Management of seasonal allergic conjunctivitis: guide to therapy

Seasonal allergic conjunctivitis (SAC) is an inflammatory response of the conjunctiva triggered by exposure to seasonal allergens. Treatment options for SAC include artificial tears, antihistamines, decongestants, mast cell stabilizers, nonsteroidal anti‐inflammatory drugs, dual antihistamine/mast cell stabilizers, immunotherapy and corticosteroids. Topical, intranasal and systemic formulations of corticosteroids have traditionally provided the most effective relief of the inflammation and signs and symptoms associated with severe, acute exacerbations of SAC. However, steroid‐induced ocular and systemic side‐effects have limited the prescribing of these agents. This limitation of traditional corticosteroids led to the development of modified corticosteroids that retain the anti‐inflammatory mechanism of action of traditional corticosteroids with a much‐improved safety profile because of their rapid breakdown to inactive metabolites after exerting their activity. The development of one such novel corticosteroid, loteprednol etabonate (LE), led to the insertion of an ester (instead of a ketone) group at the carbon‐20 (C‐20) position of the basic corticosteroid structure. Clinical trials assessing this C‐20 ester corticosteroid have demonstrated similar efficacy to C‐20 ketone corticosteroids in the prevention or treatment of the signs and symptoms of SAC but with a greatly improved safety profile, as the C‐20 ester corticosteroid is less likely to elevate intraocular pressure. In addition, the ketone at the C‐20 position has been implicated in the formation of cataract, while nonketolic corticosteroids do not form Schiff base intermediates with lens proteins, which is a common first step in cataractogenesis. The clinical relevance of the C‐20 ester corticosteroid class, as modelled by LE, is that they provide both effective and safe treatment of the inflammation associated with SAC and relief of its signs and symptoms. Loteprednol etabonate offers a well‐tolerated treatment option for patients with debilitating acute exacerbations as well as chronic forms of the disease.     

Effect of anti-inflammatory therapy on the treatment of dry eye syndrome

Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.     

Hipertensión ocular como causa de obstrucción de arteria ciliorretiniana en el paciente joven,a propósito de un caso

Clinical caseA 16-year-old patient seen in the Emergency Department due to loss of visual acuity (VA) in the left eye (LE), and oppressive headache of 1 day onset. The patient was on treatment with topical corticosteroids for viral conjunctivitis. The VA was 1.00 in the right eye and 0.05 in LE. The intraocular pressure was 42 mmHg in both eyes. In the LE, the funduscopy revealed retinal ischaemic oedema in the papillomacular bundle. The optical coherence tomography angiography (OCT-A) showed an obstruction of the cilioretinal artery. The systemic study was normal, the cardiac and supra-aortic trunks ultrasound was normal, with ocular hypertension secondary to corticosteroids being the only causative agent identified. This case shows that in the event of an obstruction of the cilioretinal artery, a systemic study should be performed in order to identify possible embolic phenomena. Ocular hypertension is one of the possible causes that may be responsible for this condition.     

干燥环境相关性干眼的发病机制研究进展

干燥环境相关性干眼是指由长期处于低湿度环境中引起的干眼,与生活环境密切相关。目前干燥环境相关性干眼的发病机制尚不完全明确。炎症是干眼发病机制的关键一环,暴露于干燥环境在干眼的炎症进程中起着重要的作用,主要表现为干燥应激对眼表各方面产生不利影响,促进炎症,进而引起干眼。本文将从干燥环境出发,从眼表免疫稳态失衡、泪膜稳定性下降、氧化应激、神经调控异常几个方面对干燥环境因素在眼表炎症中的作用进行综述,以期全面认识干燥环境对干眼发病的影响,重视干燥环境因素在干眼诊疗中的作用。     

The Use of Topical Corticosteroids for Treatment of Dry Eye Syndrome

Dry eye disease (DED) is a multifactorial disease that results in symptoms of discomfort, visual disturbance, and damage to the ocular surface. Because chronic inflammation plays an important role in DED, treatment with topical corticosteroids has been demonstrated to ameliorate the signs and symptoms of the disease. Although these agents have proven short-term efficacy, their long-term use may cause intraocular pressure elevation and cataract progression. A carefully review of the different studies shows that differences between corticosteroids may exist regarding the incidence of side effects and evidence of efficacy in DED patients.     

充分认识儿童过敏性结膜炎的干眼症问题

儿童过敏性结膜炎以春季角结膜炎为主。儿童过敏性结膜炎合并的干眼症的发生与泪膜稳定性降低有关。嗜酸性粒细胞活化、炎性因子释放以及结膜上皮细胞和杯状细胞受损、丢失，粘液层缺乏，导致泪膜稳定性下降及干眼症。此种干眼症的症状以瞬目次数增加为主，其次是眼痒、眼红和畏光。诊断儿童过敏性结膜炎时应考虑是否合并干眼症，给予恰当的处理可避免其引起的严重眼表损害。     

