作者：桑姗，钱涛，李一壮
作者单位：210008 中国江苏省南京市，南京大学医学院附属鼓楼医院眼科 南京宁益眼科中心
【摘要】目的：探讨准分子激光原位角膜磨镶术（LASIK）后角膜知觉的变化及其对干眼的影响与切削深度的关系。
方法：观察上方蒂做瓣的LASIK手术30 例(60眼)，观察指标包括患者术中切削深度及术前，术后1wk，1mo，3mo的角膜中央知觉、基础泪液分泌量、泪膜破裂时间（BUT）、角膜荧光素钠染色评分、干眼主觉症状评分。
结果：术后1wk，1mo角膜知觉敏感度与术前相比差异均非常显著(P<0.01),术后3mo平与术前相比差异无统计学意义(P >0.05)；术后1wk患者的主觉症状与术前相比无显著差异（P=0.079>0.05）,术后mo时差异显著(P =0.025<0.05),术后3mo时差异极其显著(P=0.001<0.01)；患者术后泪流量在术后1wk；1mo时明显低于术前（P <0.01），直至术后3mo仍未恢复至术前水平（P<0.01）；术后1wk，1mo，3mo泪膜破裂时间缩短,术后3mo时与术前相比差异显著（P<0.01）；角膜荧光素钠染色评分方面，术后1mo时角膜上皮损伤最明显，术后3mo时与术前仍有显著差异（P<0.01）直线回归与相关分析结果，说明在两者之间存在直线相关的关系r=0.798,P<0.01。
结论：LASIK术后角膜中央知觉明显下降并随时间延续而逐渐恢复，3mo时与术前无统计学差异；但是干眼的相关指标并未随之恢复至术前水平；术后角膜知觉的下降与术中切削深度间存在正相关。
【关键词】 准分子激光原位角膜磨镶术 角膜知觉 干眼 切削深度
INTRODUCTION
LASIK is now becoming the most popular form of refractive surgery in the world with its high safety, effectiveness, stability, and predictability. More and more patients with the purposes to be handsome or convenient choose LASIK to help them get out of the trouble of wearing glasses. With the increase of surgical cases, the problem of dry eye syndrome after the surgery gradually comes to the surface. In our clinical trials, we studied the regularity of the changes of corneal sensation and the incidence of dry eye, and also evaluated the relations between the changes of corneal sensitivity and the laser ablation depth, which is now reported as follows.
PATIENTS AND METHODS
Patients (A)30 patients (60 eyes) were selected who had bilateral myopic.LASIK surgery during December 2007 to March 2008, in our eye center, from 18 to 42 years old with the average age of 22.4 years.(B) Selection criteria (a)age: from 18 to 50 years old; (b)diopter stable for more than two years; (c)have stopped wearing soft contact lenses more than one week or have stopped wearing rigid contact lenses more than three weeks; (d)ruled out patients with systemic diseases and other serious diseases for they were not suitables for the surgery.
Preoperative Examination Uncorrected and best corrected visual acuity, and slit lamp, directophthalmofundoscope, Schirmers basic tear secretion test, tear breakup time, corneal fluorescein staining, intraocular pressure, OPD examination, corneal thickness measurement, contrast sensitivity, pupil diameter and a questionnaire containing three questions evaluating dry eye obtained from each patient.
Corneal sensation The HANDAYA corneal aesthesiometer,produced in Japan, was used to assess corneal sensation. It consisted of a thin 60mm adjustable nylon monofilament touching the cornea.The filament was soft when fully extended and becomes firm when retracted into the handpiece, creating a pressure gradient that ranges from 1.47 to 132.5g/mm3. To measure corneal sensation, the filament was applanated against the corneal surface perpendicularly until a small bend was noted. We began from the length of 60mm, subsequently, the filament is retracted 5mm each time until the patient felt it (The patient blinked two times in three tests at a certain point was positive). The length of the filament at this point was the numeric measurement of corneal sensation. The fiber length would be converted to pressure gradient according to the following table which was provided by the Toray Fibers Institute in Japan.
Table 1 Corneal sensation conversion（略）
Table 2 The corneal sensation of 60 eyes before and after LASIK（略）
Table 3 Comparison of changes of the dry eye related indicators before and after LASIK
aP <0.05;bP <0.01 vs Preop
Schirmer basic secretion test A sterile standardized Schirmer tear test strip was placed in both inferior fornices at the junction of the lateral and middle third and then measured at 5 minutes. The strip wetting was measured and recorded in millimeter.
