their right eyes as N.S group. Eight rabbits were in control group and did notreceive operation. Samely TGF-β_2 ASON was given to their left eyes as TGF-β_2ASON group and the N.S to their right eyes as N.S group. We took out of theircorneas on the 4th,7th,14th and 28th day after operation. Six rabbits were executed oncetime.
Observation index: observing the morphologic changes of cornea scars with slitlamp, detecting theα-SMA staining of fibroblasts and FN with immunohisto-chemistry, analyzing the mRNA expression of TGF-β_2 with real time fluorescencequantitative RT-PCR. Thenevaluating the TGF-β_2 toxicant effect and the influence to the cornea rehabilition.
Results
1.Slitlamp observation
TGF-β_2 ASON group: Bulbar conjunctiva hyperemia slightly, the cornea edmaaroud the suture, aqueous flare (0～+), iris clear, the pupil round, IOP normal. Theinflammation released gradually and eliminated utterly 1 week after operation NSgroup: The cornea edema apparently, aqueous flare (+～++),iris blurred, the pupilirregular, IOP normal. There are lots of new vessels near limbus. The inflammationreleased gradually and eliminated utterly 2 weeks after operation, but the new vesslesaren't vanished.
2.Histopathology results
The TGF-β_2 ASON group: Epithelial cells grew 1～2 layers on the 4th day afteroperation and fibroblasts increased to 9/HP in the stroma, whose bodies became largeand applanatus. On the 7th day, epithelial cells grew 4～5 layers, arrangingirregularly,and fibroblasts in the stroma increased to 12/HP. On 14th day, epitheliumalmost became integrity, fibroblasts reduced and collogen fibril arranged loosely.The N.S group: epithelial cells grew 4～6 layers on the 4th day after operation andfibroblast increased to 21/HE On the 7th day, epithelial cells grew 4～5 layers,arranging irregularly, and fibroblasts in the stroma increased to 18/HP. On the 14thday,epithelium arrange irregularly little, fibroblasts increased persistently andcollogen fibril arranged closely.
In the control group, the appearance of the TGF-β_2 ASON group were similar tothe N.S group under the high power lens, which proved TGF-β_2 ASON was safe.
3.Immunohistochemistry results
The TGF-β_2 ASON group: positive fibroblasts ofα-SMA staining rised to peakon the 7th day after operation and returned to the basic line on the 14th day. The N.Sgroup: positive fibrobiasts ofα-SMA staining rised to peak on the 4th day afteroperation and reduced gradually, but on the 14th day, there were still a few positivefibroblasts. On the 4th and 7th days after operation,positive fibroblasts in the TGF-β_2ASON group were fewer than that in the N.S group and the difference is significant statistically (P＜0.05).
Fibronectin: fibronectin stained in the TGF-β_2 ASON group was fewer than inthe N.S group and loosely distributed in the stroma layer aroud the cornea wound,butin the N.S group fibronectin distributed thickly.
4.The results of the real time RT-PCR
The TGF-β_2 ASON group: the mRNA of TGF-β_2 expression in 4d, 7d, 14d, 28dis respectively 0.0851±0.0034, 0.1371±0.0086, 0.0756±0.0031, 0.0660±0.0008. theN.S group is 0.1921±0.0103,0.1892±0.0109, 0.1622±0.0110, 0.1280±0.0135. In thesame periods, the difference of TGF-β_2 mRNA expression is significantstatistically(p＜0.05).
Conclusions
1.TGF-β_2 ASON can specificly block the transcription and translation of TGF—β_2 and restrain the synthesis of TGF-β_2 mRNA, so to regulate the healing process ofcornea injuries. In the process, TGF-β_2 reduce scar forming by restrained fibroblasticactivation and accumulation of collagen and fibronectin.
2.After suture of injured cornea the most activating period of fibroblast migrationand proliferation is 4d～7d after operation. The evident restraining effect ofTGF-β_2 ASON to positiveα-SMA fibroblast is within 14 days after operation, thusregulating corneal rehabilation in the early period is the key of reducing scarsforming.
3. Real time fluorescence quantitative RT-PCR is feasible technique to examinethe microamount gene expression of rabbit cornea. It is high specific, quantitateaccurately, and reliable.
PartⅡThe regularity study of traumatic corneal astigmatism and the operationexplore of correcting corneal astigmatism
Objective
This research was divided into two parts.The first part was to explore the relationship andregularity between traumatic corneal scars and astimagtism.The second part systematicallyelucidated the operation methods and provided theory ground for astigmatism correction operation
ChapterⅠThe regularity study of traumatic corneal astigmatism
Methods
30 cases(30 eyes) of suffering from corneal perforation injuries and consistingof screening standard were collected in the study and accepted examinations ofcorneal topography,computer and retinoscopy optometry(＜35y applying forcycloplegica) and took photographs under slitlamp.The following items wereprecisely surveyed and recorded: the shape, length and location of corneal scars, theastigmatism power and axial direction. In order to explore the relationships betweencorneal scars and the power of corneal astigmatism, these datas were entered into thetable and made correlation analysis and regression analysis.
