小牛血去蛋白提取物对LASEK与LASIK术后角膜神经修复作用的研究

目的 探讨准分子激光角膜上皮瓣下磨镶术(LASEK)与准分子激光原位角膜磨镶术(LASIK)术后早期应用小牛血去蛋白提取物对角膜神经修复的作用.方法 采用前瞻性随机对照双盲的方法.2009年1至2月在复旦大学附属眼耳鼻喉科医院视光学中心行LASEK患者25例(49只眼)和LASIK患者23例(44只眼),采用随机数字表法分别随机分为2组:LASEK术后小牛血去蛋白提取物眼用凝胶治疗组16例(32只眼)和未用药对照组9例(17只眼);LASIK术后小牛血去蛋白提取物眼用凝胶治疗组13例(24只眼)和未用药对照组10例(20只眼).所有患者均接受常规准分子激光术前检查和常规操作.术后给予治疗组小牛血去蛋白提取物眼用凝胶每日3次涂眼治疗,连续使用3个月.分别在术前、术后1、3、6个月及1年时采用共焦显微镜检查角膜上皮下神经,并测量角膜中央知觉,泪膜破裂时间(BUT).采用独立样本t检验、配对t检验和非参数检验对数据进行统计学分析.结果 LASEK和LASIK术后1年,共聚焦显微镜观察小牛血去蛋白提取物眼用凝胶治疗组和对照组间角膜神经修复的差异均无统计学意义(均为Z=0.0000,P=1.00),但LASEK治疗组在术后3个月即观察到神经交通支形成.LASEK和LASIK术后1年,角膜上皮下神经的形态仍未恢复到术前水平.LASEK术后1个月,LASIK术后1和3个月小牛血去蛋白提取物眼用凝胶治疗组和对照组角膜中央知觉分别为(4.95±0.84)μm、(3.29±1.40) μm、(4.31±1.61) μm和(3.62±1.38) μm、(2.35±1.51)μm、(3.18±1.62) μm,差异有统计学意义(t=4.23,P<0.01;t=2.10,P<0.05;t=2.31,P<0.05).术后6个月,LASEK治疗组、对照组和LASIK治疗组角膜中央知觉分别为(5.81±0.35) μm、(5.79±0.36)μm及(5.25±0.91)μm,与术前相比差异均无统计学意义(t=-1.26,P>0.05;t=-0.70,P>0.05;t=-1.87,P>0.05).LASEK和LASIK术后1年时,治疗组BUT分别为(8.13±2.18) μm和(7.71±2.14) μm,对照组BUT分别为(8.76±1.64)μm和(7.45±2.37)μm,差异均无统计学意义(t=-0.90,P>0.05;t=0.30,P>0.05).结论 LASEK和LASIK术后早期应用小牛血去蛋白提取物能在一定程度上促进术后角膜神经的修复.(中华眼科杂志,2011,47:539-545)

Abstract：

Objective To evaluate the effects of protein-free calf blood extract for recovery of corneal nerve after LASEK and LSEIK. Methods A prospective, randomized, control and double-blind study was carried out from January through February 2009 at Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University. Forty-nine eyes of 25 patients who underwent LASEK were randomly divided into two groups. One group with 16 patients (32 eyes) was treated by protein-free calf blood extract eye gel which was defined as drug treated group and the other group with 9 patients (17 eyes) was not treated by protein-free calf blood extract eye gel which was defined as no drug treated group. Forty-four eyes of 23 patients who underwent LASIK were also randomly divided into two groups. One group with 13 patients (24 eyes) was treated by protein-free calf blood extract eye gel which was defined as drug treated group and the other group with 10 patients (20 eyes) was not treated by protein-free calf blood extract eye gel which was defined as no drug treated group. Protein-free calf blood extract eye gel was delivered in both drug treated groups 3 times per day for three months after surgery. Laser scanning confocal microscopic examinations were performed on 48 eyes in vivo. Central corneal sensitivity and tear break-up time (BUT) were tested on 93 eyes preoperatively and 1,3,6 months, and 1 year after surgery. The obtained dates in the study were analyzed using independent samples t-test, paired t-test and Mann-Whitney Test. Results The morphology oserved by confocal microscope of sub-basal nerve fibers was not different between drug treated group and no drug treated group until the last follow up after LASIK or LASEK(Z=0.0000,P=1.00)and(Z=0.0000,P=1.00). Nerve fibers with interconnections were observed in drug treated group at 3 months after LASEK. The morphology of sub-basal nerve fibers had not recovered completely until 1 year after surgery. The central corneal sensitivity was better in drug treated group than in no drug treated group at 1 month after LASEK [(4.95±0.84)μm,(3.62±1.38) μm;t=4.23,P<0.01] and at 1 and 3 months after LASIK [(3.29±1.40)μm,(2.35±1.51)μm;t=2.10,P<0.05],[(4.31±1.61) μm,(3.18±1.62) μm; t=2.31,P<0.05]. At 6 months postoperatively, the central corneal sensitivity of both drug treated group and no drug treated group which underwent LASEK was not significantly different from pre-operation[(5.81±0.35) μm;t=-1.26,P>0.05],[(5.79±0.36)μm;t=-0.70,P>0.05]. At 6 months postoperatively, the central corneal sensitivity of drug treated group which underwent LASIK was not significantly different from pre-operation[(5.25±0.91)μm;t=-1.87, P>0.05]. No significant difference was seen in BUT between drug treated group and no drug treated group after LASEK or LASIK until 1 year after surgery[(8.13±2.18) μm,(8.76±1.64)μm;t=-0.90,P>0.05],[(7.71±2.14) μm,(7.45±2.37)μm;t=0.30,P>0.05]. Conclusion Protein-free calf blood extract could significantly promote the recovery of corneal nerve in the early period after LASEK and LASIK.

