Allergic conjunctivitis and dry eye.

AIMS: Differential diagnosis of allergic conjunctivitis or dry eye is sometimes very difficult to diagnose by symptoms and clinical examination alone, especially in older patients. It was hypothesised that clinically allergic patients who were serum antigen specific IgE negative were candidates for dry eye. METHODS: Sixty patients were studied prospectively who were clinically diagnosed with allergic conjunctivitis by their itchy sensation and papilla formation of conjunctiva. They consisted of 30 serum antigen specific IgE positive and 30 IgE negative patients, with no significant differences in age. Dry eye examination and serum total IgE were performed on these two groups. RESULTS: No significant differences were seen between the two groups with regard to age (p = 0.76) and sex ratio. The antibody negative group had lower Schirmer's test scores (p = 0.002), lower tear clearance (p = 0.0001), lower tear function index (p = 0.0001), and lower serum total IgE (p = 0.04) than the antibody positive group. CONCLUSION: This study suggests that the evaluation of serum antigen specific IgE and tear dynamics are important for the differential diagnosis of patients with allergic conjunctivitis and dry eye. Clinically diagnosed allergic conjunctivitis with negative serum antigen specific and total IgE can be one form of dry eye.     

富马酸依美斯汀联合氟米龙滴眼液治疗过敏性结膜炎

目的：评价富马酸依美斯汀滴眼液联合氟米龙滴眼液治疗过敏性结膜炎的疗效。

方法：回顾性研究。选取2020-06/2022-08于我院就诊接受治疗的过敏性结膜炎患者115例230眼,在常规使用富马酸依美斯汀滴眼液治疗的同时根据是否联合使用氟米龙滴眼液分为观察组(56例112眼)和对照组(59例118眼)。分别于治疗前、治疗4 wk后评估两组患者的眼部临床症状和体征评分、泪膜破裂时间(BUT)、角膜荧光素染色评分,并记录治疗期间并发症发生情况。

结果：治疗后两组患者眼部症状和体征评分均降低,且观察组低于对照组(P<0.05); 两组患者BUT均长于治疗前,且观察组长于对照组(P<0.05); 两组患者角膜荧光素染色评分均降低,且观察组低于对照组(P<0.05)。两组患者治疗期间并发症总发生率(3.6% vs 5.1%)无明显差异(P>0.05)。

结论：富马酸依美斯汀滴眼液联合氟米龙滴眼液治疗过敏性结膜炎可明显减轻患者的眼部症状与体征,延长泪膜破裂时间,降低角膜荧光素染色评分,提高疗效,且不增加并发症发生风险,安全性和有效性较高。     

氯雷他定联合双氯芬酸钠滴眼液治疗过敏性结膜炎临床研究

目的：：探讨氯雷他定联合双氯芬酸钠滴眼液治疗过敏性结膜炎的临床效果,以改善过敏性结膜炎患者预后。方法：选取过敏性结膜炎患者154例158眼,随机分为两组。对照组患者单纯给予氯雷他定片治疗,观察组患者在对照组基础上加用双氯芬酸钠滴眼液进行治疗。对两组患者症状和体征积分进行比较,并对治疗效果进行评价并比较。结果：治疗前,两组患者患眼症状积分和体征积分无统计学差异(P>0.05)。经过治疗,观察组患眼眼痒、流泪、畏光、烧灼感以及异物感积分分别为1.03±0.10、0.83±0.10、0.62±0.06、0.80±0.05和1.10±0.09分,结膜充血水肿、分泌物、睑结膜乳头滤泡、角膜缘改变、角膜上皮改变以及眼睑和球周组织水肿得分分别为0.95±0.08、0.63±0.05、1.32±0.13、0.67±0.06、0.72±0.06和0.55±0.04分,均明显低于对照组,两组比较差异有统计学意义(P<0.05)。对照组患者患眼显效、总有效率分别为30.4％和68.4％;观察组分别为50.6％和86.1％,观察组患者患眼显效率和总有效率均明显高于对照组,两组患眼比较差异有统计学意义(P<0.05)。结论：在全身使用氯雷他定的基础上给予双氯芬酸钠眼液点眼,可以更好地缓解过敏性结膜炎患者的临床症状和体征,提高治疗效果,而且给药方便,是一种有效的治疗方案。     