Results
1. The correlation analysis showed that the correlation coefficient between thelength of corneal scars and the astigmatism power is 0.563(p＜0.01), which provedcorrelation between the scars length and astigmatism. The regression equation is thefollowing: Y=1.703+0.478X. Hypothesis test of the equation model indicated F=13.023,P=0.001,which proved to be positive correlation between them, I.e.the scars lengthincrease 1 mm,the power of astigmatism will increase 0.478D correspondingly
2. The relations among the shape, length, and location of corneal scars and thetype of astigmatism and the astigmatism power are the following:①the scarsparallelling to the corneal limbus resulted in myopic astigmastism as the suture madethe meridian perpendicular to the scar steep②the scars perpendicular to the corneallimbus resulted in hypermetropic astigmastism as the suture made the meridianperpendicular to the scar flat.
ChapterⅡThe study of correcting corneal astigmatism by operation
Methods
22 patients(22 eyes) of traumatic corneal astigmism were collected randomlywhich were 3 months after the corneal suture operation and whose types ofastigmatism are variant. The astigmatism power of all the cases exceeded 2.5D,the length of corneal scars exceeded 4mm.
1.preoperative examination
Including slitlamp examination, fundus examination, IOP measurement,measuring the scars length precisely,recording the shape and position of scars,computer and retinoscopy optometry: recording naked vision,corrected vision,theastigmatism power and axial direction, corneal topography examination(TMS,AMOOBSCANⅡ): recording the astigmatism power and axial direction and analyzingcorneal steep and flat meridian, examinations of contrast sensitivity, stereoscopicvision and wavefront diffrence.
2. The design and principle of operation
(1)the shape and location of incision: to remain apparent cornea utmostly,theincisions were designed to locate in flat meridian behind corneal limbus0.5～1.0mm,which are a pair of symmetrical bracket-shaped incisions parallelling tocorneal limbus. The length of incisions are 90°radian and the depth is 3/4 sclera'sthickness. Then we wedge excised little tissue of sclera and sutured the incision, sothe flat meridian became steep after the operation,meanwhile the steep meridianbecame flat due to "the couple effect", so the myopic astigmatism was corrected.
(2)The width calculation of wedge excision: According to Gullstrand'sschematic ocular,a calculating formula was deduced as following: D_V=(n′-n)/(r-x/π)-D_AD_V represents the corrected power of astigmatism, x represents the width of wedgeexcision. Such as, when x is 0.1mm, the Dv is 0.73. Due to the "coupling effect", theactual corrected power of astigmatism is: 0.73×(1+1/2)=1.1D, which is similar withTroutman's test value. However, when x is 0.2ram, the actual corrected power ofastigmatism is 1.4D, and when x is 0.3mm the corrected value is 1.7D. Similarily we cancalculate the the width of wedge excision according to the preoperative astigmatismpower.
(3)The calculation of corrected astigmatism power: the corrected astigmatism power must be considered preoperatively according to "the laws of cornea flexiblehemisphere" and "the couple effect". According to Troutman's theories, for example,when wedge excision and stretching suture were done on the flat 90°meridian,themeridian will become steep, meanwhile the 180~ meridian will become flat. Theproportion of refractive power change is 2:1.
3. Operation method
A pair of incisions on the corneal fiat meridian behind corneal limbus 0.5-1ramwere made symmetrically.The length of incisions is 90°radian and the depth is 3/4sclera's thickness. The width of incision is the calculation according to the formulathat had been deduced, then we sutured the incisions with 10-0 polypropylene stitchand adjusted the tensity with the Placidou ophthalmometer and buried the knot.
Results
1.The change of postoperative dioptric state
The preoperative power of corneal astigmatism was averagely 5.13±0.85D andthe postoperative power of corneal astigmatism was 1.42+0.22D, reduced 3.71Daveragely. The remain power of astigmatism didn't exceed 2.0D and the axialdirection of astigmatism changed within 5°～10°. The astigmatism powerfluctuated within 0.5～1.0D 3 months after operation.
2.The change of visual function
(1)The postoperatative visual: the preoperative average uncorrected vision was0.23±0.12 and the postoperative vision improved to 0.62±0.26. The preoperativeaverage corrected vision was 0.8±0.25 and the postoperative corrected vision was0.94±0.18. The difference is significant statistically (P＜0.01)
(2) The postoperatative OrbScan-Ⅱexamination: the preoperative value ofSimK was 45.03±2.16D and the postoperative value was 43.75±1.98D,which wasapproximate to normal value of 43.05±1.20D. The postoperative corneal topographyimproved apparently
(3) Postoperative CS test: There are no significant difference betweenpreoperation and 1 month after operation, but the CS between preoperation and 3months after operation showed significant difference (P＜0.01).
