二次穿透性角膜移植术后的临床结果及角膜各项指标的观察
发布时间：2018-08-20 14:31
【摘要】：角膜盲是导致视力残疾的主要原因之一。1906年Zirm首次报道同种异体角膜移植手术,经过近百年的发展,目前穿透性角膜移植术(Penetrating Keratoplasty, PKP)已成为治疗角膜病致盲患者最常使用的手术之一。尽管PKP具有操作简单、手术适应症广、术后视力恢复较快等优点,免疫排斥反应仍然是导致手术失败的首要原因。除此之外,供体角膜本身的质量、保存的方法、患者的原发疾病、手术操作、植片大小、手术时间长短、术后并发症、供体ABO血型及HLA系统的是否匹配等因素,都与角膜植片失功能密切相关。 随着人类平均寿命的延长和对于生活品质的要求提升,因角膜植片失功能而行二次PKP的人数日益增多。近年来的研究发现,接受二次PKP的患者人数已占所有接受PKP总人数的22-41%。目前对二次PKP的研究以回顾性研究为主,可能存在研究对象记录缺失或不完整等问题。与初次PKP相比,接受二次PKP的患者的原发疾病、术后的视力预后和临床转归、排斥反应的发生比例、以及第二次手术后的并发症等是否有所差异,目前国内外都缺乏系统的前瞻性研究。术后植片的厚度变化、植片的上皮细胞、角膜细胞、基质细胞、内皮细胞等细胞密度与初次PKP患者相比有无变化,这些变化是否与植片的最终预后相关,这些问题也亟待解决。因此,本课题采取前瞻性研究,分析二次PKP患者的一般情况、术前原发疾病、术后最佳矫正视力和屈光状态、术后并发症及排斥反应,观察活体状态下角膜植片各项指标的变化规律,并与初次PKP患者进行比较,探讨二次PKP患者的临床转归,为接受二次PKP患者的临床诊疗提供更为完善的理论依据。 第一部分 二次PKP的临床疗效分析研究 目的 分析接受二次PKP手术的患者临床特征及术后预后情况。 方法 自2010年10月至2013年1月在本院行二次PKP的患者资料按入组标纳入研究。分析患者初次手术前的原发疾病、二次手术的植片和植床直径、手术时间、术中和术后并发症、末次随访时的最佳矫正视力(Best corrected visual acuity,BCVA)及屈光度。 结果 共49人(49眼)纳入研究,男29人,女20人,平均年龄47.8±17.7岁,术前平均视力LP～FC/BE;初次手术前诊断为真菌性角膜炎(Fungal Keratitis)11眼、大泡性角膜病变(Bullous keratopathy)10眼、眼外(Ocular trauma)9眼、单纯疱疹病毒性角膜炎(Herpes simplex keratitis, HSK),又称单疱角膜炎8眼、角膜营养不良(Corneal dystrophy)8眼、先天性角膜白斑(Congenital leucoma)2眼、虹膜角膜内皮综合征(Iridocorneal endothelial syndrome, ICE)1眼；植片平均直径7.82±0.26mm；手术顺利,无手术并发症。 术后随访时间为10.67±7.46月,随访期间有高眼压12眼(24.5%)、继发性青光眼13眼(26%)、排斥反应11眼(21.6%)；术后末次随访时,BCVA为0.25±0.17,等效球径(Diopters sphere)度数-1.47±2.45D,散光度(Diopters cylinder)为-3.41±1.413D。 结论 接受二次PKP的患者中,初次手术的原发疾病以感染性眼表疾病为主；高眼压、继发性青光眼及排斥反应皆是二次PKP术后常见的并发症。 第二部分 二次PKP患者术后的植片影像学检查和分析 目的 使用眼前节光学相干断层成像术(Anterior Segment Optical coherence tomography, AS-OCT)和激光活体共聚焦显微镜(In vivo confocal microscopy, IVCM)观察二次PK.P术后的角膜植片形态学变化,探讨二次PKP术后角膜植片各种细胞的变化规律。 方法 自2010年10月至2013年1月在本院行二次PKP的患者资料按入组标准纳入研究。术后1周、2周、1月、2月、3月、6月、9月、12月、15月、18月、21月、24月随访,每次随访时进行AS-OCT和IVCM。测量角膜植片厚度和角膜上皮厚度；分析角膜上皮基底层细胞、角膜浅基质层细胞、角膜内皮细胞及朗格汉斯细胞(Langerhans cells, LCs)的形态及密度变化。 结果 入选人群的基本情况以及初次手术的术前诊断与第一部分相同。术后第一个月时角膜植片厚度为538.67±66.17μm,术后第一年内(术后1月-12月)植片厚度逐渐下降至475.60士60.90μm；但在术后第二年(12月-24月),植片厚度又逐渐上升,至术后24个月时,植片平均厚度增至509.33±70.29μm(X2=35.21,P=0.000)。