无干眼症状儿童过敏性结膜炎中的泪膜稳定性研究

目的 观察无干眼症状的儿童过敏性结膜炎患者的泪膜稳定性。设计 回顾性病例系列。研究对象 无干眼症状的儿童季节性过敏性结膜炎患者30例（60眼）。无干眼症状的屈光不正患儿20例（40眼）为正常对照组。方法 受试者进行病史询问以及外眼、眼前节及干眼相关检查,包括泪膜破裂时间（BUT）、基础泪液分泌试验（SIt）、角膜荧光素染色（FL）。荧光素染色评分0~12分,无染色为0分。主要指标 BUT、SIt和FL评分。结果 观察组与对照组BUT分别为（7.35±2.46）s、（11.95±2.183）s（ t =9.569,P=0.000）;SIt分别为（18.28±5.123）mm、（16.50±5.149）mm（ t =1.702,P=0.092）;FL评分不为0者分别为13例（20眼）、6例（6眼）（χ2=4.193,P=0.041）。观察组中FL评分、BUT与病史长短无显著相关性。结论 无干眼症状的儿童季节性过敏性结膜炎患者也可能存在泪膜稳定性下降和角膜上皮完整性受损的改变。（眼科,2015,24：268-271）     

Tear osteopontin levels in patients with allergic conjunctival diseases

BACKGROUND: Recent reports have revealed the importance of several cytokines in chronic conjunctival allergic diseases (ACD) such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). Osteopontin (OPN) is a noncollagenous adhesive matrix protein that is expressed by activated macrophages. There has been considerable interest in the potential role of OPN in monocyte infiltration at sites of inflammation. We measured OPN level in tears using ELISA, to determine whether the level of this cytokine is elevated in ACD. METHODS: The level of OPN in tears was measured by ELISA using samples from patients with VKC, AKC or allergic conjunctivitis (AC) and from normal subjects. The level of OPN in tears was compared with the clinical severity of ACD and serum level of total IgE. RESULTS: The level of OPN in tears in AKC patients was significantly higher than that in AC and normal controls. Tear level of OPN in patients with VKC was also significantly elevated compared to those with AC and to normal controls. The clinical severity of ACD correlated significantly with the level of OPN. However, no correlation was observed between tear OPN level and serum level of total IgE. CONCLUSIONS: These results indicate that OPN plays an important pathophysiological role in severe ocular allergic conditions and that an elevated level of OPN in tear fluid reflects the local clinical status of ocular allergy, which may be an example of tissue remodeling.     

干眼症和前睑缘炎及季节性过敏性结膜炎中三种检测方法结果的比较

目的:比较三组临床患者和对照组患者的泪液功能测试,眼表染色以及结膜印象细胞学检测的结果。方法:这是一个单中心,前瞻性,双盲,随机对照试验。研究包括泪液分泌分数小于10mm和泪膜破裂时间(TBUT)小于10s的20例干眼症患者,有干燥和结痂睫毛的20例前睑缘炎患者,上眼睑睑板结膜乳头肥大的20例季节性过敏性结膜炎患者和20例对照组患者。比较泪液分泌的分数,泪膜破裂时间,眼表染色(牛津分级方案),杯状细胞密度(尼尔森分级方案评估所有患者的印象细胞学和化生分数)。结果:三组患者和对照组患者在泪液功能测试结果,眼表染色评分,杯状细胞密度和化生分数上有显著差异(P<0.001)。结论:结果证明这三种疾病的炎症反应造成严重眼表损害,并在局部产生炎症。这种损伤产生非常严重的影响,尤其是对结膜杯状细胞密度和化生。杯状细胞损伤程度与临床研究结果有关联。     

Correlation between tear IgE levels and HLA-DR expression by conjunctival cells in allergic and nonallergic chronic conjunctivitis

