Performance profile of sodium hyaluronate in patients with lipid tear deficiency: randomised, double-blind, controlled, exploratory study

AIM: To assess the short-term efficacy of hypotonic 0.18% sodium hyaluronate in patients with evaporative tear-sufficient dry eye due to lipid tear deficiency (LTD). METHODS: This was a randomised, double-blind, controlled, exploratory study. A total of 10 patients with dry eye due to LTD were treated as follows: one drop of hypotonic 0.18% sodium hyaluronate in one eye and one drop of isotonic 0.3% hydroxypropyl-methylcellulose (HPMC)/0.1% dextran in the other eye. Non-invasive tear film break-up time (NIBUT) evaluated by using a tear scope with grid pattern and subjective ocular symptoms of dry eye were assessed at 15, 30, 60 and 90 min after instillation. RESULTS: Both sodium hyaluronate and HPMC/dextran caused a significant (p<0.05) improvement in NIBUT and symptoms. Mean (SD) NIBUT in the sodium hyaluronate group was 3.2 (1.0), 6.4 (2.8), 5.5 (1.9), 5.3 (1.3) and 3.9 (1.7) s at 0, 15, 30, 60 and 90 min, respectively, compared with 3.6 (1.9), 5.5 (3.2), 5.0 (1.5), 4.4 (2.2) and 3.5 (1.2) s in the HPMC/dextran group. However, increase in NIBUT was significantly (p<0.05) greater and longer in the sodium hyaluronate group than in the HPMC/dextran group. CONCLUSION: Treatment with sodium hyaluronate and HPMC/dextran eye drops is useful for treating patients with dry eye due to LTD. However, sodium hyaluronate caused a significantly (p<0.05) greater increase in NIBUT values than HPMC/dextran in such patients.     

Repeated measurements of dynamic tear distribution on the ocular surface after instillation of artificial tears

PURPOSE: To determine the repeatability of real-time optical coherence tomography (OCT) measurements of tear film thickness (TFT) and variables of tear film menisci. METHODS: Forty eyes were imaged with a custom-built, real-time OCT to obtain heights, curvatures, and cross-sectional areas of upper and lower tear menisci simultaneously. The central TFT was indirectly determined as the difference between the combined thickness of the central cornea and tear film and the true corneal thickness obtained after instillation of artificial tears. Dynamic tear distribution was determined by OCT imaging immediately and 5, 20, 40, and 60 minutes after tear instillation. Measurements taken after two blinks of one eye at each visit were repeated on the next day. Measurements from the companion eye were made on separate days. RESULTS: There were no significant differences between the two measurements of each variable made on consecutive days. At baseline, upper tear meniscus variables were strongly correlated with the comparable lower meniscus variables. However, there were no significant correlations between TFT and any tear meniscus variable. Immediately after instillation of artificial tears, all measured variables increased significantly. TFT, upper and lower menisci heights, and upper meniscus area remained elevated for at least 5 minutes. In addition there were significant correlations between TFT and the lower tear meniscus height and area. CONCLUSIONS: The custom-built OCT showed good repeatability and holds promise in measuring the dynamic distribution of artificial tears on the ocular surface.     

Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation

In rabbit studies, we found that extended exposure of the ocular surface to existing ophthalmic solutions resulted in gross surface abnormalities and decreases in conjunctival goblet cell density. We developed an electrolyte solution (solution 15) that preserves normal gross appearance, goblet cell density, corneal epithelial glycogen levels, and ocular surface morphologic characteristics after extended exposure to the rabbit ocular surface. We created an artificial tear formulation by adding a demulcent and a buffering system to solution 15 and reducing its osmolarity to 162 mOsm/l. We then compared our artificial tear formulation to Hypotears in a double-masked, crossover study involving 11 patients with dry-eye disorders. Our artificial tear formulation was more effective than Hypotears in decreasing tear film osmolarity and rose bengal staining, and was preferred subjectively by an eight-to-one margin.     

