Tear cytokine levels in the diagnosis and severity assessment of ocular chronic graft-versus-host disease(GVHD)

PurposeTo analyse the tear cytokine levels of patients diagnosed with ocular chronic graft-versus-host disease(GVHD)and examine the consistency of these levels with different ocular surface parameters.Methods23 ocular chronic GVHD patients were selected for the assessment of tear cytokine levels and ocular surface parameters (TBUT, CFS, OSDI, and Schirmer's test), and 16 dry eye disease(DED)patients without systemic immune disease were selected as the control group. The 23 cytokines were measured using microsphere-based immunoassay analysis and their consistency with different ocular surface parameters was studied.ResultsICAM-1, IL-1β, IL-6, and IL-8 showed elevated levels in the eyes of oGVHD patients compared to DED [P < 0.001]. IL-7 and EGF showed lower levels in the eyes of patients with oGVHD than in those of patients with DED [P < 0.0001]. Furthermore, the levels of IL-6 and IL-8 showed a stronger correlation with corneal fluorescein staining (CFS) (P < 0.05), and the levels of IL-6 and ICAM-1 were most consistent with fluorescein tear film break-up time (TBUT) (P < 0.05).ConclusionsOur study demonstrated certain tear cytokines, including ICAM-1, IL-1β, IL-6, IL-8 IL-7 and EGF, as promising new possible diagnostic markers of chronic oGVHD and criteria for chronic ocular GVHD severity. Because tear sampling is noninvasive and simple, this method is expected to be an overwhelming applicable for the screening and diagnosis of chronic GVHD.     

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。     

Tear inflammatory mediators and protein in eyes of post allogenic hematopoeitic stem cell transplant patients

Aim

To analyze tear cytokines levels and their correlation to ocular surface parameters in allogenic hematopoietic stem cell transplants (allo-HSCT) patients.

Efficacy and retention of silicone punctal plugs for treatment of dry eye in patients with and without ocular graft-versus-host-disease

PurposeTo examine the retention rates and efficacy of silicone punctal plugs for the treatment of dry eye disease (DED) in patients with ocular graft-versus-host-disease (oGVHD) in comparison to dry eye disease due to non-oGVHD etiologies.MethodsWe reviewed the case-records of 864 consecutive patients with DED who were symptomatic despite topical therapy and had silicone punctal plugs placed over an eight-year- period at a single academic center. We compared plug retention rates in oGVHD and non-oGVHD DED patients using Kaplan–Meier analyses. Furthermore, we analyzed changes in objective ocular surface parameters including tear breakup time (TBUT), Schirmer's test, and corneal fluorescein staining (CFS) score in plug-retaining patients at two-, six- and twelve-month follow-up.ResultsMedian age of dry eye patients was 58 years, and 606 (70%) of patients were women. In the cohort, 264 (31%) patients were diagnosed with oGVHD. Plug retention was significantly lower in oGVHD-DED patients compared to non-oGVHD-DED patients (p < 0.0001). We observed significant improvement in CFS scores in plug retaining-oGVHD and non-oGVHD DED patients at all time points. Tear break-up time was significantly prolonged at six- and twelve-months follow-up in non-oGVHD patients, whereas significant change in TBUT in oGVHD patients was recorded only at twelve months post plug placement. Schirmer's score improved significantly in plug retaining-non-oGVHD DED patients at six- and twelve-months follow-up, however no significant change was observed in Schirmer's score in oGVHD DED patients.ConclusionsAn improvement in ocular surface disease parameters was observed in both plug-retaining oGVHD and non-oGVHD DED patients. However, a majority of oGVHD DED patients spontaneously lost their punctal plugs within 90 days of placement. Therefore, regular follow-up after plug placement is recommended to detect plug loss and ensure adequate disease control.     

Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease

PurposeTo determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD).DesignRetrospective cohort study.MethodsWe performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients.Main outcome measurePrevalence of NK in chronic oGVHD.ResultsWe identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients.ConclusionsThe prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.     

