神经营养性角膜病变是一种与角膜神经退行性改变有关的疾病,表现为角膜神经的知觉和营养功能受损,导致角膜上皮缺损、角膜溃疡和角膜穿孔。目前对神经营养性角膜病变的主要治疗方式有药物治疗、非手术干预治疗和手术治疗,但是对于重度病变患者行药物治疗、非手术干预治疗通常效果不佳。对未恢复角膜神经营养功能的患者行角膜移植术,可能导致角膜移植术后上皮持续不愈合,因此恢复角膜神经营养功能是该类患者复明的重要前提。角膜神经移植术是重度神经营养性角膜病变患者恢复角膜神经营养功能,提高角膜知觉,改善角膜透明度的重要和有效的治疗方法。角膜神经移植术通过将具有正常功能的供体神经移植到麻痹眼角膜缘周围,使神经末梢重新长入角膜基质,恢复角膜知觉功能。随着角膜神经移植术的术式的不断改进,其良好的术后效果和优点已经渐渐凸显。文章基于作者结合团队在角膜神经移植术方面经验结合近年研究进展阐述了神经营养性角膜病变的治疗手段和不同术式在角膜神经移植术中的应用,并进行展望。
Neurotrophic keratopathy is a disease related to degenerative changes in corneal nerves, resulting in impaired sensory and nutritive functions of corneal nerves. This leads to corneal epithelial defects, corneal ulcers, and corneal perforation. Currently, the main treatment modalities include pharmacotherapy, non-surgical interventions, and surgical treatment. However, drug therapy and non-surgical interventions often yield unsatisfactory results for severe neurotrophic keratopathy patients. Performing corneal transplantation in patients with unrecovered corneal sensation may result in persistent epithelial defect. Therefore, the restoration of corneal sensation is a crucial prerequisite for visual rehabilitation. Corneal neurotization emerges as an important and effective therapeutic approach for severe cases of neurotrophic keratopathy, aiming to restore corneal sensation and enhance corneal transparency. The procedure involves transplanting nerves from a donor with normal sensory function to the paralyzed sub-Tenon perilimbal space, allowing nerve endings to regenerate into the corneal stroma and restoring corneal sensory function. With continuous improvements in the technique of corneal neurotization, its favorable postoperative outcomes and advantages are becoming increasingly evident. This article, based on the team's experience in corneal neurotization, elaborates on the treatment modalities for neurotrophic keratopathy and the application and prospects of various surgical techniques in corneal neurotization.
眼部移植物抗宿主病发生在超过一半的慢性移植物抗宿主病患者中,涉及眼表持续的炎症以及纤维化改变,最常见的表现为干燥性角膜结膜炎。严重的眼部移植物抗宿主病不但影响患者的工作和生活质量,同时也增加了其他眼部并发症的风险。慢性眼部移植物抗宿主病的治疗主要包括局部应用人工泪液、血清类制剂、抗炎药物等药物治疗,佩戴隐形眼镜、睑板腺按摩等物理治疗、封闭泪点、重建眼表等手术治疗。随着对眼部移植物抗宿主病发病机制的深入研究,许多新的治疗药物和治疗手段涌现临床。总结目前慢性眼部移植物抗宿主病在药物治疗、物理治疗、手术治疗方面的最新研究进展,将有助于为慢性眼部移植物抗宿主病的治疗带来更多选择和更新的研究思路。
More than half of the patients developed chronic graft-versus-host disease after accepting allogeneic hematopoietic stem cell transplantation suffer from ocular graft-versus-host disease. Ocular graft-versus-host disease involves persistent inflammation and fibrosis of the ocular surface and keratoconjunctivitis sicca is the most common symptom. Severe ocular graft-versus-host disease not only affects patients’ life quality, but also increases the risk of other ocular complications. The treatment of chronic ocular graft-versus-host disease mainly includes drug treatment, such as local application of artificial tears, serum eye drops and anti-inflammatory drugs; physical treatment, such as wearing contact lenses and meibomian gland massage; surgical treatment, such as punctal occlusion and reconstructing ocular surface. With the in-depth study of the pathogenesis of ocular graft-versus-host disease, many new therapeutic drugs and methods have emerged. Summarizing the latest research progress in drug, physical and surgical therapy of chronic ocular graft-versus-host disease will give us insights into treatment options and hot spot of research.
慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)是骨髓移植后最具有破坏性并发症之一。移植物抗宿主病(graft-versus-host disease,GVHD)发生在10%~80%的造血干细胞移植(hematopoietic stem cell transplantation)受者中,而眼睛是人身体最脆弱的器官之一,有40%~60%接受HSCT的患者发生眼部GVHD,它主要影响泪腺、睑板腺、角膜和结膜等。cGVHD相关性干眼(dry eye associated with chronic graft-versus-host disease,cGVHD-DE)是眼部GVHD最多见的表现形式。cGVHD-DE的长期治疗因涉及多学科、多重结合治疗,至今仍然具有挑战性,其除了全身免疫抑制和眼部润滑剂外,通常还使用局部类固醇、环孢霉素和他克莫司滴眼液。针对中度和重度cGVHD-DE的治疗干预包括使用自体血清滴眼液和佩戴巩膜镜等,新兴起的治疗方案包括重链透明质酸 (heavy chain-hvaluronan/穿透素(pentraxin 3)结膜下注射、间充质基质细胞静脉注射、抑制纤维化药物等。
Chronic graft-versus-host disease (cGVHD) is one of the most devastating complications following bone marrow transplantation. GVHD develops in 10–80% of patients after hematopoietic stem cell transplantation (HSCT). The eye is one of the most vulnerable organs of the human body. Ocular GVHD occurs in 40–60% of patients with GVHD undergoing HSCT, and it mostly affects the lacrimal glands, meibomian glands, cornea, and conjunctiva. The most common form of ocular GVHD is dry eye disease (DED). The long-term treatment of cGVHD-related dry eye syndrome remains challenging and involves a multidisciplinary approach. Besides systemic immunosuppression and ocular lubricants, topical steroids, topical cyclosporine, and topical tacrolimus are commonly prescribed. Newer therapeutic interventions for moderate and severe cGVHD-related DED include using serum eye drops and scleral contact lenses. Emerging treatment options include subconjunctival injection of heavy chain-hyaluronan (HC-HA)/ pentraxin 3 (PTX3), intravenous injection of mesenchymal stromal cells, antifibrotic drugs, etc. This article reviews the mechanisms, clinical findings, and treatment of cGVHD-related dry eye syndrome.
神经营养性角膜病变是一种与角膜神经退行性改变有关的疾病,角膜神经的知觉和营养功能受损,导致角膜上皮缺损、角膜溃疡甚至角膜穿孔。目前人工泪液、治疗性角膜绷带镜、泪点栓塞、羊膜移植,睑缘缝合等治疗措施仍是治疗神经营养性角膜病变的主要治疗方式,对于轻中度病变患者,具有较好的治疗效果,而对于重度病变患者,药物治疗及简单的手术干预治疗效果不佳,病情反复发作。由于重度神经营养性角膜病变患者的角膜神经完全消失,丧失角膜感觉,对未恢复角膜神经营养功能的角膜白斑或溃疡患者行角膜移植术,可能导致角膜移植术后上皮持续不愈合,因此恢复角膜神经营养功能是复明的重要保障手段。角膜神经移植术是重度神经营养性角膜病变患者恢复角膜神经营养功能,提高角膜知觉,改善角膜透明度的重要和有效的治疗方法。角膜神经移植术通过将具有正常功能的供体神经移植到麻痹眼角膜缘周围,使神经末梢重新长入角膜基质,恢复角膜知觉功能。随着角膜神经移植术的术式的不断改进,其良好的术后效果和优点已经渐渐突显。角膜神经移植术包括直接角膜神经移植和间接角膜神经移植,促使角膜神经重新生长,重建角膜神经的营养和知觉功能。角膜神经移植手术已有40年历史,1981年Samii等首次报告了角膜神经移植术,2009年Terzis等成功地实施了第1例直接角膜神经移植术,2014年Elbaz等进行了第1例以腓肠神经作为间置移植物的间接角膜神经移植。封面展示了神经营养性角膜病变患者未接受治疗前的和接受角膜神经移植术后的眼表角膜图像。由于角膜神经退行性改变,角膜失去神经支配,继而出现角膜上皮缺损,角膜缘新生血管形成,经角膜神经移植后,角膜上皮愈合,角膜透明度改善,同时角膜缘新生血管消退。