Background: Chronic conjunctival inflammatory diseases may depend upon various mechanisms. Discriminating allergy from nonspecific inflammation has become of striking importance for diagnosis and treatment. We investigated conjunctival inflammatory response by comparing two objective biological tools, tear IgE and HLA-DR expression by conjunctival epithelium, as indirect indicators of activation of the Th2 and Th1 subsets, respectiv-ely. Methods: Eighty-two patients with chronic conjunctivitis underwent tear IgE measurement by an ELISA technique and quantitation of HLA-DR expression in impression cytology specimens. Forty-two had direct or indirect clinical indications of allergic mechanisms, 26 had chronic conjunctivitis without any sign of allergy, and 14 suffered from isolated nonallergic dry eyes. Results: Patients clinically considered as allergic only showed positive IgE in 47 of 84 eyes (56%), whereas 21% and 25% of eyes with nonspecific conjunctivitis and dry eyes respectively were also positive. IgE levels were significantly higher in the allergic group than in the other two groups. HLA-DR positivity in epithelial cells was found in 28.5%, 48% and 50% of eyes, respectively. HLA-DR expression by epithelial cells was negatively correlated with tear IgE, as most specimens positive to one criterion were negative to the other one (49 eyes DR+, IgE–; 47 eyes DR–, IgE+; only 9 eyes positive to both criteria; chi-square: P=0.0001). Conclusion: As IgE synthesis and HLA-DR induction may represent indirect indicators of the activation of the Th2 and Th1 subsets, association of these two simple tests could be interesting for the routine assessment of the mechanisms of inflammatory ocular surface diseases. Received: 22 February 2000 Revised: 4 May 2000 Accepted: 16 May 2000     

氯雷他定联合双氯芬酸钠滴眼液治疗过敏性结膜炎的临床价值

目的:分析氯雷他定联合双氯芬酸钠滴眼液治疗过敏性结膜炎的疗效及对泪膜稳定性和泪液相关指标的影响。方法:前瞻性选择2019-01/2020-01我院收治的过敏性结膜炎患者93例186眼,随机分为观察组(47例94眼,采用氯雷他定联合双氯芬酸钠滴眼液治疗)与对照组(46例92眼,采用氯雷他定治疗),均连续治疗2wk。治疗前、治疗2wk均评估眼部症状、体征改善情况;进行基础泪液分泌试验(SⅠt),检测泪膜破裂时间(BUT),评估泪膜稳定性;采用眼前节相干光断层扫描仪测定泪河高度、泪河深度、泪河横截面面积;留取泪液标本,检测泪液透明质酸(HA)、ⅡA型分泌型磷脂酶A2(sPLA2-Ⅱa)、嗜酸性细胞阳离子蛋白(ECP)等指标的变化;统计治疗不良反应发生情况。结果:治疗2wk,两组患者主要症状、体征积分均较同组治疗前降低(P<0.05),且观察组均低于对照组(P<0.05);两组患者SⅠt、BUT均较同组治疗前增加(P<0.05),且观察组均长于对照组(P<0.05);与同组治疗前比较,两组患者泪河高度均上升,泪河深度均增加,泪河横截面面积均增加(P<0.05),且观察组泪河高度、泪河深度、泪河横截面积均高于对照组(均P<0.05);两组患者泪液HA、ECP、sPLA2-Ⅱa水平均较同组治疗前降低(P<0.05),且观察组均低于对照组(P<0.05)。治疗期间,两组治疗不良反应发生率比较无差异(12.8%vs 10.9%,P>0.05)。结论:氯雷他定联合双氯芬酸钠滴眼液治疗过敏性结膜炎整体疗效优于单纯应用氯雷他定,可改善患者症状及体征,提高泪膜稳定性,降低泪液炎性介质浓度,促进泪膜功能恢复,安全可行。     

Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms

OBJECTIVE: To correlate and compare the Schirmer 1 test and a new method of measuring tear fluorescein clearance with the CytoFluor II fluorometer with the severity of ocular irritation symptoms, clinical signs of meibomian gland disease, corneal fluorescein staining scores, and corneal and conjunctival sensitivity. DESIGN: Case-control study. PARTICIPANTS: Forty patients presenting with a chief complaint of ocular irritation, and 40 asymptomatic control subjects of similar age distribution. INTERVENTION: All subjects completed a symptom questionnaire, a baseline ocular examination, fluorescein clearance test (FCT), and Schirmer 1 test. MAIN OUTCOME MEASURES: The FCT was performed with a CytoFluor II fluorophotometer by measuring the fluorescein concentration in minimally stimulated tear samples collected from the inferior tear meniscus 15 minutes after instillation of 5 microl of 2% sodium fluorescein. Severity of ocular irritation was assessed with a symptom questionnaire. Schirmer 1 test, biomicroscopic meibomian gland evaluation, corneal fluorescein staining score, and corneal and conjunctival sensation scores were assessed with the Cachet-Bonnet anesthesiometer in all subjects. RESULTS: Irritation symptoms correlated with higher log tear fluorescein concentration (symptomatic 3.08 +/- 0.62 units/,microl, normal control 1.89 +/- 0.7 units/microl, P < 0.005) and lower Schirmer 1 test scores (symptomatic 12.6 mm, normal control 22.3 mm, P < 0.005). The FCT showed greater predictive value for identifying ocular irritation than the Schirmer 1 test. A fluorescein concentration of 274 units//microl eliminated 80% of the normal subjects (specificity) and identified 85% of the abnormal subjects (sensitivity). Log of tear fluorescein concentration and the Schirmer 1 test correlated with meibomian gland orifice metaplasia (2.81 +/- 0.78 units/microl and 14.47 +/- 9.53 mm in those with metaplasia vs. 1.83 +/- 0.71 units/microl and 23.14 +/- 7.67 mm in those without metaplasia, P < 0.001) and with the percentage of acinar dropout. Both log of tear fluorescein concentration and the Schirmer 1 test correlated with corneal fluorescein staining (Pearson correlation of 0.394 P < 0.0001 for Schirmer 1 test and 0.312 P < 0.005 for log of tear fluorescein). In addition, log of tear fluorescein and Schirmer 1 test scores correlated with corneal and conjunctival sensation scores (Spearman's rho for corneal sensation: log of tear fluorescein -0.38, P < 0.003, Schirmer 1 test -0.39, P < 0.002, and for conjunctival sensation: log of tear fluorescein -0.391, P < 0.001, Schirmer 1 test -0.23, P < 0.061). CONCLUSIONS: The FCT shows a greater predictive value for ocular irritation than the Schirmer 1 test. It correlates better with age, meibomian gland dysfunction, and decreased corneal and conjunctival sensation. Decreased tear clearance was identified as a risk factor for ocular irritation, even in subjects with normal Schirmer scores. This simple technique may provide new clues into the mechanism and therapy of ocular irritation.     

Demographic aspects of allergic ocular diseases and evaluation of new criteria for clinical assessment of ocular allergy

Background The clinical features of allergic ocular diseases (AOD) are characterized by their wide variety. Clinical evaluation criteria are essential not only for objective assessment in clinical trials, but also for clinical studies on etiological aspects of AOD. However, there have been no internationally established criteria for clinical evaluation and classification of the severity of AOD. We established new criteria and applied them to many cases of AOD, and evaluated their usefulness for clinical purposes. We also studied whether each clinical entity of AOD [allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC)] can be distinguished by these criteria. Methods A prospective study was carried out to assess the differential diagnosis of 1079 patients with AOD (439 male and 640 female patients). Differential diagnosis of AC, AKC or VKC was made. These diseases were diagnosed and classified based on local and systemic clinical findings. Ten objective ocular clinical findings of conjunctival, limbal and corneal lesions were graded on a 4-point scale, and the total score, with a highest value of 30, was used as the clinical score. Results Among a total of 1079 cases, seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), AKC and VKC accounted for 876 (81.2%), 115 (10.6%), 47 (4.4%) and 41 (3.8%) respectively. The mean age in each disease was 52.9, 56.1, 25.7 and 16.6 years respectively. Total clinical score in SAC, PAC, AKC and VKC was 1.54, 2.13, 3.72 and 12.68 respectively. Both mean age and total clinical score in all combinations of two diseases showed significantly different results. Conclusions These results suggest that AOD can be classified by our new clinical grading system, and this system is sensitive enough for clinical evaluation of AOD. Re-evaluation of AOD is essential for constructing future strategies for the treatment of AOD, which are consists of various categories of ocular disorders. The authors have no financial relationship with the organization that sponsored the research. The authors have full control of all primary data, and agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