造血干细胞移植术后的眼部观察

目的 观察造血干细胞术后移植物抗宿主病(GVHD)及预处理措施对眼部的影响。方法 对35例行造血干细胞移植患者的眼科检查进行回顾性分析。结果 35例中慢性GVHD14例，占异基因造血干细胞移植的70％。其中8例合并有干眼，占GVHD患者的57．14％；6例睑板腺功能障碍并伴有干眼。眼部其他并发症有结膜瘢痕、睑球粘连、角膜溃疡、白内障、急性结膜炎、眼底出血或结膜出血。自体造血干细胞移植不出现移植物抗宿主病及干眼。结论 干眼是异基因造血干细胞移植术后的主要眼部并发症，仅见于发生GVHD的患者。异基因造血干细胞移植的眼部并发症明显高于自体干细胞移植。     

An overview on dry eye disease diagnosis: options for new non-invasive testing technologies

This literature review intends to provide an overview of the new non-invasive testing technologies and their role in the diagnosis of dry eye disease (DED). Including imaging technologies of tear volume, tear film stability, meibomian glands morphology and function, corneal morphology, biomarkers and ocular surface temperature, as well as tear osmolarity, optical quality, blinking test and so on. New testing technologies can provide an indirect and objective assessment of the ocular surface, tear condition and visual quality. Testing technologies, such as tear volume, meibography and tear osmolarity have been widely recognized and applied in clinical practice, showing higher specificity and sensitivity than traditional tests. Others, such as strip meniscometry, interferometer, light scattering technology, double-pass system, blinking test and so on, are currently in the stage of clinical research and improvement, and may translate to routine clinical detection techniques in the future. The new non-invasive testing technologies can non-invasively evaluate the ocular surface and tears, and measure the changes of components related to the disease, which play an important role in the diagnosis, classification, clinical management and curative effect evaluation of DED.     

诊断干眼的非侵入性新检测技术及应用价值

本文对诊断干眼的非侵入性新检测技术及其在干眼诊断中的作用进行综述,其中包括泪液量、泪膜稳定性、睑板腺形态及功能、角膜形态、生物标志物、眼表温度的成像技术,以及泪液渗透压、光学质量、眨眼测试等。新的检测技术可提供客观参数以评价眼表、泪液情况及视觉质量等。泪液量、睑板腺成像和泪液渗透压等检测技术已被广泛认可并应用于临床,与传统测试相比表现出了更高的特异性和敏感性。其它检测技术,如SM技术,干涉术、光散射技术、双通道系统,眨眼测试等目前处于临床研究阶段,未来或将转化为临床常规检测技术。新的检测技术,可无创评估眼表及泪液情况,并测量与病情相关的成分变化,在干眼的诊断、分类、临床管理和疗效评估中发挥重要作用。     

Keratitis in Dry Eye Disease and Topical Ciclosporin A

Tear film alterations in dry eye disease (DED) include reduced tear volume and an increase in inflammatory cytokines. Instability and reduced tear production initiate a vicious cycle where hyperosmolarity, ocular inflammation, and apoptosis may induce damage of the ocular surface including keratitis. Topical cyclosporine (CsA) has been used for the treatment of moderate-to-severe DED; however, previous studies failed to demonstrate its benefits by the European Agency standards. A new formulation of CsA 0.1% has been recently approved in the EU to treat severe keratitis in DED patients. Patients with severe keratitis showed a better improvement after 6 months of treatment with CsA compared with vehicle. HLA-DR expression was significantly reduced by CsA treatment. The clinically significant improvement in keratitis associated with the inflammatory biomarker HLA-DR confirms the efficacy of CsA to improve inflammation and its damaging effect on the ocular surface in DED patients.     

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation

AIM: To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life (QOL) in patients after allogeneic hematopoietic stem cell transplantation (ALLO-HSCT). METHODS: Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020. They completed two questionnaires: the Ocular Surface Disease Index (OSDI) and the quality-of-life scale for Chinese patients with visual impairment (SQOL-DV1). Ocular conditions and systemic conditions were also assessed. RESULTS: Eye damage was correlated with total bilirubin (P=0.005), and gamma-glutamyl transferase (GGT) (P=0.021). There was no significant correlation between the overall QOL score and OSDI (P=0.8226) or SQOL-DV1 (P=0.9526) scores. The OSDI and the overall QOL score were not correlated with ocular conditions, including best-corrected visual acuity (BCVA), intraocular pressure, Schirmer tear test II, sodium fluorescein staining, tear film breakup time, and tear meniscus height. SQOL-DV1 was correlated with BCVA (P=0.0007), sodium fluorescein staining (P=0.007), and tear film breakup time (P=0.0146). CONCLUSION: In some patients, early ocular symptoms are not evident after ALLO-HSCT, while ocular surface complications can be observed after a comprehensive ophthalmological examination. Especially for those with elevated total bilirubin or GGT, regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease (oGVHD), especially for patients with elevated total bilirubin or GGT.     

