Article

Lipid-Containing Lubricants for Dry Eye: A Systematic Review

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Abstract

Purpose: Dry eye is a common eye condition with significant impact on its sufferers' quality of life. We conducted a systematic review of randomized controlled treatment trials to assess the effectiveness of lipid-containing lubricants (LCLs) on dry eye treatment. Methods: An online database was searched without any language or date restrictions. Clinical trials on LCL with non-lipid-containing control eyedrops were included. The outcome measures of each study (including symptoms and clinical signs), their risk of bias (assessed using the Cochrane tool), and strength of evidence were discussed. Results: Three studies on liposomal lid sprays and four on lipid-containing eyedrops were included. All studies found significant improvements in most of the symptoms/signs of dry eye in patients who used LCL during the study period. Subjects in all trials reported greater symptom relief with LCLs, although this was shown to be short lived in two studies. Lipid layer structure improvement after LCLs application was demonstrated in two studies, although only up to 90 min in one study. Improvement in Schirmer test results was shown in two out of four studies, tear breakup time in four out of five studies, meibomian gland status in three out of three studies, conjunctival folds and tear evaporation rates in two out of two studies each. None of the studies were completely free of risks of bias; only three studies were double masked. Three of the studies were assigned high level of evidence, three were assigned as moderate evidence, and the final one low level of evidence. Conclusions: Most studies have demonstrated the effectiveness of LCLs on improving select signs of dry eye. Based on the overall substantial level of evidence, this type of eyedrop can be recommended for use in clinical practice where the aim is to reduce the signs and symptoms of dry eye.

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... Meibum inspissation and gland blockage in MGD has an adverse impact on the tear lipid layer, necessitating application of heat to encourage natural meibum restoration, and/or supplementation with artificial lipid products. Various treatments have been developed for evaporative dry eye to supplement the tear film lipid layer [18][19][20][21][22]. Lipidcontaining lubricant eye drops contain an emulsion of mineral oils and phospholipids [18,19,23], while liposomal sprays deliver phospholipids across the lid margins [20][21][22]. ...
... Meibum inspissation and gland blockage in MGD has an adverse impact on the tear lipid layer, necessitating application of heat to encourage natural meibum restoration, and/or supplementation with artificial lipid products. Various treatments have been developed for evaporative dry eye to supplement the tear film lipid layer [18][19][20][21][22]. Lipidcontaining lubricant eye drops contain an emulsion of mineral oils and phospholipids [18,19,23], while liposomal sprays deliver phospholipids across the lid margins [20][21][22]. ...
... Random assignment of two lipid-based tear supplements to either the left or right eye of participants, occurred such that one eye was assigned a lipid-containing lubricant eye drop (Systane 1 Balance, Alcon 1 , Texas, USA), and the contralateral eye a phospholipid liposomal spray (Tears Again 1 , Optima Pharmazeutische GmbH, Germany). The lubricant eye drop contains an emulsion of phospholipids and mineral oils [18], while the primary active ingredient of the liposomal spray is phosphatidylcholine [20]. Following pre-treatment clinical assessment, a single drop of lubricant eye drop was applied to one eye, while the fellow eye received a single liposomal spray onto closed eyelids from a distance of 10 cm, according to the respective manufacturer's instructions. ...
Article
Purpose: To compare the effects on tear film parameters and contamination in cosmetic eyeliner wearers, after single application of two lipid-based dry eye treatments: a lipid-containing lubricant eye drop and a phospholipid liposomal spray. Methods: Fifty participants were enrolled in a prospective, randomised, paired-eye, investigator-masked trial. Pencil eyeliner (Body Shop(®) Crayon Eye Definer) was applied to the upper eyelid periocular skin of both eyes, anterior to the lash line. Baseline tear film quality was assessed fifteen minutes after eyeliner application. A lubricant drop (Systane(®) Balance) was then applied to one eye (randomised), and liposomal spray (Tears Again(®)) to the contralateral eye. Tear film contamination, lipid layer grade, non-invasive tear film break-up time and tear evaporation rate were evaluated fifteen minutes post-treatment and compared to pre-treatment values. Results: Pre-treatment measurements did not differ between eyes assigned to lubricant drop and liposomal spray. Tear film contamination was observed in a greater proportion of eyes following both treatments (both p<0.05), with no significant difference between treatments (p=0.41). Both treatments improved lipid layer thickness (both p≤0.01), but effected no significant change in non-invasive tear film break-up time or tear evaporation rate (all p>0.05). Changes in tear film parameters did not differ between treatments (all p>0.05). Conclusions: Both the lipid-containing lubricant eye drop and phospholipid liposomal spray result in clinically apparent tear film contamination in eyeliner cosmetic wearers. Although both treatments effected an increase in lipid layer thickness, neither displayed clinical efficacy in improving tear film stability.
... Conventional management of MGD includes eyelid hygiene, topical lubricants, topical and systemic antibiotics with antiinflammatory properties and topical steroids. 19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57 However, there are current and emerging treatment approaches such as various devices (see Section Eyelid hygiene) 54,55,56,57 or topical and systemic therapies. 19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41 ,42,43,44,45,46,47,48,49,50,51,52,53 Eyelid hygiene Eyelid hygiene is regarded as the cornerstone or mainstay treatment of MGD. ...
... Artificial tears are believed to replenish and stabilise the lipid layer of the tear film by reducing tear evaporation and ameliorate the signs of MGD. 35,36 The commonly used artificial lubricants include Optive Plus (Allergan) and Systane (Alcon). Eyelid cleanser and Tears Away lipidcontaining eyelid spray have also been shown to relieve symptoms of dry eye disease. ...
... The spray is applied to the closed eye and the liposomes enters the tear film via the lid margins. 35 It has been shown that a single application of lipid-containing spray significantly increases the tear film stability for up to 90 min. ...
Article
Full-text available
Background: Meibomian gland dysfunction (MGD) is one of the leading causes of evaporative dry eye disease and one of the most common ophthalmic conditions found in clinical practice. Meibomian gland dysfunction tends to be overlooked because its signs and symptoms do not cause blindness. Meibomian gland dysfunction is characterised by the obstruction of the meibomian gland terminal ducts resulting in tear film instability. Aim: The purpose of this article was to provide an update on MGD’s diagnosis and treatment. Method: A literature review was conducted using search engines such as Google Scholar, Medline and ScienceDirect databases. Keywords such as MGD diagnosis and management and treatment of MGD were used to search the databases. Results: A total of 44 relevant papers were reviewed. These papers were then curated to include only those concerning diagnosis of meibomian gland dysfunction, treatment of meibomian gland dysfunction and management options of meibomian gland dysfunction. The references of individual papers from the curated results were checked to yield a further 13 papers. Conclusion: Meibomian gland dysfunction is not a single entity but is multifactorial in origin; however, our understanding of the condition is evolving rapidly because of newer imaging technology. There is no gold standard treatment option for MGD, but many options are available that include medications and other procedures.
... Non-lipid drops effect tear film aqueous augmentation, increase lubrication and reduce ocular surface desiccation [9]. Lipomimetic drops, consisting of an emulsion of mineral oils and phospholipids, seek to provide additional fortification to the lipid layer which inhibits tear film aqueous evaporation [9][10][11][12]. ...
... Nevertheless, the initial improvements in tear film stability following instillation in that study appeared to be transient for both treatments, with a reduction in NIBUT with simulated environment exposure. This would suggest that frequent re-application of both supplements may be required for sustained protection [8][9][10]. ...
... Asterisks denote statistically significant differences (p < 0.05). promotes greater stability of the tear lipid layer, in addition to the aqueous augmentation effects afforded by the non-lipid drops [9,10]. This extra mechanism of action may be associated with the greater prophylactic potential observed with lipomimetic instillation. ...
Article
Purpose: To compare the prophylactic efficacy of single application of lipid and non-lipid containing tear supplements, prior to exposure of symptomatic dry eye subjects to a simulated adverse environment. Methods: Thirty subjects with mild-to-moderate dry eye symptoms participated in the prospective, randomised, double-masked, paired-eye trial. A lipomimetic drop (Systane(®) Balance) was applied to one eye (randomised), and a non-lipid containing drop (Systane(®) Ultra) applied simultaneously to the contralateral eye. Subjects were subsequently exposed to a validated simulated adverse environment model created by a standing fan directed towards the eye, at a distance of 1m, for 2.5min. Low contrast glare acuity, lipid layer grade (LLG), non-invasive tear break-up time (NIBUT), temperature variation factor (TVF), and tear meniscus height (TMH) were evaluated at baseline, following eye drop instillation and following simulated adverse environment exposure. Results: Both therapies resulted in increased NIBUT (both p<0.001), and prevented its decline below baseline with simulated adverse environment exposure (both p>0.05). However, only the lipomimetic drop increased LLG (p<0.001) and precluded its fall below baseline post-adverse environment exposure (p=0.15). Furthermore, post-instillation and post-exposure LLGs and NIBUT were significantly higher in the lipomimetic group (all p<0.05). No significant changes were observed in glare acuity, TVF and TMH (all p>0.05). More subjects (67%) reported greater ocular comfort in the eye receiving the lipomimetic. Conclusions: Single application of both lipid and non-lipid containing eye drops conferred protective effects against exposure to adverse environmental conditions in subjects with mild-to-moderate dry eye, although the lipomimetic demonstrated superior prophylactic efficacy.
