角膜移植免疫排斥反应局部治疗的研究进展

角膜移植术后免疫排斥反应是角膜移植失败的重要原因。角膜移植术后局部抗排斥治疗以其用药剂量小而局部药物浓度高、副反应少,具有巨大的发展潜力。本文主要回顾了近年来用于局部抗角膜移植排斥反应药物的相关研究,分析该类药物的作用机制,并评价其疗效及安全性,探讨局部用药防治角膜移植术后免疫排斥反应的发展方向。     

免疫抑制剂治疗角膜移植免疫排斥反应的研究进展和展望

角膜移植术后免疫排斥反应是目前导致手术失败的首要原因，应用免疫抑制剂是预防和治疗术后排斥反应的主要措施。本文就近年来研究开发的各种新型免疫抑制剂的作用机理，实验结果及部分药物的临床应用作一综述。     

免疫抑制剂治疗角膜移植免疫排斥反应的研究进展和展望

角膜移植术后免疫排斥反应是目前导致手术失败的首要原因，应用免疫抑制剂是预防和治疗术后排斥反应的主要措施。本就近年来研究开发的各种新型免疫抑制剂的作用机理，实验结果及部分药物的临床应用作一综述。     

免疫耐受对角膜移植片长期存活的价值

穿透性角膜移植是治疗角膜盲的主要手段,尽管角膜是器官移植的免疫赦免部位,但同种异体免疫排斥反应仍是角膜移植片失败的主要原因.据统计,18%的常规角膜移植或75%的高危角膜移植患者会发生排斥反应.目前临床使用的各种免疫抑制剂主要通过作用于T淋巴细胞达到抑制免疫排斥反应的目的,但长期使用费用昂贵,且为非特异性免疫抑制.当免疫抑制剂不足时就会发生排斥反应,而抑制过强易诱发感染或肿瘤,并且阻断受体形成免疫耐受.     

加强我国角膜移植免疫研究

通过角膜移植更换混浊或病变的角膜,是帮助角膜盲患者恢复视力的有效措施,但植片排斥反应的发生是导致角膜移植手术远期失败的主要原因,如何减少因植片排斥引起的再次致盲是角膜病研究的重点。本文分析了我国角膜移植免疫研究存在的问题：（1）没有建立标准的抗排斥治疗方案;（2）缺乏安全、有效的抗排斥反应治疗药物;（3）忽视围手术期的并发症处理;（4）角膜移植免疫基础研究薄弱。针对上述问题产生的原因,提出了相应的处理措施和建议,以增强角膜病专科医生对角膜移植免疫临床和基础研究的重视,促进我国角膜盲的防治工作取得更大的发展。     

角膜移植免疫排斥反应影响因素及治疗进展

角膜移植失败的主要原因是免疫排斥反应,有效地防治角膜移植术后免疫排斥反应的发生是眼科治疗中亟待解决的实际问题,本文就目前有关角膜移植免疫排斥反应的影响因素和防治进展作一综述。     

角膜移植免疫排斥反应防治的研究进展

角膜移植是众多器官和组织移植中成功率最高的,然而移植后的免疫排斥反应仍是导致角膜移植术失败的主要原因。本文综述角膜移植后免疫排斥反应发生的机制、排斥反应的预防及其治疗等几个方面的研究进展。     

角膜移植免疫学研究进展

移植排斥反应是角膜移植失败的首要原因。揭示其中的机理是预防和治疗免疫排斥反应的基础。本文综合了关于角膜移植免疫免性和免疫排斥方面的研究进展。     

角膜移植免疫学研究进展

移植排斥反应是角膜移植失败的首要原因，揭示其中的机理是预防和治疗免疫排斥反应的基础。本文综述了关于角膜移植免疫赦免性和免疫排斥方面的究研进展。     

角膜移植排斥反应患者红细胞免疫功能初探

研究角膜移植排斥反应患者红细胞免疫功能。方法对２６例角膜移植排斥反应患者进行红细胞免疫检测，并对照分析，结果红细胞Ｃ３ｂ受体花环率降低，红细胞免疫复合物环率升高。结论红细胞免疫与角膜移植排斥反应密切相关，能预见排斥反应发生和指导治疗。     