角膜上皮厚度的变化规律与植片厚度变化基本一致(F=2.76,P=0.002)。术后一个月时角膜上皮基底层细胞密度为9072±579cell/mm2,术后第一年内(术后1月-12月)上皮密度逐渐增加至9811±221cell/mm2;但在术后第二年(12月-24月),上皮细胞密度又逐渐下降至9502±224cell/mm2(Χ2=128.0,P=0.000),在术后6个月开始,角膜上皮下基质层和前弹力层可见再生的角膜神经纤维。角膜浅基质细胞密度也存在先上升后下降的规律,但细胞密度峰值出现在术后3个月,达293±79cell/mm2,至术后两年时下降至157±45cell/mm2(Χ2=107.69,P=0.000)。术后角膜内皮细胞密度持续下降,术后第一个月时为2765±341cell/mm2,至术后2年时仅有1302±555cell/mm2(X2=130.70,P=0.000)。 结论 术后一年时角膜厚度开始增加,角膜内皮细胞密度持续减少,提示术后一年之后植片内皮功能明显下降。 第三部分 二次PKP与初次PKP患者术后角膜植片形态特征的比较研究 目的 使用眼AS-OCT和激光活体共聚焦显微镜分别观察二次PKP和初次PKP术后的角膜植片形态学变化,探讨二次手术对角膜植片的形态变化的影响。 方法 自2011年10月至2013年1月在本院行一次及二次PKP的患者资料按入组标准纳入研究,术后1周、1月、2月、3月、6月、9月及12月随访。每次随访时均接受AS-OCT和IVCM检查。观察指标与第二部分相同。 结果 本研究中,二次PKP患者36人(36眼),男22人,女14人,平均年龄为43.1+16.7岁；初次PKP患者47人(47眼),男28人,女19人,平均年龄为46.3±19.1岁。除术后第一个月时二次PKP的角膜上皮厚度较高外(二次PKP：53.59+8.79μm对比初次PKP:50.22±7.97μm; t=-2.713,P=0.008),其余各时间点二次手术和初次手术患者的植片上皮厚度并无明显差异。术后各时间点比较初次与二次PKP患者的角膜植片厚度、角膜上皮基底层细胞密度和角膜浅基质层细胞密度,结果均无明显差异,初次PKP组于术后3个月可观察到神经再生,早于二次PKP组。然而,二次PKP术后的角膜内皮细胞衰减速度远高于初次PKP,从术后3月(months, mhs)起两组间比较均有显著统计学差异；初次PKP：2946±165cell/mm2(3mhs),2948±221cell/mm2(6mhs),2621±399cell/mm2(9mhs),2664±553cell/mm2(12mhs);而在二次PKP:2370±457cell/mm2(3mhs),2127±560cell/mm2(6mhs),1993±449cell/mm2(9mhs),1650±453cell/mm2(12mhs); P值均0.001)。 结论 与初次PKP相比,二次PKP术后早期植片上皮水肿较为明显,且手术3个月后内皮衰减明显,提示对于二次PKP的患者术后随访时需要更加密切地关注内皮细胞的变化。
[Abstract]:Corneal blindness is one of the major causes of visual impairment. In 1906, Zirm first reported allograft keratoplasty. After nearly a century of development, penetrating keratoplasty (PKP) has become one of the most commonly used procedures for the treatment of corneal blindness. In addition, the quality of the donor cornea, the method of preservation, the patient's primary disease, the operation, the size of the graft, the length of the operation, the postoperative complications, the matching of the donor ABO blood group and the HLA system are all related to the quality of the donor cornea itself. Corneal graft dysfunction is closely related.