Tear and serum soluble leukocyte activation markers in conjunctival allergic diseases

PURPOSE: To measure markers of leukocyte activation in patients with an exclusively ocular inflammatory or bacterial disease. METHODS: Neutrophil myeloperoxidase, eosinophil cationic protein, eosinophil neurotoxin, and soluble interleukin-2 receptor were measured in serum and tears of 17 patients with allergic vernal keratoconjunctivitis, seven with atopic keratoconjunctivitis, 11 with seasonal allergic conjunctivitis, seven with giant papillary conjunctivitis, 13 with rosacea blepharokeratoconjunctivitis, seven with bacterial conjunctivitis, and 13 normal subjects as controls. RESULTS: In serum of patients with vernal and atopic keratoconjunctivitis, levels of eosinophil cationic protein, eosinophil neurotoxin, and interleukin-2 receptor were significantly increased compared with control subjects but were not correlated with the severity of ocular symptoms. In tears of patients with vernal and atopic keratoconjunctivitis and seasonal allergic conjunctivitis, as well as in the nonallergic diseases, rosacea blepharokeratoconjunctivitis and bacterial conjunctivitis, levels of eosinophil cationic protein, neurotoxin, and interleukin-2 receptor were significantly increased compared with control subjects. The highest values of these markers were found in vernal keratoconjunctivitis samples. Neutrophil myeloperoxidase was significantly increased in vernal and atopic keratoconjunctivitis, rosacea blepharokeratoconjunctivitis, and bacterial conjunctivitis. In vernal keratoconjunctivitis, tear markers were correlated to the clinical score of the disease, but not with cytology. CONCLUSIONS: Tear histamine was measured in 10 allergic patients after allergen challenge. Although none of the above markers can be considered specific to a single disease, their measurement may still be useful for the quantification of local cell activation in ocular inflammatory diseases.     

Non-contact confocal microscopy of the tear film in unoperated eyes

PURPOSE: The NIDEK ConfoScan4 (CS4) is a digital scanning slit confocal microscope. The corneal structure and tear film can be viewed, magnified, measured, and photographed at magnifications up to 500x, in vivo, in a noninvasive manner. The objective of this study was to evaluate and illustrate various conditions related to dry eye using the CS4 confocal microscope with the 20x noncontact lens. METHODS: The CS4 was used to evaluate the natural tear film in 58 eyes of 29 patients with normal examinations, allergic conjunctivitis, nonspecific conjunctivitis, and dry eyes. In a subset of this patient population, subjective and objective findings were used to classify mild, moderate, and severe dry eye disease states. The usefulness of confocal microscopy as an objective tool to diagnose and manage different tear film-related ocular disease was also evaluated. RESULTS: The differences in tear film composition were visible using confocal microscopy. Photographs demonstrate confocal noncontact 20x microscopy as a diagnostic tool. CONCLUSIONS: Noncontact confocal microscopy is a valuable tool in the diagnosis and treatment of dry eye syndrome and other ocular states such as allergic and nonspecific conjunctivitis. It provides a simple and effective way to observe, classify, and treat the tear film. As investigators visualize and learn more, understanding of this structure will continue to improve.     

疏风明目方超声雾化对过敏性结膜炎患者泪膜稳定性及泪液相关指标的影响

目的：观察疏风明目方超声雾化对过敏性结膜炎患者泪膜稳定性及泪液相关指标的影响。

方法：将140例过敏性结膜炎患者随机分为两组,对照组70例给予盐酸奥洛他定滴眼液联合生理盐水雾化治疗,观察组70例给予盐酸奥洛他定滴眼液联合疏风明目方超声雾化治疗。连续治疗14d后,比较两组临床疗效、治疗前后单项症状(流泪、痒感、畏光、异物感)、泪膜稳定性(BUT、FL)、泪液相关指标\〖嗜酸性细胞阳离子蛋白(ECP)、HA、IgE\〗。