Antiinflammatory therapy for dry eye

PURPOSE: To present evidence establishing the relationship between inflammation and dry eye and supporting the use of antiinflammatory therapy for dry eye. DESIGN: Analysis of literature. METHODS: Research studies that evaluated inflammation in dry eye pathogenesis and clinical trials of antiinflammatory therapies for dry eye were reviewed. RESULTS: There is increasing evidence that decreased tear secretion, decreased tear turnover, and desiccation promote inflammation on the ocular surface. An increase in soluble mediators (cytokines and proteases) in the tear fluid, adhesion molecule expression by the conjunctival epithelium, and T-cell infiltration of the conjunctiva have been observed in dry eye patients. This inflammation appears to have a role in the pathogenesis of the ocular surface epithelial disease, termed keratoconjunctivitis sicca (KCS), that develops in dry eye. Clinical improvement of KCS has been observed after therapy with antiinflammatory agents including corticosteroids, cyclosporin and doxycycline. Cyclosporin A emulsion was approved by the Food and Drug Administration as therapy for dry eye. Randomized placebo-controlled FDA clinical trials showed that cyclosporine A was superior to vehicle in stimulating aqueous tear production, decreasing corneal punctuate fluorescein staining, reducing symptoms of blurred vision, and decreasing artificial tear use in patients with KCS. No ocular or systemic toxicity was observed from this medication. CONCLUSIONS: Ocular surface and lacrimal gland inflammation has been identified in dry eye that plays a role in the pathogenesis of KCS. Antiinflammatory therapy has efficacy for treating KCS. Cyclosporin A is the first FDA approved therapy for this indication. It improved signs and symptoms of KCS, and it is safe for long-term use.     

Recent developments on dry eye disease treatment compounds

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film.     

Wakayama symposium: interface between innate and adaptive immunity in dry eye disease

Although the mechanism of dry eye disease is not clearly understood, it is certain that inflammation and the immune response play a major role in determining the health of the ocular surface in dry eye patients. Accurate ocular surface characterization during the early stages of dry eye disease is critical for successful treatment, because there exists no single standard, objective test to diagnose the early phase of dry eye disease. The treatment target should be direct to prevent the perpetuation of chronic inflammation and immune responses. Numerous studies have categorized dry eye disease as an autoimmune-related inflammatory disease. However, relatively little is known about how innate immune mechanisms act following a local insult, why some patients are particularly vulnerable, and why local inflammation fails to resolve in these patients. Within this review, particular attention will be given to the very early events and corresponding defense mechanism in dry eye disease. The transition from innate to adaptive immunity will also be discussed.     

泪液渗透压在干眼发病机制中的作用及诊疗进展

干眼是一种以眼表稳态丧失,泪膜不稳定性增加为特征的多因素疾病,伴有眼干涩、异物感、灼烧感、眼红、疼痛、畏光、流泪、眼疲劳、视力下降、分泌物增多、对外界刺激敏感等眼部症状,其病理生理机制主要是泪膜不稳定、泪液渗透压(tear osmolarity, Tosm)升高、眼表炎症和损伤及神经感觉异常。Tosm是维持泪膜稳定性和眼表舒适度的重要因素。Tosm升高可造成干眼患者眼部不适、角膜上皮损伤、杯状细胞丢失及眼部炎症反应,炎症反应可进一步降低泪膜稳定性和增加Tosm,使干眼陷入恶性循环。为了更全面地了解泪液高渗(tear hyperosmolarity, THO)与干眼的关系,本文将从病理生理学方面,重点讨论THO在干眼发病机制、干眼诊断、干眼严重程度分级中的作用,及其针对性治疗。     

Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization

AIM: To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. METHODS: We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. RESULTS: Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P<0.05), but with no such effects in non-dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P<0.05). The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreased compared with those in the PBS subgroup in the dry eye group. CONCLUSION: Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.     

特异性促炎症消退介质在眼表疾病中的研究进展

特异性促炎症消退介质(SPM)是一类由多不饱和脂肪酸代谢产生并介导炎症消退反应的脂质介质。SPM信号分子及其受体在眼表组织与细胞高度表达,共同构成内源性SPM网络,对于维持眼表健康和免疫稳态具有重要作用。近年来研究表明,SPM及其类似物在促进角膜伤口愈合与角膜神经再生的同时,还可抑制角膜移植排斥反应、过敏性结膜炎、微生物角膜炎的免疫炎症反应,并有望成为治疗干眼的潜在性药物靶点,同时为眼表疾病的发病机制研究与临床诊治提供了新的思路。本文将就SPM在维持眼表稳态的重要作用及其在多种眼表疾病中的治疗潜力进行综述。     

干眼症眼表损害炎症机制

干眼症为一种多因素造成泪膜稳定性和眼表功能损害的疾病,易引起眼部不适、视力障碍、泪膜不稳定与眼表的潜在危害,可伴有泪液渗透压升高及眼表炎症反应。炎症是干眼发病中最关键因素,多种免疫细胞和炎症因子参与了干眼症的发生与发展过程。细胞凋亡、神经调节异常、性激素失调等也共同参与了干眼的发病过程。最近尽管在阐述干眼的病理生理和发病机制取得了一定进展,但目前还未形成统一标准。本文将对炎症造成干眼症眼表和泪液功能损害的可能机制进行综述。     