... 34 Furthermore, a systematic literature review of randomized controlled studies revealed strong clinical evidence for the effective use of lipidcontaining lubricants in the treatment of DED. 35 Of note, the U.S. Food and Drug Administration Code of Federal Regulations Title 21 part 349 recommends that lipids can be used as ''emollients'' (or ''lubricants'') in ophthalmic products (eg, lanolin, light mineral oil, mineral oil, paraffin, petrolatum, white ointment, white wax, and yellow wax) indicated for ''the temporary relief of burning and irritation due to dryness of the eye'' or ''the use as a lubricant to prevent further irritation or to relieve dryness of the eye.'' 36 ...
... Components in the aqueous phase of the emulsions (eg, osmoprotectants such as glycerin, emulsifiers, or polymers) may also provide additional effect on the ocular surface (eg, lubrication, osmoprotection). Oil-in-water emulsions reduce the signs and symptoms of all types of dry eye, 35,62 but are particularly recommended for lipid-deficient dry eye patients. 63 Cationic emulsions provide optimal ocular spreading and residence time with ocular surface benefits to improve DED, especially in MGD patients. ...
Article
Full-text available
Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.
... 19,20 In the literature, several studies on the clinical effects of ATs and on the comparison between them are reported. 13,[21][22][23][24][25][26][27][28][29] Some of these studies concern the retention time on the ocular surface and both symptoms and signs in patients with dry eye. In rat and rabbit animal models of dry eye, sodium hyaluronate was reported to show a significantly longer retention time than other ATs, including carboxymethylcellulose and hydroxypropyl methylcellulose. ...
... 12,13,22,27 In patients with deficient lipid layers, lipid emulsion eyedrops were also found to produce positive effects. 23,25 Rinsing and replacement of tear film were not enough to produce any clear and statistically significant OR and comfort benefit in the case of 1-month replacement CLs of the same material used during the day for 8±1 hours a day for 2 weeks (BW-Ws). This can be due to various reasons. ...
Article
Full-text available
Purpose: To compare the effects of artificial tears (ATs) in wearers of biweekly replacement silicone hydrogel contact lenses (BW-Ws) and wearers of daily disposable contact lenses (DD-Ws) of the same material. Materials and methods: The aqueous-supplementing ATs, OPTOyalA and OPTOidro, were assigned to be used for 2 weeks to healthy and young subjects: 1) 20 (8 and 12, respectively) BW-Ws wearing silicone hydrogel somofilcon A CLs (Clariti Elite), 2) 18 (9 and 9, respectively) DD-Ws wearing silicone hydrogel somofilcon A CLs (Clarity 1 Day), and 3) a control group of 33 (16 and 17, respectively) N-Ws. Ocular symptoms and comfort, tear volume and stability, and ocular surface condition were assessed by Ocular Surface Disease Index (OSDI), 5-Item Dry Eye Questionnaire (DEQ5), tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), and evaluation of ocular redness (OR). The assessment was performed before and after 15 days of use of the ATs in the 3 groups (BW-Ws, DD-Ws, and N-Ws). Results: No clear significant difference was noted in symptoms and signs between OPTOyalA and OPTOidro irrespectively of the group of people studied. ATs use for 15 days produced a significant improvement in DEQ5 and OR in DD-Ws (Δ=-34%, p=0.006; Δ=-23%, p<0.001) and in N-Ws (Δ=-21%, p=0.001; Δ=-10%, p=0.006) but not in BW-Ws (Δ=-5%, p=0.072; Δ=-2%, p=0.257). No significant change was noted for TMH. Conclusion: In young and healthy subjects, the aqueous-supplementing effect of the ATs under consideration is more a rinsing and tear replacem ent effect than an increase in tear volume, and it produces an improvement of the eye redness and ocular symptoms. Contact lens wear influenced the effectiveness of ATs in a way which is correlated with the CL replacement schedule.
... 34 Furthermore, a systematic literature review of randomized controlled studies revealed strong clinical evidence for the effective use of lipidcontaining lubricants in the treatment of DED. 35 Of note, the U.S. Food and Drug Administration Code of Federal Regulations Title 21 part 349 recommends that lipids can be used as ''emollients'' (or ''lubricants'') in ophthalmic products (eg, lanolin, light mineral oil, mineral oil, paraffin, petrolatum, white ointment, white wax, and yellow wax) indicated for ''the temporary relief of burning and irritation due to dryness of the eye'' or ''the use as a lubricant to prevent further irritation or to relieve dryness of the eye.'' 36 ...
... Components in the aqueous phase of the emulsions (eg, osmoprotectants such as glycerin, emulsifiers, or polymers) may also provide additional effect on the ocular surface (eg, lubrication, osmoprotection). Oil-in-water emulsions reduce the signs and symptoms of all types of dry eye, 35,62 but are particularly recommended for lipid-deficient dry eye patients. 63 Cationic emulsions provide optimal ocular spreading and residence time with ocular surface benefits to improve DED, especially in MGD patients. ...
Article
Purpose: The aim of the present study was to investigate the antiangiogenesis effect of pirfenidone. Methods: The proliferation of human umbilical vein endothelial cells (HUVECs) and human Tenon's fibroblasts (HTFs) were detected by WST-1 assay. The cell viability of HUVECs was measured by Trypan Blue together with lactate dehydrogenase, Annexin 5 experiment, and Ki-67 immunofluorescence assay. The functions of HUVECs and HTFs were demonstrated using cell migration assay, transwell invasion assay, and tube formation assay. The expression levels of vascular endothelial growth factor-A (VEGF-A), VEGF receptor-2 (VEGFR-2), neuropilin-1(NRP-1), and their downstream signaling proteins p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mechanistic target of rapamycin (mTOR) were indicated by western blot assay. The secretion of VEGF-A was detected by enzyme-linked immunosorbent assay. Results: Pirfenidone inhibited proliferation, migration, invasion, and tube formation of HUVECs in vitro, and had an equivalent antiangiogenesis effect when compared with Ranibizumab in HUVECs and HTFs. Pirfenidone downregulated VEGF-A/VEGFR-2, VEGF-A/NRP-1, and its downstream signaling pathway protein expression. Conclusions: Pirfenidone has an antiangiogenesis effect in the wound healing process and may become an ideal multitarget antiscarring agent after glaucoma filtration surgery.
... Given the lipid layer is compromised frequently in DED, it would be rational to add lipids in order to compensate this dysfunction. AT with a lipid component are thought to replenish the lipid layer, providing a longer residence time in the tear film, reducing the tear evaporation rate, and finally ameliorating the signs and symptoms of DED [56][57][58]. ...
... A systematic review of lipid-containing AT published in 2012 states that without a lipid component in lubricating eyedrops, it is likely that the AT will evaporate just as quickly as, if not faster than, the natural tears. This review finally affirms that there is sufficiently strong evidence that lipid-containing lubricants should be recommended for the treatment of DED [56]. ...
Article
Full-text available
Background: Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface that results in symptoms such as discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface. The principal pathological mechanisms of DED are hyperosmolarity and inflammation. These mechanisms are deeply interrelated and lead to a self-perpetuating "vicious circle". Methods: The objective of this review is to describe novel pharmacological and non-pharmacological treatments for DED. Results: Based on the better understanding of the physiopathology of the disease, new treatment strategies have been developed. Conclusion: The focus of the management of DED has been taken away from just reducing symptoms and redirected towards specific targets of its physiopathology, being inflammation the most addressed topic.
... The addition of a lipid component to artificial lubricants is proposed to replenish the lipid layer of the tear film [80]. These artificial lubricants have been shown to stabilise the TFLL, have a long residence time in the tear film, reduce the tear evaporation rate and improve the signs of MGD [80,94]. The lipids used in these artificial lubricants are as follows: ...
... Moreover, lipid-containing eyelid sprays such as Tears Away (OCuSOFT liposomal spray have been shown to relieve the symptoms of DED and were favoured over an eye gel preparation [94,99]. The phospholipid liposomal spray is applied to the closed eyelids, and the liposomes migrate, via the lid margins, into the tear film [100]. ...
