玻璃酸钠降低滴眼剂中防腐剂不良反应的作用

防腐剂在滴眼剂中的应用广泛。已有很多研究显示，长期应用含防腐剂的滴眼剂会对角膜结膜上皮细胞产生不良反应。活性氧的产生是加防腐剂的滴眼剂诱导细胞凋亡的最根本机制。玻璃酸钠具有抗氧化、保湿、润滑、促修复等作用，可有效降低滴眼剂中防腐剂的不良反应。就防腐剂的不良反应机制及玻璃酸钠如何降低其不良反应进行综述。     

应用于眼表的缓释药物

眼结膜囊内滴滴眼液是眼科疾病常用的治疗方法 ,除住院患者外 ,大部分患者自我用药。所以用药的依从性、点眼液方法的正确性都会影响用药效果。而且眼睛有其自然的保护机制 ,包括眨眼、反应性流泪和泪水从鼻泪管排出。此外 ,还有诸如结膜囊容量小 (结膜囊最多容纳 10 μL 液体而不致溢出 [1 ] )、活跃的泪液分泌 (泪液更新率约 16 %· min- 1 )和角膜屏障作用。一般滴眼液容器每滴容量为 2 5～ 70μL ,很显然超过 80 %的所用滴眼液会溢出 ,加上泪液更新 90 %以上眼结膜囊的局部用药经泪液的稀释、冲洗渗出眼外或经鼻泪道和粘膜而全身吸收。…     

长期使用青光眼药物对眼表的影响

目的 探讨长期使用青光眼药物对患者眼表的影响.方法 收集局部使用青光眼药物3个月以上的患者65例108只眼,分为单种药物使用组(A组)和多种药物使用组(B组);另收集正常对照组(c组)25例25只眼.对所有观察对象进行泪膜破裂时间测定(BUT)、基础泪液分泌试验(ST)、角膜上皮荧光素染色、结膜上皮虎红染色以及结膜印迹细胞(IC)检查.结果 正常对照组BUT(12.25±5.40)s,ST(11.65±4.66)mm,A组BUT(6.97±4.87)8 9ST(7.19±5.36)mm,明显低于正常对照组(BUT P=0.000;STP=0.001). B组BUT(4.81±2.45)s,显著短于正常对照组(P=0.000)和A组(P=0.008);ST(5.20±2.97)mm,显著少于正常对照组(P=0.000)和A组(P=0.026).A组和B组的角膜荧光素染色评分和结膜虎红染色评分显著高于正常对照组.与正常对照组相比,A组和B组IC评分2-3级所占比例明显增高,结膜上皮表现出鳞状上皮化趋势.结论 长期使用青光眼药物会导致患者泪膜稳定性下降、泪液分泌减少,角膜上皮荧光素染色增多,结膜上皮杯状细胞减少、上皮细胞呈鳞状上皮化等泪膜、角膜和结膜的损伤.     

关注滴眼剂的眼表毒性

滥用滴眼剂所致的眼表毒性常被忽视。其临床表现多为非特异性,易与其他原因引起的眼表疾病相混淆。不同滴眼剂所致眼表毒性的发病机制不尽相同。临床眼科医师应关注滴眼剂对眼表的毒性作用,并预防和治疗滴眼剂对眼表的毒性损害。     

白内障超声乳化术对泪膜及眼表的影响

目的前瞻性研究白内障超声乳化术后泪膜及眼表的变化。方法选取连续就诊手术的白内障患者共52例67眼，分为两组，A组为术前存在干眼症患者，共9例12眼；B组为术前无干眼症患者，共43例55眼。两组患者均行上方角膜缘蓝线自闲式隧道切口超声孔化术联合后房型折叠式人工晶状体植入术。分别于术前第1天，术后第1天、第2天、第7天、第30天进行干眼症相关症状调查、无麻醉下泪液分泌试验（Sehimer试验）、泪膜破裂时间（break-up time，BUT）、角膜荧光素染色检查并积分，比较各项结果在术后不同时间与术前的差异以及手术对两组患者影响程度的差异。结果两组患者分别与术前比较，术后不适主诉增加。Sehimer试验值在术后第1天书第2天明显高于术前，BUT在术后第1天、第2天和第7天较术前缩短，角膜荧光素染色积分在术后第1天、第2天高于术前，差异均有显著性（P〈0．05）。结论白内障超声乳化术可在短期内影响患者的泪膜和眼表。     

