环孢霉素A滴眼剂治疗角膜移植排斥反应

应用０．５％环孢霉素Ａ滴眼剂治疗穿透性角膜移植术后免疫排斥患者１５例（１５眼），愈８例，好转６例，无效１例。随防５～２４个月，２例因停药复发，一例于拆线后复发，继续用药或增加用药后治愈。研究表明０．５％环孢霉素Ａ滴眼剂治疗术前移植床条件较好，角膜移植术后发生免疫排斥的患者可得到良好的效果，而对术前移植床条件较差，角膜移植术后发生免疫排斥的患者有一定的疗效。对眼局部应用环孢霉素Ａ滴眼治疗角膜移植排斥     

局部应用环孢霉素A对角膜移植术后排斥反应高危病例的疗…

应用环孢霉素Ａ局部滴眼，治疗严重血管化角膜行角膜移植的患者３３例３５眼，平均随访期２１个月，其中２３眼未发生排斥反应，透明成功率占６５．７％。发生排斥反应的１２眼，其中５眼内皮排斥，１眼为上皮排斥，６眼为混合型排斥；经增用药次数及结合短期内使用激素，部分病例排斥反应得以控制。     

局部应用环孢霉素A防治角膜移植排异反应

用环霉孢素Ａ对１５例部分穿透性角膜移植病人局部滴眼预防及治疗角膜移植术后排异反应。角膜移植植片全部透明１３只眼，半透明２只眼，混浊１只眼，随访时间最长１．５年，最短半年。环孢霉素Ａ对角膜移植片的排异反应疗效满意，为今后开展角膜移植，提供了一种新型强效免疫抑制剂。     

局部应用环孢霉素A防治角膜移植排异反应

用环霉孢素Ａ对１５例部分穿透性角膜移植病人局部滴眼预防及治疗角膜移植术后排异反应。角膜移植植片全部透明１３只眼，半透明２只眼，混浊１只眼，随访时间最长１．５年，最短半年，环孢霉素Ａ对角膜移植片的排异反应疗效满意，为今后开展角膜移植，提供了一种新型强效免疫抑制剂。     

环孢霉素A在高危角膜移植免疫排斥应用观察

目的：探讨环孢霉素A在高危角膜移植手术后防治角膜移植排斥反应的疗效。方法：对在我院施行穿透性及槔层角膜移植术中属于高危角膜移植的病共24例26只眼,其中≥9mm的大植片的有12只眼（占50％）,在术后26只眼均用环孢霉素A口服及环孢霉素A液滴眼。结果：角膜移植术后出现角膜排斥反应的有10例11只眼（占42．3％）,经过治疗后角膜植片均透明,术后角膜移植片最终透明者有24只眼（占92．3％）,未见严重副作用。结论：证明在高危角膜移植术应用环孢霉素A治疗角膜移排斥反应是确实有效。     

环孢霉素A滴眼治疗角膜移植排斥反应疗效观察

环孢霉素Ａ滴眼治疗角膜移植排斥反应疗效观察洛阳铁路分局医院眼科朱兰香，宁虹穿透性角膜移植手术后，植片排斥反应常是导致手术失败的主要原因，迄今仍无特效措施．既往多采用类固醇类药物治疗，虽取得了一定疗效，但长期用药可致多种并发症。我科多年来在开展角膜移植...     

局部应用环孢霉素A对角膜移植术后排斥反应高危病例的疗效观察

应用环孢霉素Ａ（简称ＣＳＡ）局部滴眼，治疗严重血管化角膜行角膜移植的患者３３例３５眼，平均随访期２１个月，其中２３眼未发生排斥反应，透明成功率占６５．７％。发生排斥反应的１２眼，其中５眼为内皮排斥，１眼为上皮排斥，６眼为混合型排斥；经增加用药次数及结合短期内使用激素，部分病例排斥反应得以控制。用药８周后测试体内一些免疫指标较用药前有明显下降。Ｅｔ－ＲＦＣ，Ｅａ－ＲＦＣ值，淋巴细胞转化率，以及Ｔ－淋巴细胞亚群中的ＯＫＴ３、ＯＫＴ４、ＯＫＴ８的值均有所下降。观察结果表明：局部应用环孢霉素Ａ对角膜移值排斥反应的高危病例有明显的预防及治疗移植免疫排斥反应的效果。     

