丝裂霉素C诱导PRK后角膜基质细胞凋亡的实验研究

目的 探讨丝裂霉素C(MMC)对准分子激光角膜切削术(PRK)后角膜基质细胞凋亡的影响.方法 30只兔随机取1只眼行PRK并术中使用0.02%MMC为PRK MMC组,另1只眼仅行PRK设为PRK组,2只兔设为正常对照组.观察角膜上皮下混浊(haze)程度;采用苏木精-伊红染色法、TUNEL法和免疫组织化学法观察角膜细胞.结果 术后1周,1、2、3个月角膜haze差异均有统计学意义(P＜0.05).术后1周,1、2、3个月PRK MMC组与PRK组TUNEL染色、α-SMA阳性细胞数相比,差异均有统计学意义(P＜0.05).结论 术中眼局部应用0.02%MMC溶液可促进活化的角膜基质细胞凋亡,减轻PRK术后haze.     

PRK联合术中丝裂霉素矫正高度近视的临床研究

目的:探讨准分子激光屈光性角膜切削术(photorefractive keratectomy,PRK)联合术中使用0.2g/L丝裂霉素(MMC)矫治高度近视的安全性、有效性、稳定性。方法:对109例201眼高度近视的患者行PRK术,激光切削后使用0.2g/LMMC20s,观察术后角膜上皮愈合时间、观察术后1,3,6,12mo时裸眼视力、矫正远视力、屈光状态、haze形成情况及并发症情况、角膜内皮细胞计数等。结果:角膜上皮愈合时间为3.68±0.35d。术后裸眼视力均有明显提高,术后12mo裸眼视力达到1.0以上的者189眼(94%),等效球镜在±0.5D以内者153眼(76%)。术后矫正远视力下降1行者7眼(3%),无1例矫正远视力下降2行或2行以上。术后3mo与术后12mo相比,屈光度变化≤0.5D者占96%。手术前后角膜内皮细胞计数、变异系数比较均无显著性差异(P1=0.71;P2=0.83)。术后12mo,0～0.5级haze者189眼(94%),1级haze者12眼(6%);未见2级以上haze。术后未见丝裂霉素毒性反应及并发症。结论:准分子激光屈光性角膜切削术联合术中使用0.2g/LMMC20s矫治高度近视安全、有效。     

丝裂霉素预防准分子激光屈光性角膜切削术后角膜混浊的临床研究

目的:探讨准分子激光屈光性角膜切削术中使用0.2g/L丝裂霉素(MMC)预防术后角膜上皮下混浊(haze)的安全性、有效性。方法:对120例(240眼)屈光不正的患者进行准分子激光屈光性角膜切削术,术中使用0.2g/L丝裂霉素,作用时间为20~90s,观察术后角膜上皮愈合时间、观察术后1,3,6,12mo时裸眼视力、矫正视力、屈光状态、haze形成情况及并发症、角膜内皮细胞计数等。结果:角膜上皮愈合时间为3.01±0.72d;手术前后角膜内皮细胞计数统计学上无显著性差异(P=0.62);术后1,3,6,12mo时裸眼视力、矫正视力、屈光状态统计学上无显著性差异;术后6mo0~0.5级haze218眼(90.8%),1级haze21眼(8.75%),2级haze1眼(0.83%),术后12mo1级haze12眼(5%);术后未见丝裂霉素毒性反应及并发症。结论:使用0.2g/L丝裂霉素预防准分子激光屈光性角膜切削术后角膜上皮下混浊安全、有效。     

丝裂霉素在LASEK术中的应用

目的：观察中高度近视在准分子激光上皮下角膜磨镶术(laser-assisted subepithelial keratomileusis,LASEK)中应用0.1g/L丝裂霉素(mitomycin-C,MMC)抑制术后角膜上皮下雾状混浊(haze)的疗效。

方法：对78例156眼患者行LASEK,随机分成MMC组(86眼)及对照组(70眼),术中两组分别采用含0.1g/L MMC与平衡盐溶液(BSS)的吸水棉签点蘸激光切削后的基质床。观察患者术后1,3,5,7d; 2wk; 1,3,6mo的症状,裸眼视力,角膜上皮愈合时间及haze形成情况。