抗癌药物的眼表影响研究进展

有效的抗癌药物是治疗癌症的重要武器,它可以帮助患者争取更长的生存时间。尽管癌症生存率上升,但抗癌药物带来的副作用也逐渐凸显出来,一些不良反应带来的眼表副作用可能会显著影响患者的生活质量,如细胞毒性化疗会带来上睑下垂、结膜炎、角膜糜烂等副作用,分子靶向药物可能会引起眼睑皮炎、倒睫、干眼等发生,眼球运动障碍则出现在免疫疗法的应用中。目前阐明眼表副作用的研究较少,发生机制尚未完全明确,但已有研究表明,眼表黏膜容易因长期暴露于含一定浓度化疗药物的泪液中而发生炎症;此外,眼表细胞的受体如雌激素受体和表皮生长因子受体可以与特异性抗癌药物发生反应,从而发生病理性改变。泪膜性质的改变也提示了抗癌药物带来的眼表影响及可能的机制。本文旨在陈述抗癌药物对眼表产生的潜在不良影响并探讨可能机制,以便在发生眼部不良反应时能够明确是否为药源性,从而调整治疗方案,避免眼表毒性的发生。     

滴眼液中防腐剂的利弊及其使用对策

多剂量滴眼液如果主药本身不具有充分的抗菌活性就应添加适宜的防腐剂,以防止在使用过程中因微生物污染对眼造成的危害,但长期应用含防腐剂（主要是苯扎氯铵）的滴眼液对眼表的损伤已从体内外实验及临床研究中得到充分证实。控制滴眼液的微生物污染并减轻滴眼液中防腐剂对眼表的损害是一项系统工程,其中既有药品监管部门的职责和医护人员合理用药的责任,又需要科研工作者的创新性研究,从而使广大眼病患者获得更大的利益。     

无防腐剂滴眼液包装瓶的问题与改进

随着对滴眼液中防腐剂毒性作用的关注,无防腐剂滴眼液应运而生。目前,滴眼液中不加防腐剂,主要是通过包装瓶的改进而达到的,从单剂量包装瓶到多剂量包装瓶,各有其优劣。单剂量包装瓶携带方便,开启后暴露时间短,可基本避免微生物污染,但生产成本高,易导致滴眼液浪费增加。多剂量包装瓶,既做到了无防腐剂,又能多次使用,但需要患者改变使用习惯,对滴眼液的黏滞度也有一定要求,且眼药瓶本身的生产成本比例增大。随着对滴眼剂包装瓶研究设计的深入,滴眼液包装瓶应旨在安全简便、成本“亲民”、剂量可控。     

严重眼表瘢痕性疾病的诊治

眼表瘢痕性疾病可以由物理及化学损伤、手术、感染、免疫性眼皮肤粘膜异常、药物和各种系统疾病引起。它可以导致眼睑位置异常、干眼症以及角膜病变，严重者造成视力损害。眼表瘢痕性疾病的诊断依靠仔细询问病史、对患者全面体检和多种辅助检查，重点是寻找病因及对病情评价。治疗应全面兼顾药物治疗和手术治疗。药物治疗以抑制外源性刺激物、治疗干眼症、抗感染和免疫抑制为目的，针对不同的病因和病情进行选择；外科手术主要是纠正倒睫及眼睑位置异常、治疗干眼症，进行结膜移植、粘膜移植、角膜缘干细胞移植、羊膜移植、角膜移植手术重建眼表功能，对于并发白内障或继发青光眼的患者也应同时采取相应处理。     

Assessment of retention and drug-release of ophthalmic ointment on the ocular surface

PURPOSE: The dynamics of ophthalmic ointment on the ocular surface were investigated using a fluorescent ointment. METHODS: Ten healthy volunteers were enrolled. Ointment (1.0 cm length, 0.05 g) containing 0.1% flavin adenine dinucleotide sodium was squeezed out from the tube and placed in the left lower conjunctival sac. The eyes were then closed for 30 seconds and permitted to blink naturally. Two examinations including observation of tear film lipid layer interference pattern and fluorophotometric measurement of fluorescence intensity, both at the center of the cornea, were performed before examination and at 1, 3, 6, 9, 12, 15, 30, 60 minutes after instillation. RESULTS: In all cases, even 1 hour after instillation, tear film interference patterns were observed, and fluorescence intensity greater than before instillation, was present. CONCLUSION: Ointment placed in the conjunctival sac is thought to remain and release agents on the ocular surface for at least one hour.     

