發(fā)布時(shí)間：2018-08-20 14:31

【摘要】：角膜盲是導(dǎo)致視力殘疾的主要原因之一。1906年Zirm首次報(bào)道同種異體角膜移植手術(shù),經(jīng)過近百年的發(fā)展,目前穿透性角膜移植術(shù)(Penetrating Keratoplasty, PKP)已成為治療角膜病致盲患者最常使用的手術(shù)之一。盡管PKP具有操作簡單、手術(shù)適應(yīng)癥廣、術(shù)后視力恢復(fù)較快等優(yōu)點(diǎn),免疫排斥反應(yīng)仍然是導(dǎo)致手術(shù)失敗的首要原因。除此之外,供體角膜本身的質(zhì)量、保存的方法、患者的原發(fā)疾病、手術(shù)操作、植片大小、手術(shù)時(shí)間長短、術(shù)后并發(fā)癥、供體ABO血型及HLA系統(tǒng)的是否匹配等因素,都與角膜植片失功能密切相關(guān)。 隨著人類平均壽命的延長和對(duì)于生活品質(zhì)的要求提升,因角膜植片失功能而行二次PKP的人數(shù)日益增多。近年來的研究發(fā)現(xiàn),接受二次PKP的患者人數(shù)已占所有接受PKP總?cè)藬?shù)的22-41%。目前對(duì)二次PKP的研究以回顧性研究為主,可能存在研究對(duì)象記錄缺失或不完整等問題。與初次PKP相比,接受二次PKP的患者的原發(fā)疾病、術(shù)后的視力預(yù)后和臨床轉(zhuǎn)歸、排斥反應(yīng)的發(fā)生比例、以及第二次手術(shù)后的并發(fā)癥等是否有所差異,目前國內(nèi)外都缺乏系統(tǒng)的前瞻性研究。術(shù)后植片的厚度變化、植片的上皮細(xì)胞、角膜細(xì)胞、基質(zhì)細(xì)胞、內(nèi)皮細(xì)胞等細(xì)胞密度與初次PKP患者相比有無變化,這些變化是否與植片的最終預(yù)后相關(guān),這些問題也亟待解決。因此,本課題采取前瞻性研究,分析二次PKP患者的一般情況、術(shù)前原發(fā)疾病、術(shù)后最佳矯正視力和屈光狀態(tài)、術(shù)后并發(fā)癥及排斥反應(yīng),觀察活體狀態(tài)下角膜植片各項(xiàng)指標(biāo)的變化規(guī)律,并與初次PKP患者進(jìn)行比較,探討二次PKP患者的臨床轉(zhuǎn)歸,為接受二次PKP患者的臨床診療提供更為完善的理論依據(jù)。 第一部分 二次PKP的臨床療效分析研究 目的 分析接受二次PKP手術(shù)的患者臨床特征及術(shù)后預(yù)后情況。 方法 自2010年10月至2013年1月在本院行二次PKP的患者資料按入組標(biāo)納入研究。分析患者初次手術(shù)前的原發(fā)疾病、二次手術(shù)的植片和植床直徑、手術(shù)時(shí)間、術(shù)中和術(shù)后并發(fā)癥、末次隨訪時(shí)的最佳矯正視力(Best corrected visual acuity,BCVA)及屈光度。 結(jié)果 共49人(49眼)納入研究,男29人,女20人,平均年齡47.8±17.7歲,術(shù)前平均視力LP～FC/BE;初次手術(shù)前診斷為真菌性角膜炎(Fungal Keratitis)11眼、大泡性角膜病變(Bullous keratopathy)10眼、眼外(Ocular trauma)9眼、單純皰疹病毒性角膜炎(Herpes simplex keratitis, HSK),又稱單皰角膜炎8眼、角膜營養(yǎng)不良(Corneal dystrophy)8眼、先天性角膜白斑(Congenital leucoma)2眼、虹膜角膜內(nèi)皮綜合征(Iridocorneal endothelial syndrome, ICE)1眼；植片平均直徑7.82±0.26mm；手術(shù)順利,無手術(shù)并發(fā)癥。 術(shù)后隨訪時(shí)間為10.67±7.46月,隨訪期間有高眼壓12眼(24.5%)、繼發(fā)性青光眼13眼(26%)、排斥反應(yīng)11眼(21.6%)；術(shù)后末次隨訪時(shí),BCVA為0.25±0.17,等效球徑(Diopters sphere)度數(shù)-1.47±2.45D,散光度(Diopters cylinder)為-3.41±1.413D。 結(jié)論 接受二次PKP的患者中,初次手術(shù)的原發(fā)疾病以感染性眼表疾病為主；高眼壓、繼發(fā)性青光眼及排斥反應(yīng)皆是二次PKP術(shù)后常見的并發(fā)癥。 第二部分 二次PKP患者術(shù)后的植片影像學(xué)檢查和分析 目的 使用眼前節(jié)光學(xué)相干斷層成像術(shù)(Anterior Segment Optical coherence tomography, AS-OCT)和激光活體共聚焦顯微鏡(In vivo confocal microscopy, IVCM)觀察二次PK.P術(shù)后的角膜植片形態(tài)學(xué)變化,探討二次PKP術(shù)后角膜植片各種細(xì)胞的變化規(guī)律。 