Tear breakup time (TBUT) The fluorescein dyeing strip (HAAGSTREIT, Switzerland) was put into inferior fornices, and the tear film was observed under cobalt blue filtered light. The interval between the last complete blink and the first appearance of randomly distributed dry spots was measured. The average of three measurements was obtained.
Cornea fluorescence staining score standards The cornea would be divided into four quadrants under the microscope of slit lamp, and we scored it according to the coloring: 0 point: fluorescence staining was negative; 1 point: scattered point fluorescence staining; 2 points: more coarctate scattered point fluorescence staining; 3 points: flaky fluorescence staining. The entire cornea fluorescence staining score was from 0 to 12 points.
The score of subjective dry eye symptoms We chose three most common symptoms that patients with dry eye syndrome have, ie. dry sensation, foreign body sensation, burning sensation.We scored them according to the degree of severity: 0 point: asymptomatic; 0.5 points: occasional; 1 point: frequent; 2 points: apparente and sustained.
Surgical Methods A conventional LASIK surgery. We used Moria corneal lamellar knife to make a flap with a superior hinge from (11:00 to 1:00), the thickness of corneal flap is about 110μm, and used excimer laser (NIDEK EC5000 CX II) to ablate the cornea (optical diameter: 5.5mm). There were no free flaps, crumpled flaps, incomplete flaps, ruptured flaps in all the eyes. All operations were finished by the same experienced doctor.
Administration of the Eyedrops Preoperatively, all patients were given floxacin eye drops (Talim Tarivid) and naphthazoline hydrochloride chlorphenamine maleate and vitamine B12 eye drops both three times a day for three days; postoperatively, Talim Tarivid continued to be used three times a day; all patients were given Cortilet four times a day for a week then the next week three times a day and so on until withdrawal it. Patients were also directed to use artificial tears three to six times a day as needed.
Postoperative Review Every patient had postoperative (one week, one month, and three months) evaluations as preoperative.
Statistical Methods Paired test was used to compare values within the time points of all those items, and relevant linear regression analysis was used to evaluate the relation between the changes of corneal sensation and the laser ablation depth by SPSS15.0 application of data processing software package.
RESULTS
Changes of Corneal Sensation Table 1 shows that the higher the number obtains, the more sensitive the cornea is. From Table 2 we know that, preoperatively, the corneal sensation in this group of cases is up to 1.47g/mm3, 42(70%) of 60, the minimal was 2.79g/mm3, 1(2.38%) of 60; postoperatively, after one week the maximal of corneal sensitivity is 1.94g/mm3, 9(15%)of 60, the minimal 40.3g/mm3, 6(10%) of 60; after one month, there are 10% (6 eyes) recovered to the preoperative highest level 1.47g/mm3; and three months after LASIK, there are 66.67% (40 eyes) recovered to the preoperative highest level, and the minimal was 2.48g/mm3, with only one eye(2.38%). Table 3 shows that, after one week and one month the average of corneal sensation are 10.2072g/mm3 and 3.3548g/mm3. Compared with the preoperative, the differences are all very significant (P<0.01), and the greatest decrease in sensitivity was present at 1 week. After three months the average of corneal sensation is 1.6183g/mm3, compared with preoperative level (1.6065g/mm3). There is no statistical difference (P>0.05).To sum up, corneal sensation declines significantly in the early stage after LASIK, with gradual returned to baseline levels at 3 months.
Changes of Dry Eye Related Indicators Compared with the preoperative values, the score of subjective dry eye symptoms was no significant difference at one week after LASIK (P= 0.079> 0.05); at one month, the difference was significant (P = 0.025 <0.05), and at three months the difference was very significant (P= 0.001 <0.01).
Postoperatively, tear secretion was significantly reduced at one week (P <0.01), then it increased gradually, but a significant reduction was still observed at three months (P <0.01).
Significant reductions in tear breakup time were found after one week, one month and three months(P <0.01). They increased gradually within three months, but there was still very significant deference three months after LASIK(P <0.01).
Corneal fluorescent staining score The corneal epithelial defect was most obvious at one month after the surgery(P<0.01), at three months there are still eight eyes (13.3%) with epithelial staining. Compared with the preoperative values, there was still a statistical difference (P<0.01 ).
The Relationship Between the Laser Ablation Depth and the Changes of Corneal Sensation We used linear regression analysis and relevant to evaluate the relation between the changes of corneal sensation and the laser ablation depth and found that, r=0.798, P<0.01, there was positive linear correlation between them.
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