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。     

Corneal graft rejection: donor and receiver implication

PURPOSE: The purpose of our study was to evaluate the relationship between corneal graft failure and different factors related to both donors and recipients. PATIENTS: and methods: We conducted a retrospective control study on cases treated from January 1998 to December 2000. All records for donors to the eye bank unit of the Sfax forensic medicine department and all records for penetrating keratoplasty operations done in the Sfax Ophthalmology department were reviewed. For every donor we specified age, sex, cause of death, time and corneal deduction technique, as well as storage delay. For every recipient we specified age, sex, keratoplasty indication, state of the cornea, type of anesthetics and intervention. We analyzed the factors for graft rejection taking into consideration all parameters related to donors and recipients using the chi square test, with alpha=0.01. We defined graft rejection as the irreversible corneal edema despite local or general treatment combining corticoids and antivirals. RESULTS: Of the 184 cases followed up, 22 cases (12%) of graft rejection were recorded. Concerning the donor, a statistically significant relation was found between young age and short storage time indicating an increase in the rate of graft rejection. The younger the patient was, the greater the risk, and the longer the tissue had been preserved, the lower the risk of rejection. For the recipient, old age, a history of graft rejection and the state of the receiver bed significantly increased the rate of graft rejection. In terms of surgical stage, the suturing technique and a graft diameter 8 mm or greater increased the rate of graft rejection. CONCLUSION: In addition to neovascularization of the corneal bed and a history of graft rejection, universally recognized as risk factors for transplant rejection, other parameters related to both donors and receivers, such as age, storage time, graft diameter, and suturing technique, must be taken into account in order to ensure the survival of the graft.     

Corneal graft rejection

Penetrating keratoplasty is the most widely practiced type of transplantation in humans. Irreversible immune rejection of the transplanted cornea is the major cause of human allograft failure in the intermediate and late postoperative period. This immunological process causes reversible or irreversible damage to the grafted cornea in several cases despite the use of intensive immunosuppressive therapy. Corneal graft rejection comprises a sequence of complex immune responses that involves the recognition of the foreign histocompatibility antigens of the corneal graft by the host's immune system, leading to the initiation of the immune response cascade. An efferent immune response is mounted by the host immune system against these foreign antigens culminating in rejection and graft decompensation in irreversible cases. A variety of donor- and host-related risk factors contribute to the corneal rejection episode. Epithelial rejection, chronic stromal rejection, hyperacute rejection, and endothelial rejection constitute the several different types of corneal graft rejection that might occur in isolation or in conjunction. Corneal graft failure subsequent to graft rejection remains an important cause of blindness and hence the need for developing new strategies for suppressing graft rejection is colossal. New systemic pharmacological interventions recommended in corneal transplantation need further evaluation and detailed guidelines. Two factors, prevention and management, are of significant importance among all aspects of immunological graft rejection. Preventive aspects begin with the recipient selection, spread through donor antigenic activity, and end with meticulous surgery. Prevention of corneal graft rejection lies with reduction of the donor antigenic tissue load, minimizing host and donor incompatibility by tissue matching and suppressing the host immune response. Management of corneal graft rejection consists of early detection and aggressive therapy with corticosteroids. Corticosteroid therapy, both topical and systemic, is the mainstay of management. Addition of immunosuppressive to the treatment regimen helps in quick and long term recovery. Knowledge of the immunopathogenesis of graft rejection may allow a better understanding of the immunological process thus helping in its prevention, early detection and management.     

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.     

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     

Acute graft rejection in a COVID-19 patient: Co-incidence or causal association?

A 32-year-old man with a clear and compact graft following a penetrating keratoplasty 6 years back, developed an episode of acute graft rejection, coinciding with the COVID-19 disease. Subsequent to the infection with the novel coronavirus, he developed symptoms of acute graft rejection concurrent with the development of respiratory distress and peak systemic symptoms. This was the phase of cytokine storm as evidenced by the raised inflammatory markers in his blood tests. Such a case of acute corneal graft rejection coinciding with SARS-CoV-2 infection has been reported only once in the literature and this unique association needs to be researched further.     

Randomised controlled trial of corticosteroid regimens in endothelial corneal allograft rejection

AIM: To determine whether the addition of systemic corticosteroid to local intensive corticosteroid therapy of endothelial corneal allograft rejection improves outcome. METHODS: A prospective randomised treatment trial was carried out at a tertiary referral centre. 36 consecutive corneal graft recipients, presenting with a first episode of endothelial graft rejection, received either (i) one intravenous pulse of methylprednisolone 500 mg in addition to local corticosteroid treatment, or (ii) local treatment only. The regimen of local treatment standardised in all cases for the first 24 hours consisted of one subconjunctival betamethasone 2 mg injection and dexamethasone 0.1% drops in the affected eye every hour for 24 hours. RESULTS: Failure to reverse the graft rejection episode was found in 3/36 (8%) patients. Each of these had been treated with local steroid only. Graft failure from any cause occurred in 9/36 (25%) within 2 years of follow up. No statistically significant difference was found between the two groups with regard to reversal of the graft rejection episode, later recurrence of graft rejection, or graft failure. CONCLUSIONS: In treatment of graft rejection, additional systemic treatment with 500 mg methylprednisolone yields no significant benefit over intensive local corticosteroid alone. Graft survival following treatment of a rejection episode with local corticosteroid treatment alone is good in those patients without other risk factors for graft failure and much higher than reported previously.     