(4)Postoperative stereoacuity test: comparing to 17 (77.3％) patients included inthe 400"～200" group preoperatively, only 8(36.4％) patients were remained 3months after operation. Datas showed that more than 60％had the stereoacuitywithin 100" 3 months after operation.
(5)The test of postoperative wavefront aberrations: the majority could not beensurveied as severe aberration made by corneal scars, so the datas had not been dealwith statistically.
Conclusions
1. Among the patients of traumatic corneal astigmatism, the scars parallelling tocorneal limbus formed myopic astigmatism, and the scars perpendicular to corneallimbus formed hypermetropia astigmatism.
2. On the paracentral, peripheral and limbal zone of cornea, the length of linear scarsand the astigmatism power is positive correlation, the linear regression equation is:Y=1.703+0.478X. I.e.the scars length increase 1ram, the power of astigmatism willincrease 0.478D correspondingly
3. Paired wedge shape excision combined stretching suture behind limbus is asafe and effective surgical operation for correcting astigmatism. It can correct thesimple or compound hypermetropic astigmatism between +2.50D～+4.00D and themyopia astigmatism which lower than -2.00D.
4.According to Gullstrand's schematic ocular,a calaculating formula was deduced.Caculating and analyzing indicated: it is nonlinear correlation between the width of thewedge shape excision and corrected astigmatism power. But the accurate details andthe applied perspective need more investigation and verification.
眼外伤在临床上极为常见。角膜创伤愈合后，常遗留瘢痕而形成角膜散光，影响视功能的恢复和美观，严重者可形成框架镜或准分子激光手术等亦难以矫正的屈光参差。一个多世纪以来，通过手术矫正散光以获得良好的裸眼视力，一直是眼科医师们不懈努力的方向和屈光手术关注的课题，并对散光手术进行着多样化的尝试，不断地进行着技术改进和创新，虽然都取得了一定的疗效，但也存在有一定的局限性和不足。尤其是对外伤性角膜散光的手术矫治尚未见有关的文献报道。
本研究从基础和临床两部分入手探索外伤性角膜散光的防治措施。基础部分：在角膜损伤后愈合过程的早期，通过药物干预减少瘢痕形成从而降低角膜散光；临床部分：在角膜愈合瘢痕形成稳定后3个月，通过手术矫正将角膜散光降低到可控制的范围，即可以通过框架镜或准分子激光手术等来矫正，以改善患者的裸眼视力，将眼外伤对视功能造成的损害减少至最低限度。
第一部分TGF-β_2反义寡核苷酸对兔角膜损伤修复的影响
目的
研究表明转化生长因子—beta(Transforming growth factor-β_2，TGF-β)在机体伤口愈合过程中起到重要的调节作用，其中TGF-β_2是角膜创伤修复的启动因子，通过调控TGF—β_2的活性可调控角膜创伤的修复过程。本实验采用实验动物兔制作角膜穿孔伤模型，设计应用TGF-β_2的反义寡核苷酸(TGF-β_2antisense oligonucleotide，TGF-β_2 ASON)转染角膜外伤缝合术后的瘢痕组织，然后通过裂隙灯观察、HE染色、免疫组化和荧光定量PCR等检测方法，从大体形态、组织结构、蛋白数量及基因水平等不同层面观察分析TGF-β_2反义寡核苷酸对TGF-β_2的活性的影响，为实现药物干预减少瘢痕形成以控制外伤性角膜散光的设想提供理论依据。
方法
1．TGF-β_2反义寡核苷酸(anti-sense oligodeoxynucleotide，ASON)的制备：根据兔TGF-β_2 mRNA序列(Gene bank号AY429466)，由上海生工生物技术有限公司合成一段21bp的ASON，其序列为5′-AGAAGTTGGCATTATACCCTT-3′，并合成一段错义寡核苷酸(missense oligodeoxynucleotide，MSON)作为对照。
2．选用清洁级健康无眼病的新西兰大白兔24只，雌雄兼用，月龄为3个月。
随机分组：实验组16只，双眼均制备角膜穿孔伤缝合术后模型。左眼术后滴TGF-β_2 ASON，为TGF-β_2 ASON组；右眼滴生理盐水，为生理盐水组；对照组8只，不做手术，同样左眼滴TGF-β_2 ASON，右眼滴生理盐水。两组分别于手术后4、7、14、28天取角膜标本，每次6只，实验组4只，对照组2只。