Effect of laser in situ keratomileusis for hyperopia on tear film and ocular surface

PURPOSE: To examine the effects of laser in situ keratomileusis (LASIK) for hyperopia on the tear film and ocular surface. METHODS: A retrospective 12-month analysis of 88 eyes (88 participants) who had LASIK for hyperopia was performed. Participants were evaluated before and after (2 weeks, 1, 3, 6, and 12 months) surgery for dry eye symptoms (McMonnies Dry Eye Survey primary symptoms), tear film stability (fluorescein break-up time), tear volume (phenol red thread test), ocular surface staining (fluorescein), and conjunctival goblet cell density. RESULTS: Chronic dry eye was experienced by 32% of participants; symptoms were significantly associated with female gender, preoperative dry eye symptoms, lower tear film stability after surgery, greater ocular surface staining after surgery, lower tear volume before and after surgery, and lower goblet cell densities after surgery. Regression rate 12 months after surgery was 32% and significantly associated with female gender, chronic dry eye symptoms, lower tear film stability after surgery, greater ocular surface staining before and after surgery, and lower tear volume before and after surgery. CONCLUSIONS: Dry eye, particularly in females, is problematic after LASIK for hyperopia and is associated with refractive regression. Current methods for managing the tear film and ocular surface may not control LASIK-induced dry eye, particularly in some females during the first 6 months after surgery.     

Non-invasive methods of assessing the tear film

The interaction between the tear film and the ocular surface epithelium is crucial for the maintenance of ocular surface health; interference with this relationship may cause dry eye. Several diagnostic techniques have been developed to assess the tear film and diagnose dry eye but many of these tests are invasive and modify the parameter which they are designed to measure. Non-invasive or minimally invasive tests may overcome this problem and provide more reproducible and objective data. One test of this kind is meniscometry, which is particularly useful in assessing tear volume indirectly by measuring tear meniscus radius. The newly developed video-meniscometer, which enables calculation of the meniscus radius digitally, is useful for the diagnosis of tear-deficient dry eye. Video-meniscometry also has other applications, to the study of tear and eye drop turnover, determining the indication for punctal plugs and in demonstrating dysfunction of the tear meniscus. Interferometry of the tear film lipid layer is useful in screening and evaluating dry eye severity and in selecting dry eye candidates for punctal occlusion. It is also useful for analysing tear lipid layer pathophysiology more clearly, especially in combination with meniscometry. Meibometry is a minimally invasive technique to quantify the amount of meibomian lipid on the lid margin. Lipid is blotted onto a plastic tape and the change in optical density is used to calculate lipid uptake. Laser meibometry has increased the scope of this technique for the assessment of meibomian gland dysfunction; also, the delivery of lipids from the lid reservoir to the preocular tear film can be analysed using interferometry and laser meibometry. The present report reviews the application of these techniques to the study of tear film physiology and dry eye.     

眼表成像技术在干眼患者泪膜分析评价中的应用

干眼是一种复杂的眼表疾病,主要由于泪膜不稳定或眼表微环境失衡所导致。临床上常用泪膜破裂时间、角膜荧光染色评分和泪液分泌试验等指标来评估干眼,这些指标具有较强的主观性,且侵入性的操作也会干扰患者眼表。近年来出现各种客观无创的眼表成像技术用于泪膜分析,如角膜地形图、泪膜干涉测量、泪膜蒸发速率测量、眼前节光学相干断层成像和像差测量等。这些检测手段有助于对干眼进行诊断和疗效评估。本文就眼表成像技术在干眼患者泪膜分析评价中的应用作一综述。     