Effects of a 0.9% sodium chloride ophthalmic solution on the ocular surface of symptomatic contact lens wearers

BACKGROUND: Ocular surface-related discomfort is the main reason for stopping contact lens wear. We carried out a study to evaluate the efficacy of preservative-free artificial tears containing 0.9% sodium chloride on ocular surface signs and symptoms in contact lens wearers experiencing discomfort and its possible influence on the duration of contact lens wear. METHODS: We studied 49 contact lens wearers experiencing discomfort who had normal results of slit-lamp biomicroscopy, a fluorescein tear film break-up time (BUT) of 10 seconds or more, and wetting greater than 5 mm in 5 minutes on the Schirmer 1 test with and without anesthesia. Twenty-nine subjects (16 men and 13 women with a mean age of 32.5 years [standard deviation (SD) 8.7 years]) received one instillation of the 0.9% sodium chloride solution four times daily in the lower conjunctival fornix for 21 days. Twenty subjects (12 men and 8 women with a mean age of 35.1 [SD 6.2] years) received no drops and served as a control group. The overall comfort and duration of contact lens wear, results of tear film analysis and adverse events were recorded on days 7 and 21. Patients rated their symptoms (while not receiving any medications or hydrating solutions) on a 100-mm visual analogue scale with "Excellent (lenses not felt)" at the left and "Very uncomfortable (lenses cause irritation or discomfort)" at the right. Measurement of corrected visual acuity, slit-lamp examination, determination of the tear film BUT, the Schirmer 1 test with and without anesthesia, and assessment of the colour and surface of the lens were performed at baseline and at day 21. We analysed the data for the more uncomfortable eye or, if the eyes were equally uncomfortable, the right eye. RESULTS: Significant lessening of ocular discomfort was observed in the treatment group during the study: the mean rating on the visual analogue scale at baseline was 60.2 mm (SD 12.7 mm), compared with 35.8 mm (SD 18.0 mm) at day 21 (p < 0.001, Student's t test). The duration of contact lens wear was significantly longer at day 21 than at baseline (7.0 [SD 2.6] hours vs. 6.4 [SD 2.6] hours, p < 0.05, Student's t test), and the proportion of subjects with conjunctival hyperemia was significantly lower at day 21 (48.3% vs. 82.8%, p < 0.05, chi2 test). No statistically significant changes were observed in tear film BUT, results of the Schirmer 1 test, corneal punctate staining by fluorescein or results of tear film analysis. The treatment was well tolerated by all patients. No significant differences in any of the variables studied were observed in the control group. INTERPRETATION: Treatment with a preservative-free 0.9% sodium chloride ophthalmic solution reduced ocular surface discomfort and extended the duration of contact lens wear without interfering with the tear film or contact lens materials. Long-term studies are needed to confirm the role of this solution in reducing discomfort experienced by contact lens wearers.     

Effects of environment pollution on the ocular surface

The twenty-first century is fraught with dangers like climate change and pollution, which impacts human health and mortality. As levels of pollution increase, respiratory illnesses and cardiovascular ailments become more prevalent. Less understood are the eye-related complaints, which are commonly associated with increasing pollution. Affected people may complain of irritation, redness, foreign body sensation, tearing, and blurring of vision. Sources of pollution are varied, ranging from gases (such as ozone and NO₂) and particulate matter produced from traffic, to some other hazards associated with indoor environments. Mechanisms causing ocular surface disease involve toxicity, oxidative stress, and inflammation. Homeostatic mechanisms of the ocular surface may adapt to certain chronic changes in the environment, so affected people may not always be symptomatic. However there are many challenges associated with assessing effects of air pollution on eyes, as pollution is large scale and difficult to control. Persons with chronic allergic or atopic tendencies may have a pre-existing state of heightened mucosal immune response, hence they may have less tolerance for further environmental antigenic stimulation. It is beneficial to identify vulnerable people whose quality of life will be significantly impaired by environmental changes and provide counter measures in the form of protection or treatment. Better technologies in monitoring of pollutants and assessment of the eye will facilitate progress in this field.     

Trimethoprim-polymyxin B ophthalmic solution in treatment of surface ocular bacterial infections

A safety and efficacy study comparing the clinical and bacteriologic effectiveness of trimethoprim-sulfacetamide-polymyxin B-neomycin-gramicidin in a group of patients with surface ocular bacterial infections was conducted. The results demonstrated TSP to be as effective as the other solution (both clinically and bacteriologically), with fewer adverse experiences. A second study was conducted comparing TSP with trimethoprim-polymyxin B (TP) and found TP to be superior to TSP in effecting bacteriologic cures. Clinical response was similar in both groups, and the low incidence of mild adverse experiences was approximately the same. It appears that the combination of trimethoprim with polymyxin B is safe and highly efficacious, both clinically and microbiologically, for the treatment of surface ocular bacterial infections.     