神经营养性角膜病变是一种与角膜神经退行性改变有关的疾病,角膜神经的知觉和营养功能受损,导致角膜上皮缺损、角膜溃疡甚至角膜穿孔。目前人工泪液、治疗性角膜绷带镜、泪点栓塞、羊膜移植,睑缘缝合等治疗措施仍是治疗神经营养性角膜病变的主要治疗方式,对于轻中度病变患者,具有较好的治疗效果,而对于重度病变患者,药物治疗及简单的手术干预治疗效果不佳,病情反复发作。由于重度神经营养性角膜病变患者的角膜神经完全消失,丧失角膜感觉,对未恢复角膜神经营养功能的角膜白斑或溃疡患者行角膜移植术,可能导致角膜移植术后上皮持续不愈合,因此恢复角膜神经营养功能是复明的重要保障手段。角膜神经移植术是重度神经营养性角膜病变患者恢复角膜神经营养功能,提高角膜知觉,改善角膜透明度的重要和有效的治疗方法。角膜神经移植术通过将具有正常功能的供体神经移植到麻痹眼角膜缘周围,使神经末梢重新长入角膜基质,恢复角膜知觉功能。随着角膜神经移植术的术式的不断改进,其良好的术后效果和优点已经渐渐突显。角膜神经移植术包括直接角膜神经移植和间接角膜神经移植,促使角膜神经重新生长,重建角膜神经的营养和知觉功能。角膜神经移植手术已有40年历史,1981年Samii等首次报告了角膜神经移植术,2009年Terzis等成功地实施了第1例直接角膜神经移植术,2014年Elbaz等进行了第1例以腓肠神经作为间置移植物的间接角膜神经移植。封面展示了神经营养性角膜病变患者未接受治疗前的和接受角膜神经移植术后的眼表角膜图像。由于角膜神经退行性改变,角膜失去神经支配,继而出现角膜上皮缺损,角膜缘新生血管形成,经角膜神经移植后,角膜上皮愈合,角膜透明度改善,同时角膜缘新生血管消退。
目的: 比较新鲜羊膜和保存羊膜治疗睑球粘连的疗效差异, 分析影响疗效的因素。方法: 共 51 例 55 只眼因陈旧性化学伤、热烧伤或 Stevens-Johnson 综合征而发生睑球粘连的临床连续病例接受睑球粘连分离联合新鲜羊膜移植(22 只眼) 或保存羊膜移植(33 只眼) 。其中男 30 例 32 只眼, 女 21 例 23 只眼。年龄 4~51 岁, 平均(34.2 ± 4.3) 岁。其中 11 只眼在烧伤后5~11个月, 平均(7.4 ± 1.6) 个月时接受手术, 40 只眼在烧伤后 1~8 年, 平均(2.0 ± 0.7) 年进行手术。结果: 术后随访 12~32 个月, 平均(19.3 ± 4.1) 个月 。所有移植在结膜眼表面的羊膜(包括新鲜羊膜) 植片在术后早期均未见溃烂和溶解, 周边对合良好。31/55(56.4%) 只眼形成了足够深的穹窿部且恢复了眼球运动功能。9/55(16.4%) 只眼发生部分睑球粘连, 眼球运动轻度受限,但其面积远较术前为小。15 /55(27.3%) 眼术后发生中度以上的睑球粘连。新鲜羊膜和保存羊膜重建眼结膜表面的效果相似( X 2 = 0.466, P = 0.797) ; 不同程度睑球粘连的患者其羊膜移植术后的效果不同(新鲜羊膜, X2=27.995, P=0.000; 保存羊膜, X2=33.610, P=0.000) ; 在眼表烧伤后1年内手术比 1 年以上进行羊膜移植的效果也不同(X 2= 4.243, P = 0.039) 。结论: 新鲜羊膜和保存羊膜一样可以有效地用于重建睑球粘连解除后的结膜眼表。患眼术前睑球粘连程度以及烧伤后其眼表炎症是否处于安静状态等因素都会直接影响羊膜移植重建眼结膜表面的远期疗效。
Purpose: To compare the effect of fresh versus preserved amniotic membrane transplant-ation for conjunctival surface reconstruction after symblepharon lysis and analyze the associated factors.Methods: Fifty-one consecutive cases (55 eyes) with symblepharon at different degree due to eye burns or Stevens-Johnson syndrome were accepted lysis of symblepharon and amniotic membrane transplantation. Twenty-two eyes of them were performed with fresh amnion grafts, the others (33 eyes) with preserved human amniotic membrane. Eleven eyes were performed within 1 year and forty eyes in 1 to 8 years (mean value, 2.0 ± 0.7 years) after eye burns.Results: The follow-up time varied from 12 to 32 months (mean value, 19.3 ± 4.1 months) . Fifty-six point four percent (31/55) eyes