Article
Full-text available
Meibomian gland dysfunction (MGD) is a common and chronic disorder that has a significant adverse impact on patients' quality of life. It is a leading cause of evaporative dry eye disease (DED), as meibomian glands play an important role in providing lipids to the tear film, which helps to retard the evaporation of tears from the ocular surface. MGD is also often present in conjunction with primary aqueous-deficient DED. Obstructive MGD, the most commonly observed type of MGD, is the main ocus of this article. MGD is probably caused by a combination of separate conditions: primary obstructive hyperkeratinization of the meibomian gland, abnormal meibomian gland secretion, eyelid inflammation, corneal inflammation and damage, microbiological changes, and DED. Furthermore, skin diseases such as rosacea may play a part in its pathology. Accurate diagnosis is challenging, as it is difficult to differentiate between ocular surface diseases, but is crucial when choosing treatment options. Ocular imaging has advanced in recent years, providing ophthalmologists with a better understanding of ocular diseases. This review presents a literature update on the 2011 MGD workshop and an optimized approach to accurate diagnosis of MGD using currently available methods and tests. It also outlines the emerging technologies of interferometry, non-contact meibography, keratography and in vivo confocal laser microscopy, which offer exciting possibilities for the future. Selected treatment options for MGD are also discussed.
... 3 Many artificial tears replace only the aqueous components of the tear film and require frequent administration to maintain efficacy. 4 Longer-acting formulations are needed that have increased hydration and lubrication effects. 5 In a randomized double-masked study of dry eye patients with aqueous tear deficiency or noninflammatory meibomian gland disease, artificial tears containing the demulcents propylene glycol and polyethylene glycol demonstrated significantly longer precorneal residence time compared with saline alone, suggesting that these demulcents may prolong the action of dry eye formulations. ...
Article
Full-text available
To measure the penetration of fluorescein into the anterior ocular compartments after exposure of the cornea to a mist of aerosol droplets. This was an open-label proof-of-principle trial. Eighteen healthy volunteers were asked to participate. A conventional (50 μL) drop of fluorescein solution (20 mg/mL) was administered to the right eye; an ocular mist (10 μL) of the same solution was applied to the left eye. Autofluorescence (photons/s) was measured in the cornea, the anterior chamber (AC), and the lens before administration and at 1, 2, 5, 10, 20, 50, and 100 min thereafter. The area under the curve (AUC) was calculated. For the vitreous cavity, measurements were performed at baseline and after 100 min. All participants completed the study. AUC (mean±SD) for the cornea was (363±431)×10(4) photons after drop application and (154±265)×10(4) photons after the mist (P=0.005). For the AC, these values were (6.9±10.3)×10(4) and (2.9±5.4)×10(4) photons, respectively (P=0.14). Autofluorescence data obtained in the lens did not allow reliable AUC calculations. Autofluorescence in the vitreous at 100 min did not significantly exceed the level at baseline. It was demonstrated that fluorescein applied to the ocular surface with the spray device enters the AC. The total amount of fluorescein molecules reaching the ocular surface by the 2 methods of administration, however, is not equivalent. Therefore, no definitive conclusions on relative bioavailability can be drawn from this experiment.
... All rights reserved. petrolatum ointment at night if nocturnal lagophthalmos exists (27)(28)(29)(30)(31). Lipidcontaining eye drops are effective in improving symptoms and signs of dry eye and particularly recommended in the presence of meibomian gland dysfunction (27,32). ...
Article
Full-text available
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert‐based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis. This article is protected by copyright. All rights reserved.
... Lipid-containing lubricants have demonstrated benefit for improving some signs of dry eye, including lipid layer structure, tear stability and tear evaporation rate. 198 It has recently been shown that a phospholipid liposomal spray (Tears Again, bioRevive) increased tear film stability, lipid layer thickness and subjective comfort in silicone hydrogel contact lens wearers, without adversely affecting visual acuity or lipid deposits on the contact lens surface, 199 supporting the utility of these products in soft contact lens wearers. ...
Article
The human tear film is a highly ordered structure consisting of a thin layer of lipid on the surface and a thicker aqueous-mucin phase, which increases in mucin concentration toward the corneal epithelial cell layer. The health of the tear film and ocular surface influences the likelihood of being able to achieve successful contact lens wear. Contact lens discomfort and dryness are the most frequent reasons why contact lens wearers experience reduced wearing times, which can eventually lead to contact lens discontinuation. Comprehensive clinical assessment of tear film integrity and ocular surface health is therefore essential prior to commencing contact lens wear, to enable the ocular surface environment to be optimised to support lens wear. These parameters should also be evaluated over the course of contact lens wear, in order to identify any aspects requiring clinical management and ensure maintenance of optimal lens-wearing conditions. This review summarises current knowledge relating to the effects of soft contact lens wear on the tear film and ocular surface. It also provides a systematic approach to evaluating tear film and ocular surface integrity, in order to guide the clinical management of tear film anomalies with respect to contact lens wear.
... preliminary research stage and only a small portion of them have been translated into clinical therapies. 17,18 In what follows, properties and applications of different nanomaterials being used for ocular drug delivery purposes are summarized. ...
... The lipid layer of the tear film has an important role to play in preventing tear evaporation [138]. Lipidcontaining eye drops are growing in both availability and popularity [139,140], primarily due to the increased attention being paid to MGD and lipid deficiency. A variety of oils, such as mineral oils and phospholipids, have been incorporated in ocular lubricant formulations to help restore the lipid layer of the tear film [46,141,142]. ...
Article
The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size.
... 33 These lipid-containing lubricants exhibit long retention times and can stabilise the tear film lipid layer, reduce tear evaporation, and improve the signs of MGD. 52 Additionally, lipid-containing lubricants have a longer-lasting effect and cause minimal interference of patient vision. Commercially available lipid-containing lubricants include mineral oil, highpurity castor oil, mixtures of light and standard mineral oil, and mixtures of polar phospholipid surfactant and mineral oil. ...
Article
Full-text available
Dry eye disease is one of the most common ophthalmic complaints; it results from the activity of various pathways and is considered a multifactorial disease. An important factor that contributes to the onset of dry eye disease is meibomian gland dysfunction. Meibomian gland dysfunction causes a disruption in the tear film lipid layer which affects the rate of tear evaporation. This evaporation leads to tear hyperosmolarity, eventually triggering the onset of dry eye disease. Dry eye disease and meibomian gland dysfunction are strongly associated with each other, such that many of their risk factors, signs, and symptoms overlap. This review aimed to provide an update on the association between dry eye disease and meibomian gland dysfunction. A stepwise approach for diagnosis and management is summarised.
... Reduced tear film stability and lipid layer thickness and higher tear evaporation rate have been observed during lens wear. 2 A systematic review of the effect of exogenous supplements in tear film concluded that the lipid-based emulsion drops and sprays showed beneficial effects on the tear lipid layer by increasing the layer thickness and slowing down the tear evaporation rate among a nonYcontact lens wearing dry eye population. 5 The effectiveness of anionic-based phospholipid emulsion drops have been studied by Korb et al. 6 They compared drops containing anionic (negatively charged, phosphatidylglycerol) and zwitterionic (neutral charge, phosphatidylcholine) phospholipids. The phosphatidylglycerol drop significantly improved lipid layer thickness, and in conjunction with a metastable oil emulsion, the drop retained the thickness up to 80% for 60 minutes whereas phosphatidylcholine drop did not change the thickness in this healthy population of nonYlens wearers. ...
Article
Purpose: To establish the effect of lipid supplements on the tear lipid layer and their influence on lens wear comfort in habitual lens wearers. Methods: Forty habitual soft contact lens wearers were recruited to a double-masked, randomized crossover trial. An emulsion drop containing phosphatidylglycerine (Systane Balance; Alcon) and a saline drop as a placebo or a liposomal spray containing phosphatidylcholine (Tears again; BioRevive) and a saline spray as a placebo were used three times a day for 2 weeks with 48 hours washout between each intervention. Ocular comfort, lipid layer grade, and stability of the tear film using a Tearscope and tear evaporation rate using a modified VapoMeter were assessed after 6 hours of lens wear with lenses in situ. Results: Neither of the lipid supplements improved lens wear comfort compared to baseline. The noninvasive surface drying time significantly reduced with the placebo spray at day 1 (p = 0.002) and day 14 (p = 0.01) whereas the lipid spray had no effect. With the lipid drop and placebo, noninvasive surface drying time was unchanged compared to baseline (p > 0.05) on day 1, but by day 14, noninvasive surface drying time was reduced with the lipid drop (p = 0.02) and placebo (p < 0.001). Symptomatic wearers showed shorter noninvasive surface drying time compared to asymptomatic wearers with the spray treatment on both days (p = 0.03) but not with the lipid drop (p = 0.64). The placebo drop significantly changed the lipid layer distribution (p = 0.03) with a higher percentage of thinner patterns compared to the baseline distribution at day 14. A weak but significant correlation was shown between ocular comfort and noninvasive surface drying time (r = -0.21, p = 0.003) and tear evaporation rate (r = 0.19, p = 0.008). Ocular comfort was not associated with lipid layer patterns (r = 0.13, p = 0.06). Conclusions: Ocular comfort during contact lens wear improved with increased tear film stability and a reduced tear evaporation rate. However, the lipid supplements did not improve ocular comfort from baseline.