结果：术后MMC组haze发生率低于对照组,两组haze形成差异有统计学意义(P<0.05); 术后角膜上皮愈合时间及裸眼视力均无明显差异。

结论：LASEK术中点蘸法应用0.1g/L MMC可抑制haze的形成。     

丝裂霉素C辅助PRK的临床观察及并发症分析

目的： 观察丝裂霉素C(mitomycin C, MMC)辅助准分子激光角膜切削术(PRK)的疗效及并发症分析。

方法：回顾性临床病例研究。随机选择2009年40例80眼实施PRK治疗近视的患者作为常规组,2010年PRK术中应用0.2g/L MMC 20s的40例80眼作为MMC组。术后7d; 1,3,6,12mo观察裸眼视力、屈光状态以及角膜上皮愈合、发生糜烂、角膜干燥和haze情况,两组数据进行对比分析。

结果：术后12mo随访期间,两组裸眼视力、术后等效球镜、角膜上皮愈合及干眼情况差异无统计学意义。常规组有2眼,MMC组有9眼发生角膜糜烂伴丝状角膜炎,两组差异有统计学意义(Pearson χ²=4.783,P<0.05)。全部病例均治愈,没有复发病例。常规组、MMC组术后1,3,6,12mo haze的发生率分别为26%,6%,2%,0和44%,25%,10%,2%,术后1mo(Pearson χ²=5.385,P<0.05)、3mo(Pearson χ²=10.667,P=0.001)差异有统计学意义。

结论：PRK术中使用0.2g/L MMC可以减少术后haze的发生。MMC对PRK术中保留的角膜上皮的影响可能是术后角膜糜烂发生的原因之一,术中要避免接触到治疗区外保留的正常角膜上皮。     

高度近视眼准分子激光治疗前后角膜冷却对疗效的影响

目的探讨准分子激光角膜切削术（photorefractivekeratectomy,PRK）治疗高度近视眼前后角膜冷却对其疗效的影响。方法回顾性地对－6．00～－10．00D近视眼的63眼角膜冷却组和58眼对照组随访6mo,分析2组角膜haze表面形态统计值等的差异。结果角膜冷却组PRK术后角膜haze0．5～1级发生率6mo内明显比对照组低,PRK术后冷却组角膜愈合过程中对形态影响小。结论PRK治疗高度近视时对角膜表面的切削有一定的致热作用,该因素可能是导致术后角膜haze和形态恢复时间长的原因之一,PRK术前后角膜冷却对减少并发症有一定的作用。     

高度近视行Trans-PRK术中联合MMC对术后haze的影响

目的：评价经上皮准分子激光角膜切削术(Trans-PRK)联合0.02%丝裂霉素C(MMC)治疗高度近视预防角膜上皮下雾状混浊(haze)的临床效果。

方法：回顾性病例分析。收集我院2016-01/2017-12行Trans-PRK手术治疗的高度近视患者89例142眼,其中94眼联合使用0.02% MMC设为MMC组,MMC的使用时间为30～45s; 48眼未使用MMC设为对照组。两组患者术后均规律使用类固醇激素滴眼液治疗4mo,随访6mo。采用树模型分析探讨不同相关因素与haze发生的相关性。

结果：按照Fantes分级进行haze评估。MMC组术后haze发生率为8.5%(8/94),对照组为33.3%(16/48)(P=0.001)。树模型结果显示,切削光区直径和切削深度是haze发生的主要相关因素(P<0.01)。当切削光区直径≤5.6mm时发生haze的可能性越大,当切削光区直径>5.6mm时,最大切削深度成为haze发生的主要影响因素。

结论：对于薄角膜及角膜形态异常的高度近视患者,在选择Trans-PRK治疗时应考虑切削光区直径及切削深度,同时应联合使用0.02% MMC,可以安全有效地减少haze发生。     

高三尖杉酯碱对PRK后角膜浑浊的影响

目的　了解兔眼准分子激光角膜屈光切削术 (PRK)后 ,局部应用高三尖杉酯碱 (HHT)对角膜上皮下雾状浑浊(haze)抑制作用的效果。方法　将 3 0只健康家兔随机分为A、B、C 3组 ,每组 10只 ( 2 0眼 )。每组兔眼均用准分子激光屈光切削 -10 0DS。A组术后即以浸有 1mg/mLHHT的滤纸贴附于角膜切削区 5min ,用量约 0 1mL ,并用平衡盐液冲洗 ;B组自术后第 3天起双眼滴用 0 1mg/mLHHT ;C组为对照组 ,滴用生理盐水。分别观察 3组术后不同时期的眼部反应及角膜haze形成差别 ,并行组织病理学观察。结果　术后观察 3月 ,A组haze明显轻于B、C两组 (P <0 0 5 )。病理结果显示 ,A组角膜成纤维细胞增生程度明显轻于B、C两组 ,且未见明显毒副作用。结论　PRK术后应用浸有HHT的滤纸贴附切削区可抑制haze形成。     