Dry eye: an update on clinical diagnosis,management and promising new treatments

Dry eye conditions are prevalent with one in four to five patients presenting to eye care practitioners having dry eye signs and/or symptoms. An intimate relationship exists between the ocular surface and the tear film. The cycle of tear film instability and ocular surface damage characteristic of dry eye conditions suggests that dry eye represents a dysfunction of an integrated ocular surface‐lacrimal gland unit. Therefore, dry eye is a multifactorial condition and an approach based on clinical subtypes is required for diagnosis and management. There is increasing evidence that inflammation is a contributing and exacerbating factor in dry eye conditions and anti‐inflammatory or immunomodulatory therapy for chronic dry eye conditions may facilitate ocular surface healing. Other promising new treatments for dry eye include new generation artificial tear polymers and preservative systems, secretagogues, topical androgen supplements and surgical techniques for ocular surface reconstruction.     

眼针疗法治疗“气阴两虚型”干眼的临床研究

目的：观察眼针疗法治疗“气阴两虚型”干眼的临床疗效及其作用机制。方法：前瞻性随机对照研 究。收集2021年1—4月于辽宁中医药大学附属第二医院确诊为“气阴两虚型”干眼患者74例,通 过随机数字表法将74例患者分为眼针疗法组和常规针法组,各37例。常规针法组给予常规针刺治 疗,主穴为攒竹、四白、阳白、丝竹空、太阳;配穴为太溪、合谷、足三里、三阴交。眼针疗法组予 以眼针治疗,取肝区、肺区、脾区、肾区四穴治疗。疗程均为14 d。记录2组治疗前后眼表疾病指 数（OSDI）评分;检测无表麻泪液分泌试验（SⅠT）和角膜荧光素染色（CFS）;使用K5M眼表分析仪 采集首次泪膜破裂时间（NIBUTf）和平均泪膜破裂时间（NIBUTav）。数据采用t检验、Wilcoxon秩和 检验、χ2 检验进行统计分析。结果：常规针法组与眼针疗法组的OSDI评分、SⅠT、CFS、NIBUTf、 NIBUTav在组内治疗前后比较,差异均有统计学意义（均P<0.05）。治疗后2组患者的OSDI评分、 SⅠT、NIBUTf、NIBUTav比较,差异均有统计学意义（均P<0.05）;治疗后组间CFS比较差异无统计 学意义。结论：常规针法与眼针疗法均能有效治疗“气阴两虚型”干眼,眼针疗法在改善干眼的眼 表症状、泪液分泌及泪膜破裂时间方面优于常规针法治疗,其优效性和依从性更高。     

Inflammation and dry eye disease—where are we?

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.     

Inflammation and dry eye disease—where are we?

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.     

Conjunctival subepithelial fibrosis and meibomian gland atrophy in ocular graft-versus-host disease

Purpose

Dry eye symptoms greatly impact patients' quality of life in ocular graft-versus-host disease (oGVHD). Various ocular surface changes have been reported in oGVHD, including meibomian gland atrophy (MGA) and clinical conjunctival scarring or subepithelial fibrosis (CSEF). The relationships between CSEF, MGA, and other ocular surface changes in oGVHD were examined.

干眼症临床检查的新进展

完整的泪膜是维持眼表健康和功能的基础,而泪液的产生、保留、稳定排泄是维持这种健康状态的必备条件。任何原因引起眼表面泪膜的异常均将引起干眼。当前干眼症的临床检查方法很多,主要针对泪液或泪膜的不同方面,如:检测泪液的量、物理特性、化学成分,泪膜的厚度、稳定性等,力求为干眼症的诊断和治疗提供有力的依据。但由于至今尚未有一种检查方法在干眼症的诊断上能称之为"金标准",因而必须联合至少3种检查法综合判定干眼情况。     

Lacrimal gland regeneration: The unmet challenges and promise for dry eye therapy