got enough deep conjunctival fornix and resolution of eye movement restrict. Sixteen percent of them (9/55) recurred less symblepharon and remained slightly eye movement restrict. Fifteen- five eyes of them (27.3%) recurred moderate symblepharon. The effects of surgery were similar between fresh and preserved AMT (X 2 = 0.466, P = 0.797) . The effects of AMT for those patients with symblepharon at different degree had significant difference statistically (fresh amnions, X 2= 27.995, P = 0.000; preserved amnions, X 2 =33.610, P = 0.000) . The same results were observed between those patients who were performed in different time periods after eye burns ( X 2 = 4.243, P = 0.039) .Conclusion: Fresh amnion has the same effect as preserved one for conjunctival surface reconstruction. The degree of symblepharon and the surgical environment of the ocular surface in the affected eye before surgery will influence the results of amniotic membrane transplantation for conjunctival surface reconstruction.
目的:探讨大泡性角膜病变(bullous keratopathy,BK)患者行飞秒激光辅助的角膜内皮移植术(endothelium keratoplasty,EK)的围手术期护理。方法:回顾性分析在南京总医院眼科行飞秒激光辅助角膜内皮移植的BK20例患者,分析并总结患者术前的心理疏导、术前准备、眼科检查、术中如何配合医生、术后特殊体位、高眼压的护理及如何正确用药和出院健康教育等。结果:患者得到及时、有效的护理,术后视力均有所提高,内皮贴伏好,无排斥反应及其他并发症的发生。结论:通过对患者围手术期的护理,可提高护理质量,缩短患者住院时间。
Objective: To observe the perioperative nursing of femtosecond laser-assisted corneal endothelial transplantation in the treatment of patients with bullous keratopathy. Methods: A retrospective analysis of 20 patients with bullous keratopathy with femtosecond laser-assisted corneal endothelial transplantation in our department. The preoperative psychological counseling, preoperative preparation, ocular examination, how to cooperate with the doctors in operation, nursing of special position, high intraocular pressure after surgery, how to use eye drops correctly and health education after discharge were summarized. Results: Nursing were performed to the patients timely and effectively. Postoperative visual acuity of all the patients were improved, the endothelial and corneal stroma bed are well combined and no graft rejection and other complications occurred in the patients postoperatively. Conclusion: We concluded that the quality of nursing was improved and the time of hospitalization was shortened after perioperative nursing.