PRK+MMC与LASEK治疗高度近视效果比较

目的比较PRK术中预防性使用丝裂霉素C（MMC）治疗高度近视和LASEK治疗高度近视的疗效.方法将高度近视（-6.0～-10.0D）随机分为PRK＋MMC组40例（80眼）和LASEK组38例（76眼）.另以早年PRK手术屈光状态与之相似的40例（80眼）作为对照.PRK＋MMC组在PRK术中使用0.02%MMC,LASEK组采用常规LASEK,评价术后角膜上皮下雾状浑浊（haze）,屈光回退、视力及角膜内皮细胞改变等情况.结果PRK＋MMC组未出现2级或2级以上haze,无术后矫正视力下降者,术后欠矫小于-0.5D者70眼;LASEK组有6眼出现2级及2级以上haze,有6眼出现术后矫正视力下降,术后欠矫小于-0.5D者56眼.两组的差异有显著性.使用MMC未见明显毒副作用.结论PRK术中预防性使用MMC,在术后减少haze、防止屈光回退、改善视力方面较LASEK为优.     

准分子激光上皮瓣下角膜磨镶术后中央角膜厚度切削变动的临床观察

目的:探讨准分子激光上皮瓣下角膜磨镶术(laser-assisted subepithelial keratomileusis,LASEK)术中联合低浓度(0.2g/L)丝裂霉素C(MMC)局部应用后中央角膜厚度(central corneal thickness,CCT)切削变动百分率的变化.方法:前瞻性分析2009-03/2014-11于我院行LASEK治疗近视的患者220例440眼,其中低、中度组(等效球镜≤6.0DS)138例276眼,高度组(6.0DS<等效球镜≤10.0DS)82例164眼.术前根据随机表法分别将两组患者均分为试验组和对照组,试验组:切削后双眼使用0.2g/L MMC均质棉片浸润基质面;对照组:双眼均行常规手术.采用变异系数(CV)评估参数重复性,组内及组间数据比较采用配对样本t检验分析.结果:中央角膜厚度及切削值,术后3mo各组间差异均有统计学意义(P<0.05).避免受个体中央角膜厚度差异的干扰采用角膜切削变动百分率:术后1mo角膜切削变动百分率最低,术后3mo角膜切削变动百分率最高,与该组术后其它各期角膜切削变动百分率差异均有统计学意义(P<0.05);各组对照组和试验组术后各期角膜切削变动百分率组间差异均有统计学意义(P<0.05).结论:中央角膜厚度切削变动百分率的观察研究,进一步表明低浓度MMC具有减轻术后角膜前基质层增殖反应、抑制haze产生的作用.     

丝裂霉素C在LASEK术中应用于高度近视患者预防haze的临床研究

目的:探讨LASEK术中应用丝裂霉素C于高度近视患者中预防haze的可行性。方法:选取24例48眼高度近视患者,随机分为2组,其中11例22眼为对照组,13例26眼为试验组,对照组进行常规LASEK术,试验组在LASEK术中激光切削完毕未回复上皮瓣前使用浸泡0.2g/L丝裂霉素C棉片覆盖于激光切削区约12s,冲洗后回复上皮瓣并置入隐形眼镜5d。随访观察术后视力、角膜haze情况等6mo。结果:术后6wk试验组与对照组haze无统计学意义,术后3,6mo试验组haze轻于对照组(P<0.05)。结论:丝裂霉素C在LASEK术中应用于高度近视患者能有效预防haze的形成。     

Mitomycin C reduces haze formation in rabbits after excimer laser photorefractive keratectomy