3．观察指标：应用裂隙灯观察角膜瘢痕组织的形态变化；HE染色观察角膜基质细胞，即成纤维细胞的激活、增生、分化情况；免疫组织化学法(SP法)检测α-SMA及纤维连接蛋白(FN)的染色情况；应用实时荧光定量PCR观察TGF-β_2的mRNA表达情况，评价TGF-β_2反义寡核苷酸对角膜创伤修复过程的影响及毒副作用。
结果
1．裂隙灯观察
TGF-β_2 ASON组：球结膜轻度充血，角膜缝线附近水肿，前房闪辉(0～+)，虹膜纹理清晰，瞳孔圆居中，眼压正常。随着时间的延长，眼前段炎症反应逐渐减轻，至术后1周完全消失。生理盐水组：角膜明显水肿，前房闪辉(+～++)，虹膜纹理不清晰，瞳孔欠圆，眼压正常，角膜缘同时期出现大量新生血管。随着时间的延长，眼前段炎症逐渐减轻，至术后2周完全消失，但角膜缘新生血管未消退。
2．HE染色组织病理学观察
TGF-β_2 ASON组：术后4d上皮细胞生长1～2层，基质层成纤维细胞体积增大，扁平，数量增多，平均每个高倍镜下9个染色细胞；术后7d，上皮增生4～5层，排列不规则，基质层成纤维细胞数目增多，平均每个高倍镜下12个染色细胞；术后14d，上皮基本趋于完整，基质层成纤维细胞数量少；胶原纤维排列疏松。生理盐水组：术后4d上皮细胞生长4～6层，基质层成纤维细胞体积增大，扁平，数量增多，平均每个高倍镜下21个染色细胞；术后7d，上皮增生4～5层，排列不规则，基质层成纤维细胞数目增多，平均每个高倍镜下18个染色细胞；术后14d，上皮层排列稍有些不规则，基质层成纤维细胞数量增生；胶原纤维排列致密紊乱。同时期两组相比较，差异具有统计学意义(P＜0.05)。
对照组：滴TGF-β_2 ASON的和滴生理盐水的兔角膜组织高倍镜下表现一致。表现为上皮4—5层，基质层中偶有细胞，扁平；基质疏松。说明TGF-β_2 ASON对正常角膜无毒副作用。
3．免疫组化观察
(1) TGF-β_2 ASON组：α-SMA染色阳性的成纤维细胞数于术后7d达到高峰，术后14d回到基线水平已检测不到；生理盐水组：α-SMA染色阳性的成纤维细胞数于术后4d达到高峰，以后逐渐减少，术后14d尚有少许α-SMA阳性的成纤维细胞。两组均随着造模时间的延长，α-SMA染色阳性的成纤维细胞数逐渐减少；并且在术后4d和7d TGF-β_2 ASON组的α-SMA阳性的成纤维细胞数均比生理盐水组少，差异具有统计学意义(P＜0.05)。
(2) FN：可见TGF-β_2 ASON组FN染色明显减弱，呈板层散在分布于角膜伤口周围的基质层内；生理盐水组FN呈浓密板层分布于伤口周围的基质层内。
4．实时荧光定量PCR的检测结果
TGF-β_2 ASON组：兔角膜组织中TGF-β_2的mRNA于术后4d、7d、14d、28d相对表达量均明显减少，分别为0.0851±0.0028、0.1389±0.0079、0.0753±0.0026、0.0658±0.0007；与同时期生理盐水组：TGF-β_2的mRNA于术后4d、7d、14d、28d相对表达量分别为0.1943±0.0094、0.1915±0.0101、0.1623±0.0090、0.1318±0.0134比较，差异均具有统计学意义(p＜0.05=。
结论
1．TGF-β_2 ASON可特异性的阻断TGF-β_2的转录和翻译，从基因水平抑制TGF-β_2 mRNA的合成并影响TGF-β_2活性，从而调控角膜损伤修复的愈合过程。即抑制成纤维细胞的活化增生、胶原和纤维连接蛋白等ECM的堆积，从而发挥抗瘢痕化的作用。
2．角膜损伤缝合术后成纤维细胞移行、增生最活跃的时期是术后4 d～7 d，TGF-β_2反义寡核苷酸对α-SMA阳性的成纤维细胞数明显的抑制作用也是在术后的14天以内。在角膜损伤修复这个动态级联过程的早期，即术后14 d内进行干预调控是减少术后瘢痕形成的关键。
3．实时荧光定量RT-PCR对于检测兔角膜这样微量标本的基因表达是一个切实可行的技术，具有特异性高、定量准确、结果可靠及可重复性强等优点。
第二部分外伤性角膜散光规律的及手术矫正的探讨
目的
本研究分两部分，第一部分拟通过对外伤性角膜散光规律的分析，找出角膜瘢痕与散光之间的相关关系；第二部分，对手术矫正散光的方法、术前手术量的设计与计算、手术效果的预测等进行系统研究，为散光的手术矫治提供理论依据。
一、外伤性角膜散光规律的探讨
方法
收集30例外伤性角膜散光患者，接受裂隙灯下角膜摄像、角膜地形图的检测，电脑及检影验光(35岁以下患者麻痹睫状肌)。精确测量并记录瘢痕的形状长度及与角膜缘的位置关系、散光度及其轴向。将上述患者的资料与数据对比列表，进行相关分析和回归分析，探讨角膜瘢痕的长度与散光度之间的相关性。对瘢痕所致的角膜散光进行定性和定量的研究。
结果
1．相关分析结果显示：瘢痕长度(mm)与散光度(D)的相关系数为0.563，P值0.00＜0.01，说瘢痕长度与散光度数之间有相关性。进一步以Y(散光度)为因变量，X(瘢痕长度)为自变量进行线性回归分析，求得直线回归方程为：Y=1.703+0.478X。方程模型的假设检验：F=13.023，P=0.001，有统计学意义，说明瘢痕长度与散光度之间呈正相关关系，即瘢痕每改变1mm，散光度将会增加0.478D。
(2)角膜瘢痕的形状、长度及部位与所引起的散光类型有关：①平行于角膜缘切线方向的横形瘢痕，引起与瘢痕长轴相垂直的角膜经线变陡峭，形成近视散光。②垂直于角膜缘切线方向的纵形瘢痕：引起与瘢痕长轴相平行的角膜经线变平坦，形成远视散光。
二、外伤性角膜散光手术矫正的探讨
方法
随机收集角膜穿孔伤缝线拆除后3个月以上的外伤性角膜散光患者22例(22眼)，其中单纯近视散光6例，复性近视散光4例，复性远视散光2例，混合性散光10例，所有病例角膜散光度数均＞2.5D，瘢痕长度≥4mm。
1．术前检查：常规的裂隙灯眼前节检查和检眼镜眼底检查，测量眼压，电脑和检影验光(35岁以下的患者麻痹睫状肌)：检测裸眼视力、矫正视力、散光度及其轴向。角膜地形图检查：分析角膜陡峭经线和平坦经线。对比敏感度、立体视觉和波阵面像差的相关检查。
2．手术设计及原理
(1)切口位置及形状：为了最大限度保存透明角膜，切口设计做在角膜平坦经线上，角膜缘灰白交线前0.5～1.0mm处，平行于角膜缘做一对对称的弧行楔形切除，长度达90°弧度，深度达3／4角膜厚度。通过楔形切除+牵张缝线使平坦的经线变陡峭，矫正远视散光。同时，还可通过“偶联效应”使与其垂直的陡峭经线变平坦，矫正近视散光。