... In dry eye, there is a significant decrease in the aqueous tear secretion from the lacrimal gland, while the evaporative form is mainly due to deficient or unstable tear film lipid layer, resulting in excessive evaporation of the aqueous tear layer (154). The lipid layer of tears is generated by the meibomian gland and helps control tear evaporative rate. ...
Article
Full-text available
Dry eye disease (DED) is a tear film disorder resulting in hyperosmolarity of the tear film and inflammation of the ocular surface. DED is also referred to as keratoconjunctivitis sicca (KCS) and dry eye syndrome. DED represents a significant public health issue, particularly in older adults, and needs more research and attention. Despite the urgent need for safe and effective pharmacotherapies, there is currently only one approved medication, Restasis®, to tackle DED. In this review article, we present an overview of DED, classification, epidemiology, pathophysiology, diagnosis, and risk factors of DED. Special emphasis is placed on current treatment options for DED such as artificial tears, lipid-containing lubricants, liposomal spray, inserts, anti-inflammatory or immunosuppressant drops, antibiotics, dietary omega-3 essential fatty acids, autologous serum, intense-pulsed-light (IPL), punctual plugs, moisture-retaining eyeglasses, hydrophilic bandage contact lenses and secretagogues. The review also summarizes trends in DED treatment that are patented and are currently under investigation in clinical trials.
... Liposomal lid sprays and eye drops containing lipids such as triglycerides, phospholipids, and castor oil are also available for patients with underlying MGD [87][88][89]. Randomized controlled trials with these emulsion drops have shown significant improve- ments in symptoms and signs of dry eye, as well as thickness and spread of the lipid layer [90][91][92]. Eye drops containing omega-3 fatty acids, which are known for their anti-inflammatory properties, are also currently being investigated in animal models [93]. ...
Article
Purpose of review: To provide a summary of the mechanisms that may cause dry eye after cataract surgery and discuss available and upcoming treatment modalities. Recent findings: Development or worsening of dry eye symptoms after cataract surgery is multifactorial with corneal nerve transection, inflammation, goblet cell loss, and meibomian gland dysfunction commonly cited as underlying disorders. With increasing awareness of the prevalence of dry eye disease, current surgical techniques are being analyzed for their contribution to the issue. Although many classic interventions, such as artificial tears and anti-inflammatory drops, remain first-line treatment options, they may not adequately address abnormalities of the tear film. The trend has been to create new drugs and technologies that target meibomian gland deficiencies and restore goblet cell numbers. Summary: Therapy for postoperative dry eye symptoms should be determined based on symptom severity and which underlying cause is most prominent at a given time. Patients with high-level risk factors for dry eye should be evaluated preoperatively to determine whether they have preexisting dry eye disease or if they are susceptible to developing disease after surgery.
... Artificial tears are the first-line treatment for dry eye (7). Many commonly used formulations, such as saline, temporarily supplement the aqueous component of the tear film but must be used frequently to relieve the signs and symptoms of dry eye (8) and may not increase TFBUT (9). Lubricant eyedrops formulated with lipids or viscosityincreasing agents are thought to provide longer-lasting effects by increasing residence time on the ocular surface (10,11) and by restoring multiple components of the tear film to improve tear film stability (11). ...
Article
To demonstrate the superior efficacy of a propylene glycol-based, micro-emulsion eye drop (SYSB; Systane® Balance) over Preservative-Free 0.9% Saline (PFS) Solution in patients with lipid-deficient dry eye.
... Zinc oxide [236] Magnesium oxide [237] Titanium dioxide [238] Octyl or ethylhexyl methoxycinnamate (OMC) with SLN and PLGA [118,239] Skin care, wounds, antioxidants Vitamin E with polymer [172] Antioxidants/anti-aging Coenzyme Q10 with liposome [117] Intended therapeutic effect Type of nanoparticle Reference Ocular Glaucoma Nano-emulsion [240] Liposomes [241] SLN [242] Polymeric nanoparticles [243] Dendrimers [243] Ocular inflammation Liposomes [244] SLN [244] Polymeric nanoparticles [245] Chronic dry eye Nano-emulsion [244] Liposomes [246] SLN [247] Eye cancer Polymeric nanoparticles [248] Intraocular infections SLN [249] (continued on next page) response to varied glucose concentrations has been demonstrated in vitro [22]. Alginate is an anionic polysaccharide derived from algae. ...
Article
This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has - and will continue to have - a profound impact on both clinical outcomes and the development of new products.
... Given the MGD overlay, a lipidcontaining lubricant would be justified. 43 Although there are no gold standard guidelines for review periods in managing DED, we consider that clinical reevaluation within 4 to 6 weeks would be reasonable for this patient. The chronic nature of the condition, and the importance of maintaining therapy, which is noncurative, should be emphasized. ...
Article
: Dry eye disease (DED) is a highly prevalent chronic ocular disorder that can lead to significant discomfort and visual disturbance. It is a potentially debilitating condition that can have significant negative impact on quality of life. A diverse range of management options exists for DED, including tear supplement products, anti-inflammatory agents, immunomodulators, punctal occlusive devices, and environmental modifiers. Although the availability of a variety of treatment approaches provides clinical flexibility and can enable individualized care, it can also complicate clinical management decisions and lead to variability in the nature of the clinical care provided to patients. By considering two dry eye case scenarios, this review evaluates the currently available evidence relating to DED therapy to describe a pragmatic clinical approach to best-practice management of dry eye patients.
... Use of essential fatty acid supplements for dry eye treatment has been reported117,118 to be potentially beneficial.119,120 An important obstacle in conducting high-quality trials of these supplements is the lack of standardization in the various formulations in a largely unregulated industry. ...
... This finding was not consistent with several studies on the association between blink rate and dry eye symptoms. 21 In dry eye, low contrast sensitivity will result from a central superficial punctate keratitis (SPK). 22 This implies that severe states of dry eye will cause a reduction in contrast sensitivity. ...
Article
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Purpose To evaluate the association between subjective dry eye symptoms and the results of the clinical examinations. Methods The study was a clinical-based survey involving 215 first-year students selected consecutively during a regular ocular health examination at the University of Cape Coast Optometry Clinic. The data collection process spanned for a period of four months. Out of the 215 students, 212 returned their completed questionnaires and were subsequently included in the study. Dry eye tests including meibomian gland assessment, tear break up time, fluorescein staining, Schirmer test, and blink rate assessment, were performed on each subject after completion of the Ocular Surface Disease Index (OSDI) questionnaire. Shapiro–Wilk test was used to determine the normality of the clinical tests, and Spearman's correlations co-efficient was used to determine the correlations between the clinical test results and dry eye symptoms. Results Statistically significant associations were found between OSDI scores and blink rate (rs = 0.140; P < 0.042), and associations between OSDI scores and contrast sensitivity scores (rs = 0.263; P < 0001). However, the results of corneal staining (rs = −0.006; P < 0.926), Schirmer test (rs = −0.033; P = 0.628), tear break up time (rs = −0.121; P < 0.078), meibomian gland expressibility (rs = 0.093; P < 0.180), and meibomian gland quality (rs = 0.080; P < 0.244) showed no significant association with OSDI. The correlation coefficients range from −0.006 to 0.263 showed low to moderate correlation between dry eye symptoms and the results of clinical test. Conclusion Associations between dry eye symptoms and clinical examinations are low and inconsistent, which may have implications for the diagnoses and treatment of dry eye disease.
... Depending on viscosity of the lubricant (macromolecular complexes that increase the residence time of the supplement in the tear film) and thickness of supplement they may cause blurred vision; gels are more viscous than solutions, ophthalmic ointments are the thickest of lubrications. Typically, ointments are used before bedtime to provide DED symptoms, enabling sleep [28,32,54,56,57]. ...
Chapter
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Abstract Sjögren’s syndrome (SS) is an autoimmune disease of exocrine glands, which is characterized by dry mouth and dry eye, though ocular disturbances, such as dry eye disease, may be the first sign of the problem. In pathogenesis of SS, activated T-cells and B-cells infiltrate the lacrimal glands and autoimmune process leading to cell destruction. This process causes hyposecretion of tears and aqueous-deficient dry eye disease. Evaporative dry eye disease is connected with Meibomian gland dysfunction (MGD) and/or goblet cell loss. There are many questionnaires and tests to dry eye disease diagnosing, but there is no “gold standard.” Correlation of data from symptom questionnaires and results of ocular staining score, Schirmer test I (without anesthesia), and break-up-time make it easier to diagnose. The treatment of SS includes both local (tear drops and moistures) and systemic (nonsteroidal anti-inflammatory drugs—NSAIDs, glucocorticoids, and disease-modifying antirheumatic drugs—biologics) therapies, but it is individual. We would like to present recent data on the ocular involvement and perspective of dry eye disease diagnosis and treatment in patients with SS.
... Both the observer and the subject were masked from the previous results throughout the study. As both sprays are CE marked, have been commercially available for many years and have been evaluated in different independent studies, 8,10,[13][14][15][16][17]22 the safety of the spray was not part of the study design. ...