The effects of protein-free calf blood extract for recovery of corneal nerve after LASEK and LASIK

Objective To evaluate the effects of protein-free calf blood extract for recovery of corneal nerve after LASEK and LSEIK. Methods A prospective, randomized, control and double-blind study was carried out from January through February 2009 at Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University. Forty-nine eyes of 25 patients who underwent LASEK were randomly divided into two groups. One group with 16 patients (32 eyes) was treated by protein-free calf blood extract eye gel which was defined as drug treated group and the other group with 9 patients (17 eyes) was not treated by protein-free calf blood extract eye gel which was defined as no drug treated group. Forty-four eyes of 23 patients who underwent LASIK were also randomly divided into two groups. One group with 13 patients (24 eyes) was treated by protein-free calf blood extract eye gel which was defined as drug treated group and the other group with 10 patients (20 eyes) was not treated by protein-free calf blood extract eye gel which was defined as no drug treated group. Protein-free calf blood extract eye gel was delivered in both drug treated groups 3 times per day for three months after surgery. Laser scanning confocal microscopic examinations were performed on 48 eyes in vivo. Central corneal sensitivity and tear break-up time (BUT) were tested on 93 eyes preoperatively and 1,3,6 months, and 1 year after surgery. The obtained dates in the study were analyzed using independent samples t-test, paired t-test and Mann-Whitney Test. Results The morphology oserved by confocal microscope of sub-basal nerve fibers was not different between drug treated group and no drug treated group until the last follow up after LASIK or LASEK(Z=0.0000,P=1.00)and(Z=0.0000,P=1.00). Nerve fibers with interconnections were observed in drug treated group at 3 months after LASEK. The morphology of sub-basal nerve fibers had not recovered completely until 1 year after surgery. The central corneal sensitivity was better in drug treated group than in no drug treated group at 1 month after LASEK [(4.95±0.84)μm,(3.62±1.38) μm;t=4.23,P<0.01] and at 1 and 3 months after LASIK [(3.29±1.40)μm,(2.35±1.51)μm;t=2.10,P<0.05],[(4.31±1.61) μm,(3.18±1.62) μm; t=2.31,P<0.05]. At 6 months postoperatively, the central corneal sensitivity of both drug treated group and no drug treated group which underwent LASEK was not significantly different from pre-operation[(5.81±0.35) μm;t=-1.26,P>0.05],[(5.79±0.36)μm;t=-0.70,P>0.05]. At 6 months postoperatively, the central corneal sensitivity of drug treated group which underwent LASIK was not significantly different from pre-operation[(5.25±0.91)μm;t=-1.87, P>0.05]. No significant difference was seen in BUT between drug treated group and no drug treated group after LASEK or LASIK until 1 year after surgery[(8.13±2.18) μm,(8.76±1.64)μm;t=-0.90,P>0.05],[(7.71±2.14) μm,(7.45±2.37)μm;t=0.30,P>0.05]. Conclusion Protein-free calf blood extract could significantly promote the recovery of corneal nerve in the early period after LASEK and LASIK.