随着移植技术逐年发展,异基因造血干细胞移植患者的生存期延长,长期并发症成为影响患者预后及生活质量的主要原因。眼移植物抗宿主病是异基因造血干细胞移植术后最常见的眼部并发症,发生率可高达50%以上。根据发病时间可分为急性及慢性眼移植物抗宿主病,临床上最常以慢性炎症及眼表组织纤维化为特点,主要表现为干眼和不同程度的角结膜炎,治疗较为棘手,可不同程度影响患者视觉质量及生活质量,严重可致盲。近年来眼移植物抗宿主病越来越受到国内外学者重视,其发病机制、临床特点、诊断及治疗相关研究逐渐深入,文章针对眼移植物抗宿主病的临床诊疗新进展进行综述。总体而言,眼移植物抗宿主病早期识别仍较为困难,早期诊断策略有待进一步探索。目前治疗对眼移植物抗宿主病的效果较为有限,或缺乏充足的循证医学证据,临床上缺乏针对不同严重程度及疾病活动度的分级诊疗策略,未来有待进一步探索新的治疗靶点及疾病活动监测指标,将有助于改善患者长期预后及生活质量。
Despite advancements in allogeneic hematopoietic stem cell transplantation techniques leading to improved overall survival rates, long-term complications have emerged as the primary contributors to poor prognosis and diminished quality of life. Ocular graft-versus-host disease (oGVHD), a prevalent complication affecting over 50% of patients post-transplantation, frequently manifests as refractory dry eye, often accompanied by keratoconjunctivitis. Patients with oGVHD routinely suffer from visual impairment and a decline in their quality of life.Currently, research into the mechanisms, clinical features, diagnosis, and treatment of oGVHD has progressively deepened. This article reviews the latest advancements in the clinical diagnosis and management of oGVHD. Notably, there is a pressing need for strategies focused on early diagnosis and treatment, as early recognition of oGVHD remains challenging. Existing treatments for oGVHD either exhibit limited efficacy or lack robust clinical evidence to support their use as the best available options.Further research is imperative to develop tiered diagnostic and treatment approaches, including the exploration of novel therapeutic targets and biomarkers for disease detection. Such endeavors hold the promise of enhancing patients' long-term prognosis and quality of life.
随着角膜疾病治疗技术的不断进步,前弹力层移植技术(包括Inlay和Onlay技术)已成为晚期圆锥角膜治疗的重要手段,能有效改善患者的角膜地形图和视力结果,稳定角膜扩张,提高患者的生活质量。该文综述了前弹力层移植技术的理论基础、移植物的来源与制备技术、手术技术、临床疗效以及相关并发症,为晚期圆锥角膜的治疗提供了新的视角。研究表明,这种先进的移植技术相较于传统方法,在减少手术风险、简化手术流程以及加快术后恢复方面具有明显优势,特别是在降低异体移植物排斥反应及手术并发症的风险上,前弹力层移植表现出色。Onlay技术作为一种近期开发的新方法,其独特优势是无需剖离角膜,更好地保护角膜结构。此外这种技术的高度适应性和可逆性,为患者提供了更多的治疗选择和更好的视觉恢复。尽管如此,技术细节如移植物的尺寸和形状定制、手术深度的最优化等方面仍需进一步研究和优化,以提高整体治疗效果。
With the continuous advancement of corneal disease treatment technology, Bowman layer transplantation (including Inlay and Onlay technology) has become an important means for the treatment of advanced progressive keratoconus, which can effectively improve the corneal topography and visual acuity of patients, stabilize corneal dilation, and improve the quality of life of patients. Tis article reviews the theoretical basis of Bowman layer transplantation, the source and preparation of grafs, surgical techniques, clinical efcacy, and related complications, which provides a new perspective for the treatment of advanced keratoconus. It is stated in the research that this advanced transplantation technique has significant advantages over traditional methods in reducing surgical risks, simplifying the surgical procedures, and improving postoperative recovery. Especially in reducing the risk of allograft rejection and surgical complications, the bowman layer transplantation performs excellently. As a novel developed method, Onlay technology has the unique advantage of eliminating the need to dissect the cornea, which beter protects the corneal structure. In addition, due to the highly adaptable and reversible nature of this technique, it provides patients with more treatment options and beter visual recovery. However, in terms of technical details such as customizing the size and shape of the transplant, optimizing the surgical depth, etc., it is needed to conduct further research and optimization to improve the overall treatment efect.