泪膜动态改变对视觉质量的影响

泪膜的动态变化包括泪膜厚度、脂质层和泪膜破裂区域的动态变化.干眼患者常伴有视力波动,泪膜对视觉质量的作用主要取决于泪膜的同质性及均匀性.近年来使用Hartmann-Shack波前像差仪、视觉质量分析系统等仪器定量连续测量健康眼及干眼瞬目后持续睁眼状态时及其应用人工泪液后泪膜动态改变对视觉质量影响.正常人瞬目后持续睁眼视觉质量下降,高阶像差和客观散射指数呈现出与干眼相似的上升趋势.干眼患者泪膜动态改变较正常人出现更早,高阶像差和客观散射指数均较正常眼增大.长期使用人工泪液可以改善干眼患者泪膜稳定性及瞬目后的视觉质量.视觉质量的动态检测可反映泪膜动态变化,有助于敏感地发现泪膜不稳定,及早进行临床诊治.     

The ocular surface and tear film and their dysfunction in dry eye disease

The ocular surface, tear film, lacrimal glands, and eyelids act as a functional unit to preserve the quality of the refractive surface of the eye and to resist injury and protect the eye against changing bodily and environmental conditions. Events that disturb the homeostasis of this functional unit can result in a vicious cycle of ocular surface disease. The tear film is the most dynamic structure of the functional unit, and its production and turnover is essential to maintaining the health of the ocular surface. Classically, the tear film is reported to be composed of three layers: the mucin, aqueous, and lipid layers. The boundaries and real thickness of such layers is still under discussion. A dysfunction of any of these layers can result in dry eye disease.     

Prophylactic action of lipid and non-lipid tear supplements in adverse environmental conditions: A randomised crossover trial

PurposeTo evaluate the prophylactic benefits of lipid-based and non-lipid-based artificial tear lubricants, in dry eye disease, after adverse environmental exposure.MethodsTwenty-eight participants with dry eye disease were recruited in a prospective, double-masked, randomised crossover trial. On separate days, participants were randomised to receive a single application of a lipid-containing tear supplement (Systane Complete) to one eye, and a non-lipid containing eye drop (Systane Ultra) to the contralateral eye. Participants were then exposed to a previously validated simulated adverse environment. Symptoms, non-invasive tear film breakup time, lipid layer grade, and tear meniscus height were assessed at three time points; baseline, following eye drop instillation, and after exposure to the adverse environment.ResultsBoth treatments effected improvements in symptoms and non-invasive tear film stability following instillation (all p < 0.05), although an improvement in lipid layer quality was limited to the lipid-containing nano-emulsion tear supplement (p = 0.003). Although protective effects were conferred by both treatments following exposure to the simulated adverse environment, more favourable symptomology scores, non-invasive tear film stability, and lipid layer quality were observed in the lipid-containing tear supplement group (all p < 0.05). No significant changes were observed in tear meniscus height in both treatment groups (all p > 0.05).ConclusionsBoth the lipid and non-lipid-based artificial tear supplement demonstrated prophylactic benefits in a simulated adverse environment. However, the ability to preserve tear film quality and reduce dry eye symptomology was greater with the lipid-containing eye drop.Trial registration numberACTRN12619000361101     

周边虹膜切除术对泪液膜影响的研究

目的 研究周边虹膜切除术对泪膜的影响。方法 急性闭角型青光眼126例，一只眼接受周边虹膜切除术，另一只眼点1％匹罗卡品。治疗后观察受检者的症状和体征，包括畏光、眼痒、异物感、烧灼感、干涩感、视疲劳、结膜充血、角膜丝状物、Schirme I试验、泪膜破裂时间(BUT)、角膜荧光素染色情况。用TMS-1角膜地形图对其中的82人角膜表面规则指数和角膜表面不对称指数进行测定。以t检验比较手术组和药物组症状、体征和干眼症诊断性试验结果的差异性，以χ^2检验比较手术组和药物组干眼症发生率的差异性。结果 手术组与药物组在青光眼的类型、病程、年龄、性别等方面差异无显著性，手术组干眼的症状及体征比药物组明显，手术组Schirmer I试验及BUT测定明显低于药物组，角膜染色试验手术组比药物组严重，手术组干眼症的发生率明显高于药物组，所有这些差异均有统计学意义。结论 周边虹膜切除术能引起泪膜功能受损，使泪膜稳定性受到破坏。应用人工泪液可以改善手术组的于眼症状。     