干眼的免疫机制研究进展

干眼是一种由多因素所致,发病机制众多的常见眼表疾病。随着我国干眼发病率逐年升高,干眼逐渐引起人们的重视。干眼的发病机制较为复杂,其中炎症、角结膜上皮细胞改变、泪膜成分改变、角膜神经改变、睑板腺功能异常改变等均为重要因素。泪膜高渗导致眼表上皮细胞高渗,刺激炎症发生级联反应,眼表炎症反应为干眼发病机制中最为关键的环节。该过程中有多种炎症介质和免疫细胞参与,越来越多的人认为干眼是一种抗原特异性自身免疫性炎症疾病且二者存在联系。临床治疗中,各类抗炎药物及促进泪液分泌药物在一定程度上标志着干眼药物治疗的快速发展,但干眼治疗并非仅仅为了改善症状,而要根据具体病因展开治疗。近年关于干眼免疫机制的研究日益增多,据此本文就干眼的免疫机制研究进展进行综述,希望系统性了解免疫在干眼发生发展过程中的作用及临床意义。     

Dry eye disease: an immune-mediated ocular surface disorder

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management.     

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.     

普拉洛芬滴眼液治疗干眼症眼表炎症的临床评价

目的:观察1g/L普拉洛芬滴眼液控制干眼症患者眼表炎症的疗效和安全性。方法:选择我院2008-04/2008-10门诊诊断为干眼症的患者60眼,随机分成两组,A组为试验组:1g/L普拉洛芬滴眼液及人工泪液联合应用,4次/d点眼,每次1滴。B组为对照组:人工泪液单独应用,4次/d点眼,每次1滴。试验疗程为14d。所有的患者符合入选标准,用药后3,7,14d观察患者的自觉症状、体征、泪膜破裂时间(BUT)、SchirmerⅠ试验、荧光素染色评分等。比较两组的结果,进行统计分析。结果:1g/L普拉洛芬滴眼液及人工泪液联合应用治疗干眼症患者的效果明显优于单纯使用人工泪液治疗组,两组结果有统计学差异。结论:普拉洛芬可以有效控制干眼症患者眼表炎症,是辅助治疗干眼症的有效药物。     

New aspects in drug therapy of ocular allergies

Ophthalmic allergoses belong to highly prevalent ocular diseases. According to the records of the first center of allergic diseases of the eye set up in 1971 at Helmholtz Institute of Ocular Diseases in Moscow, the most prevalent clinical forms are seasonal pollenosis conjunctivitis, drug allergies, spring keratoconjunctivitis, large-papillary conjunctivitis, chronic allergic conjunctivitis, allergy associated with the "dry eye" syndrome, atopic keratoconjunctivitis, and ocular involvement in systemic immune diseases. Therapy of ocular allergies is based on the three main principles: removal of the allergen responsible for disease, immunotherapy, and symptomatic drug therapy. The main agents used in local antiallergic therapy are antihistaminic drugs (antasoline and acelastin), drugs inhibiting mast cell degranulation (chromoglycates and lodoxamide), and accessory drugs: corticosteroids (dexamethasone and deosonide), nonsteroid antiinflammatory agents (diclofenak), immunosuppressants (cyclosporin), and vasoconstrictors (tetrisoline). Antiallergic drugs can be used as monotherapy or in combinations, as they differ by the mechanism of action. Antiallergic drugs are used with good results in combined therapy of infectious conjunctivitis and keratitis.     

Practical approach to the use of corticosteroids in patients with uveitis

Corticosteroids constitute the first line of therapy for patients with noninfectious ocular inflammatory disease. We review factors contributing to the clinical effectiveness of various corticosteroid preparations in patients with uveitis and discuss practical aspects regarding treatment indications, when to administer various agents, and how best to dose and monitor for both treatment and adverse effects. Topically administered corticosteroids are typically indicated for the treatment of anterior uveitis, whereas periocular or intravitreal agents are employed most often in the management of intermediate or posterior intraocular inflammation. Patients with vision-threatening uveitis, bilateral inflammation, or uveitis occurring in the setting of systemic involvement may require oral or intravenous administration of corticosteroids. Noncorticosteroid immunosuppressive agents play an important role in limiting the toxic effects of long-term corticosteroid use.     

Toll样受体在干眼发病机制中的研究进展

最近研究显示眼表引发免疫炎症反应的部分原因是眼表存在一类称为Toll样受体（TLRs）的蛋白家族。TLRs在眼部的表达受到感染和各种炎症环境的影响,例如单疱病毒、细菌、真菌性角膜炎,变态反应性结膜炎和干眼综合征。TLRs信号通路对抗原递呈细胞和T细胞介导的免疫炎症反应的激活起重要作用。近些年随着眼科学的发展,对TLRs在干眼发病机制方面的研究逐渐增多,现就TLRs的结构与配体,TLRs的信号转导路径,TLRs在眼表中的表达位置及表达模式,以及与干眼的相关性作一综述。