增视性角膜移植术及其排斥反应防治的临床观察

角膜移植病人２５５例（２６５眼），植片透明率达９６．０９％，混浊者占３．９１％，术前视力均在０．１以下，术后视力提高率为９０．８３％，达到当前国内最佳水平，眼局部滴用环孢霉素Ａ，有明显防治排斥反应作用。     

蚕蚀性角膜溃疡的临床特点分析

探讨蚕蚀性角膜溃疡患者的临床特点和比较治疗方法的效果。方法对连续治疗的蚕蚀性角膜溃疡患者５５０例的患病年龄,性别,眼别,溃疡部位,溃疡穿孔,溃疡复发情况,以及球结膜切除术,板层角膜移植术及板层角膜移植术联环孢霉素Ａ滴眼的疗效进行分析情况,以及球结膜切除术,板层角膜移植术及板层角膜术联合环孢霉素Ａ滴眼的疗效进行分析。结果平均患病年龄４８．４岁;男：女之比为１：０．７４;双眼患病者１６５例,其中青年患     

角膜移植术后应用环孢霉素滴眼液的临床观察

目的对比研究穿透性角膜移植术不同术后处理方法及其术后排斥反应的发生率。方法2组（48例）行穿透性角膜移植术角膜病患者，一组术后单独使用0．1％地塞米松滴眼，另一组采用环孢霉素A（1％CsA）和0．1％地塞米松（0．1％DXM）联合滴眼，对比2组术后排斥反应的发生率。结果采用1％CsA联合0．1％DXM，术后治疗组排斥反应发生率明显低于单纯使用地塞米松组（P〈0．05）。结论术后采用CsA联合DXM治疗，可有效降低角膜移植术后的排斥反应发生率。     

Long-term outcome of topical cyclosporine treatment following penetrating keratoplasty]

PURPOSE: To evaluate the long-term outcome of 2% topical cyclosporine A (CsA) treatment as an adjunct to topical corticosteroid in 86 eyes after penetrating keratoplasty (PK). MATERIAL AND METHODS: The subjects were 86 eyes of 83 patients who had undergone PK and received topical CsA treatments. Ninety-seven eyes of 95 patients who had undergone PK and received similar postoperative treatments except for topical CsA treatments served as control: The clinical outcome of PK was evaluated by rates of graft survival and rejection-free graft survival using Kaplan-Meier's method and compared with the log-rank test. The patients were subdivided into high-risk and low-risk groups. The high-risk patients were those who had corneal vascularization in 2 or more quadrants of the cornea preoperatively or who received regrafting. All other patients were assigned to the low-risk group. Thirty-six eyes of the CsA group and 50 eyes of the control group were high-risk cases. RESULTS: In the high-risk patients, the rejection-free graft survival rate was 69.7% in the CsA group and 45.4% in the control group (p = 0.030). However, there was no significant difference in the graft survival rate between the two groups. In the low-risk patients, there was no significant difference in the rates of rejection-free graft survival and graft survival between the CsA and the control group. CONCLUSION: 2% topical cyclosporine is effective in reducing the risk of allograft rejection in high-risk recipients.     