(2)手术量的计算：据Gullstrand模型眼，将眼球看成一个近似圆球，推导出角膜缘楔形切除宽度的计算公式：D_V=(n′-n)/(r-x/π)-D_A
(3)手术矫正量的设计：根据散光矫正的“偶联效应”，术中楔形切除的宽度应以所需矫正散光量的三分之二来设计，即按拟矫正散光量的2／3来设计楔形切除的宽度。
(4)术后屈光状态的预测：在计算散光矫正手术量时，应预测患眼术后的屈光状态，是否与健眼的屈光状态相一致，力争恢复舒适而满意的视觉效果。
3．手术方法
依据角膜地形图、验光数据及术前设计的手术量标记散光轴向、切口的位置和长度、楔形切除的宽度，用锋利的刀片或单刃金刚石刀沿标记线做一对平行于角膜缘的楔形切除，长90弧度，切口深达3／4角膜厚度。用10～0聚丙稀缝线间断缝合切口并埋藏线结。术中用Placidou氏角膜计适时调整缝线的松紧度。
结果
1．术后屈光状态的改变：
本组术前平均散光度为5.13±1.85D，术后平均散光度为1.42±0.22 D，平均下降3.71D，两者差异有统计学意义(P＜0.001)；残余散光度均在2.0D以内，散光轴变化在5°～10°，随访3个月疗效稳定，散光度波动在0.5 D～1D范围内。
2．术后视功能的改变
(1)术后视力：本组22眼平均裸眼视力术前为0.23±0.12，术后为0.62±0.26，矫正视力术前为0.8±0.25，术后为0.94±0.18，较术前有不同程度的提高，差异具有统计学意义(P＜0.001)。
(2)术后OrbScan-Ⅱ检测：术后3个月复查OrbScan-Ⅱ，模拟角膜镜读数(simulated keratoscope reading，SimK)，由术前的45.03±2.16D改变为43.75±1.98D，接近与正常的43.05±1.20D；术后角膜表面地形情况明显改善，差异均有统计学意义(P＜0.01)。
(3)术后对比敏感度的检查：术后1个月与术前相比无明显差异，术后3个月与术前相比，差异均有统计学意义(P＜0.01)。
(4)术后立体视的检查：与术前400″～200″组有17人(占77.3％)相比，术后3个月时仅剩8人(36.4％)；术后3个月超过60％的患者立体视在100″以内，差异均有统计学意义(P＜0.01)。
(5)术后波阵面相差的检查：因瘢痕造成角膜屈光界面发生较大畸变，大多数患者无法测出结果，故未进行统计学处理。
结论
1．外伤性角膜瘢痕的形状与散光的类型有一定的关系，平行于角膜缘切线方向的横形瘢痕，引起与瘢痕长轴垂直经线的近视散光；垂直于角膜缘切线方向的纵形瘢痕，引起与瘢痕长轴平行经线的远视散光。
2．瘢痕长度与散光度呈正相关关系。即瘢痕每改变1mm，散光度将会增加0.478D。
3．角膜缘对称楔形切除+牵张缝线术，矫正外伤性角膜散光是一种安全有效的、简便易行的手术方法，适用于矫正+4.00D以下的远视散光和混合性散光，及—2.00D以下的近视散光。与透明角膜的松弛性切开术相比，具有保存透明角膜、手术损伤轻、疗效稳定、可预测性强、切口愈合快、并发症少等优点。
4．根据Gullstrand模型眼，将眼球看成一个近似圆球，推导出角膜缘楔形切除量的计算公式，通过计算分析发现：角膜缘楔形切除的量与散光矫正的量之间存在非线性相关关系，增强了手术的安全性和可预测性。但其准确性和应用前景，尚待在今后的研究中进一步加以验证。
Background
Ocular trauma is common clinically. After cornea wound healing, astigmatismemerged and disturbed visual function as scar formed. Sometimes the astigmatism isdifficult to be corrected by spectacles or excimer laser. Oculists have been striving toexplore and improve operation methods to correct corneal astigmatism for a century.These operations are effective in astimagtism treatment, but there are also manydefects and restricts in practice. Up to now, correcting traumatic corneal astimagtismby operation hasn't been reported. Based on the anatomical and physiologicalchataracters of cornea and the pathophysiology procedure of corneal wound healing,this research explored the prevention and treatment measures about traumatic cornealastigmatism from foundational and clinical aspects. The foundational part studieddrugs effects on lessening corneal scars forming in the early healing period of cornealwounds. In the clinical part, operations were designed and performed to correcttraumatic corneal astigmatism 3 months after cornea wounds suture, meanwhileoperations effects were investgated. The results confirmed that the traumatic cornealastagmatism can be corrected effectively by drugs and operations. On the basis of thetreatments mentioned above, spectacles and excimer laser proved practical.