Article
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Objectives: To evaluate the effect of eye spray phospholipid concentration on symptoms and tear film stability. Methods: High-concentration (Tears Again, Optima Pharma GmbH, Hallbergmoos, Germany) and low-concentration (Ocuvers, Innomedis AG, Germany) phospholipid eye sprays were sprayed onto the closed eyelids of 30 subjects (33.2±1.8 years; 20 women) in a multicentered, prospective, crossover study. Ocular comfort (visual analog scale) and noninvasive tear film stability (NIBUT) of each eye were evaluated before application (along with the Ocular Surface Disease Index), 10 min after application, and 30 min after application. Results: Comfort (high concentration: 68.5±16.4 vs. low concentration: 70.7±14.5 phospholipid) and NIBUT (high concentration: 11.5±4.6 sec vs. low concentration: 11.2±6.0 sec phospholipid) were not different (P>0.3) between sprays before application, but comfort (by 12 points, P=0.001) and NIBUT (by 5 sec, P=0.016) were significantly better with a high-concentration phospholipid spray at both 10 min and 30 min time points than those with the low-concentration phospholipid spray. Conclusions: The liposomal eye spray with higher concentration of phospholipids significantly improved ocular comfort and tear film stability in contrast to the eye spray with lower concentration of phospholipids, hence practitioners need to choose an appropriate eye spray to maximize the patient benefit.
... Lid scrubs with dilute detergents decrease the seborrheic or bacterial load, thereby breaking the proinflammatory cycle of MGD. 6 Lipid-containing eyelid sprays have been shown to relieve the symptoms of DED. 7 Systemic and topical antibiotics are used in the treatment of MGD to reduce the bacterial load on the ocular surface. Systemic doxycycline 100mg B.D. for two weeks have been shown to decrease local inflammation and improve meibomian gland function after several weeks. ...
... A variety of oils, such as mineral oils and phospholipids, have been incorporated in formulations to help restore the lipid layer of the tear film by mimicking natural meibum. [66][67][68][69] Other agents have been shown to reduce symptoms of DED such as mucolytics (N-acetylcysteine). [70][71][72] Treatments for Tear Conservation ...
Article
Full-text available
The purpose of this article is to provide a framework for general ophthalmologists in Singapore to manage dry eye. This framework considers the evidence in the literature as well as recommendations from expert panels such as the Tear Film & Ocular Surface Society Dry Eye Workshop II and the Asia Cornea Society Workgroup.This article covers the assessment of patient medical history and ask triage questions to identify local and systemic causes of dry eye disease (DED), excluding other possible causes, as well as the risk factors for DED and ocular surface inflammation. Evaluation of clinical signs to establish the diagnosis of DED and differentiation from other causes of irritable, red eyes are described. Tests for understanding the underlying disease processes and severity of DED are also presented.Management of dry eye should involve patient education and engagement. Information about the natural history and chronic nature of DED should be provided to improve long-term management of the disease and enhance compliance. Aggravating factors should be removed or lessened.We provide a guide to determine the most appropriate treatment (or combination of treatments) based on the severity and cause(s) of the disease, as well as the patient's needs and preferences. The aim of the management is to relieve ocular discomfort and prevent worsening of symptoms and signs, as well as to optimize visual function and minimize structural ocular damage. We also discuss the systematic follow-up and assessment of treatment response, as well as monitoring side effects of treatment, bearing in mind continuous support and reassurance to patients.
... The study also included gamma-linolenic acid (GLA) -a derivative of LA and an ω-6 FA, and oleic acid (OA) -an ω-9 FA, for comparing effects due to varying degree of unsaturation in FAs (Fig. 1). Another reason for including OA was that eye drops for treating dry eye often contain oils that have OA which can act as a lubricant and emollient [22,23] drug carrier [24], or corneal permeability enhancer [25]. Being lipid in nature, topically added OA might interact with the TFLL and alter its stability. ...
Article
Purpose: Essential fatty acids (EFAs) as dietary supplements are used in treating dry-eye for reducing inflammation at the ocular surface. Their topical application in eye drops to deliver fatty acid (FA) directly to the ocular surface requires thorough investigation. Being lipids in nature EFAs can interact with tear lipids and affect tear stability. This study aimed at investigating the biophysical interactions of EFAs with Meibomian lipids. Methods: Rheology of mixtures of Human Meibomian lipids with EFAs (LA-linoleic acid; ALA-alpha-linolenic acid), OA (oleic acid), and GLA (gamma-linolenic acid) was studied using Langmuir trough technology on an artificial tear solution at the ocular surface temperature. Pressure-area profiles were used to determine compressibility and elasticity of the mixed films. Results: LA enhanced spreading of Meibomian lipids and increased their compressibility and elasticity which can be beneficial for tear stability. ALA condensed Meibomian lipids film with less elasticity deemed unfavourable for tear stability. OA expanded Meibomian lipids but decreased elasticity at high compressions making films less stable. GLA had little or no favourable effect on tear stability. Higher concentrations of FAs made films less stable. Conclusions: EFAs or OA in topical ophthalmic preparations can affect spread and stability of the tear film lipid layer. Rheology of mixed films should be tested using Langmuir trough technology to determine suitable type and amount of a lipid additive for therapeutic eye drops. In topical applications, the omega-6 LA (not omega-3 FA) at low concentrations (20 mol%) can be beneficial for enhancing tear stability in dry eye patients.
... All rights reserved. petrolatum ointment at night if nocturnal lagophthalmos exists (27)(28)(29)(30)(31). Lipidcontaining eye drops are effective in improving symptoms and signs of dry eye and particularly recommended in the presence of meibomian gland dysfunction (27,32). ...
Article
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Ichthyosis is the term used to describe continual and widespread scaling of the skin. There are several genetic types which are present from birth and persist life‐long – the “congenital ichthyoses”. There is no agreed treatment ‐ different doctors use different approaches, so this group of experts from all over Europe worked together to develop guidelines. They reviewed the medical literature and met to discuss the evidence and to make recommendations. A separate paper (Part 1) covered treatments for the skin condition itself. This paper, Part 2, provides guidelines for managing complications of the congenital ichthyoses. Itch, pain and infections are common, particularly fungal infection, and cancers sometimes occur. Tight skin often prevents eyelids from shutting properly so the eye surface must be protected with lubricant; eyelid massage may help and retinoid medicine may soften tight skin but can dry the eyes further. Surgical options include injecting filler or grafting extra skin to the eyelid: if the patient's own ichthyotic skin is used the problem eventually recurs and mucous membrane from inside the mouth is a promising alternative. Hearing is commonly affected: blockage of ears by a build‐up of skin may be prevented by regular oil drops but syringing or suction may be necessary. In children, growth may be affected and vitamin D supplements are usually recommended. There are special considerations for newborn babies and those with complex ichthyotic disorders such as Netherton Syndrome, epidermolytic ichthyosis and Ichthyosis Prematurity Syndrome. These treatment guidelines should help to improve outcomes and quality of life for patients with congenital ichthyoses. Linked Article: Mazereeuw‐Hautier et al. Br J Dermatol 2019; 180:484–495
... [111][112][113][114] For patients with MGD, lipid-containing supplements can be considered. 115 Step 2 ...
Article
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Dry eye disease (DED) has a higher prevalence than many important systemic disorders like cardiovascular disease and diabetes mellitus, representing a significant quality of life burden for the affected patients. It is a common reason for consultation in general eye clinics worldwide. Nowadays, the diagnostic and therapeutic approach at the high corneal and ocular surface specialty level should be reserved for cases of severe and chronic dry eye disease associated with systemic autoimmune diseases or complicated corneal and ocular surface pathologies. In such cases, the diagnostic and therapeutic approach is often complex, elaborate, time-consuming, and costly due to the use of extensive dry eye questionnaires, noninvasive electronic diagnostic equipment, and clinical laboratory and ancillary tests. However, other eye care specialists attend a fair amount of DED cases; therefore, its diagnosis, classification, and management should be simple, practical, achievable, and effective. Considering that many patients attending non-specialized dry eye clinics would benefit from better ophthalmological attention, we decided to elaborate a practical DED classification system based on disease severity to help clinicians discriminate cases needing referral to subspecialty clinics from those they could attend. Additionally, we propose a systematic management approach and general management considerations to improve patients' therapeutic outcomes according to disease severity.
... All these lubricants have been shown to improve the symptoms and signs of MGD under certain conditions. A summary of the studies conducted with these lubricants is included in a review by Lee and Tong [27] . A more recent review by Garrigue et al [19] examines the currently marketed artificial tears. ...
