HLA—DRB1基因配型与高危角膜移植排斥关系的回顾性研究

目的 评价HLA基因配型在减少高危角膜移植免疫排斥反应中的作用。方法 对91例高危穿透性角膜移植病例，术后双盲法进行供受体HLA－DRB1基因分型和临床观察，随访12－26mo，对其基因配型情况和术后排斥反应的关系进行回顾性分析。结果 91例患者中61例随访资料完整。其中16例供受体有1个基因位点相符，在这些配型良好的病例中，5例（31．24％）发生免疫排斥反应，但随访期间无植片混浊；45例配型不好的患者中，术后23例（51．11％）发生免疫排斥反应，其中5例发生了植片混浊。结论 HLA－DRB1基因配型未能显著减少角膜移植术后的免疫排斥反应。     

穿透角膜移植术后免疫排斥反应高危因素分析

为确立角膜移植术后免疫排斥反应的有效防治策略。对穿透角膜移植术后发生免疫排斥反应的８６个病例（１００只眼）进行回顾性总结。统计分析结果表明：血管化角膜、大植片移植、植床术前的活动性炎症，偏中心移植、多次移植、联合手术均应视为穿透角膜移植术后免疫排斥反应的高危因素，而移植片上皮反复脱落、旧病复发、术眼再次手术、缝线松解与拆线等可能是诱导排斥反应发生的促发因素。结论：从分子水平减少供受体间的抗原差异，研制新一代高效安全的免疫抑制剂、创造免疫耐度的理想环境可能是控制高危角膜移植免疫排斥反应的有效防治措施。     

角膜移植术后免疫排斥反应的防治进展

由于角膜的免疫赦免地位 ,角膜移植是众多器官和组织移植中成功率最高的 ,也是角膜盲患者复明的唯一手段。然而移植后的免疫排斥反应仍然是造成角膜移植术后失败的主要原因。尤其二次移植、新生血管化植床等高危因素的患者 ,术后的免疫排斥发生率高达 6 0～ 90 %。而目前我国多数为高危因素的患者。因此 ,有效的控制角膜移植术后免疫排斥反应的发生就成为角膜植片能否长期存活的关键所在。目前用于减少或防治角膜移植术后免疫排斥反应的方法综合如下 :1 组织配型组织配型主要包括主要组织相容性抗原 (HLA)配型和ABO血型抗原配型。在心脏…     

HLA-A/B、DR抗原的基因配型对穿透性角膜移植免疫排斥反应影响的研究

目的 探讨HLA-A/B、DR抗原的基因配型对穿透性角膜移植术后免疫排斥的影响。设计实验研究。研究对象北京同仁医院穿透性角膜移植角膜供受体材料150对。方法 回顾角膜供受体的基本信息、免疫排斥反应发生情况、可能引起排斥反应的高危因素。对供体角膜环和受体病变组织采用多聚酶链式反应-序列特异性引物(PCR-SS)法进行HLA-A/B、DR抗原的基因检测及配型。根据供体与受体HLA配型是否一致分为配型符合组及配型不符合组。采用χ²检验对组间排斥反应率进行比较。采用Logistic回归分析基因配型及其他相关危险因素对发生排斥反应的发生风险。主要指标不同HLA抗原基因配型的排斥反应发生率;发生排斥反应的OR值。结果 150对角膜组织中HLA-A/B配型符合组64例,3例(4.69%)发生免疫排斥反应;配型不符合组86例中23例(33.72%)发生排斥反应(χ²=18.430,P<0.001)。HLA-DR配型符合组34例,9例(25.71%)发生免疫排斥反应,配型不符合组115例,23例(20%)发生免疫排斥反应(χ²=0....     