With the prolongation of life expectancy and the improvement of quality of life, the number of secondary PKP patients due to corneal graft dysfunction is increasing. Recent studies have found that the number of patients receiving secondary PKP has accounted for 22-41% of all PKP recipients. Compared with primary PKP, there is no systematic prospective study on primary disease, postoperative visual prognosis, clinical outcome, rejection rate, and complications after second PKP. The density of epithelial cells, corneal cells, stromal cells and endothelial cells in the graft is different from that in the patients with primary PKP. Whether these changes are related to the final prognosis of the graft remains to be solved. Visual acuity, refractive status, postoperative complications and rejection were observed. The changes of corneal graft parameters in vivo were compared with those in primary PKP patients, and the clinical outcome of secondary PKP patients was discussed.
Part one
Clinical analysis of two times PKP
objective
The clinical characteristics and postoperative prognosis of two patients undergoing PKP operation were analyzed.
Method
Data of patients with secondary PKP from October 2010 to January 2013 were included in the study according to grouping criteria. Primary diseases, graft and implant diameter, operative time, intraoperative and postoperative complications, best corrected visual acuity (BCVA) and diopter at the last follow-up were analyzed.
Result
A total of 49 patients (49 eyes) were included in the study, 29 males and 20 females, with an average age of 47.8 (+ 17.7) years. The average preoperative visual acuity was LP-FC/BE. 11 eyes were diagnosed as fungal keratitis, 10 eyes with bullous keratopathy, 9 eyes with extraocular trauma, and 9 eyes with herpes simplex keratitis before primary surgery. SK, also known as herpes simplex keratitis in 8 eyes, corneal dystrophy in 8 eyes, congenital leukoplakia in 2 eyes, iris corneal endothelial syndrome (ICE) in 1 eye; the average diameter of the graft was 7.82 (+ 0.26 mm); the operation was successful without any complications.
Postoperative follow-up time was 10.67 [7.46], 12 eyes (24.5%) had high intraocular pressure, 13 eyes (26%) had secondary glaucoma and 11 eyes (21.6%) had rejection. At the last follow-up, BCVA was 0.25 [0.17], Diopters sphere degree was - 1.47 [2.45 D], and Diopters cylinder was - 3.41 [1.413 D].
conclusion
Infectious ocular surface disease is the main primary disease in patients with secondary PKP. High intraocular pressure, secondary glaucoma and rejection are common complications after secondary PKP.
The second part
Imaging examination and analysis of two patients with PKP after operation
objective
Anterior Segment Optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) were used to observe the morphological changes of corneal grafts after secondary PK.P, and to investigate the changes of corneal graft cells after secondary PKP.
Method
Patients with secondary PKP from October 2010 to January 2013 were included in the study according to the inclusion criteria. All patients were followed up for 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months after surgery. AS-OCT and IVCM were used to measure corneal graft thickness and corneal epithelial thickness. Changes in morphology and density of Langerhans cells (LCs) and cells.
Result
The corneal graft thickness was 538.67 [66.17] micron in the first month after the operation, and gradually decreased to 475.60 [60.90] micron in the first year (1-12 months after the operation), but gradually increased to 24 months after the operation (12-24 months). At month 1, the average thickness of the graft increased to 509.33 [70.29] Um (X2 = 35.21, P = 0.000). The change of corneal epithelial thickness was basically consistent with that of the graft thickness (F = 2.76, P = 0.002). At month 1, the density of corneal epithelial cells in the basal layer was 9072 [579] cells / mm2, and gradually increased to 981 [221] cel within the first year (1 - 12 months after surgery). L/mm2; however, the epithelial cell density gradually decreased to 9502 (+224) cell/mm2 (_2 = 128.0, P = 0.000) in the second year (December-24) after surgery. At 6 months after surgery, regenerated corneal nerve fibers were observed in the subepithelial and anterior elastic layers of the cornea. The corneal endothelial cell density (ECD) decreased continuously from 2 765 341 cell/mm2 at the first month to 1 1302
conclusion
Corneal thickness began to increase one year after operation and corneal endothelial cell density continued to decrease, suggesting that the endothelial function of grafts decreased significantly one year after operation.
The third part
Comparison of corneal graft characteristics between two PKP and initial PKP patients
objective
The morphological changes of corneal grafts after secondary PKP and primary PKP were observed by laser in vivo confocal microscopy and AS-OCT respectively.