Article
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Aim: To study the effect of uncrosslinked and crosslinked hyaluronic acid combined with other artificial tear components in patients with dry eye caused by moderate meibomian gland dysfunction. Methods: Prospective, single-blind, contralateral eye study. Fifty eyes (25 patients) were analyzed. Eye selection for each tear type was random, and the eye drop formulations, 0.4% uncrosslinked hyaluronic acid and 0.2% galactoxyloglucan (tear A) and 0.15% crosslinked hyaluronic acid, crocin, and liposomes (tear B) were used. The determined dosing schedule was three times a day for six weeks, and the study participants underwent a clinical examination before and 45d after lubricant treatment. The Schirmer test, tear breakup time (TBUT) test, and Ocular Surface Disease Index (OSDI) questionnaire were applied before and after instillation period with both types of artificial tears. Results: On the Schirmer test, a significant improvement was obtained with both tear A (P<0.01) and tear B (P<0.01). On the TBUT test, a significant improvement was obtained with tear A (P<0.01) and tear B (P<0.01). The OSDI score significantly decreased after instillation period with both artificial tear types (P<0.01). Conclusion: Uncrosslinked hyaluronic acid combined with other components, such as tamarind seed polysaccharide, and crosslinked hyaluronic acid combined with liposomes and crocin are effective for management symptoms of dry eye disease.
... The intensity of staining and the dye distribution pattern are evaluated semi-quantitatively for all dyes. Dry eye is indicated by staining around the palpebral fissure [25]. ...
... Newer osmoprotectants, such as Trehalose, can protect the ocular surface from desiccation, apoptosis, and oxidative stress and maintain corneal epithelial homeostasis, which could be invaluable if initiated in the early stages of DED [53]. Lipid-based preparations or emulsions have been gaining popularity and are reported to be useful, especially in MGD and lipid layer deficiency, as they address the root cause of poor lipid layer quality [54]. Other newer drugs, such as topical secretagogues, are also being explored in the treatment of DED. ...
Article
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Dry eye disease (DED) is an emerging health concern causing significant visual, psychological, social, and economic impact globally. In contrast to visual rehabilitation undertaken at late stages of DED, measures instituted to prevent its onset, establishment, or progression can alter its natural course and effectively bring down the associated morbidity. This review attempts to present the available literature on preventive strategies of DED at one place, including strategies for risk assessment and mitigation, targeting a wide range of population. A literature search was conducted using PubMed and an extensive literature review on preventive strategies for DED was compiled to put forth a holistic and strategic approach for preventing DED. This can be undertaken at various stages or severity of DED directed at different tiers of the health care system. Conclusion: This review intends to put emphasis on preventive strategies being adopted as an integral part of routine clinical practice by general ophthalmologists and specialists to tackle the burden of DED and improve the quality of the lives of the patients suffering from it.
... It has been demonstrated that OA have possible therapeutic benefits in enhancing both hydrophilic and lipophilic compound ocular drug delivery [12]. Moreover, several studies have indicated that lipid-based lubricants can help relieve some symptoms of dry eye [13]. Thus, we believe, due to its inflammatory actions, enhancing drug delivery and improving dry eye effects, OA addition to topical ophthalmic preparations is worth to be extensively studied in certain eye disorders. ...
Article
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Background Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though not fully compensating all body requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters. The main body of the abstract This review capitalizes on the major omega-9 pharmacological activities in context of inflammation management for its different natural forms in different dietary sources. The observed anti-inflammatory effects reported for oleic acid (OA), mead acid, and erucic acid were directed to attenuate inflammation in several physiological and pathological conditions such as wound healing and eye inflammation by altering the production of inflammatory mediators, modulating neutrophils infiltration, and altering VEGF effector pathway. OA action mechanisms as anti-tumor agent in different cancer types are compiled for the first time based on its anti- and pro-carcinogenic actions. Conclusion We conclude that several pathways are likely to explain the anti-proliferative activity of OA including suppression of migration and proliferation of breast cancer cells, as well stimulation of tumor suppressor genes. Such action mechanisms warrant for further supportive clinical and epidemiological studies to confirm the beneficial outcomes of omega-9 consumption especially over long-term intervention.
Chapter
The treatment of meibomian gland dysfunction (MGD) first requires both proper diagnosis of the condition and identification of contributory ocular surfaces disorders that may confuse proper attribution of both patient symptoms and signs. Nomenclature remains confusing as many clinicians alternate between diagnosing patients with dry eye, evaporative dry eye, MGD, ocular rosacea, or, more generically, ocular surface disease. While all of these terms are valid descriptors of ocular surface disease, this chapter will focus on treatment of MGD, to be understood as the evaporative dry eye caused by the tear film dysfunction created by stagnant and/or dysfunctional meibum as well as ocular surface inflammation, whether present within occluded glands in the eyelid, conjunctival and corneal epithelium, and the tear film itself.
Article
Dry eye disease (DED) is a common disorder that remains challenging from a clinical perspective. Unstable or deficient tear film is a major factor contributing to DED and the inability to resolve the loss of tear film homeostasis that accompanies DED can result in a vicious circle of inflammation and treatment-refractory disease. Recently recognized as a multifactorial disease, the main etiological subtypes of DED are aqueous-deficient and evaporative which exist on a continuum, although evaporative dry eye (EDE) is the more frequent classification. Although attaining greater recognition in recent years, there is currently no consensus and no clear recommendation on how to manage EDE. Clarity on the early diagnosis and treatment of EDE may facilitate the avoidance of progression to chronic inflammation, permanent damage to the ocular surface, and treatment-refractory disease. The purpose of this review was to identify current best practice for management of EDE in order to help clinicians in providing accurate diagnosis and optimized treatment. We summarize recent literature considering the role of the lipid layer on tear film stability, the importance of its composition and of its dynamic behavior, and the link between its malfunction and the insurgence and maintenance of tear film-related diseases. We have provided an assessment of the best management of lipid-deficient EDE based upon an understanding of disease pathophysiology, while indicating the flow of current treatments and possible future evolution of treatment approaches. Lipid containing eye drops may be considered as a step closer to natural tears from artificial aqueous tears because they more closely mimic the aqueous and lipid layers and may be used in combination with other management approaches. As a next step, we recommend working with a wider expert group to develop full guidelines to enable patient-centered management of EDE. Key pointsDry eye is a multifactorial disease of variable presentation with the tendency to become a chronic disease for which it is essential to identify and treat the main pathogenic mechanisms involved and tailor the treatment to the individual patient.Early intervention is needed to prevent the vicious cycle of DED and may require a multi-faceted management approach.EDE is not just a problem of MGD but can be the result of anything affecting blinking, mucin spreading, aqueous layer volume and content.Lipid-containing eye drops may provide significant relief of symptoms by improving the lipid layer and its spreading ability and, as such, are an appropriate component of the overall management of lipid-deficient EDE; natural lipid-containing eye drops should be the preferred treatment.
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Wax esters are unique surface lipids found on the surface of terrestrial organisms. After a brief review of the composition, the mechanisms used in their biosynthesis by sebaceous glands are summarized. The molecular biology of biosynthesis of methyl-branched, short chain and very long chain acids, and the biochemical mechanism of the loss of the carboxyl carbon of the elongated very long chain acids to generate alkanes are reviewed. The molecular biology of biosynthesis of the major types of molecules contains the hydroxyl group(s) to which the acids are esterified and the molecular biology of the esterification process are reviewed. The molecular bases of seasonal and hormonal regulation of biosynthesis of wax esters that implicate some functions of the wax esters are reviewed.
Article
: Dry eye disease and other ocular surface diseases are complex multifactorial disorders often characterized by ocular surface inflammatory changes, instability of the tear film, and functional vision impairment. Recent research has led to new concepts regarding diagnosis and management, and therapeutic interventions now include ocular lubricants, secretagogues, topical and systemic anti-inflammatory and immunosuppressive agents, tear preservation, and, for advanced cases, a variety of surgical approaches. This review considers contemporary procedures for treatment of advanced ocular surface diseases, including thermal and electrocautery of the lacrimal puncta, lid surgeries such as tarsorrhaphy, and multiple procedures to protect the exposed or compromised ocular surface.
Article
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Background: Dry eye disease (DED) is common; its prevalence around the world varies from 5% to 34%. Its putative pathogenetic mechanisms include hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal gland. Dry eye is clinically subdivided into two subtypes: one with decreased tear secretion (aqueous-deficient DED), and one with increased tear evaporation (hyperevaporative DED). Methods: This review is based on pertinent publications retrieved by a selective PubMed search and on the authors' own clinical and scientific experience. Results: The diagnostic evaluation of dry eye disease should include a detailed patient history, thorough split-lamp examination, and additional tests as indicated. Few randomized controlled therapeutic trials for dry eye have been published to date. Artificial tears of various kinds are recommended if the symptoms are mild. Lid hygiene is helpful in the treatment of hyperevaporative dry eye, while collagen or silicon plugs can be used for partial occlusion of the efferent lacrimal ducts to treat severe hyposecretory dry eye. The benefit of long-term topical anti-inflammatory treatment of moderate or severe dry eye disease with corticosteroids or cyclosporine A eye drops has been documented in clinical trials on a high evidence level. Orally administered tetraycycline derivatives and omega-3 or omega-6 fatty acids are also used. Conclusion: The treatment of dry eye has evolved from tear substitution alone to a rationally based therapeutic algorithm. Current research focuses on pathophysiology, new diagnostic techniques, and novel therapies including secretagogues, topical androgens, and new anti- inflammatory drugs.