二次穿透性角膜移植术的临床研究

目的 对穿透性角膜移植术后植片混浊的原因及二次穿透性角膜移植术的临床技巧及疗效进行初步研究.方法 回顾性研究,对40例因植片混浊行二次穿透性角膜移植术的患者,对原发病、植片混浊原因和两次手术时间二次移植的植片的大小进行分析,随访观察植片透明度、视力及免疫排斥情况.结果 感染性角膜炎居原发病首位.免疫排斥反应为植片混浊的主要原因,其次为植片感染性角膜炎复发、再发或继发.10例因植片感染于6个月及以内更换植片,30例因植片混浊于6个月以上更换植片.5例原直径过大而采用小直径植片;29例原直径≤8.25mm而采用等直径植片;6例因复发感染累及植片周边而扩大植片直径.随访32例植片(≤8.25mm)透明,视力较术前明显提高.8例植片混浊,其中5例混浊由免疫排斥所致.结论 造成二次穿透性角膜移植术的主要原因为植片免疫排斥和感染性角膜炎复发、再发或继发,据植片混浊不同病因采取不同直径的二次植片可有效减低免疫排斥反应发生率及治疗原发病复发或再发,延长植片透明时间.     

高危角膜移植的围手术期治疗

目的　探讨高危角膜移植患者围手术期的处理措施 ,以降低术后免疫排斥反应率。方法　对 6 80例有完整随访记录的穿透性角膜移植中的 12 4例 (137眼 )高危角膜移植患者 ,分别在围手术期 (术前、术中、术后早期 )进行相应处理。结果　经围手术期处理后 ,本组 137眼高危患者穿透性角膜移植后的免疫排斥率为 37% ,植片透明率为 80 .1% .结论　重视高危角膜移植围手术期的处理 ,是减少术后免疫排斥反应和提高植片透明率的重要措施     

角膜内皮移植治疗穿透性角膜移植术后植片失代偿的长期疗效观察

目的 观察角膜内皮移植手术（EK）治疗穿透性角膜移植术（PKP）后植片失代偿的长期临床效果。设计 回顾性病例系列。 研究对象 选取2008至2010年爱尔眼科医院收治的接受PKP术后植片内皮失代偿的患者6例（6眼）。 方法 对上述患者实施EK手术,对患者的临床资料进行回顾性分析。记录并分析患者术后视力、眼压、内皮细胞密度、排斥反应及并发症等。平均随访时间为（36.17±10.11）个月。主要指标  视力、眼压、内皮细胞密度、排斥反应及并发症。结果 术后所有患者植片均恢复透明,视力较前有不同程度提高,症状缓解。末次随访时,1例患者角膜失代偿,其余5例内皮细胞密度从986~1914个/mm2。随访期内,1例术后1天发生植片半脱位,经再次前房注气后贴附良好;1例术后5个月发生免疫排斥反应,经药物治疗植片保持透明;另1例患者未规律随诊,内皮移植术后26个月时发生排斥反应,导致失代偿。结论 对于反复发生免疫排斥反应导致植片混浊的高危患者,角膜内皮移植手术是可供选择的治疗方法。     

FK-506抑制高危角膜移植免疫排斥反应的研究

目的 :探讨FK -5 0 6抑制高危角膜移植免疫排斥反应临床应用的可行性及有效性。方法 :应用前瞻性评估研究方法 ,将行高危角膜移植术 (全角膜移植术、带巩膜环的全角膜移植术、血管化角膜的角膜移植术及角膜再移植术 ) 5 6例 (5 6只眼 )患者按随机原则进行分组 (投药组及对照组 ) ,投药组 (2 8只眼 )滴用 0 5mg/ml的FK -5 0 6滴眼液联合典必珠滴眼液 ,对照组 (2 8只眼 )滴用 1%CsA滴眼液联合典必殊滴眼液 ;平均随访 8 1个月 ,以术后视功能、植片透明维持时间、植片新生血管、水肿及混浊程度作为临床主要评估指标。结果 :随防期内投药组及对照组角膜移植片免疫排斥反应发生率分别为 63 6%及 95 2 % ,差异有显著性 (χ2 =4 72 ,P <0 0 5 )。用药期间未发现该药有任何毒副作用。结论 :局部应用FK -5 0 6可有效抑制高危角膜移植免疫排斥反应的发生。     

