口唇粘膜移植眼表重建的临床疗效及其术后上皮特性的研究
发布时间：2018-08-14 10:16
【摘要】：目的 拟创建一种全新的口唇粘膜移植重建眼表的手术技术,重建疤痕期眼表角膜缘功能,矫正睑球粘连,并行二期光学性角膜移植。通过临床病例随访分析及手术标本的实验室研究,评估手术疗效并探讨术后眼表上皮细胞的形态和性质。方法研究对象为2011年8月至2014年3月期间在我院眼科住院接受口唇粘膜移植眼表重建手术的疤痕期眼表疾病患者。对患者主观不适症状(包括畏光、疼痛、干眼)、视力、睑球粘连程度、新生血管程度及角膜混浊度进行等级评分并进行术前术后比较,评估手术疗效。对部分眼表成功重建的病例行二期光学性角膜移植手术,观察术后的视力、眼表上皮、新生血管以及植片情况等。同时通过眼表印记细胞、二期角膜移植手术标本的组织病理切片、免疫组织化学染色和扫描电镜等实验室技术,对术后眼表上皮细胞的形态和性质进行探讨和研究。结果1.第一部分结果共计88例患者(89眼)被纳入研究,平均年龄42.7±12.40岁,其中男性77人(86.5%)。病因包括化学烧伤47眼(52.8%),热烧伤33眼(37.1%),爆炸伤3眼(3.4%),Steven-Johnson综合征3眼(3.4%)和多发胬肉3眼(3.4%)。平均随访355.9±233.8天,最长达847天,43.8%的病例随访超过1年。其中52眼(58.4%)施行了全周口唇粘膜移植,37眼(41.6%)行部分范围的口唇粘膜移植,5例病人因剩余角膜基质过薄联合了深板层角膜移植术或板层角膜移植术,所有病例术后粘膜植片生长良好。术后20眼并发羊膜下积血,平均31.89±19.90天完全吸收,未见其他术中及术后并发症及不良事件,口唇切口约9天愈合,患者无不适主诉及并发症。术后74眼(83.1%)主观不适症状较术前改善,术后评分1.02±0.64较术前2.24±1.09明显下降(P0.01),其中畏光、疼痛、干眼的改善率分别为84.7%、76.4%、 69.1%；43眼(48.3%)视力较术前提高；84眼(94.3%)角膜新生血管程度下降,血管深度和范围分别较术前下降1.48±0.83和0.99±0.87个等级(P0.01)；术前睑球粘连眼(57眼)术后皆得到改善,睑球粘连程度较术前平均下降1.44±0.69个等级(P0.01),长期随访过程仅5眼(8.8%)有局部复发；25眼(28.9%)角膜混浊度较术前下降。粘膜移植术后,88眼(98.9%)上皮化完成,平均需时29.95±61.13天,其中12眼(14.6%)术后早期出现小范围反复持续性上皮缺损(PED),经过辅助治疗恢复稳定无并发症,1眼(1.1%)持续存在PED至末次随访(501天)并发局部基质浸润。相关性分析示上皮化完成时间与以下因素相关：术前眼表不适症状(r=0.336,P0.01)、术前PED(r=0.364,P0.01)、角膜混浊程度(r=0.331,P0.01)及角膜缘干细胞缺失范围(r=0.375,p0.01)。2.第二部分结果口唇粘膜移植术后15眼接受了姚氏法全植床深板层角膜移植(Yao's-DLK),4眼接受了穿透性角膜移植(PKP),平均随访305.1±152.4天。所有病例植片生长良好,内皮细胞密度监测平稳,未见排斥反应。术后角膜混浊度、新生血管程度较一期术后进一步降低。其中16眼(84.2%)视力较术前提高,13眼(68.4%)由术前的手动或指数提高至0.05及以上,8眼(42.1%)至0.2及以上。术后早期有7眼(36.8%)上皮出现小范围上皮持续缺损(PED),辅助治疗后6眼上皮恢复稳定,1眼持续缺损至末次随访(461天),其中4眼并发局部基质浸润混浊,有3眼对视力产生影响。DLK术中并发症有后弹力层小穿孔至术后双前房1眼,术后1月自行恢复；PKP术后并发症有激素性青光眼1眼,改用低浓度激素后好转；并发性白内障1眼,随访病情稳定。3.第三部分结果眼表印记细胞学检查示口唇粘膜移植术后眼表上皮形态学上皆不同于三种上皮(口唇粘膜上皮、角膜上皮和结膜上皮)。术后眼表不同部位的细胞大小、形态、排列、层数、染色、核质比等皆不同,角膜中央部位的细胞较周边部位分化更好,术后时间越长,眼表细胞分化越好。手术标本石蜡切片HE染色示术后上皮的层数多于正常角膜但少于口唇粘膜,周边上皮较厚,中央上皮较薄。部分移植的病例上皮分化较全周移植的好,上皮更接近正常角膜。扫描电镜结果示口唇粘膜移植术后眼表上皮的超微机构皆不同于三种上皮；中央部位上皮微绒毛分化较周边部位更明显,部分移植的病例较全周移植更接近角膜上皮。免疫组织化学染色结果示新生上皮来源于口唇粘膜,但兼具角膜上皮和口唇粘膜上皮的部分特性,且有着丰富的上皮干细胞层。结论 本课题设计的口唇粘膜移植手术能有效的重建疤痕期眼表并成功施行二期光学性角膜移植；直接移植的自体口唇粘膜上皮在眼表可出现细胞转分化,转分化后的上皮细胞具备部分角膜上皮的特性。因此,口唇粘膜组织是较为理想的角膜缘上皮替代性组织。
[Abstract]:Objective To establish a new surgical technique for reconstruction of ocular surface by lip mucosa transplantation, to reconstruct the limbal function of ocular surface, to correct blepharoplasty and to perform secondary optical keratoplasty. Methods Patients with ocular surface diseases in scar stage who underwent lip mucosa transplantation for ocular surface reconstruction in our ophthalmology department from August 2011 to March 2014 were evaluated for subjective discomfort symptoms (including photophobia, pain, dry eyes), visual acuity, degree of symblepharon adhesion, degree of neovascularization and corneal opacity. The visual acuity, ocular surface epithelium, neovascularization and grafting were observed in some cases of successful ocular surface reconstruction. The ocular surface imprinted cells, histopathological sections of secondary corneal transplantation specimens, immunohistochemical staining and scanning electron microscopy were used. Results 1. Results A total of 88 patients (89 eyes) with an average age of 42.7 (+ 12.40 years) were included in the study, including 77 males (86.5%). The etiology included chemical burns in 47 eyes (52.8%), heat burns in 33 eyes (37.1%), explosive injuries in 3 eyes (3.4%) and explosive injuries in 3 eyes (Steven-Johnson). Three eyes (3.4%) with syndrome and three eyes (3.4%) with multiple pterygium were followed up for an average of 355.9 (+ 233.8) days, up to 847 days. 43.8% of the patients were followed up for more than one year. Among them, 52 eyes (58.4%) underwent full-cycle lip mucosa transplantation, 37 eyes (41.6%) underwent partial lip mucosa transplantation, and 5 patients underwent deep lamellar keratoplasty or lamellar keratoplasty because of the thin residual corneal stroma. After corneal lamellar transplantation, the grafts grew well in all cases. Subamniotic hemorrhage was found in 20 eyes (31.89 The improvement rates of photophobia, pain and dry eye were 84.7%, 76.4% and 69.1%, 43 