PartⅠThe influence of TGF-β_2ASON to the corneal injuries rehabilition
Objective
Researchs have proved that TGF-βplays an important role in organism wound healing. Among them,TGF-β_2 is the initiator of corneal wounds repair and it isfeasible to controll the repair procedure by regulating the actaviting of TGF-β_2
In this study, rabbit models of corneal perforating injuries were made andTGF-β_2 ASON were designed and applied to transfect the scars tissue of post-suturecorneal perforation. To reveal the influence of TGF-β_2 ASON to TGF-β_2 actaviting incorneal injuries rehabilition, the changes in morphous, histio-structure、cell proteinquantities and gene expression were observed and analysised by slitlamp observation、HE staining、immunohistochemistory and real-time PCR. The results provided atheoretical ground for the presumption of reducing corneal scars forming by drugs.
Methods
1. The preparation of TGF-β_2 anti-sense oligodeoxynucleotide (TGF-β_2ASON)
Reference to the sequence of TGF-β_2 mRNA (Gene bank AY429466),ShanghaiSangon Biotechnology co. synthesized a piece of ASON that is 21 bp.Its sequence is5'-AGAAGTTGGCATTATACCCTT-3'. as a control, a piece of missense oligodeoxy-nucleotide(MSON) were synthesized.
2.A total of 24 clearing, healthy Newzealand rabbits which are three monthsold were used.
Randomization: Experiment group were sixteen, all whose corneas were madecornea perforating injuries and then sutured. After surgery the TGF-β_2 ASON wasgiven to their left eyes as TGF-β_2 ASON group and the normal saline(N.S) was givento their right eyes as N.S group. Eight rabbits were in control group and did notreceive operation. Samely TGF-β_2 ASON was given to their left eyes as TGF-β_2ASON group and the N.S to their right eyes as N.S group. We took out of theircorneas on the 4th,7th,14th and 28th day after operation. Six rabbits were executed oncetime.
Observation index: observing the morphologic changes of cornea scars with slitlamp, detecting theα-SMA staining of fibroblasts and FN with immunohisto-chemistry, analyzing the mRNA expression of TGF-β_2 with real time fluorescencequantitative RT-PCR. Thenevaluating the TGF-β_2 toxicant effect and the influence to the cornea rehabilition.
Results
1.Slitlamp observation
TGF-β_2 ASON group: Bulbar conjunctiva hyperemia slightly, the cornea edmaaroud the suture, aqueous flare (0～+), iris clear, the pupil round, IOP normal. Theinflammation released gradually and eliminated utterly 1 week after operation NSgroup: The cornea edema apparently, aqueous flare (+～++),iris blurred, the pupilirregular, IOP normal. There are lots of new vessels near limbus. The inflammationreleased gradually and eliminated utterly 2 weeks after operation, but the new vesslesaren't vanished.