穿透性角膜移植排斥反应危险因素分析

目的:探讨穿透性角膜移植术后植片排斥的危险因素。方法:回顾性分析我院2001-01/2008-01实施穿透性角膜移植发生排斥反应的病例,分析各因素在植片排斥反应病例中所占的比率及各种病例中植片排斥的发生率。结果:总排斥反应率为31.0%,其中普通组为25.5%,高危组为59.4%(P<0.05)。眼部化学伤排斥反应发生率最高48.1%(P<0.05)。高危组发生排斥反应早且病情严重。结论:引起角膜植片排斥的多种因素中,不同疾病的穿透性角膜移植的发生率不同,排斥反应的发生与术前原发病,植床情况,手术设计操作术后预防有密切关系,其中植床新生血管是植片排斥的高危因素。     

他克莫司滴眼液预防高危角膜移植免疫排斥反应的研究

目的观察他克莫司滴眼液预防高危角膜移植免疫排斥反应的效果。方法回顾性研究。选取山东省眼科医院2013年至2015年间成功施行角膜移植术的高危免疫排斥患者48例(50只眼),根据术后局部免疫抑制剂使用种类,分为他克莫司组23例(25只眼)和环孢素组25例(25只眼)。术前对所有患者进行排斥风险评分,以排斥反应指数(RI)判断是否出现植片免疫排斥反应,当RI≥5时视为发生免疫排斥反应,所有患者术后随访1年,对比1年内患者术后植片免疫排斥发生率。结果两组各25只眼,排斥风险评分他克莫司组与环孢素组不具有统计学差异(t=0.65,P=0.52>0.05)。术后1年内免疫排斥发生率,环孢素组10例(10只眼)发生排斥,免疫排斥发生率为40.00%,他克莫司组3例(3只眼)发生排斥,免疫排斥发生率为12.00%,他克莫司组免疫排斥率明显低于环孢素组,差异具有显著性(χ~2=5.09,P<0.05)。结论他克莫司滴眼液对高危角膜移植免疫排斥反应有较好的预防和治疗作用。     

Matching for Human Leukocyte Antigens (HLA) in corneal transplantation – To do or not to do

As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma, rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts.     

Influence of HLA-A, HLA-B, and HLA-DR matching on rejection of random corneal grafts using corneal tissue for retrospective DNA HLA typing

AIM: To establish if coincidental HLA-A, HLA-B, and HLA-DR tissue matching is associated with a reduced likelihood of corneal graft rejection. METHODS: Organ culture preserved random donor corneas were used for penetrating keratoplasty (PKP). Corneal tissue from all graft recipients and donors or blood samples from recipients after repeated transplantation were obtained in order to perform retrospective molecular HLA typing. A group of 21 recipients with a rejection episode (cases) after corneal transplantation was compared with a control group of non-rejectors (n = 43). 31 graft recipients were considered as high risk patients. The influence of HLA-A, HLA-B, and HLA-DR matching on rejection free graft survival time was analysed with Kaplan-Meyer statistics and Cox regression. RESULTS: A prolonged rejection free survival time was observed in graft recipients with one or two HLA-A matches (log rank test, p = 0.034). This effect was also observed in high risk graft recipients with one or two HLA-DR matches (log rank test, p = 0.030). CONCLUSIONS: Coincidental HLA-A and HLA-DR matches were observed and associated with a prolonged rejection free survival time in the total group and in the high risk group, respectively. These results support the beneficial effect of prospective HLA-A and HLA-DR typing upon corneal graft survival.     