PURPOSE: To investigate the effects of mitomycin C on haze after photorefractive keratectomy (PRK). METHODS: Twenty of 24 rabbits underwent bilateral 193-nm excimer laser PRK to correct -10.00 D of myopia; the remaining four rabbits were not operated (no PRK group). The right eyes of the 20 rabbits were treated with 0.02% mitomycin C during surgery (PRK+MMC group) and the left eyes did not receive 0.02% mitomycin C (PRK alone group). Clinical and histopathologic examinations were performed. RESULTS: The most severe haze in the PRK alone group after PRK reached grade 3; the PRK+MMC group did not exceed grade 1 haze. Statistically significant differences were found between the PRK+MMC and PRK alone groups from week 2 to week 26 after treatment (P<.01). Epithelial thickening appeared for 26 weeks in both PRK groups; no statistically significant differences were found between the two PRK groups (P>.05). A marked reduction of keratocytes in the anterior stroma of the PRK+MMC group was observed. At week 1, 2, and 4 after PRK, keratocytes of the PRK+MMC group were only 3.1+/-2.6, 6.8+/-4.7, and 12.4+/-5.7 keratocytes x 10(4)/microm2, respectively, while those of the PRK alone group were 41.2+/-80, 42.3+/-7.8, and 40.0+/-3.3 keratocytes x 10(4)/microm2, respectively. There were statistically significant differences between the two groups (P<.001). CONCLUSION: A single intraoperative application of topical mitomycin C during PRK in rabbits reduced corneal haze by inhibiting the proliferation of keratocytes.     

Corneal haze following PRK with mitomycin C as a retreatment versus prophylactic use in the contralateral eye

PURPOSE: To report photorefractive keratectomy (PRK) treated with mitomycin C (MMC) for previous corneal haze in one eye and PRK with MMC to prevent corneal haze formation in the fellow eye. METHODS: A 40-year-old woman underwent PRK with MMC to treat previous corneal haze (secondary to previous PRK without MMC) for residual refractive error of +0.50 +0.25 x 165 in the left eye and PRK with MMC to prevent corneal haze in the right eye. RESULTS: Postoperative slit-lamp examination revealed no haze in the right eye, but continued mild haze in the left eye. CONCLUSIONS: Treatment with PRK and MMC for previous corneal haze is not as effective as primary PRK with MMC in preventing postoperative corneal haze formation.     

Mitomycin C alters corneal stromal wound healing and corneal haze in rabbits after argon-fluoride excimer laser photorefractive keratectomy.

PURPOSE: To investigate the effects of mitomycin C (MMC) on rabbit cornea wound healing after photorefractive keratectomy (PRK). MATERIALS AND METHODS: Rabbit corneas were stained with dichlorotriazinyl aminofluorescein immediately after PRK. MMC was applied to the right eye and phosphate-buffered salt solution (PBS) to the left. Corneal epithelial wound healing rate and corneal haze were examined. Ultrasound pachymetry was performed. Stromal collagen regeneration was evaluated by fluorescent microscopy. We used terminal deoxyribonucleotidyl transferase-mediated D-uridine 5'-triphosphated-digoxigenin nick-end labeling (TUNEL) assay and transmission electron microscopy (TEM) to evaluate keratocyte apoptosis. RESULTS: In eyes treated with MMC, there was no delay to the healing rate of corneal epithelial wound, and less haze 4 weeks after PRK. Ultrasound pachymetry showed thinner corneal thickness in MMC-treated eyes at week 4. Corneal stromal thickness regression was less in MMC-treated eyes observed by fluorescent microscope at week 4. Keratocyte apoptosis was noted in both MMC- and PBS-treated eyes by TUNEL assay and TEM observation. This study discovered the phenomenon that MMC prolongs keratocyte apoptosis. CONCLUSIONS: Applying MMC after PRK is an effective method to decrease haze formation and corneal stromal thickness regression in rabbit corneas. The effect may be related to MMC prolonging keratocyte apoptosis.     

Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy

PURPOSE: To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation. METHODS: The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone. Sponges soaked with 0.02% MMC were applied to the right eyes of Group 1 rabbits for 2 minutes. Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02% MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK. Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm2 C UV-B radiation. Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks. Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain. The tissues were evaluated immunohistochemically with antibody to alpha-smooth muscle actin (SMA). Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy. RESULTS: Corneal haze was observed after PRK and was aggravated by UV-B irradiation. A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes. Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation. Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks. Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy. Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups. CONCLUSIONS: MMC is a potent inhibitor of corneal haze induced by PRK. MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation. Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK.     