Method
Patients with primary and secondary PKP in our hospital from October 2011 to January 2013 were included in the study according to the inclusion criteria. All patients were followed up 1 week, 1 month, 2 months, 3 months, 6 months, 9 months and 12 months after operation. All patients were examined by AS-OCT and IVCM at each follow-up.
Result
In this study, 36 patients with secondary PKP (36 eyes), 22 males and 14 females, with an average age of 43.1+16.7 years; 47 patients with primary PKP (47 eyes), 28 males and 19 females, with an average age of 46.3+19.1 years. There was no significant difference in corneal graft thickness, basal layer cell density and superficial stromal cell density between primary and secondary PKP patients at all time points. The results were not significantly different in primary PKP group and primary PKP group 3 months after operation. However, the attenuation rate of corneal endothelial cells after the second PKP was much higher than that of the first PKP, and there was significant difference between the two groups from 3 months after the second PKP, the first PKP: 2946 (+ 165 cell / mm2 (3mhs), 2948 (+ 221 cell / mm2 (6mhs), 2621 (+ 399 cell / mm2) (9mhs), 2664 (+ 553 cell / mm2) and the second PKP (12mhs). Secondary PKP:2370+457 cell/mm2(3mhs),2127+560 cell/mm2(6mhs),1993+449 cell/mm2(9mhs),1650+453 cell/mm2(12mhs).
conclusion
Compared with the primary PKP, the early graft edema was more obvious after the second PKP, and the endothelial attenuation was obvious after 3 months of operation, suggesting that the patients with the second PKP should pay more attention to the changes of endothelial cells during the follow-up.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R779.65
本文编号：2193958
[Abstract]:Corneal blindness is one of the major causes of visual impairment. In 1906, Zirm first reported allograft keratoplasty. After nearly a century of development, penetrating keratoplasty (PKP) has become one of the most commonly used procedures for the treatment of corneal blindness. In addition, the quality of the donor cornea, the method of preservation, the patient's primary disease, the operation, the size of the graft, the length of the operation, the postoperative complications, the matching of the donor ABO blood group and the HLA system are all related to the quality of the donor cornea itself. Corneal graft dysfunction is closely related.
With the prolongation of life expectancy and the improvement of quality of life, the number of secondary PKP patients due to corneal graft dysfunction is increasing. Recent studies have found that the number of patients receiving secondary PKP has accounted for 22-41% of all PKP recipients. Compared with primary PKP, there is no systematic prospective study on primary disease, postoperative visual prognosis, clinical outcome, rejection rate, and complications after second PKP. The density of epithelial cells, corneal cells, stromal cells and endothelial cells in the graft is different from that in the patients with primary PKP. Whether these changes are related to the final prognosis of the graft remains to be solved. Visual acuity, refractive status, postoperative complications and rejection were observed. The changes of corneal graft parameters in vivo were compared with those in primary PKP patients, and the clinical outcome of secondary PKP patients was discussed.
Part one
Clinical analysis of two times PKP
objective
The clinical characteristics and postoperative prognosis of two patients undergoing PKP operation were analyzed.
Method
Data of patients with secondary PKP from October 2010 to January 2013 were included in the study according to grouping criteria. Primary diseases, graft and implant diameter, operative time, intraoperative and postoperative complications, best corrected visual acuity (BCVA) and diopter at the last follow-up were analyzed.
Result
A total of 49 patients (49 eyes) were included in the study, 29 males and 20 females, with an average age of 47.8 (+ 17.7) years. The average preoperative visual acuity was LP-FC/BE. 11 eyes were diagnosed as fungal keratitis, 10 eyes with bullous keratopathy, 9 eyes with extraocular trauma, and 9 eyes with herpes simplex keratitis before primary surgery. SK, also known as herpes simplex keratitis in 8 eyes, corneal dystrophy in 8 eyes, congenital leukoplakia in 2 eyes, iris corneal endothelial syndrome (ICE) in 1 eye; the average diameter of the graft was 7.82 (+ 0.26 mm); the operation was successful without any complications.