Osmolality and tear film dynamics

The tear film is a nourishing, lubricating and protecting layer that bathes the ocular surface. It is continuously replenished through cycles of production and elimination via evaporation, absorption and drainage. These processes are often referred to as tear film dynamics. Osmolality is an objective clinical measurement that provides insight into the balance of these complex tear film dynamics. Balanced tear production and elimination is vital for tear film integrity, stability and normal osmolality. Imbalances cause alterations of the tear film structure and composition, ultimately leading to tear film instability and measurable tear film hyperosmolality. Elevated tear film osmolality is considered a core mechanism in dry eye, forming the basis of dry eye symptoms and leading to ocular surface damage. Despite its immense potential in the diagnosis of dry eye, tear film osmolality is not commonly assessed. This review will focus on the current knowledge of tear film dynamics and tear film osmolality.     

Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis

PURPOSE: To identify evidence-based, best practice strategies for managing the ocular surface and tear film before, during, and after laser in situ keratomileusis (LASIK). METHODS: After a comprehensive review of relevant published literature, evidence-based recommendations for best practice management strategies are presented. RESULTS: Symptoms of ocular irritation and signs of dysfunction of the integrated lacrimal gland/ocular surface functional gland unit are common before and after LASIK. The status of the ocular surface and tear film before LASIK can impact surgical outcomes in terms of potential complications during and after surgery, refractive outcome, optical quality, patient satisfaction, and the severity and duration of dry eye after LASIK. Before LASIK, the health of the ocular surface should be optimized and patients selected appropriately. Dry eye before surgery and female gender are risk factors for developing chronic dry eye after LASIK. Management of the ocular surface during LASIK can minimize ocular surface damage and the risk of adverse outcomes. Long-term management of the tear film and ocular surface after LASIK can reduce the severity and duration of dry eye symptoms and signs. CONCLUSIONS: Strategies to manage the integrated ocular surface/lacrimal gland functional unit before, during, and after LASIK can optimize outcomes. As problems with the ocular surface and tear film are relatively common, attention should focus on the use and improvement of evidence-based management strategies.     

Sequential changes of lipid tear film after the instillation of a single drop of a new emulsion eye drop in dry eye patients

PURPOSE: The lipid tear film stabilizes the tears by lowering the surface tension and preventing aqueous tear evaporation and may be analyzed by kinetic analysis of the tear interference images. This study investigated changes in the lipid film after application of a new emulsion-based eye drop of Refresh Endura (Allergan, Irvine, CA) in normal subjects and patients with dry eyes. DESIGN: Comparative, nonrandomized interventional study. PARTICIPANTS: Five normal subjects and 10 aqueous tear deficiency (ATD) patients with or without lipid tear deficiency were enrolled prospectively. METHODS: A complete eye examination was performed, including symptom score, tear break-up time, dye staining, and fluorescein clearance test. One eye received a single dose of emulsion eye drop (EED), whereas the other eye received nonpreserved saline as a control. Kinetic analysis of tear interference images taken by DR-1 (Kowa, Japan) was performed before and at various times after instillation of the drops. MAIN OUTCOME MEASURES: Symptoms, pattern, thickness, and spread time of the tear film. RESULTS: Compared with the control, all eyes receiving EED showed rapid restructuring of the preexisting lipid film. In normal persons, restructuring resulted in a thick lipid band across the cornea and a significant increase of the lipid film thickness. For ATD patients, EED application resulted in either a scant, irregular tear film, which became covered by the lipid film, or a modified lipid film changed without forming a band or irregularities. Emulsion eye drops tended to be more comfortable in patients with more severe ATD. Kinetic analysis showed that the mean spread time improved for all patients after EED when compared with baseline or with controls (P<0.05). CONCLUSIONS: Emulsion eye drop produces significant changes in the tear film of normal and dry eye patients. Further investigation with a prolonged period of treatment is warranted to establish whether EED may help improve the spread and thickness of the lipid tear film in moderate and severe dry eyes.     

