慢性眼部移植物抗宿主病相关干眼的研究与治疗现状

异基因造血干细胞移植(allo-HSCT)是治疗多种血液系统恶性肿瘤的主要方法,但术后的慢性移植物抗宿主病(cGVHD)是一种常见的并发症,其中眼部移植物抗宿主病(oGVHD)是最常见的一种,主要累及泪腺、睑板腺、角膜和结膜,典型症状为以纤维化为特征的干眼综合征。oGVHD相关干眼导致患者生活质量显著下降,已引起广泛关注。oGVHD的治疗除了应用全身免疫抑制剂和眼润滑剂外,通常联合局部使用糖皮质激素和环孢素。对于中重度oGVHD较新的治疗措施还包括使用自体血清滴眼液和角巩膜接触镜。本文主要就oGVHD及其相关干眼的治疗现状进行综述,以期为临床诊疗提供思路。     

眼部移植物抗宿主病治疗进展

异基因造血干细胞移植是治疗血液系统良恶性肿瘤的有效疗法,但移植物抗宿主病的发生会影响全身各脏器和组织,使患者身体受到重大的损伤,不仅严重影响患者的生活质量,还可能增加移植后患者的死亡率。眼部移植物抗宿主病是眼部排斥反应的表现,60%~90%的慢性移植物抗宿主病患者伴发眼部移植物抗宿主病,可表现为干眼、结膜炎、角膜炎等症...     

单倍体半相合非清髓性异基因造血干细胞移植后并发视网膜病变

造血干细胞移植是目前治疗恶性血液病最主要也是有效的方法，甚至是治愈某些血液病的唯一方法。然而晚期并发症如移植物抗宿主病（graft versus host disease，GVHD）影响移植效果和患者的生活质量。GVHD可以引起全身多种组织器官损害，眼部也不例外，多见于眼前段组织，眼后段的并发症报道甚少。我们遇一例非何杰金氏淋巴瘤患者，在接受半相合非清髓性异基因造血干细胞移植后出现双眼进行性视网膜病变，最终导致盲目，兹报道如下。     

慢性移植物抗宿主病相关性干眼的研究进展

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...     

慢性移植物抗宿主病干眼相关生物标志物

异基因造血干细胞移植术(allo-HSCT)是治疗血液系统恶性及非恶性疾病常见的治疗方法, 而allo-HSCT后常见慢性移植物抗宿主病(cGVHD)干眼等眼部并发症, 严重影响患者的生存质量, 严重者可能会导致角膜穿孔甚至盲。随着allo-HSCT技术不断成熟, 移植人数逐渐增多、移植后患者生存时间延长, cGVHD干眼的发生率也不断升高。目前对该病的发病机制、诊断及治疗方面的研究尚不完善, 生物标志物的研究对其早期预防、诊断及治疗具有极其重要的作用。本文主要从泪腺、角结膜、睑板腺、泪液及外周血中cGVHD干眼的生物标志物研究进展做一综述。     

移植物抗宿主病相关的干眼病

目的 观察异基因造血干细胞移植术后移植物抗宿主病的眼部表现。方法 对20例异基因造血干细胞移植术后白血病患者的随访结果进行回顾性研究,随访的主要眼科检查项目包括视力、裂隙灯显微镜、荧光素染色、虎红染色、泪膜破裂时间、Schirmer Ⅰ和SchirmerⅡ试验,部分患者行共焦显微镜检查、结膜印迹细胞检查和病理活检。结果 术后14例患者出现移植物抗宿主病。8例出现干眼病,占移植物抗宿主病患者的57％。其中4例为严重干眼病,患者伴有视力明显下降,甚至角膜溃疡;病理检查结果示：结膜杯状细胞消失或明显减少,结膜上皮角化,角膜上皮鳞状化生,结膜炎性反应细胞以T淋巴细胞为主。结论 于眼病是慢性移植物抗宿主病的主要眼部合并症,严重影响患者生活质量,应引起足够重视。     

慢性移植物抗宿主病干眼相关生物标志物

异基因造血干细胞移植术(allo-HSCT)是治疗血液系统恶性及非恶性疾病常见的治疗方法,而allo-HSCT后常见慢性移植物抗宿主病(cGVHD)干眼等眼部并发症,严重影响患者的生存质量,严重者可能会导致角膜穿孔甚至盲。随着allo-HSCT技术不断成熟,移植人数逐渐增多、移植后患者生存时间延长,cGVHD干眼的发生...     