方法 自2010年10月至2013年1月在本院行二次PKP的患者資料按入組標(biāo)準(zhǔn)納入研究。術(shù)后1周、2周、1月、2月、3月、6月、9月、12月、15月、18月、21月、24月隨訪,每次隨訪時(shí)進(jìn)行AS-OCT和IVCM。測(cè)量角膜植片厚度和角膜上皮厚度；分析角膜上皮基底層細(xì)胞、角膜淺基質(zhì)層細(xì)胞、角膜內(nèi)皮細(xì)胞及朗格漢斯細(xì)胞(Langerhans cells, LCs)的形態(tài)及密度變化。 結(jié)果 入選人群的基本情況以及初次手術(shù)的術(shù)前診斷與第一部分相同。術(shù)后第一個(gè)月時(shí)角膜植片厚度為538.67±66.17μm,術(shù)后第一年內(nèi)(術(shù)后1月-12月)植片厚度逐漸下降至475.60士60.90μm；但在術(shù)后第二年(12月-24月),植片厚度又逐漸上升,至術(shù)后24個(gè)月時(shí),植片平均厚度增至509.33±70.29μm(X2=35.21,P=0.000)。角膜上皮厚度的變化規(guī)律與植片厚度變化基本一致(F=2.76,P=0.002)。術(shù)后一個(gè)月時(shí)角膜上皮基底層細(xì)胞密度為9072±579cell/mm2,術(shù)后第一年內(nèi)(術(shù)后1月-12月)上皮密度逐漸增加至9811±221cell/mm2;但在術(shù)后第二年(12月-24月),上皮細(xì)胞密度又逐漸下降至9502±224cell/mm2(Χ2=128.0,P=0.000),在術(shù)后6個(gè)月開始,角膜上皮下基質(zhì)層和前彈力層可見再生的角膜神經(jīng)纖維。角膜淺基質(zhì)細(xì)胞密度也存在先上升后下降的規(guī)律,但細(xì)胞密度峰值出現(xiàn)在術(shù)后3個(gè)月,達(dá)293±79cell/mm2,至術(shù)后兩年時(shí)下降至157±45cell/mm2(Χ2=107.69,P=0.000)。術(shù)后角膜內(nèi)皮細(xì)胞密度持續(xù)下降,術(shù)后第一個(gè)月時(shí)為2765±341cell/mm2,至術(shù)后2年時(shí)僅有1302±555cell/mm2(X2=130.70,P=0.000)。 結(jié)論 術(shù)后一年時(shí)角膜厚度開始增加,角膜內(nèi)皮細(xì)胞密度持續(xù)減少,提示術(shù)后一年之后植片內(nèi)皮功能明顯下降。 第三部分 二次PKP與初次PKP患者術(shù)后角膜植片形態(tài)特征的比較研究 目的 使用眼AS-OCT和激光活體共聚焦顯微鏡分別觀察二次PKP和初次PKP術(shù)后的角膜植片形態(tài)學(xué)變化,探討二次手術(shù)對(duì)角膜植片的形態(tài)變化的影響。 方法 自2011年10月至2013年1月在本院行一次及二次PKP的患者資料按入組標(biāo)準(zhǔn)納入研究,術(shù)后1周、1月、2月、3月、6月、9月及12月隨訪。每次隨訪時(shí)均接受AS-OCT和IVCM檢查。觀察指標(biāo)與第二部分相同。 結(jié)果 本研究中,二次PKP患者36人(36眼),男22人,女14人,平均年齡為43.1+16.7歲；初次PKP患者47人(47眼),男28人,女19人,平均年齡為46.3±19.1歲。除術(shù)后第一個(gè)月時(shí)二次PKP的角膜上皮厚度較高外(二次PKP：53.59+8.79μm對(duì)比初次PKP:50.22±7.97μm; t=-2.713,P=0.008),其余各時(shí)間點(diǎn)二次手術(shù)和初次手術(shù)患者的植片上皮厚度并無明顯差異。術(shù)后各時(shí)間點(diǎn)比較初次與二次PKP患者的角膜植片厚度、角膜上皮基底層細(xì)胞密度和角膜淺基質(zhì)層細(xì)胞密度,結(jié)果均無明顯差異,初次PKP組于術(shù)后3個(gè)月可觀察到神經(jīng)再生,早于二次PKP組。然而,二次PKP術(shù)后的角膜內(nèi)皮細(xì)胞衰減速度遠(yuǎn)高于初次PKP,從術(shù)后3月(months, mhs)起兩組間比較均有顯著統(tǒng)計(jì)學(xué)差異；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)。 結(jié)論 與初次PKP相比,二次PKP術(shù)后早期植片上皮水腫較為明顯,且手術(shù)3個(gè)月后內(nèi)皮衰減明顯,提示對(duì)于二次PKP的患者術(shù)后隨訪時(shí)需要更加密切地關(guān)注內(nèi)皮細(xì)胞的變化。
[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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R779.65

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