The impact of corneal allograft rejection on the long-term outcome of corneal transplantation

PURPOSE: To examine the influence of corneal allograft rejection on the survival of penetrating corneal transplantation, to review the status of conventional therapies to improve graft survival, and to consider prospects for alternative approaches to reduce the impact of rejection. DESIGN: Perspective, including prospective, observational cohort study. METHODS: An examination of the literature on human corneal graft rejection and data from the Australian Corneal Graft Registry, reviewed in the context of clinical experience. RESULTS: Corneal graft outcome is not improving with era. The sequelae of inflammation, whether occurring before corneal transplantation or subsequently, exert a profound influence by predisposing the graft to rejection. Of the developments that have been instrumental in reducing rejection in vascularized organ transplantation, living-related donation is not an option for corneal transplantation. However, HLA matching may be beneficial and requires reassessment. The evidence base to support the use of systemic immunosuppressive agents in corneal transplantation is thin, and topical glucocorticosteroids remain the drugs of choice to prevent or reverse rejection episodes. Experimental approaches to local allospecific immunosuppression, including the use of antibody-based reagents and gene therapy, are being developed but may be difficult to translate from the laboratory bench to the clinic. CONCLUSIONS: Corneal allograft rejection remains a major cause of graft failure. High-level evidence to vindicate the use of a particular approach or treatment to prevent or treat corneal graft rejection is lacking. In the absence of extensive data from randomized, controlled clinical trials, corneal graft registers and extrapolation from experimental models provide some clinically useful information.     

Rejection of corneal allografts

Corneal graft rejection is the major cause of penetrating keratoplasty failure. It is a complex immunological process that involves recognition of alloantigens from the corneal graft by the host's immune system, leading to an efferent immune response against the graft. Each layer of the cornea can undergo rejection, endothelial rejection being the most severe form. In some cases, rejection will lead to corneal graft failure. Many donor- and host-related risk factors contribute to corneal graft rejection. Corticosteroid therapy, topical or systemic, is the gold-standard in the preventive and curative treatment of rejection. Other immunosuppressive agents are promising but require further evaluation. Early detection of rejection is essential to establish an aggressive treatment and reduce the risk of graft failure. Prevention of rejection is also based on tissue matching between donor and recipient. In high-risk patients, ABO compatibility decreases the risk of rejection. HLA compatibility could positively influence corneal graft survival in some cases.     

Interim results from the prospective "Erlanger Non-high-risk Penetrating Keratoplasty Study" in 207 patients

BACKGROUND: Immunologic graft rejection targeted against corneal endothelium is the most frequent cause for graft failure after corneal transplantation. The purpose of this prospective study was to assess the frequency, early symptoms, prophylaxis and therapy monitoring of corneal graft rejection following non-high-risk penetrating keratoplasty (PK). PATIENTS AND METHODS: From February 1997 to May 1999, 237 patients undergoing non-high-risk PK have been enrolled in this prospective study. We evaluated 207 patients (103 female, 113 right eyes, recipient age 54 +/- 20 years, donor age 59 +/- 17 years). In 2 randomized treatment studies we compared the efficacy of postoperative short-term (ST = 6 months) versus long-term (LT = 12 months) topical steroid therapy on the incidence of graft rejection and the effect of high- versus low-dose systemic steroid therapy on the prognosis after a graft rejection. Follow-up examinations included, laser-tyndallometry, corneal topography analysis, endothelial cell count and pachymetry. RESULTS: The main indications for PK were keratoconus (n = 93), endothelial dystrophy Fuchs (n = 52) and bullous keratopathy (n = 35). In 151 (73%) patients, non mechanical trephination with the 193 nm Excimer laser was performed. Up to now, 78 patients were randomized into two groups comparing the postoperative therapy with topical steroids. During follow-up (median: ST: 13.5 months; LT: 12.5 months, maximum 25.3 months) episodes of endothelial graft rejection (3 chronic focal, 8 acute diffuse) showed 11 eyes of 11 patients. Five patients each had short-term and long-term topical steroid treatment. In 1 patient the graft rejection occurred before randomization at 6 months. Six patients with graft rejection episodes underwent a PK only (54% of graft rejections, 4.4% of all patients). In the remaining 5 patients, PK was combined with a lens surgery (46% of graft rejections, 6.9% of all patients). Ten of 11 corneal grafts regained their full function under treatment with systemic and local steroids. CONCLUSION: The frequency of episodes of graft rejection in our study was lower than usually reported in the literature. A good compliance of patients appears to be a major factor for improved prognosis of the graft after PK and in case of graft rejection. Until now no significant differences between short-term or long-term postoperative topical steroid therapy could be detected regarding the incidence of corneal graft rejection.