Corneal graft survival in HLA-A- and HLA-B-matched transplantations in high-risk cases with retrospective review of HLA-DR compatibility

In 107 HLA-A- and HLA-B-matched corneal transplantations performed in high-risk patients, the 3-year graft survival was 60.5%. The criteria used for the definition of high risk were vascularization of the recipient cornea and/or one or more previous failed grafts; they were also the indications for HLA typing and matching. Donor/recipient compatibility was defined by the presence of only 0 or 1 HLA-A or HLA-B mismatches. When non-immunological factors leading to graft failure were excluded, the 3-year survival was 76.3%. During that follow-up period, a total of 33 grafts failed; in 13 cases, the cause was allograft rejection. When only first transplants were considered, a 3-year graft survival of 81.0% was observed. Retrospective DR typing was possible in 33 cases. Because only three graft rejections occurred in that group, we were unable to assess the importance of DR compatibility on the survival of corneal allografts.     

HLA-A,HLA-B and HLA-DR matching reduces the rate of corneal allograft rejection

Purpose The purpose of this study is to determine the effectiveness of HLA typing in preventing corneal allograft rejection.Methods This retrospective single-center study analyzed 459 consecutive HLA-typed patients who underwent perforating keratoplasty (PKP) between 1983 and 2001. Grafts were postoperatively transparent after donor-recipient selection by HLA-A, -B and -DR typing. Patients were divided into a low- and a high-risk group based on their preoperative diagnosis.Results The estimated 1-, 5- and 10-year graft survival (Kaplan-Meier) was 93, 88 and 67% in low-risk patients and 73, 43 and 38% in high-risk patients. We found a significant correlation between the number of HLA mismatches and the rate of allograft rejections: a donor-recipient match of two or more alleles in HLA-A, -B or -DR reduces the rejection rate by at least 10% in low-risk (10 years after PKP; P<0.04) and 40% in high-risk patients (3 years after PKP; P<0.0001). Especially HLA-B mismatches are important prognostic factors for both low- (P<0.008) and high-risk patients (P<0.003). Considering both HLA-B and -DR mismatches significantly reduces the rate of allograft rejection, particularly in high-risk patients (P<0.0001). Matching on a split typing level offers no significant advantage over broad level matching.Conclusion Clinical results confirm theories developed to explain the function of the HLA (MHC) receptor. The closest possible donor-recipient match of HLA antigens based on broad level typing significantly reduces the rate of allograft rejection and thus improves the prognosis for long-term transparency of corneal grafts in both high- and low-risk patients.This work was presented in part at the 100th meeting of the German Society of Ophthalmology, Berlin, 26–29 September 2002     

Long-term outcome in high-risk corneal transplantation and the influence of HLA-A and HLA-B matching

PURPOSE: To evaluate long-term follow-up of high-risk corneal transplants allocated after matching for broad HLA-A and HLA-B antigens and to establish whether matching for HLA-A and -B antigen "splits" would result in a reduced risk of immunologic graft failure. METHODS: A total of 303 high risk corneal transplants was included. Class I antigen-matched donor corneas were obtained using broad HLA-A and -B antigen data and accepting 0 or 1 mismatch at each locus. Analysis of HLA antigens was performed also on the split typing level. The influence on immunologic graft failure for an increasing number of matched class I antigens based on split typing was analyzed with Kaplan-Meier statistics and Cox regression. Graft survival and indication for transplantation were investigated. RESULTS: Rejection was the cause of 34% of all graft failures. A significantly higher immune failure free graft survival was found in a group with 0 or 1 HLA-A and -B mismatch based on split typing (log-rank test, P = 0.002). A beneficial effect of matching for split antigens was shown with multivariate analysis (odds ratio, 0.41). CONCLUSIONS: One third of graft failures in our high-risk population was caused by irreversible graft rejection. Allocation of donor corneas based on a 0 or 1 split antigen mismatch at both HLA-A and -B loci could contribute to a higher immune failure free graft survival and could result in a higher overall graft survival.     