2.Histopathology results
The TGF-β_2 ASON group: Epithelial cells grew 1～2 layers on the 4th day afteroperation and fibroblasts increased to 9/HP in the stroma, whose bodies became largeand applanatus. On the 7th day, epithelial cells grew 4～5 layers, arrangingirregularly,and fibroblasts in the stroma increased to 12/HP. On 14th day, epitheliumalmost became integrity, fibroblasts reduced and collogen fibril arranged loosely.The N.S group: epithelial cells grew 4～6 layers on the 4th day after operation andfibroblast increased to 21/HE On the 7th day, epithelial cells grew 4～5 layers,arranging irregularly, and fibroblasts in the stroma increased to 18/HP. On the 14thday,epithelium arrange irregularly little, fibroblasts increased persistently andcollogen fibril arranged closely.
In the control group, the appearance of the TGF-β_2 ASON group were similar tothe N.S group under the high power lens, which proved TGF-β_2 ASON was safe.
3.Immunohistochemistry results
The TGF-β_2 ASON group: positive fibroblasts ofα-SMA staining rised to peakon the 7th day after operation and returned to the basic line on the 14th day. The N.Sgroup: positive fibrobiasts ofα-SMA staining rised to peak on the 4th day afteroperation and reduced gradually, but on the 14th day, there were still a few positivefibroblasts. On the 4th and 7th days after operation,positive fibroblasts in the TGF-β_2ASON group were fewer than that in the N.S group and the difference is significant statistically (P＜0.05).
Fibronectin: fibronectin stained in the TGF-β_2 ASON group was fewer than inthe N.S group and loosely distributed in the stroma layer aroud the cornea wound,butin the N.S group fibronectin distributed thickly.
4.The results of the real time RT-PCR
The TGF-β_2 ASON group: the mRNA of TGF-β_2 expression in 4d, 7d, 14d, 28dis respectively 0.0851±0.0034, 0.1371±0.0086, 0.0756±0.0031, 0.0660±0.0008. theN.S group is 0.1921±0.0103,0.1892±0.0109, 0.1622±0.0110, 0.1280±0.0135. In thesame periods, the difference of TGF-β_2 mRNA expression is significantstatistically(p＜0.05).
Conclusions
1.TGF-β_2 ASON can specificly block the transcription and translation of TGF—β_2 and restrain the synthesis of TGF-β_2 mRNA, so to regulate the healing process ofcornea injuries. In the process, TGF-β_2 reduce scar forming by restrained fibroblasticactivation and accumulation of collagen and fibronectin.
2.After suture of injured cornea the most activating period of fibroblast migrationand proliferation is 4d～7d after operation. The evident restraining effect ofTGF-β_2 ASON to positiveα-SMA fibroblast is within 14 days after operation, thusregulating corneal rehabilation in the early period is the key of reducing scarsforming.
3. Real time fluorescence quantitative RT-PCR is feasible technique to examinethe microamount gene expression of rabbit cornea. It is high specific, quantitateaccurately, and reliable.
PartⅡThe regularity study of traumatic corneal astigmatism and the operationexplore of correcting corneal astigmatism
Objective
This research was divided into two parts.The first part was to explore the relationship andregularity between traumatic corneal scars and astimagtism.The second part systematicallyelucidated the operation methods and provided theory ground for astigmatism correction operation
ChapterⅠThe regularity study of traumatic corneal astigmatism
Methods
30 cases(30 eyes) of suffering from corneal perforation injuries and consistingof screening standard were collected in the study and accepted examinations ofcorneal topography,computer and retinoscopy optometry(＜35y applying forcycloplegica) and took photographs under slitlamp.The following items wereprecisely surveyed and recorded: the shape, length and location of corneal scars, theastigmatism power and axial direction. In order to explore the relationships betweencorneal scars and the power of corneal astigmatism, these datas were entered into thetable and made correlation analysis and regression analysis.
Results
1. The correlation analysis showed that the correlation coefficient between thelength of corneal scars and the astigmatism power is 0.563(p＜0.01), which provedcorrelation between the scars length and astigmatism. The regression equation is thefollowing: Y=1.703+0.478X. Hypothesis test of the equation model indicated F=13.023,P=0.001,which proved to be positive correlation between them, I.e.the scars lengthincrease 1 mm,the power of astigmatism will increase 0.478D correspondingly
2. The relations among the shape, length, and location of corneal scars and thetype of astigmatism and the astigmatism power are the following:①the scarsparallelling to the corneal limbus resulted in myopic astigmastism as the suture madethe meridian perpendicular to the scar steep②the scars perpendicular to the corneallimbus resulted in hypermetropic astigmastism as the suture made the meridianperpendicular to the scar flat.
ChapterⅡThe study of correcting corneal astigmatism by operation
Methods
22 patients(22 eyes) of traumatic corneal astigmism were collected randomlywhich were 3 months after the corneal suture operation and whose types ofastigmatism are variant. The astigmatism power of all the cases exceeded 2.5D,the length of corneal scars exceeded 4mm.