Postoperative follow-up time was 10.67 [7.46], 12 eyes (24.5%) had high intraocular pressure, 13 eyes (26%) had secondary glaucoma and 11 eyes (21.6%) had rejection. At the last follow-up, BCVA was 0.25 [0.17], Diopters sphere degree was - 1.47 [2.45 D], and Diopters cylinder was - 3.41 [1.413 D].
conclusion
Infectious ocular surface disease is the main primary disease in patients with secondary PKP. High intraocular pressure, secondary glaucoma and rejection are common complications after secondary PKP.
The second part
Imaging examination and analysis of two patients with PKP after operation
objective
Anterior Segment Optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) were used to observe the morphological changes of corneal grafts after secondary PK.P, and to investigate the changes of corneal graft cells after secondary PKP.
Method
Patients with secondary PKP from October 2010 to January 2013 were included in the study according to the inclusion criteria. All patients were followed up for 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months after surgery. AS-OCT and IVCM were used to measure corneal graft thickness and corneal epithelial thickness. Changes in morphology and density of Langerhans cells (LCs) and cells.
Result
The corneal graft thickness was 538.67 [66.17] micron in the first month after the operation, and gradually decreased to 475.60 [60.90] micron in the first year (1-12 months after the operation), but gradually increased to 24 months after the operation (12-24 months). At month 1, the average thickness of the graft increased to 509.33 [70.29] Um (X2 = 35.21, P = 0.000). The change of corneal epithelial thickness was basically consistent with that of the graft thickness (F = 2.76, P = 0.002). At month 1, the density of corneal epithelial cells in the basal layer was 9072 [579] cells / mm2, and gradually increased to 981 [221] cel within the first year (1 - 12 months after surgery). L/mm2; however, the epithelial cell density gradually decreased to 9502 (+224) cell/mm2 (_2 = 128.0, P = 0.000) in the second year (December-24) after surgery. At 6 months after surgery, regenerated corneal nerve fibers were observed in the subepithelial and anterior elastic layers of the cornea. The corneal endothelial cell density (ECD) decreased continuously from 2 765 341 cell/mm2 at the first month to 1 1302
conclusion
Corneal thickness began to increase one year after operation and corneal endothelial cell density continued to decrease, suggesting that the endothelial function of grafts decreased significantly one year after operation.
The third part
Comparison of corneal graft characteristics between two PKP and initial PKP patients
objective
The morphological changes of corneal grafts after secondary PKP and primary PKP were observed by laser in vivo confocal microscopy and AS-OCT respectively.
Method
Patients with primary and secondary PKP in our hospital from October 2011 to January 2013 were included in the study according to the inclusion criteria. All patients were followed up 1 week, 1 month, 2 months, 3 months, 6 months, 9 months and 12 months after operation. All patients were examined by AS-OCT and IVCM at each follow-up.
Result
In this study, 36 patients with secondary PKP (36 eyes), 22 males and 14 females, with an average age of 43.1+16.7 years; 47 patients with primary PKP (47 eyes), 28 males and 19 females, with an average age of 46.3+19.1 years. There was no significant difference in corneal graft thickness, basal layer cell density and superficial stromal cell density between primary and secondary PKP patients at all time points. The results were not significantly different in primary PKP group and primary PKP group 3 months after operation. However, the attenuation rate of corneal endothelial cells after the second PKP was much higher than that of the first PKP, and there was significant difference between the two groups from 3 months after the second PKP, the first PKP: 2946 (+ 165 cell / mm2 (3mhs), 2948 (+ 221 cell / mm2 (6mhs), 2621 (+ 399 cell / mm2) (9mhs), 2664 (+ 553 cell / mm2) and the second PKP (12mhs). Secondary PKP:2370+457 cell/mm2(3mhs),2127+560 cell/mm2(6mhs),1993+449 cell/mm2(9mhs),1650+453 cell/mm2(12mhs).
conclusion
Compared with the primary PKP, the early graft edema was more obvious after the second PKP, and the endothelial attenuation was obvious after 3 months of operation, suggesting that the patients with the second PKP should pay more attention to the changes of endothelial cells during the follow-up.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R779.65
【参考文献】
相关期刊论文 前2条
1 赵峰;徐建江;郑天玉;;再次穿透性角膜移植术的病因分析[J];中国眼耳鼻喉科杂志;2008年03期
2 ;2006年第二次全国残疾人抽样调查主要数据公报[J];中国康复理论与实践;2006年12期
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