Penetrating keratoplasty for endothelial decompensation in eyes with buphthalmos

PURPOSE: To evaluate the prognosis and complications of penetrating keratoplasty (PKP) for corneal decompensation in eyes with buphthalmos and to analyze the risk factors for graft failure. PATIENTS AND METHODS: Clinical records of 13 adult and three pediatric patients who underwent PKP for endothelial decompensation with a previous diagnosis of congenital glaucoma of a total of 3,663 corneal transplantations performed in our department between January 1987 and December 2001 were reviewed retrospectively. During the study period, a total of 33 PKPs was performed in 20 eyes with buphthalmos. The median age of the patients at the time of PKP was 39 years (range, 3 to 72). All patients had a history of intraocular surgery, including multiple glaucoma surgeries, cataract extraction, and PKP. The impact of pre-, intra-, and postoperative factors on graft failure and duration of graft clarity was analyzed. RESULTS: Fifty-five percent (11/20) of the eyes received only one graft, 25% (5/20) received two, and 20% (4/20) received three grafts. During a mean follow-up of 87.2 months (range, 4.5-72), graft failure occurred in 18 of 33 grafts (54%). Seven (7/18, 39%) had immunologic graft rejection, and 11 (11/18, 61%) had nonimmunologic graft failure. At the end of the follow-up, 75% (15/20) of the eyes had clear grafts. Duration of graft clarity was found to be significantly shorter in regrafts compared with that of primary grafts (27.0 +/- 27.7 versus 56.4 +/- 41.0 months, p= 0.02). After PKP, intraocular pressure (IOP) was uncontrolled in 12 (12/33, 36%) grafts. Nine of 20 eyes (45%) required an average of 3.2 cyclodestructive procedures per eye for pharmacologically resistant elevated IOP. The final postoperative vision improved in 70% (14/20) of the eyes and the best visual acuity postoperatively (75% > or =20/400) was significantly better than the preoperative visual acuity (25% > or =20/400, p= 0.0001). CONCLUSIONS: Endothelial decompensation due to congenital glaucoma is a very rare indication for PKP. The incidence of graft failure is high, and nonimmunologic reasons are the leading causes of graft failure in this high-risk population. Visual acuity can be significantly improved but is usually still very limited by advanced glaucomatous optic nerve damage and amblyopia. Efficient control of IOP before and after PKP is mandatory in eyes with buphthalmos to avoid graft failure and progress of glaucomatous optic nerve atrophy.     

Reducing the risk of corneal graft rejection. A comparison of different methods

Corneal graft rejection represents the leading cause of failure in corneal transplantation. Two of the major risk factors for graft rejection are previous sensitization, usually in the form of a previous rejected corneal graft and corneal vascularization. The major histocompatibility MHC antigens (HLA, A, B and DR) are the target of the corneal graft rejection process. Because HLA, A, B, and DR antigens have been found in the corneal epithelium, the corneal stroma, and the corneal endothelium, matching patients and donors would seem to reduce the incidence of rejection. The results of studies on HLA, A, B, and DR matching are discussed. Cyclosporin, a fungal by-product, prevents the proliferation of sensitized cytotoxic T cells. Its use topically in corneal transplant patients in a controlled series has also reduced the incidence of rejection. Its use systemically has also been tried in an effort to prevent corneal graft rejection.     

Corneal transplantation--immunological mechanisms of rejection episode

Organ transplantation including cornea is often only the one method of treatment in case of their irreversible destruction. The genetic difference between donor and graft recipient makes the immunological system recognizes foreign antigens and triggers off a rejection episode. This article reviews corneal graft rejection immunology and indicates possible future options for the clinical evaluation of more specific therapeutic agents that modulate the immunological mechanisms of allograft rejection. It discusses also the role of HLA matching in the survival of corneal grafts especially in "high risk" eyes.     

Conclusions of the corneal transplant follow up study

AIM—On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism.METHODS—Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991.RESULTS—Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection.CONCLUSIONS—While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.