Article
The ocular prescription application of nanometer materials are mainly concentrated in controlled release systems. Due to the unique properties of nanometer materials such as higher bioavailability and less side effects, it has great advantages in carrying ocular drugs of eye diseases compared with the traditional dosing method. As a result, nano-controlled release system has good application prospect in eye diseases. At present, a variety of different types of nano-controlled release systems have been used to enhance the efficiency of the ocular drugs including nanomicelles, nanoparticles, nanosuspensions, liposomes and dendrimers. In this article, the research progress and the application of nano-controlled release system in ophthalmic drug delivery are reviewed.
Article
The direct measurement of forces between atomically smooth mica surfaces down to sub-nanometer separation was pioneered over 50 years ago and has yielded deep understanding of a range of interfacial effects, not least the forces that determine colloidal stability and self-assembly, the properties of highly confined fluids, and the molecular origin of friction and lubrication. Here, we describe recent advances, including the use of substrates other than mica, probing the shear properties of highly confined fluids including hydration layers, and the modulation of surface forces by surface-attached macromolecules and amphiphiles, together with microscopic imaging of the surface morphology. These advances enabled novel features such as external potential control of the interacting surfaces, new understanding of lubrication in aqueous and biological systems, the design of novel nanoparticles and surface assemblies for modulating frictional dissipation, and insight into the nature of long-ranged attraction between surfactant-hydrophobized surfaces. We conclude by briefly outlining future challenges and opportunities provided by such direct surface forces studies.
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The ophthalmic application of nanometer materials are mainly concentrated on controlled releasing systems. Due to the unique properties of nanometer materials, it has great advantages in carrying ophthalmic drugs compared with the conventional method, mainly in higher bioavailability and fewer side effects. As a result, nano-controlled releasing system has good application prospect in ophthalmology. At present, a variety of different types of nano-controlled releasing systems have been used to enhance the efficiency of the ophthalmic drugs, including nanomicelle, nanoparticles, nanosuspensions, liposomes, dendrimers, etc. In this paper, the research progress as well as the application of nano-controlled releasing system on ophthalmologic administration is reviewed.
Article
Purpose: To evaluate and compare the efficacy of a lipid-based lubricant eyedrop formulation (hydroxypropyl guar/propylene glycol/phospholipid [HPG/PG/PL]) with preservative-free saline for the treatment of dry eye. Methods: This was a prospective, multicenter, randomized, single-masked, parallel-group phase 4 clinical study. Patients ≥18 years diagnosed with dry eye received 1 drop of saline 4 times daily (QID) for 15 days during a run-in phase, followed by randomization. Patients then instilled HPG/PG/PL or saline QID through day 35 and as needed through day 90. Change in tear film break-up time (TFBUT), change in total ocular surface staining (TOSS) score, and Impact of Dry Eye on Everyday Life (IDEEL) were evaluated on day 35. Results: Increase in TFBUT from baseline to day 35 was assessed during the interim and final analyses. Mean ± SE difference between the HPG/PG/PL (n = 110) and saline groups (n = 100) was 1.3 ± 0.4 seconds (interim analysis; 95% confidence interval [CI] 0.5-2.1 seconds; p = 0.0012) and 1.0 ± 0.3 seconds (final analysis; 95% CI 0.4-1.6 seconds; p = 0.0011), demonstrating the superiority of HPG/PG/PL. The mean ± SE difference between the HPG/PG/PL and saline groups for IDEEL treatment effectiveness scores was 16.0 ± 3.6 (95% CI 8.9-23.1; p<0.0001). No significant differences in TOSS scores or IDEEL inconvenience scores were observed between treatment groups. Conclusions: Thirty-five days of QID HPG/PG/PL treatment resulted in a statistically significant improvement in TFBUT and IDEEL treatment effectiveness scores compared with saline but not in TOSS or IDEEL treatment inconvenience scores. HPG/PG/PL was well-tolerated by patients.
Article
Hydroxypropyl-guar (HPG) is a thickening agent first added to lubricating eye drops in 2003. This agent, which enhances viscosity, has been used in the SYSTANE® family of lubricant eye drops (Alcon Laboratories, Inc., Fort Worth, TX, USA). HPG forms a partially linked gel with borate to prolong the retention of demulcents, such as polyethylene glycol and propylene glycol, on the eye. This helps to protect the ocular surface, thereby reducing the symptoms of dry eye disease (DED). The definition of DED has evolved with advances in research, leading to changes in HPG-containing eye care solutions. This article reviews current knowledge on the use of HPG-containing lubricating eye drops in the management of DED.
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Healthy articular cartilage, covering the ends of bones in major joints such as hips and knees, presents the most efficiently‐lubricated surface known in nature, with friction coefficients as low as 0.001 up to physiologically high pressures. Such low friction is indeed essential for its well‐being. It minimizes wear‐and‐tear and hence the cartilage degradation associated with osteoarthritis, the most common joint disease, and, by reducing shear stress on the mechanotransductive, cartilage‐embedded chondrocytes (the only cell type in the cartilage), it regulates their function to maintain homeostasis. Understanding the origins of such low friction of the articular cartilage, therefore, is of major importance in order to alleviate disease symptoms, and slow or even reverse its breakdown. This progress report considers the relation between frictional behavior and the cellular mechanical environment in the cartilage, then reviews the mechanism of lubrication in the joints, in particular focusing on boundary lubrication. Following recent advances based on hydration lubrication, a proposed synergy between different molecular components of the synovial joints, acting together in enabling the low friction, has been proposed. Additionally, recent development of natural and bio‐inspired lubricants is reviewed. Understanding the origins of the outstanding lubricity of healthy articular cartilage is crucial both to potentially treat osteoarthritis symptoms, and for the design of better biomaterials. This progress report reviews the mechanism of lubrication in the joints, in particular focusing on boundary lubrication, and explores the recent development of natural and of bio‐inspired lubricants.
Article
Objective: To determine whether the combination of meibomian gland expression (MGX) with intense pulsed light (IPL) has a better efficacy to treat meibomian gland dysfunction (MGD) than IPL alone. Methods: One hundred patients with MGD were randomly divided into three groups: MGX, IPL, and IPL+ MGX. Clinical parameters included the Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), noninvasive keratograph tear breakup time (NIBUT),redness, meibomian gland dropout, tear breakup time (TBUT), corneal fluorescent staining (CFS), eyelid margin score, meibomian gland secretion function, and Schirmer I tests were collected before treatment and at 1 and 3 months after treatment. Compare the indexes of each group before and after treatment and also compare the differences of each group on follow-up. Results: Compared to the baseline, OSDI, TBUT and meibomian gland secretion function in IPL group improved throughout the follow-up period (all P<0.05) and part of the meibomian gland secretion function increased continuously. OSDI, TBUT, lower eyelid margin scores and meibomian gland secretion function in IPL + MGX group improved at the both follow-up visits (all P<0.05),and continued improvement in meibomian gland secretion function can be observed. Lower meibomian gland dropout and CFS reduced at 1 month and 3 months respectively in IPL ± MGX group (P=0.001,P=0.001).Compared to IPL group, only CFS has reduction in IPL + MGX group at 1-month (P<0.001), CFS, upper and lower MGYCS were improved at the 3 months (P=0.037,P=0.014, P=0.049). Conclusions: MGX may have synergistic effect when combined with IPL therapy, and the effect can last at least 3 months.
Article
The multifactorial pathogenesis and interrelationship of blepharitis, meibomian gland dysfunction and dry eye disease poses challenges to any therapeutic approach. Current treatments are mostly palliative, with success limited by perceived inefficacy and poor patient compliance. Castor oil, a natural derivative of the Ricinus communis plant, is widely used as an emollient in cosmetics and personal care products, drug delivery systems and wound dressings. Castor oil is deemed safe and tolerable, with strong anti-microbial, anti-inflammatory, anti-nociceptive, analgesic, antioxidant, wound healing and vaso-constrictive properties. Its main constituent, ricinoleic acid, has a bipolar molecular structure that promotes the formation of esters, amides and polymers. These can supplement deficient physiological tear film lipids, enabling enhanced lipid spreading characteristics and reducing aqueous tear evaporation. Studies reveal that castor oil applied topically to the ocular surface has a prolonged residence time, facilitating increased tear film lipid layer thickness, stability, improved ocular surface staining and symptoms. This review summarises the properties, current uses of, and therapeutic potential of castor oil in managing ocular surface disease. The biochemical, medicinal actions of castor oil are explored from the perspective of ocular surface pathology, and include microbial and demodectic over-colonisation, inflammatory and oxidative processes, as well as clinical signs and symptoms of dryness and discomfort.