慢性移植物抗宿主病相关干眼

异基因造血干细胞移植后慢性移植物抗宿主病(cGVHD)发病率较高,其中60%出现眼部并发症,主要表现为眼表病变,干眼最为多见,虽不威胁生命却严重影响生存质量.cGVHD相关干眼的发病机制尚不明确,可能为免疫活性T细胞直接攻击结膜、泪腺上皮所致.随着研究的不断深入,其发生机制正逐渐得到揭示,一些新的治疗措施也取得了较为理想的效果,较好地提高了此类患者的生存质量.     

慢性移植物抗宿主病相关干眼纤维化发病机制研究进展

慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植(allo-HSCT)后的一个主要并发症,类似于自身免疫性疾病,累及全身多个器官。干眼是cGVHD眼部的主要表现,严重影响患者的生活质量。研究发现,慢性炎症和纤维化是cGVHD相关干眼患者眼部多个组织的主要病理生理表现。目前关于cGVHD相关干眼纤维化的发病机制尚不清楚,因此本文从成纤维细胞、免疫细胞、促纤维化细胞因子、肾素-血管紧张素系统和内质网应激方面对cGVHD相关干眼纤维化机制进行综述,以期能针对纤维化研发出新的诊断、治疗和预防策略。     

眼部移植物抗宿主病的治疗进展

眼部移植物抗宿主病(GVHD)是异基因造血干细胞移植(HCT)术后的严重并发症, 轻者可以表现为眼部不适, 重者可以出现严重的致盲性并发症。目前对于该病的治疗通常是循序渐进的, 首先局部应用人工泪液及免疫抑制剂治疗, 当症状不能缓解时考虑加用泪点栓塞、自体血清滴眼液及角膜或巩膜接触镜治疗, 单用局部治疗对于症状较轻的患者效果往往较好。若患者眼表炎症持续进展, 常需加用全身免疫抑制治疗。对于出现严重角膜病变的患者则需要考虑手术治疗, 但此时由于眼部GVHD患者眼表炎症的持续存在, 预后常常较差。随着对该病发病机制认识的深入, 多种新型治疗方法如促泌剂、JAK/SYK抑制剂、曲尼司特、利非格斯、肝素、siRNA治疗及干细胞治疗已投入临床研究及应用, 并取得了较好的治疗效果, 本文将对眼部GVHD的治疗进展进行综述, 以期为临床工作及研究提供参考。     

Dry eye after haematopoietic stem cell transplantation

AIMS—To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT).
METHODS—At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure.
RESULTS—Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjögren''s syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD.
CONCLUSIONS—Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary.

     

Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease

PURPOSE: To describe the use of allogeneic serum eye drops to treat 2 patients with chronic graft-versus-host disease (GVHD)-induced severe ocular surface disease. METHODS: Small case series. RESULTS: Conventional therapy failed to control the ocular symptoms of 2 patients with GVHD who presented with severe dry eye syndrome. Because autologous serum was unavailable in these cases, we used allogeneic serum eye drops as an alternate option for treating their ocular surface disease. Both donors had serologic tests performed before donation. Use of the allogeneic serum eye drops had a beneficial clinical effect, with marked attenuation of the patients' symptoms. This therapy proved to be safe during 10 months of treatment. CONCLUSIONS: Allogeneic serum eye drops may be a good alternative treatment for patients with severe dry eyes caused by GVHD.     