eyes (48.3%) had improved vision, 84 eyes (94.3%) had decreased degree of corneal neovascularization, and the depth and scope of blood vessels were 1.48 + 0.83 and 0.99 + 0.87 grades (P 0.01), respectively. After mucosal transplantation, the epithelialization was completed in 88 eyes (98.9%) with an average time of 29.95 [61.13 days] and 12 eyes (14.6%) with early postoperative recurrence. Small-scale recurrent persistent epithelial defect (PED) occurred in the first stage. No complications occurred after adjuvant treatment. One eye (1.1%) had persistent PED and local matrix infiltration during the last follow-up (501 days). Correlation analysis showed that the completion time of epithelialization was related to the following factors: preoperative ocular surface discomfort symptoms (r = 0.336, P 0.01), preoperative PED (r = 0.364, P 0.01), angle. Membrane opacity (r = 0.331, P 0.01) and limbal stem cell loss (r = 0.375, P 0.01). 2. Results In the second part, 15 eyes received Yao's Full-Bed Deep lamellar keratoplasty (Yao's-DLK) and 4 eyes received penetrating keratoplasty (PKP), with an average follow-up of 305.1 (+ 152.4 days). Postoperative corneal opacity and neovascularization were further reduced. Visual acuity of 16 eyes (84.2%) was improved, 13 eyes (68.4%) were improved from preoperative manual or index to 0.05 or more, 8 eyes (42.1%) to 0.2 or more. Small epithelial areas persisted in 7 eyes (36.8%) in the early postoperative period. Defects (PED) were found in 6 eyes after adjuvant therapy, and 1 eye was persistent defect until the last follow-up (461 days). Four of them were complicated with local matrix infiltration and turbidity. Three eyes had visual impairment. The third part of the results showed that the morphology of the ocular surface epithelium was different from that of the three kinds of epithelium (lip mucosa epithelium, corneal epithelium and conjunctival epithelium). The number of layers, staining and the ratio of nucleus to cytoplasm were different. The cells in the central part of cornea differentiated better than those in the peripheral part. The longer the operation time, the better the differentiation of ocular surface cells. Scanning electron microscopy showed that the ultrastructure of the ocular surface epithelium was different from the three kinds of epithelium after oral mucosa transplantation. The microvilli differentiation of the central epithelium was more obvious than that of the peripheral epithelium, and some of the transplanted cases were closer to the corneal epithelium than that of the whole-week transplantation. Conclusion The lip mucosa transplantation designed in this study can effectively reconstruct the ocular surface in the scar stage and successfully perform the second-stage optical keratoplasty. Cell transdifferentiation can occur on the ocular surface, and the differentiated epithelial cells possess some characteristics of corneal epithelium.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R779.6
本文编号：2182545
[Abstract]:Objective To establish a new surgical technique for reconstruction of ocular surface by lip mucosa transplantation, to reconstruct the limbal function of ocular surface, to correct blepharoplasty and to perform secondary optical keratoplasty. Methods Patients with ocular surface diseases in scar stage who underwent lip mucosa transplantation for ocular surface reconstruction in our ophthalmology department from August 2011 to March 2014 were evaluated for subjective discomfort symptoms (including photophobia, pain, dry eyes), visual acuity, degree of symblepharon adhesion, degree of neovascularization and corneal opacity. The visual acuity, ocular surface epithelium, neovascularization and grafting were observed in some cases of successful ocular surface reconstruction. The ocular surface imprinted cells, histopathological sections of secondary corneal transplantation specimens, immunohistochemical staining and scanning electron microscopy were used. Results 1. Results A total of 88 patients (89 eyes) with an average age of 42.7 (+ 12.40 