结果：观察组治疗后总有效率高于对照组(90.7%vs 74.3%,P<0.05); 两组治疗后单项症状积分均低于治疗前,且观察组均低于对照组(P<0.05); 两组治疗后BUT均高于治疗前,FL均低于治疗前,且观察组改善程度均优于对照组(P<0.05); 两组治疗后泪液HA、ECP、IgE水平均低于治疗前,且观察组改善程度均优于对照组(P<0.05)。

结论：疏风明目方超声雾化治疗能够改善过敏性结膜炎患者泪液相关指标,提高泪膜稳定性,有助于缓解局部变态反应,改善患者临床症状。     

眼表综合分析仪在儿童早期前睑缘炎临床分析中的应用

目的利用眼表综合分析仪对儿童早期前睑缘炎患者的眼表情况进行观察,分析其临床特点。方法描述性研究。选取2015年7月至2016年5月就诊于山西省眼科医院门诊,经裂隙灯显微镜检查确诊为早期前睑缘炎的儿童患者40例（80眼）,年龄4~14岁。对患儿睑缘炎体征进行评分,利用眼表综合分析仪检查其泪膜破裂时间（BUT）、泪河高度,并进行眼表充血、睑板腺缺失及角膜荧光素钠染色评分,对所得数据进行Spearman秩相关分析。结果80眼中,58眼（72%）BUT缩短;50眼（62%）泪河高度下降;15眼（19%）发生角膜上皮点状缺损;25眼（31%）睑板腺缺失范围＞1/3。睑缘炎体征评分与BUT、泪河高度、角膜荧光染色评分及睑板腺缺失评分不相关;睑板腺缺失评分与BUT呈负相关（r=-0.253,P=0.024）,与角膜荧光染色评分呈正相关（r=0.563,P＜0.001）。结论儿童早期前睑缘炎患者泪膜稳定性下降,同时合并睑板腺缺失的患者易继发干眼。     

Correlations between allergen-specific IgE serum levels in patients with allergic conjunctivitis in spring

Purpose: The purpose of this study was to evaluate the relation between various specific class E immunoglobulins (IgE) in serum and allergic conjunctivitis in spring. Methods: Forty patients with allergic conjunctivitis and fifty healthy volunteers were selected for this trial. Total IgE and specific IgE to twelve inhalant allergens were measured using the CAP system. Results: Specific IgE levels caused by cedar and cypress pollen, house dust, Dermatophagoides pteronyssinus , acarus, and moth allergens were higher in the allergy group than in the control group. No correlation was proven between the specific IgE levels and the total IgE level. The highest positivity rate for a specific allergen in patients with allergic conjunctivitis was 52.5% for cedar pollen, followed by cypress pollen at 37.5%. Conclusions: These results suggest that cypress pollen was the largest cause of allergic conjunctivitis and that the total IgE level had no correlation with each specific IgE.     

奥洛他定联合自体血清治疗蒿属花粉过敏性结膜炎

目的：观察奥洛他定滴眼液联合自体血清治疗蒿属花粉过敏性结膜炎的临床疗效。

方法：选取我院2016-06/2018-06蒿属过敏原检测结果为阳性的过敏性结膜炎患者305例610眼,随机分为对照组和观察组。对照组患者采用奥洛他定滴眼液治疗,观察组患者在对照组的基础上加用自体血清,均持续治疗2wk。比较两组患者治疗前后症状与体征总得分、临床疗效,观察患者治疗期间不良反应发生情况。

结果：治疗前,两组患者症状与体征总得分比较,差异无统计学意义(P>0.05); 治疗后2wk,观察组患者症状与体征总得分低于对照组(P<0.05),观察组患者临床疗效优于对照组(P<0.05)。两组患者不良反应发生率比较无差异(P>0.05)。