Combined intravenous pulse methylprednisolone and oral cyclosporine A in the treatment of corneal graft rejection: 5-year experience

PURPOSE: To report the mid-term results of a treatment strategy using topical steroids, intravenous pulse methyl prednisolone and oral cyclosporine A (CSA) for the treatment of acute corneal graft rejection. METHODS: Noncomparative, interventional case series. Treatment of corneal graft rejection included 1% prednisolone eye drops, intravenous infusion of 500 mg methyl prednisolone, and oral CSA in two regimens--standard dose was 15 mg/kg/day for 2 days, 7.5 mg/kg/day for 2 days, then adjusted to maintain trough blood levels of 100-200 microg/l; low dose was 2 mg/kg/day with no loading dose. RESULTS: Outcome in 34 eyes of 34 patients (21 M;13 F) aged 60 +/- 17.7 years (range 9-83 years), who presented after an average duration of 6.6 +/- 6.3 days (range 0-30 days) following acute corneal graft rejection, are reported. Twenty-five patients received standard dose CSA while nine patients received the low dose regimen. Mean duration of treatment before reversal of graft rejection was 13.6 +/- 12.1 days (range 3-54 days). Treatment was successful in reversing the graft rejection in 32/34 (94%) eyes. Irreversible graft failure occurred in one eye in each group. During a mean follow-up period of 19.2 +/- 16.7 months (range 1-55 months), further episodes of graft rejection were seen in 1/32 (3%) eyes. Complications due to treatment included: duodenal ulcer in one patient that responded to medical treatment, and transient elevation in serum creatinine levels in three patients, which returned to normal after decrease in dosage or cessation of oral CSA. CONCLUSION: Our 5-year experience with the use of oral CSA in the treatment of acute corneal graft rejection has shown this treatment approach to be safe and effective in reversing the rejection process. This approach may also protect the graft from subsequent episodes of allograft rejection. A randomised controlled trial to further delineate the role of CSA in reversing acute graft rejection seems warranted.     

Opinions on risk factors and management of corneal graft rejection in the United kingdom

PURPOSE: To determine the opinions regarding risk factors and practice preferences for corneal graft rejection by members of the Bowman Club (UK) and to compare them with those of members of the Castroviejo Society (USA). METHODS: A questionnaire was sent in 1999 to members of the Bowman Club (UK), who were responsible for two thirds of all corneal grafts undertaken annually. The survey included 8 questions identical to those given to members of the Castroviejo Society (USA) in a survey carried out in 1989. RESULTS: Thirty-six out of 40 surgeons replied. Factors considered by respondents to be high risk for corneal graft rejection were previous corneal graft rejection in the operated eye (97%), significant corneal vessels (97%), and previous herpetic eye disease (94%). The preferred routine preoperative treatment in "high-risk" patients included no treatment (47%), topical corticosteroids (33%), and oral prednisolone (22%). In postoperative "high-risk" patients, 100% of surgeons used topical and 42% used oral corticosteroids. Immune suppression agents were used by 44% of respondents, the majority (92%) using cyclosporine A. In previous herpes simplex patients, 47% of surgeons used oral and 14% used topical antivirals preoperatively, whereas 75% used oral and 47% used topical postoperatively. CONCLUSION: This study documents the perceived risk factors and management of corneal graft rejection by corneal surgeons in the UK. It showed wide variation in practice preferences, allowing individual surgeons a comparison with peer practice. It highlights the need for greater use of postoperative antiviral prophylaxis in the presence of previous herpetic corneal pathology.     

A case of acute endothelial corneal transplant rejection following immunization with ChAdOx1 nCoV-19 coronavirus vaccine

A 28-year-old female who underwent an uneventful femtosecond laser enabled keratoplasty (FLEK) in her left eye presented with pain, redness, and blurring of vision in the operated eye two weeks after getting immunized with COVID-19 vector vaccine (ChAdOx1 nCoV19 Vaccine Recombinant COVISHIELD, AstraZeneca). Slit-lamp examination showed donor stromal edema with Descemet’s membrane folds and Khodadoust line (KP’s on endothelium) with anterior chamber cells and flare. The patient was diagnosed with acute corneal graft rejection and advised hourly topical steroids with cycloplegics and oral steroids. The patient responded to treatment and there was progressive reversal of graft rejection with the patient achieving best spectacle-corrected visual acuity (BSCVA) of 20/30 after five weeks of treatment. Our case highlights possible immune corneal graft rejection after COVID19 vaccination and the need to step up topical steroids before vaccination.     