1.preoperative examination
Including slitlamp examination, fundus examination, IOP measurement,measuring the scars length precisely,recording the shape and position of scars,computer and retinoscopy optometry: recording naked vision,corrected vision,theastigmatism power and axial direction, corneal topography examination(TMS,AMOOBSCANⅡ): recording the astigmatism power and axial direction and analyzingcorneal steep and flat meridian, examinations of contrast sensitivity, stereoscopicvision and wavefront diffrence.
2. The design and principle of operation
(1)the shape and location of incision: to remain apparent cornea utmostly,theincisions were designed to locate in flat meridian behind corneal limbus0.5～1.0mm,which are a pair of symmetrical bracket-shaped incisions parallelling tocorneal limbus. The length of incisions are 90°radian and the depth is 3/4 sclera'sthickness. Then we wedge excised little tissue of sclera and sutured the incision, sothe flat meridian became steep after the operation,meanwhile the steep meridianbecame flat due to "the couple effect", so the myopic astigmatism was corrected.
(2)The width calculation of wedge excision: According to Gullstrand'sschematic ocular,a calculating formula was deduced as following: D_V=(n′-n)/(r-x/π)-D_AD_V represents the corrected power of astigmatism, x represents the width of wedgeexcision. Such as, when x is 0.1mm, the Dv is 0.73. Due to the "coupling effect", theactual corrected power of astigmatism is: 0.73×(1+1/2)=1.1D, which is similar withTroutman's test value. However, when x is 0.2ram, the actual corrected power ofastigmatism is 1.4D, and when x is 0.3mm the corrected value is 1.7D. Similarily we cancalculate the the width of wedge excision according to the preoperative astigmatismpower.
(3)The calculation of corrected astigmatism power: the corrected astigmatism power must be considered preoperatively according to "the laws of cornea flexiblehemisphere" and "the couple effect". According to Troutman's theories, for example,when wedge excision and stretching suture were done on the flat 90°meridian,themeridian will become steep, meanwhile the 180~ meridian will become flat. Theproportion of refractive power change is 2:1.
3. Operation method
A pair of incisions on the corneal fiat meridian behind corneal limbus 0.5-1ramwere made symmetrically.The length of incisions is 90°radian and the depth is 3/4sclera's thickness. The width of incision is the calculation according to the formulathat had been deduced, then we sutured the incisions with 10-0 polypropylene stitchand adjusted the tensity with the Placidou ophthalmometer and buried the knot.
Results
1.The change of postoperative dioptric state
The preoperative power of corneal astigmatism was averagely 5.13±0.85D andthe postoperative power of corneal astigmatism was 1.42+0.22D, reduced 3.71Daveragely. The remain power of astigmatism didn't exceed 2.0D and the axialdirection of astigmatism changed within 5°～10°. The astigmatism powerfluctuated within 0.5～1.0D 3 months after operation.
2.The change of visual function
(1)The postoperatative visual: the preoperative average uncorrected vision was0.23±0.12 and the postoperative vision improved to 0.62±0.26. The preoperativeaverage corrected vision was 0.8±0.25 and the postoperative corrected vision was0.94±0.18. The difference is significant statistically (P＜0.01)
(2) The postoperatative OrbScan-Ⅱexamination: the preoperative value ofSimK was 45.03±2.16D and the postoperative value was 43.75±1.98D,which wasapproximate to normal value of 43.05±1.20D. The postoperative corneal topographyimproved apparently
(3) Postoperative CS test: There are no significant difference betweenpreoperation and 1 month after operation, but the CS between preoperation and 3months after operation showed significant difference (P＜0.01).
(4)Postoperative stereoacuity test: comparing to 17 (77.3％) patients included inthe 400"～200" group preoperatively, only 8(36.4％) patients were remained 3months after operation. Datas showed that more than 60％had the stereoacuitywithin 100" 3 months after operation.
(5)The test of postoperative wavefront aberrations: the majority could not beensurveied as severe aberration made by corneal scars, so the datas had not been dealwith statistically.
Conclusions
1. Among the patients of traumatic corneal astigmatism, the scars parallelling tocorneal limbus formed myopic astigmatism, and the scars perpendicular to corneallimbus formed hypermetropia astigmatism.
2. On the paracentral, peripheral and limbal zone of cornea, the length of linear scarsand the astigmatism power is positive correlation, the linear regression equation is:Y=1.703+0.478X. I.e.the scars length increase 1ram, the power of astigmatism willincrease 0.478D correspondingly
3. Paired wedge shape excision combined stretching suture behind limbus is asafe and effective surgical operation for correcting astigmatism. It can correct thesimple or compound hypermetropic astigmatism between +2.50D～+4.00D and themyopia astigmatism which lower than -2.00D.
4.According to Gullstrand's schematic ocular,a calaculating formula was deduced.Caculating and analyzing indicated: it is nonlinear correlation between the width of thewedge shape excision and corrected astigmatism power. But the accurate details andthe applied perspective need more investigation and verification.
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