Photorefractive keratectomy in high myopic defects with or without intraoperative mitomycin C: 1-year results

PURPOSE: To study the results of the prophylactic use of mitomycin C (MMC) to reduce haze formation and refractive regression after excimer laser photorefractive keratectomy (PRK) for high myopic defects (>5 diopters). METHODS: Prospective, consecutive, observational study. A total of 124 eyes of 62 patients were divided into two groups of 31 patients, 62 eyes each (Groups A and B). Only Group A was treated with MMC 0.02%. The data of the two groups of eyes, related to the best-corrected visual acuity (BCVA), to the difference of refraction pre- and post-treatment, and to the corneal haze, were analyzed through combined permutation tests by using the NPC Test software . RESULTS: BCVA of Group A, 1 year after treatment, was better than that of the control Group B (one-sided p value = 0.013): Group A - 3 eyes (4.8%) had a loss of a decimal fraction and no eyes > 1; Group B - 13 eyes (20.9%) had a loss of a decimal fraction and 1 eye (1.6%) of 2. There was a smaller difference between attempted and achieved SE correction in Group A with respect to Group B (one-sided p value = 0.068): Group A - 43 eyes (69.3%) within +/- 0.50 D; Group B - 31 eyes (50%) within +/- 0.50 D. there was a smaller incidence of corneal haze in the group for which MMC was used (one-sided p value = 0.005). CONCLUSIONS: In this study, the application of MMC 0.02% solution immediately after PRK produced lower haze rates and had better predictability and improved efficacy 1 year after treatment.     

丝裂霉素C在Epi-LASIK术矫正高度和超高度近视中的应用

目的:观察丝裂霉素C(mitomycin C,MMC)应用于机械法—准分子激光上皮瓣下角膜磨镶术(epipdisaser in situ keratomileusis,Epi-LASIK)术矫正高度和超高度近视中的疗效。方法:将高度和超高度近视204例408眼随机分为两组,MMC组102例204眼;对照组102例204眼。所有手术皆运用AMOAmadeus Ⅱ Microkeratome直线式角膜上皮刀制作角膜上皮瓣,MMC组术中激光切削后置0.2g/LMMC棉片于基质床60-90s;对照组除不置MMC外余操作相同。术后随访两组角膜上皮瓣愈合时间、术后刺激症状、haze反应及裸眼视力。结果:所有患者均顺利完成手术。MMC组和对照组Epi-LASIK术后刺激症状皆轻微,316眼(77.4%)疼痛评分为0～1分。角膜上皮瓣愈合时间为3～6d。术后6mo查MMC组中199眼(97.5%)UCVA达到并超过BCVA;对照组168眼(82.4%)UCVA达到并超过BCVA;MMC组视力回退者5眼(2.5%),对照组视力回退者36眼(17.6%)。术后6mohaze反应MMC组与对照组对比,haze2级及haze2级以上差异有显著性(P<0.05),有统计学意义。结论:Epi-LASIK术矫正高度和超高度近视中应用0.2g/LMMC对减轻haze的形成、防止视力回退安全有效。     

Topical Mitomycin C for the prophylaxis of recurrent haze after excimer laser photorefractive keratectomy (PRK) - a pilotstudy of 5 patients]

PURPOSE: Corneal haze is a severe complication after excimer laser PRK and may lead to a compromised visual performance and regression. Currently, corticosteroids are topically applied to inhibit the appearance of haze. However, this therapy is not always successful in preventing haze. Various animal studies have shown that topical applied mitomycin C reduces keratocyte activity and collagen synthesis and subsequently haze. MATERIAL AND METHODS: We have treated 5 patients (5 eyes) with severe haze and regression after PRK. In all eyes we have mechanically debrided the haze and 0.02 % mitomycin C was applied to the area of previous ablation for 1 minute. In 2 eyes we have only performed the debridement, whereas in 3 eyes we also have performed a re-PRK after the laser ablation the mitomycin was applied. The postop follow-up was 9 months. RESULTS: In all eyes the surgery and the postop time was without any complications. The haze could be removed in all eyes completely and in the entire postop period recurrent haze was not more than trace. Regression could be eliminated in the three eyes with a re-PRK, whereas the 2 eyes without re-PRK still remained myop. We could not observe any mitomycin C associated complications on the conjunctiva or cornea. CONCLUSION: Topical applied mitomycin C seems to be a promising therapy to prevent recurrent haze after a second PRK procedure. As mitomycin C can be associated with a variety of serious complications, it should only be used in patients with high risk of haze.