Corneal graft rejection after penetrating keratoplasty for keratoconus in Turner's syndrome

PURPOSE: To report a patient with Turner's syndrome who developed graft rejection after penetrating keratoplasty (PK) for keratoconus and to review the ophthalmic literature on the association between keratoconus and Turner's syndrome. METHODS: A woman with bilateral keratoconus and Turner's syndrome (45,XO) was referred for progressive visual loss in the right eye. Best-corrected visual acuity was 20/400 in the right eye. Slit-lamp examination revealed corneal thinning with ectatic protrusion of the central cornea and Vogt's striae in the right eye. The patient underwent PK in the right eye in January 2001. She developed graft rejection in April 2003 and visual acuity dropped to hand motion. After treatment with topical and systemic steroids and systemic cyclosporine A, visual acuity recovered to 20/80 in July 2003. RESULTS: The authors know of only three other reported patients (six eyes) with keratoconus in Turner's syndrome. Five eyes underwent PK with good visual rehabilitation, but one developed immunologic graft rejection 7 years after surgery. On the whole, considering the current report and the other cases described in the literature, graft rejection occurred in 2 out of 6 eyes (33.3%). The graft survival rate was 80% after 2 years and 40% after 7 years. CONCLUSIONS: The results suggest that grafts for keratoconus in patients with Turner's syndrome might have an increased risk of immunologic rejection. Corneal grafts in Turner's syndrome need to be monitored closely. Early detection of graft rejection and aggressive treatment with topical and systemic steroids and systemic cyclosporine A can save the graft and restore useful vision.     

Cyclosporin A: tissue levels following topical and systemic administration to rabbits.

Plasma and aqueous levels of cyclosporin A (CsA) were determined following topical administration of CsA 1% to healthy rabbit eyes and compared with levels obtained when administered to rabbit eyes which had received corneal grafts 7-10 days previously. In addition plasma levels were determined following intramuscular administration of 50 mg CsA and the results compared with those obtained following topical administration. Topical administration to healthy rabbit eyes five times a day for three days resulted in plasma levels of CsA which were similar to those obtained over three days following an intramuscular administration of 50 mg CsA. The plasma levels in both were significantly higher than those obtained following topical administration to rabbit eyes which had received corneal grafts 7-10 days previously. Aqueous levels of CsA were lower than plasma levels, and there was no significant difference between levels obtained when CsA was administered topically to healthy eyes, to eyes which had received corneal grafts, or to the fellow eye.     

Femtosecond laser-assisted lamellar keratoplasty (FSLK) for anterior corneal stromal diseases

Our objective was to study the outcome of femtosecond-assisted lamellar keratoplasty (FSLK) in stromal corneal diseases. This is a retrospective chart review of 17 patients (20 eyes) who underwent FSLK for anterior corneal pathologies. Main outcome measures were refractive results following FSLK, complications, and graft survival. Mean follow-up time was 42 ± 15 (7–58) months. Preoperative best spectacle-corrected visual acuity (BSCVA) was ≤20/40 in 17 eyes. Postoperative BSCVA ≥ 20/40 was achieved in 12/14 at 12 months, 11/12 at 24 months, and 10/12 eyes at 36 months; postoperative BSCVA ≥ 20/25 was achieved in 8/14, 8/12, and 5/12 eyes at 12, 24, and 36 months, respectively. One eye had vertical gas break through the epithelium during the FSLK. One eye had postoperative epithelial rejection and two eyes had stromal rejection treated successfully with topical steroids. Another eye had epithelial ingrowth that was not progressive; however, the same eye developed bacterial keratitis and scarred graft 32 months post-FSLK. One eye had graft dehiscence and one eye developed excessive interface fibrosis. Five out of 20 grafts failed due to the recurrence of the original disease (3), corneal scarring (1), and excessive interface fibrosis (1). FSLK provides many advantages over conventional PK and DALK, with faster visual rehabilitation and emmetropization of the manifest refraction rather than inducing ametropia and irregular astigmatism.     