Dry eye disease (DED) is a common multifactorial disease of the tear film and the ocular surface. The problem of DED has gained attention globally, with millions of people affected by the disorder. Although the treatment strategies for DED have significantly evolved over time, most of the existing modalities fall under the category of standard palliative care when viewed from a long-term perspective. To address these limitations, different approaches have been explored by various groups to uncover alternative treatment strategies that can contribute to a full regeneration of the damaged lacrimal gland, which is responsible for producing the major aqueous component of the tear film. For this, multiple groups have investigated the role of lacrimal gland cells in DED based on their regenerating, homing, and differentiating capabilities. In this review, we discuss in detail the therapeutic mechanisms and regenerative strategies that can potentially be applied for lacrimal gland regeneration as well as their therapeutic applications. This review mainly focuses on aqueous deficiency dry eye disease (ADDE) caused by lacrimal gland dysfunction and possible future treatment strategies. The current key findings from cell and tissue-based regenerative therapy modalities that could be utilised to achieve lacrimal gland tissue regeneration are summarized. In addition, this review summarises the available literature from in vitro to in vivo studies, their limitations in relation to lacrimal gland regeneration and the possible clinical applications. Finally, current issues and unmet needs of cell-based therapies in providing complete lacrimal gland tissue regeneration are discussed.     

Characterising the ocular surface and tear film in a population-based birth cohort of 45-year old New Zealand men and women

PurposeTo assess the prevalence of dry eye disease, aqueous tear deficiency, meibomian gland dysfunction, and asymptomatic ocular surface disease in a population-based cohort of 45-year-old New Zealand men and women.MethodsThis cross-sectional study of 885 participants (442 females, 443 males) was based on a population-representative birth cohort of individuals born between April 1 1972 and March 31 1973 in Dunedin, New Zealand (the Dunedin Multidisciplinary Health and Developmental Study). Participants were assessed at 45 years of age, and dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease was made according to the validated rapid non-invasive dry eye assessment algorithm.ResultsClinical dry eye signs were present in 402 (45%) participants, of which 78 (9%) participants fulfilled the diagnostic criteria for dry eye disease, and 322 (37%) had asymptomatic ocular surface disease. Among participants with dry eye disease, 22 (2%) exhibited aqueous tear deficiency, and 65 (7%) had meibomian gland dysfunction. Females were more likely to be affected by dry eye disease, meibomian gland dysfunction, and asymptomatic ocular surface disease (all p < 0.05).ConclusionsClinical dry eye signs were present in almost half of this population-based cohort of 45-year-old New Zealanders, although only 9% of participants fulfilled the diagnostic criteria for dry eye disease. The high prevalence of asymptomatic ocular surface disease presents an opportunity for preventative public health intervention.     

Conjunctivochalasis: a systematic review

Conjunctivochalasis (CCH) is a conjunctival condition characterized by loose, redundant conjunctival folds, most typically in the inferior bulbar conjunctiva of both eyes. Although CCH is a common cause of ocular irritation and discomfort, especially in the elderly, it is often overlooked in clinical practice. CCH may be associated with various ocular and nonocular conditions; however, the most important risk factor is aging. Although often asymptomatic, CCH may cause symptoms related to tear film instability and/or delayed tear clearance. Pathogenesis of CCH remains largely unknown but may involve different elements such as aged conjunctiva, unstable tear film, mechanical friction, ocular surface inflammation, and delayed tear clearance. Contradictory results have been reported on histopathologic changes in CCH, with some studies showing a normal microscopic structure. For symptomatic CCH, medical treatment may include lubrication and anti-inflammatory medications. For symptomatic patients who fail to respond to medical treatment, a surgical procedure may be considered. Although various surgical procedures have been used for CCH, more often, it consists of conjunctival cauterization or excision of the redundant conjunctiva, with or without amniotic membrane transplantation.     

微创玻璃体切除术后干眼发生的相关因素及治疗进展

玻璃体切除术的问世解决了眼科界难以攻克且难治性眼底病的治疗,微创玻璃体切除术(MIV)是治疗眼底疾病的主要手术方式。临床中,患者在接受微创玻璃体切除术后出现干眼症状,包括流泪、异物感和视觉障碍等。我们推测微创玻璃体切除术可能会损伤结膜及角膜上皮以及相关感觉神经,以及破坏泪膜而引起局部炎症反应,从而影响眼表微环境,诱发或加重干眼症状。目前,对于微创玻璃体切除术后眼表变化的相关研究较少。本文旨在分析微创玻璃体切除术术前、术中、术后不同因素对于眼表微环境的影响,并针对不同情况提供可采取的防治措施,以便于指导临床做好术前准备,选择合适的手术方式以及减少术后罹患干眼风险。