Impact of ocular graft‐versus‐host disease on visual quality of life in patients after allogeneic stem cell transplantation: questionnaire study

Purpose: To determine the influence of ocular complications on quality of life (QoL) 3 years after allogeneic stem cell transplantation (allo‐SCT). Methods: All 54 adult patients that underwent and survived allo‐SCT in 2006/2007 in our centre received two questionnaires (VFQ‐25: visual function questionnaire‐25 and OSDI: ocular surface disease index). In addition, the following data were included: gender, age, underlying disease, presence of chronic and/or ocular graft‐versus‐host disease (GVHD), number of visits to an ophthalmologist, manifestations of dry eye disease, the duration of follow‐up and treatment for ocular GVHD. Results: Ocular GVHD developed in 26% (14 of 54) of patients and 71% (10 of 14) received treatment for ocular GVHD. The presence of ocular GVHD correlated with the severity of systemic GVHD (correlation coefficient: 0.52, p = 0.00). The Karnofsky scores were significantly lower in the patients with ocular GVHD compared to the patients with no ocular GVHD (p = 0.001). Karnofsky scores were weakly correlated with the severity of systemic GVHD (correlation coefficient: 0.25, p = 0.03. Three years after the all‐SCT, OSDI and VFQ‐25 scores were significantly impaired in patients with ocular GVHD [mean: 76.5; range (46.1–100) and mean: 31.1; range (0–72.9)] compared to patients with no ocular GVHD [mean: 89.4; range (45.2–100) and mean: 12.9; range (0–58.3); p = 0.02]. The scores of the VFQ‐25 were significantly lower in the domains of general health, ocular pain, social functioning and role difficulties. Conclusion: The long‐term vision‐related QoL measured by the OSDI and VFQ‐25 was impaired in patients with ocular GVHD.     

眼部移植物抗宿主病的研究进展

造血干细胞移植（SCT）是治疗恶性血液疾病的可靠疗法,SCT之后罹患移植物抗宿主病（GVHD）是患者致残和死亡的主要原因,根据其始发时间和临床表现的不同可分为急性和慢性2种。急性GVHD表现为一种累及皮肤、胃肠道和肝的特殊综合征;慢性GVHD则表现为一种多向的综合征,累及部位通常包括皮肤、口腔、肝脏、胃肠道、肺以及眼。接受同种异体造血干细胞移植之后大约40%～60%的患者会出现急性或慢性的眼部GVHD,导致几种严重眼部疾病并且极大地降低了患者的生活质量。然而到目前为止尚无各方认可的针对眼部GVHD的治疗方案出台。笔者概述了GVHD、眼部GVHD的最新研究进展和提高其治疗、预防水平的迫切性。     

Ocular manifestations of graft-versus-host disease

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT.Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production.Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva.Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation.     

白内障超声乳化联合人工晶状体植入手术后干眼发生的相关因素分析

目的评估不同危险因素在白内障超声乳化联合人工晶状体植入术后干眼发生中的作用,为术后干眼发生的预测及防治提供依据。方法记录93例(98只眼)术前无干眼白内障患者手术前及术后3个月常见的全身疾病,并进行干眼问卷调查及相关眼部检查,包括睑板腺功能检查、BUT、SchirmerⅠ试验、角膜荧光素染色等,对检查结果进行多因素回归分析及多元线性回归分析,分析其危险因素。结果 44例47只眼(48%)白内障术后确诊为干眼,Logistic回归分析显示:睑脂粘度(OR=2.670,P=0.025)和结膜松弛(OR=4.537,P=0.004)是白内障术后干眼发生的独立危险因素。糖尿病(OR=3.778,P=0.037)、高血脂(OR=11.645,P=0.023)、睑板腺分泌物(OR=5.660,P=0.025)及睑脂粘度(OR=2.881,P=0.018)是BUT值缩短的独立危险因素。多元线性回归分析显示:睑脂粘度与角膜染色呈正相关(F=79.282,P<0.001)。结论白内障术后干眼的发生与全身及局部多种因素相关,术前针对相关危险因素进行评估,可有助于术后干眼发生的预测并提前进行综合干预治疗。     