雷帕霉素纳米粒滴眼液联合环孢素A缓释膜治疗兔高危角膜移植术后免疫排斥反应的研究

目的 探讨局部联合应用雷帕霉素(RAPA)纳米粒滴眼液与环孢素A(CsA)缓释膜治疗兔高危角膜移植术后免疫排斥反应的效果和协同机制.方法 实验研究.(1)制备0.5%聚乳酸/胆固醇改性壳聚糖RAPA纳米粒滴眼液和聚乳酸/聚乙二醇CsA缓释膜.(2)设A组为同源对照组(17只兔),供受体均为新西兰白兔.建立102只(102只眼)新西兰白兔角膜新生血管模型,采用随机数字表法将其分为B、C、D、E、F、G6组,每组17只,供体为青紫兰兔,各组行穿透性角膜移植术.A组同源对照组;B组未治疗组;C组空白纳米粒滴眼液滴眼,每天2次共28 d;D组术中前房植入空白缓释膜;E组0.5%RAPA纳米粒滴眼液滴眼,每天2次共28 d;F组术中前房植入CsA缓释膜;G组术中前房植入CsA缓释膜并0.5%RAPA纳米粒滴眼液滴眼,每天2次共28 d.(3)术后观察100 d,隔天用显微镜观察角膜植片情况,记录免疫排斥反应发生时间和程度.(4)术后3、14、28及35 d用CD4和CD8单克隆抗体行免疫组织化学检查;用逆转录聚合酶链反应(RT-PCR)检测植片白细胞介素2(IL-2)和血管内皮生长因子(VEGF)表达.应用单因素方差分析和q检验,比较各组角膜植片平均存活时间.结果 各组兔眼角膜植片存活时间分别为A组(100.00±0.00)d、B组(8.44±1.24)d、C组(8.89±2.57)d、D组(8.56±2.30)d、E组(43.11±5.58)d、F组(43.67±9.54)d、G组(72.00±15.34)d.G组较E、F组,E、F组较B、C、D组,能显著延长角膜植片存活(qGE=11.42,qGF=11.24,qEB=13.64,qEC=13.38,qED=13.46,qFB=13.82,qFC=13.56,qFD=13.64;均P<0.01).免疫组织化学检查显示,B、C、D组术后14 d左右角膜植片中CD4+和CD8+T淋巴细胞大量聚集,呈进行性加重;E、F组术后35 d左右角膜植床与植片中CIM+和CD8+T淋巴细胞数开始出现;G组术后60 d以后,植片中CD4+和CD8+T淋巴细胞浸润.角膜植片RT-PCR检查显示,A组IL-2和VEGF始终未表达;F、G组IL-2表达在3 d开始被抑制;E、G组VEGF表达在14 d开始被抑制.结论 局部联合应用药物缓释剂治疗高危角膜移植术后免疫排斥反应较单独用药效果好,联合用药能减少单独用药的剂量和毒副作用.     