years) were included in the study, including 77 males (86.5%). The etiology included chemical burns in 47 eyes (52.8%), heat burns in 33 eyes (37.1%), explosive injuries in 3 eyes (3.4%) and explosive injuries in 3 eyes (Steven-Johnson). Three eyes (3.4%) with syndrome and three eyes (3.4%) with multiple pterygium were followed up for an average of 355.9 (+ 233.8) days, up to 847 days. 43.8% of the patients were followed up for more than one year. Among them, 52 eyes (58.4%) underwent full-cycle lip mucosa transplantation, 37 eyes (41.6%) underwent partial lip mucosa transplantation, and 5 patients underwent deep lamellar keratoplasty or lamellar keratoplasty because of the thin residual corneal stroma. After corneal lamellar transplantation, the grafts grew well in all cases. Subamniotic hemorrhage was found in 20 eyes (31.89 The improvement rates of photophobia, pain and dry eye were 84.7%, 76.4% and 69.1%, 43 eyes (48.3%) had improved vision, 84 eyes (94.3%) had decreased degree of corneal neovascularization, and the depth and scope of blood vessels were 1.48 + 0.83 and 0.99 + 0.87 grades (P 0.01), respectively. After mucosal transplantation, the epithelialization was completed in 88 eyes (98.9%) with an average time of 29.95 [61.13 days] and 12 eyes (14.6%) with early postoperative recurrence. Small-scale recurrent persistent epithelial defect (PED) occurred in the first stage. No complications occurred after adjuvant treatment. One eye (1.1%) had persistent PED and local matrix infiltration during the last follow-up (501 days). Correlation analysis showed that the completion time of epithelialization was related to the following factors: preoperative ocular surface discomfort symptoms (r = 0.336, P 0.01), preoperative PED (r = 0.364, P 0.01), angle. Membrane opacity (r = 0.331, P 0.01) and limbal stem cell loss (r = 0.375, P 0.01). 2. Results In the second part, 15 eyes received Yao's Full-Bed Deep lamellar keratoplasty (Yao's-DLK) and 4 eyes received penetrating keratoplasty (PKP), with an average follow-up of 305.1 (+ 152.4 days). Postoperative corneal opacity and neovascularization were further reduced. Visual acuity of 16 eyes (84.2%) was improved, 13 eyes (68.4%) were improved from preoperative manual or index to 0.05 or more, 8 eyes (42.1%) to 0.2 or more. Small epithelial areas persisted in 7 eyes (36.8%) in the early postoperative period. Defects (PED) were found in 6 eyes after adjuvant therapy, and 1 eye was persistent defect until the last follow-up (461 days). Four of them were complicated with local matrix infiltration and turbidity. Three eyes had visual impairment. The third part of the results showed that the morphology of the ocular surface epithelium was different from that of the three kinds of epithelium (lip mucosa epithelium, corneal epithelium and conjunctival epithelium). The number of layers, staining and the ratio of nucleus to cytoplasm were different. The cells in the central part of cornea differentiated better than those in the peripheral part. The longer the operation time, the better the differentiation of ocular surface cells. Scanning electron microscopy showed that the ultrastructure of the ocular surface epithelium was different from the three kinds of epithelium after oral mucosa transplantation. The microvilli differentiation of the central epithelium was more obvious than that of the peripheral epithelium, and some of the transplanted cases were closer to the corneal epithelium than that of the whole-week transplantation. Conclusion The lip mucosa transplantation designed in this study can effectively reconstruct the ocular surface in the scar stage and successfully perform the second-stage optical keratoplasty. Cell transdifferentiation can occur on the ocular surface, and the differentiated epithelial cells possess some characteristics of corneal epithelium.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R779.6
【相似文献】
相关博士学位论文 前1条
1 祝远方;口唇粘膜移植眼表重建的临床疗效及其术后上皮特性的研究[D];浙江大学;2014年
，本文编号：2182545
本文链接：https://www.wllwen.com/yixuelunwen/yank/2182545.html
最近更新
教材专著