目的:旨在研究按移植指征分类以及移植前角膜血管形成对手术后5年内排斥反应和移植物失败率的相对风险。方法:分析1999—2017年间,英国移植登记处记录的所有因圆锥角膜(keratoconus,KC)、人工晶状体大泡性角膜病(pseudophakic bullous keratopathy,PBK)或既往感染(病毒/细菌/真菌/原生动物)而首次进行角膜移植的成年人。统计移植前受体角膜血管化象限的数量、血管化类型、移植后排斥反应的间隔时间(如果有的话)以及移植后5年的结果。通过多变量风险调整Cox回归法进行排斥反应和移植失败的危险因素建模。结果:KC、PBK和感染患者的角膜血管形成率分别为10%、25%和67%。只有当存在浅表和(或)深部血管形成时(HR分别为1.3和1.4,P=0.004),存在两个以上象限的血管形成时,PBK患者移植排斥反应的风险才会增加(HR=1.5,P=0.0004)。因既往感染而接受移植的个体在四个象限的血管形成中发生排斥反应的风险增加(HR=1.6,P=0.003)。在任何一组中,经过风险调整后,与血管形成有关的移植失败率并未上升。对于含有血管的受体角膜,相对于穿透性KC和PBK移植,没有充分的证据显示板层移植在降低排斥反应或失败风险方面存在优势。结论:血管化是5年内角膜移植排斥反应的危险因素。移植的适应证对这种风险的具有临床意义。
Objective: To investigate the relative risk of pretransplant corneal vascularisation on rate of rejection and graft failure within 5 years of surgery when categorised by indication for transplantation. Methods: We analysed all adults recorded in the UK transplant registry who had a first cornea transplant for keratoconus (KC), pseudophakic bullous keratopathy (PBK) or previous infection (viral/bacterial/fungal/protozoan) between 1999 and 2017. We analysed the number of quadrants of the recipient cornea vascularised before transplant and type of vascularisation, the interval posttransplant to rejection, if any, and the outcome at 5 years post-transplant. Risk factors for rejection and transplant failure were modelled by multivariable risk-adjusted Cox regression. Results: Corneal vascularisation was recorded in 10%, 25% and 67% of patients with KC, PBK and infection, respectively. Individuals with PBK had an increased hazard of transplant rejection only when there were more than two quadrants of vascularisation (HR 1.5, p=0.004) when either superficial and/or deep vascularisation was present (HR 1.3 and 1.4, respectively, p=0.004). Individuals who had a transplant for previous infection had an increased hazard of rejection with four quadrants of vascularisation (HR 1.6, p=0.003). There was no risk-adjusted increase in transplant failure associated with vascularisation in any group. There was weak evidence of reduction in risk of rejection and/or failure associated with lamellar compared with penetrating transplantation in KC and PBK in vascularised recipient corneas. Conclusion: Vascularisation is a risk factor for corneal allograft rejection within 5 years. The indication for transplantation has a clinically significant effect on the magnitude of this risk.
目的:探讨睑结膜乳头切除联合自体游离结膜瓣移植术治疗春季角结膜炎的临床效果。方法:在显微镜下对11例(22眼)春季角结膜炎患者行睑结膜乳头切除联合自体游离结膜瓣移植术,观察治疗效果。结果:术后随访36~48个月,11例(22眼)春季角结膜炎患者中,治愈19眼(86.36%),有效2眼(9.09%),无效1眼(4.55%),总有效率95.45%。结论:睑结膜乳头切除联合自体游离结膜瓣移植术是治疗春季角结膜炎安全、有效的方法。
Objective: To evaluate the efficacy and safety of surgical resection of conjunctival papillae combined with autologous conjunctival graft in the treatment of vernal keratoconjunctivitis (VKC). Methods: All 11 cases (22 eyes) with VKC were treated with surgical resection of conjunctival papillae in combination with autologous conjunctival graft. Clinical efficacy and safety were evaluated. Results: After 36 to 48 months of follow-up, 19 eyes were cured (86.36%), 2 eyes were improved (9.09%), and 1 eye was ineffective (4.55%). The total effective ratewas 95.45%. Conclusion: Surgical resection of conjunctival papillae combined with autologous conjunctival graft is efficacious and safe in the treatment of VKC.