前房植入环孢素A缓释系统抑制鼠高危角膜移植术后的免疫排斥反应

目的　探讨前房内植入环孢素A缓释系统 (cyclosporineAdrugdeliverysystem ,CsADDS)抑制高危角膜移植术后免疫排斥反应的有效性和可行性。方法　 (1)对 6 0只Wistar大鼠 (6 0只眼 )用缝线法诱导角膜新生血管增生。 (2 )将发生角膜新生血管化的 4 0只Wistar大鼠 (40只眼 )随机分为4组 :对照组 ,1%CsA滴眼组 ,CsADDS结膜下植入组 ,CsADDS前房内植入组。每组均接受同种异系(Spregue Dawley大鼠 )角膜供体 ,行穿透性角膜移植术 ,术后比较各组大鼠免疫排斥反应发生的时间 ,并定期检测各组大鼠房水中CsA的浓度。 (3)正常Wistar大鼠 8只 (16只眼 ) ,随机分为 2组 ,分别在结膜下和前房内植入CsADDS ,术后 2和 4周行眼的组织病理学检查。结果　 (1) 5 1只Wistar大鼠 (5 1只眼 )经角膜基质缝线 ,成功诱导角膜新生血管增生。 (2 ) 4组共 4 0只Wistar大鼠角膜移植术后免疫排斥反应的发生时间分别为 :对照组 (8 2 0± 1 4 8)d ,1%CsA滴眼组 (10 6 0± 1 90 )d ,CsADDS结膜下植入组 (11 4 0± 2 5 0 )d ,CsADDS前房内植入组 (17 0 0± 6 0 5 )d。房水中CsA浓度均值分别为 :对照组 0 μg/L ;1%CsA滴眼组 (47 90± 3 4 8) μg/L ;CsADDS结膜下植入组术后 1、2、4周 ,房水中CsA浓度均值分别为 (5 9 0 0± 3 6 6 ) μg/     

环孢素A不同给药方式抑制兔眼穿透角膜移植术后免疫排斥反应的研究

背景环孢素A（CsA）是治疗角膜移植免疫排斥反应的主要药物,但合适的药物剂型和给药途径对提高药物利用度有重要意义。目的探讨CsA缓释微球结膜下给药、前房给药及CsA滴眼液局部点眼途径抑制兔眼穿透角膜移植术（PKP）后的排斥反应。方法健康清洁级成年新西兰白兔60只60只眼作为受体,健康清洁级青紫蓝兔30只60只眼作为供体。将受体兔按随机数字表法随机分为空白对照组、结膜下给药组、结膜下对照组、前房给药组、前房对照组和CsA滴眼液组,每组10只实验兔。所有实验兔行PKP。术毕结膜下给药组和前房给药组兔眼以相应的给药途径注射12g／LCsA缓释微球悬液0．1ml,结膜下对照组和前房对照组采取相应的给药途径注射空白微球悬液0．1ml,CsA滴眼液组每日应用质量分数1％（10g／L）CsA滴眼液点眼,空白对照组PKP术后不给予CsA药物。术后裂隙灯显微镜下定期观察各组术眼角膜植片的透明度、水肿情况、新生血管生长情况等,并计算术眼的排斥反应指数（RI）。分别于术前,术后3d,术后1、2、3周和术后1、2、3个月用Tono—pen眼压计测量眼压;分别于术后1个月、3个月获取各组植片行常规组织病理学检查。结果术后各组兔眼眼压较术前均明显下降,手术前后兔眼眼压的总体比较差异有统计学意义（F目目：29．210,P=0．000）;同一时间点各组兔眼眼压比较差异无统计学意义（F捆=0．254,P=0．938）。空白对照组、结膜下对照组及前房对照组于术后2～3周出现不同程度的角膜植片混浊和新生血管,术后4周时植片混浊加重,R1分别为8．60±1．52、8．60±0．55和8．80±0．84;结膜下给药组、前房给药组及CsA滴眼液组于术后3周时出现角膜新生血管,但未发现植片混浊,R1分别为4．40＋0．89、3．20±0．84和3．00±0．71,均明显低于空白对照组、结膜下对照组和前房对照组,差异均有统计学意义（P〈0．05）。其中前房给药组兔眼术后前房有轻度炎症反应,随时间延长逐渐减轻,至术后3个月时}肖失。组织病理学检查可见,空白对照组、结膜下对照组、前房对照组术眼角膜植片均明显增厚,有大量炎性细胞浸润和新生血管长人;而结膜下给药组、前房给药组和CsA滴眼液组植片的炎性细胞浸润明显减轻,新生血管减少。结论CsA缓释微球经不同途径给药均可抑制兔眼角膜移植术后的排斥反应,其中经前房给药途径的整体疗效较经结膜下给药途径更佳。