结论：奥洛他定滴眼液联合自体血清治疗蒿属花粉过敏性结膜炎的临床疗效确切,可有效改善患者的临床症状和体征,且安全性较高。     

胸腺基质淋巴细胞生成素和白细胞介素-4在变应性结膜炎鼠模型中的促炎作用

背景 研究表明胸腺基质淋巴细胞生成素(TSLP)为类白细胞介素(IL)-17的炎性细胞因子,在多种变应性疾病的发生和发展中发挥关键作用,但是尚未见到关于TSLP是否参与中国常见变应原诱导的变应性结膜炎的报道. 目的 研究TSLP和IL-4在由中国常见的黄花蒿诱导的变应性结膜炎小鼠模型眼表组织和颈部淋巴结中的表达变化,探讨TSLP和IL-4在变应性结膜炎发病中的作用. 方法 采用随机数字表法将6～8周龄雌性BALB/c小鼠20只随机分为正常对照组和模型组.将400μl黄花蒿花粉提取液溶解于400μl变应原(抗原)溶媒中制备成抗原溶液,将50μl抗原溶液注射于模型组小鼠足底皮垫下初次致敏,于注射后第10 ～12天用黄花蒿花粉提取液局部点右眼再次致敏,每日点眼1次;正常对照组小鼠未做任何处理.于造模后第13天采用颈椎脱臼法处死小鼠并摘取眼球,在眼科显微镜下各组分别取16只小鼠32只眼角膜上皮、结膜和颈部淋巴结组织,采用实时定量PCR法检测各种靶组织中TSLP mRNA及IL-4 mRNA的相对表达量,另每组各取4只小鼠8只眼眼睑及眼球制备石蜡切片,采用免疫组织化学法检测角膜、结膜及结膜下组织中TSLP和IL-4蛋白的表达. 结果 模型组小鼠第2次致敏后0.5h可见小鼠眼睑水肿、结膜充血水肿、溢泪、搔抓眼睑等症状,症状持续6 ～24 h,造模成功率为80％.实时定量PCR结果显示,模型组与正常对照组小鼠角膜上皮均未发现IL-4表达.模型组小鼠角膜上皮、结膜组织和颈部淋巴结组织中TSLP mRNA表达量分别是正常对照组的(1.63±0.20)、(2.71±0.48)和(1.48±0.05)倍,差异均有统计学意义(=4.44、14.16、5.01,均P＜0.05);模型组小鼠结膜和颈部淋巴结中IL-4 mRNA表达量分别是正常对照组的(2.94±0.39)倍和(1.74±0.09)倍,差异均有统计学意义(t=9.92、14.54,均P＜0.05).免疫组织化学法检测显示,正常对照组小鼠角膜上皮和结膜上皮细胞中TSLP蛋白表达强度微弱,模型组小鼠TSLP蛋白表达增强.模型组小鼠结膜下组织中可见IL-4呈强阳性表达,正常对照组小鼠结膜下组织中未发现IL-4表达.结论 TSLP主要表达于变应性结膜炎小鼠的角膜、结膜和颈部淋巴结组织,提示其参与变应性结膜炎角膜和结膜的炎症反应;IL-4主要表达于变应性结膜炎小鼠结膜下组织中,提示其主要参与结膜的炎症反应,TSLP和IL-4共同参与变应性结膜炎的发生和发展过程,这2种炎症因子为变应性结膜炎的临床治疗提供了新的靶点.     

The added benefit of local Patanol therapy when combined with systemic Claritin for the inhibition of ocular itching in the conjunctival antigen challenge model.

BACKGROUND: Allergic conjunctivitis very often occurs simultaneously with rhinitis in seasonal allergy sufferers. While systemic anti-allergic and antihistaminic agents are effective against many signs and symptoms of allergy, they may not adequately control ocular signs and symptoms in patients with multiple target organ hypersensitivity. Patanol (olopatadine hydrochloride 0.1% ophthalmic solution, Alcon Laboratories, Inc., Fort Worth, TX), a new effective anti-allergic mast cell stabilizer with antihistaminic properties, is approved for the prevention of ocular itching due to allergic conjunctivitis. OBJECTIVE: To determine whether Patanol in combination with the systemic antihistamine Claritin (loratadine, Schering, Kenilworth, NJ) reduces the ocular itching associated with allergic conjunctivitis more effectively than Claritin alone. A topical ocular antigen challenge induced the allergic conjunctivitis in 15 subjects. METHODS: This was a randomized, double-masked study in which the contralateral eye served as the control. On Visit 1, an allergen dose which elicited response scores > 2 for ocular itching was identified. Itching was graded by the subject using a 0 to 4 point scale. At Visit 2, the threshold allergen concentration was confirmed. At Visit 3, the onset of action challenge, in addition to Claritin (10 mg tablet), each subject received Patanol in one eye and placebo in the fellow eye in a randomized, double-masked fashion. Allergen was instilled one hour after dosing, and ocular itching was graded at 3, 7, 10 and 20 minutes after challenge. At Visit 4, the duration of action challenge, the same drug regimen was followed as in Visit 3. However, allergen challenge was performed eight hours after dosing, and itching graded after 3, 7, 10 and 20 minutes. RESULTS: Patient eyes treated with Patanol were significantly less itchy than those treated with systemic Claritin alone at critical time points 3, 7, and 10 minutes after the onset of action challenge (p < 0.05), and at 3 and 7 minutes after the duration of action challenge (p < 0.05). CONCLUSION: The addition of topical Patanol to systemic Claritin therapy significantly reduced ocular itching associated with allergic conjunctivitis compared to treatment with Claritin alone. These findings prove the added benefit of local Patanol therapy in the treatment of ocular allergic symptoms in patients receiving systemic antihistamines for concomitant systemic allergies.     