不同年龄段干眼症患者的睑板腺分析

目的：分析不同年龄段干眼症患者睑板腺情况。
　　方法：选取2015-11/2016-04就诊于我院的干眼症患者301例598眼,按年龄分为8组,分别为A~H组。应用眼表综合分析仪检查各组干眼症患者睑板腺腺体缺失情况、腺体形态变化、睑板腺开口阻塞及睑酯情况,分析比较各组之间的睑板腺变化规律。
　　结果：所有患者均有不同程度睑板腺腺体缺失,各组之间腺体缺失面积比较,差异有统计学意义(χ2=336, P<0.05)。 A组腺体数目无减少, B~H各组之间腺体数目减少比较,差异有统计学意义(F=36.4357,P<0.05)。腺体形态从40岁开始逐渐变细,其与年龄呈反相关。睑板腺开口阻塞情况及睑酯的性状,各组之间无明显差异。结论：眼表综合分析仪能客观精准地检查出干眼症患者的睑板腺情况,提供不同年龄段干眼症患者睑板腺变化规律的量化结果,为干眼症的病因诊断提供判断依据,指导临床治疗。     

Dry‐eye syndrome after allogeneic stem‐cell transplantation in children

Purpose: To report the prevalence of dry‐eye syndrome (DES) in children and young adults treated with allogeneic stem‐cell transplantation (SCT) during childhood; to relate DES to conditioning regimes, including total body irradiation (TBI) and chemotherapy, and to immunosuppressive drugs and graft‐versus‐host disease (GVHD). Methods: This cross‐sectional study included 60 children/young adults transplanted because of leukaemia, various haematological disorders and inborn errors of metabolism between 1986 and 2004, with a follow‐up time of 7.0 years (median, range 2–18). Clinical assessments, performed at a median age of 15.6 years (range 5.5–23.5), included an inquiry form on dry‐eye symptoms, corneal status including fluorescein staining, ‘break‐up time’ (BUT) and Schirmer test. Results: A total of 37 of 60 patients had DES defined as presence of corneal epithelial lesions with a pathological BUT and/or Schirmer test. Twenty‐nine had had staining <1–10% of the corneal surface while eight patients had staining ≥10–25% of the corneal surface. All 37 patients with objective signs of DES, graded and not graded, had significant associations to subjective symptoms of dry eyes including dry eyes, red eyes, ocular irritation, secretion and sensitivity to light. Frequent occasions (above median; n = 7) of high cyclosporine A trough levels above 250 ng/ml were associated significantly with DES (P = 0.002). However, there was no association between DES and conditioning with single‐dose (s‐TBI) or fractionated TBI (f‐TBI), busulfan or other chemotherapy. There were no associations between prolonged corticosteroid treatment or chronic GVHD and DES in the present study. DES was more common in patients with malignant diseases (P = 0.02). Malignant disease increased the risk of DES in girls but not in boys. Increased age at SCT increased the risk for DES in boys but not in girls (P = 0.02). Although severe keratitis occurred in three patients, nobody suffered corneal perforation. Conclusion: DES with epithelial punctata keratopathy was common in children/young adults treated with SCT and more common if the patients were exposed to repeated high trough levels of cyclosporine A; however, DES was not associated with irradiation, corticosteroids or GVHD in the present study. Patients with objective DES also had subjective symptoms of dry eyes, which facilitate diagnosis. Girls with malignant diseases and boys who underwent SCT at later ages seem to demand higher attention and more frequent check‐ups regarding DES. Patients with diagnosed severe DES needed frequent and continuous ophthalmological care to maintain treatment motivation.     

睑板腺功能障碍患者IntraLase-LASIK术前睑板腺处理的临床观察

目的：：观察睑板腺功能障碍患者术前行睑板腺处理对飞秒激光制瓣膜的准分子激光角膜原位磨镶术( IntraLase-LASIK)术后眼表炎症反应和泪膜状态的改变。方法：选取2014-03/09来我院屈光门诊就诊拟行IntraLase-LASIK术并有不同程度睑板腺功能障碍的患者35例70眼。随机数字法将患者分为两组：观察组17例34眼术前给予睑板腺的特殊处理,对照组18例36眼术前不进行睑板腺处理,两组其余操作相同。观察IntraLase-LASIK术后1 d和1 wk眼球结膜充血、畏光、干涩感评分及泪膜破裂时间( tear break-up time,BUT)的变化。结果：术后1 d和1 wk观察组的球结膜充血、畏光、干涩感评分及BUT均低于对照组( P<0.05)。结论：睑板腺功能障碍的患者术前睑板腺处理可以减轻术后的眼表刺激症状,对泪膜起到一定的稳定作用,提高患者术后的满意度。