Ocular surface residence times of artificial tear solutions.

Solutions of hydroxypropylmethylcellulose (HPMC) and polyvinyl alcohol (PVA) are widely used as artificial tears. However, their usefulness is limited by the short duration of their effect. Dilute sodium hyaluronate (SH) solutions exhibit non-Newtonian rheology with high viscosities at low shear rates, which would be expected to enhance their ocular surface residence time. Using quantitative gamma scintigraphy, estimates of the ocular surface residence times of 0.3% HPMC, 1.4% PVA, and 0.2% SH were made in six patients with keratoconjunctivitis sicca. The sodium hyaluronate solution had a mean half-life on the ocular surface of 321 s, significantly longer than hydroxypropylmethylcellulose (44 s; p = 0.012) and polyvinyl alcohol (39 s; p = 0.013).     

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。     

Modulation of tear film protein secretion with phosphodiesterase inhibitors

A double-blind randomized clinical study was conducted to determine whether nicardipine hydrochloride was a useful treatment for dry eye.We examined its effect on the tear film, ocular surface and ocular comfort. Nicardipine hydrochloride, 3-isobutyl-1-methylxanthine and pilocarpine hydrochloride were dissolved in an artificial tear vehicle and applied topically to one eye of 12 subjects on separate days. Ocular physiology, ocular comfort and tear volume were assessed. The trial was repeated with nicardipine in an aqueous gel vehicle. Tears were collected and assessed for protein concentration and protein profile, using electrophoresis and mass spectrometry. Nicardipine induced conjunctival redness and symptoms of dryness and irritation. There was no change in total tear protein concentration or volume. An increase in a 68 kDa protein was observed, this was probably due to conjunctival vessel dilation and leakage of albumin. The adverse symptomatology and increased conjunctival redness experienced with nicardipine make it an undesirable treatment for dry eye.     

泪液的相关研究与进展

泪液是主要由泪腺分泌的一种水样液体,通过瞬目运动覆盖在眼表面形成泪膜。当前就泪膜的特殊结构和功能等方面,已开展了大量研究,将收集到的泪液,睑板腺分泌物,印迹细胞学、刷检细胞学、结膜活组织检查收集到的眼表细胞,应用电泳、色谱分析联合质谱分析及聚合酶链式反应（PCR）等分子生物学技术,分析泪膜脂质、蛋白、黏蛋白分子及其mRNA是较常用的方法。泪液成分分析技术的进步为I临床医师了解泪膜,诊断及治疗干眼症提供了有力的依据。就泪液成分分析的基本方法和研究现状进行综述。     

A practical treatment algorithm for managing ocular surface and tear disorders

Management of ocular surface irritation and morbidity associated with dry eye has been plagued by the complex interplay of different pathogenic elements and substantial variability of ocular surface deficits in patients. A practical algorithm is proposed to achieve effective management of dry eye. When the eye is open, ocular surface health is governed by a stable tear film that is maintained by neuroanatomic integration via 2 reflexes. Any dysfunctional element in this neuroanatomic integration is potentially pathogenic and creates ocular surface deficits leading to dry eye. In general practice, 5 major dysfunctional elements have been identified: decreased ocular surface sensitivity, aqueous tear deficiency, lipid tear deficiency, delayed tear clearance, and ineffective tear spread. Clinical workup should be individualized to identify all such dysfunctional elements in each patient through history taking, external and slit-lamp examination, and special tests. However, practical management lies in the detection of delayed tear clearance. The following strategies are advised: (1) eliminate all intrinsic inflammatory, infectious, allergic, and toxic insults, especially those associated with delayed tear clearance; (2) correct diseases that impede and interfere with tear spread and capacity; (3) create delayed tear clearance for aqueous tear-deficient dry eye by punctual occlusion; and (4) treat lipid-deficient dry eye after sufficient aqueous tears have been conserved. The aforementioned algorithm ameliorates ocular surface irritation and curtails morbidity in most patients. This algorithm can also be adopted for complex cicatricial ocular surface diseases before managing the remaining deficits resulting from hydrodynamic deficiency.     

Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction

PURPOSE: To evaluate the safety and efficacy of an original warm moist air device on tear functions and ocular surface of patients with simple meibomian gland dysfunction (MGD). METHODS: Fifteen patients with simple MGD and 20 healthy volunteers were recruited in an initial prospective interventional clinical trial to evaluate the safety and short-term effects of the warm moist air device. The device was applied to the eyes of the subjects for 10 minutes. Temperatures of the eye lids and corneas were measured with an infrared thermometer. Symptoms of ocular fatigue were scored using visual analog scales (VASs). Schirmer test, tear film break-up time (BUT), DR-1 tear film lipid layer interferometry, fluorescein staining, and rose bengal staining were also performed before and after the application of the eye steamer. After the initial study, another 2-week prospective clinical trial was carried out in 10 patients with MGD who received the warm moist air treatment. Ten other patients were also recruited and received warm compress treatment with hot towels for 2 weeks to evaluate the long-term effects of the warm moist air device and the warm compresses on tear film lipid layer thickness and ocular surface health. The warm moist air device and the warm compresses were applied for 10 minutes twice a day. The changes in VAS scores for symptoms, BUT values, fluorescein, and rose bengal staining scores were examined before and after each treatment during the second trial. RESULTS: VAS scores of ocular fatigue improved significantly with short- and long-term applications of the warm moist air device in both studies. The mean corneal surface and eye lid temperatures showed significant elevation within safe limits 10 minutes after the moist air application. The mean BUT prolonged significantly in the patients receiving warm moist air applications but did not change significantly in those treated with warm compresses. DR-1 tear film lipid layer interference showed evidence of lipid expression in the patients and controls, with thickening of the tear film lipid layer after 10 minutes of warm moist air device use. In the 2-week trial, tear film lipid layer thickness increased in both warm moist air device and warm compress groups, with a greater extent of increase in the warm moist air device group. CONCLUSION: Warm moist air device use provided symptomatic relief of ocular fatigue and improvement of tear stability in patients with MGD. The new warm moist air device seems to be a safe and promising alternative in the treatment of MGD.     

Strip meniscometry: a new and simple method of tear meniscus evaluation

PURPOSE: To investigate the applicability and efficacy of a new and simple method of quantification of the volume of tear meniscus, termed "strip meniscometry," in the diagnosis of the dry eye syndromes in a prospective controlled study. METHODS: One hundred eyes of 50 patients with dry eye (19 males; 31 females) aged between 18 and 76 years (mean, 54.3 years), as well as 80 eyes of 40 normal subjects aged from 15 to 70 years (mean, 50.8 years; 12 males, 28 females) were recruited in this study. The patients and the control subjects underwent strip meniscometry for 5 seconds, tear film lipid layer interferometry, tear film break-up time measurement, and ocular surface vital staining with fluorescein and rose bengal dyes and the Schirmer-1 test. RESULTS: Strip meniscometry scores correlated with tear quantity and stability, ocular surface staining scores, and lipid layer interferometry grades and improved after 2 weeks of punctal plug occlusion. CONCLUSIONS: Strip meniscometry is a swift, noninvasive, promising new method that is expected to find application in the diagnosis and evaluation of the outcome of treatment of dry eye syndromes.