Tear and serum eosinophil cationic protein levels in seasonal allergic conjunctivitis

PURPOSE: Eosinophil cationic protein (ECP) levels in tear fluid and sera of patients with seasonal allergic conjunctivitis (SAC) were measured to assess local and systemic eosinophilic activity in SAC. The correlation between ECP levels and disease activity was evaluated. METHODS: Tears and sera were collected from 21 patients with SAC and 13 healthy control subjects. ECP levels in tears and sera were measured before and 4 weeks after treatment with 0.1% lodoxamide eyedrops. Clinical signs and symptoms of SAC were scored and the correlation of ECP levels with the clinical scores was evaluated. RESULTS: Tear and serum levels of ECP were significantly increased (p = 0.01, p = 0.02, respectively) in patients with SAC compared with the control subjects, but ECP levels were not correlated with the severity of the disease. Following treatment with topical 0.1% lodoxamide eyedrops, the mean level of ECP in tears decreased significantly (p = 0.02), whereas no significant change was observed in serum ECP levels. Furthermore, a significant decrease in clinical signs and symptoms scores was found after treatment (both p < 0.0001). CONCLUSIONS: Increased serum and tear ECP levels in patients with SAC confirms that both local and systemic eosinophil activation occurs in SAC. However, clinical signs and symptoms of SAC were not found to be correlated with the degree of eosinophilic activity. Thus ECP does not seem to have an important role in clinical manifestations of SAC.     

The role of eosinophil cationic protein (ECP) and histamine in vernal keratoconjunctivitis

Objectives: (1) to measure levels of tear eosinophil cationic protein (ECP) in patients with vernal keratoconjunctivitis (VKC); (2) to verify any correlation between ECP and the severity of the disease; (3) to verify the effect of different topical therapies on the levels of tear ECP; (4) to investigate the activity of histamine degrading enzymes in tears and plasma of VKC patients. Methods: ECP was measured by RIA in tears from 23 VKC patients before and after therapy, and from seven controls. Tear cytology, ocular signs and symptoms were also evaluated before and after treatment. Histamine was measured by ELISA in both plasma and tears from 19 VKC patients and six age-matched controls, in both acid-treated (no enzyme activity) and untreated (enzyme activity) samples. Results: (1) tear ECP levels were significantly higher in VKC patients than in healthy controls; (2) tear ECP levels showed a significant correlation to signs (p <0.005) and symptoms (p <0.001) of the disease; (3) tear ECP was reduced by both 2% cyclosporine and 0.1% dexamethasone; (4) tear and plasma histaminase activity, measured by the ratio of histamine in treated to untreated samples, were significantly lower in VKC patients compared to controls (p <0.0001 and p <0.001, respectively). Conclusions: Tear ECP levels reflect the clinical status of VKC patients. The measurement of ECP may prove to be a useful objective tool in evaluating allergic conjunctivitis and the effectiveness of specific treatments. Moreover, VKC patients show a significantly impaired histaminase capability, at both the local and systemic level. This dysfunction may exacerbate the effects of local histamine release in the course of the disease.