Effects of adrenomedullin on ocular hemodynamic parameters in the choroid and the ophthalmic artery

PURPOSE: Adrenomedullin acts as a vasodilator and may play a role in inflammatory processes in the eye. This study was designed to determine whether nitric oxide formation is involved in the response to adrenomedullin in the ocular vasculature in vivo. METHODS: The effects of systemic intravenous adrenomedullin (3.2-16.0 pmol/[kg. min])) on choroidal blood flow were assessed by measurement of fundus pulsation amplitude and laser Doppler flow in the macula, and on blood flow in the ophthalmic artery by ultrasound Doppler flow in pilot studies (n = 7). Subsequently, in a double-blind randomized placebo-controlled crossover study in eight healthy male subjects the effects of 12.8 pmol/(kg. min) adrenomedullin on ocular and systemic hemodynamics were investigated. Adrenomedullin was co-infused with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (3 mg/kg bolus and 30 micro g/[kg. min] continuous intravenous infusion) or vehicle control on separate study days. RESULTS: Adrenomedullin dose dependently increased choroidal blood flow and flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine reduced the effect of adrenomedullin on fundus pulsation amplitude, but did not alter the flow response in the ophthalmic artery. Systemic hemodynamics were unaffected by adrenomedullin infusion. CONCLUSIONS: Ocular blood flow is sensitive to changes in adrenomedullin concentrations. The acute vasodilator effects of adrenomedullin are nitric oxide-dependent in the choroid, but not in the ophthalmic artery.     

Toxic effects of ophthalmic preservatives on cultured rabbit corneal epithelium

We investigated the effects of the ophthalmic preservatives thimerosal and sorbic acid on the proliferation and survival of rabbit corneal epithelial cells in tissue culture. Normally, explants of corneal epithelium grow vigorously during the first 7 days in culture. With 0.004% thimerosal present in the culture medium, the normal proliferation of corneal cells is suppressed completely. When 0.1% sorbic acid is present, proliferation is delayed and the lifespan of the corneal cells is reduced. After a 1-h exposure to concentrations of thimerosal of 0.0005% or greater, virtually all corneal cells present in established cultures are killed. These results suggest that use of ophthalmic preparations containing these chemicals may affect the metabolic and proliferative capacity of the corneal epithelium adversely.     

长期单眼配戴角膜塑形镜对眼表的影响

目的：探讨持续单眼配戴角膜塑形镜对眼表的影响。

方法：回顾性研究2013-01/2015-12在无锡市101医院眼科门诊就诊的单眼近视眼(对侧眼为正视眼)持续配戴角膜塑形镜6mo以上的患者。观察戴镜眼和非戴镜眼在戴镜前和戴镜后各时间点(1wk,1、3、6mo)的泪膜破裂时间、泪液基础分泌量、角膜中央厚度、角膜内皮细胞密度、结膜充血、角膜上皮荧光素染色的情况。

结果：单眼持续配戴角膜塑形镜患者共53例,年龄10.43±1.70岁,等效球镜度-3.37±1.50D。戴镜眼戴镜1wk泪膜破裂时间缩短,戴镜后1wk与戴镜后1、3、6mo泪膜破裂时间相比,差异无统计学意义(P>0.05); 非戴镜眼泪膜破裂时间各时间点无明显差异(P>0.05)。戴镜眼和非戴镜眼戴镜后各时间点泪液基础分泌量与戴镜前相比,差异均不明显(P>0.05)。戴镜后各时间点角膜中央厚度和角膜内皮细胞密度与戴镜前比较,差异均无统计学意义(P>0.05)。戴镜眼角膜上皮染色主要为Ⅰ级点染,Ⅰ级点染在戴镜后1wk,1、3、6mo分别为10眼(19%)、6眼(11%)、8眼(15%)、6眼(11%),Ⅱ级点染分别为1眼(2%)、0眼、0眼、1眼(2%)。10例患者戴镜后会出现结膜充血(评分1分)。所有病例在及时停戴、使用抗生素及角膜修复剂后,角膜上皮点状染色均消失,结膜充血消退。非戴镜眼观察期内未见明显结膜充血,角膜上皮染色均为0级。

结论：持续配戴角膜塑形镜会引起泪膜稳定性的下降,结膜、角膜上皮会出现不同程度的影响,但对泪液分泌、角膜厚度和角膜内皮细胞无明显影响。非戴镜眼无明显眼表损害。