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Background There was no citation analysis about systematic review/meta-analysis published on dry eye disease (DED). The objective of this study was to identify the citations of systematic review/meta-analysis published on DED and to provide information on the achievement and development of evidence-based dry eye research. Methods Web of Knowledge Core Collection was searched for all systematic review/meta-analysis relevant to DED. The number of citations, authorship, year, journal, country, and institution were analyzed for each study. Results A total of 29 systematic reviews/meta-analyses on DED published between 2009 and 2017 were included. The number of citations ranged from 0 to 63, with a medium of 8 citations. These systematic reviews/meta-analyses were from 10 countries, and 15 of them were from China. They were published in 21 journals. Ocular Surface published most studies (n =4), followed by International Journal of Ophthalmology (n =3). The journal with highest impact factor was Nutrition Reviews (IF=5.291 in 2016). Conclusion The citations of systematic reviews/meta-analyses on DED are still low. Further systematic reviews/meta-analyses are needed for providing more evidence for DED.
Article
Purpose: To evaluate the impact of Optive (Allergan, Irvine, CA) and Optive Advanced (Allergan, Irvine, CA) on tear film stability and quality during a one-hour observation period when compared to saline (Pfizer, Perth, WA). Methods: This was a double-masked, cross-over study. Twenty participants attended three visits, randomly receiving either Optive, Optive Advanced or saline. Oculus Keratograph 5M (Oculus, Arlington, WA, USA), non-invasive keratograph break-up time (NIKBUT), Lipiview (TearScience Inc, Morrisville, NC, USA), lipid layer thickness (LLT) and comfort were measured prior to and 5, 15 and 60 min after drop instillation. Results: Optive Advanced demonstrated a significant increase in LLT between baseline (57.5 ± 12.3 nm) and both 5 min (67.5 ± 18.8 nm, p = 0.04) and 15 min (68.9 ± 17.3 nm, p = 0.04) but not 60 min (61.6 ± 14.3 nm, p = 0.47). Optive and saline were not different between timepoints for LLT (p > 0.05). There was no difference between timepoints for any of the drops for NIKBUT (p = 0.75). Comfort was significantly better at 5 min compared to baseline for Optive (8.3 ± 1.2 and 7.3 ± 1.4, respectively, p = 0.03) but not different for Optive Advance or saline (p > 0.05). Conclusions: Optive Advanced increased LLT for 15 min following instillation, returning to baseline within one hour. This did not however, translate into an improvement in tear film stability over this time period. Only Optive demonstrated an improvement in comfort.
Article
Importance Patient care should be informed by clinical practice guidelines, which in turn should be informed by evidence from reliable systematic reviews. The American Academy of Ophthalmology is updating its Preferred Practice Patterns (PPPs) for the management of the following 6 corneal diseases: bacterial keratitis, blepharitis, conjunctivitis, corneal ectasia, corneal edema and opacification, and dry eye syndrome. Objective To summarize the reliability of the existing systematic reviews addressing interventions for corneal diseases. Data Source The Cochrane Eyes and Vision US Satellite database. Study Selection In this study of published systematic reviews from 1997 to 2017 (median, 2014), the Cochrane Eyes and Vision US Satellite database was searched for systematic reviews evaluating interventions for the management of any corneal disease, combining eyes and vision keywords and controlled vocabulary terms with a validated search filter. Data Extraction and Synthesis The study classified systematic reviews as reliable when each of the following 5 criteria were met: the systematic review specified eligibility criteria for inclusion of studies, conducted a comprehensive literature search for studies, assessed risk of bias of the individual included studies, used appropriate methods for quantitative syntheses (meta-analysis) (only assessed if meta-analysis was performed), and had conclusions that were supported by the results of the systematic review. They were classified as unreliable if at least 1 criterion was not met. Main Outcomes and Measures The proportion of systematic reviews that were reliable and the reasons for unreliability. Results This study identified 98 systematic reviews that addressed interventions for 15 corneal diseases. Thirty-three of 98 systematic reviews (34%) were classified as unreliable. The most frequent reasons for unreliability were that the systematic review did not conduct a comprehensive literature search for studies (22 of 33 [67%]), did not assess risk of bias of the individual included studies (13 of 33 [39%]), and did not use appropriate methods for quantitative syntheses (meta-analysis) (12 of 17 systematic reviews that conducted a quantitative synthesis [71%]). Sixty-five of 98 systematic reviews (66%) were classified as reliable. Forty-two of the 65 reliable systematic reviews (65%) addressed corneal diseases relevant to the 2018 American Academy of Ophthalmology PPPs; 33 of these 42 systematic reviews (79%) are cited in the 2018 PPPs. Conclusions and Relevance One in 3 systematic reviews addressing interventions for corneal diseases are unreliable and thus were not used to inform PPP recommendations. Careful adherence by systematic reviewers and journal editors to well-established best practices regarding systematic review conduct and reporting might help make future systematic reviews in eyes and vision more reliable.
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La enfermedad del ojo seco (EOS) tiene una prevalencia mayor que muchas otras enfermedades sistémicas importantes, como las enfermedades cardiovasculares y la diabetes mellitus, y supone un importante menoscabo en la calidad de vida de los pacientes afectados. Es un motivo de consulta habitual en clínicas oftalmológicas en todo el mundo. Hoy en día, el diagnóstico y el enfoque terapéutico de los especialistas en córnea y superficie ocular deben reservarse para casos de ojo seco graves y crónicos asociados con enfermedades sistémicas autoinmunes o con patologías complicadas de la córnea y la superficie ocular. En dichos casos, el diagnóstico y el enfoque terapéutico suelen ser complejos, elaborados, prolongados y costosos, dado el uso de cuestionarios extensos sobre ojo seco, equipos de diagnóstico electrónico no invasivos y pruebas clínicas de laboratorio y auxiliares de diagnóstico. Más aún, otros especialistas en el cuidado ocular atienden un considerable número de casos de EOS, por lo que su diagnóstico, clasificación y manejo deberían ser algo sencillo, práctico, asequible y efectivo. Considerando que muchos pacientes que van a clínicas no especializadas para el tratamiento del ojo seco se beneficiarían de una mejor atención oftalmológica, hemos decidido elaborar un sistema práctico de clasificación de la EOS en base a su gravedad, para ayudar a los profesionales de la salud visual a discriminar los casos que precisen derivación de los pacientes a clínicas de alta especialidad. Además, proponemos un enfoque sistemático y consideraciones generales de manejo para mejorar los resultados terapéuticos de los pacientes en base a la gravedad de la enfermedad.
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National Natural Science Foundation of China (NSFC) [30872806, 30872809]; Ministry of Public Health of China; Ministry of Science and Technology of China [2006AA02A131]; Natural Science Foundation of Fujian Province [2009J06023]
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To assess the relative burden of dry eye in daily life by comparing Short Form-36 (SF-36) responses from individuals with and without dry eye against U.S. norms. Assessment of 210 people, 130 with non-Sjogren's keratoconjunctivitis sicca (non-SS KCS), 32 with Sjogren's Syndrome (SS), and 48 control subjects. The study population data and published normative SF-36 data were compared. Dry eye severity was assessed by recruited severity (control, non-SS KCS, SS), patient self-report (none, very mild/mild, moderate, severe/extremely severe), and clinician-report (none, mild, moderate, severe). Age- and gender-matched norms were compared with all defined severity groups. Compared with the norms, control subjects scored higher on all SF-36 scales. Effect size (ES) ranged from 0.15 to 0.52. Non-SS KCS patients had lower Role-Physical (ES=-0.07), Bodily Pain (ES=-0.08), and Vitality (ES=-0.11) scores, indicating more dry eye impact on those areas versus the norm. All SF-36 scale scores except Mental Health (ES=0.12) were lower in the SS group than the adjusted norm (ES range: -0.16 to -0.99). Regardless of severity classification, mild patients consistently had lower Role-Physical and Bodily Pain scores than the norm, suggesting impact on daily roles (ES < 0.2). Patients with moderately severe disease also experienced less vitality and poorer general health. The group with severe disease scored lower than the norm across all domains (ES range: -0.14 to -0.91) except Role-Emotional (ES=0.13) and Mental Health (ES=0.23). These results indicate dry eye's negative impact on everyday life, particularly in daily activities. Further research using disease-specific measures to examine dry eye's impact is underway.
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The aim was to investigate the effect of low dose doxycycline (20 mg) therapy in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy. The randomized prospective study enrolled 150 patients (300 eyes) who have chronic meibomian gland dysfunction and who didn't respond to lid hygiene and topical therapy for more than 2 months. All topical therapy was stopped for at least 2 weeks prior to beginning the study. After conducting the tear break up time test (TBUT) and Schirmer test, the authors randomly divided the patients into three groups a high dose group (doxycycline, 200 mg, twice a day), a low dose group (doxycycline, 20 mg, twice a day) and a control group (placebo). After one month, the author repeated the TBUT and Schirmer tests, and analyzed the degree of symptomatic improvement. Compared to the control group, both the high and low dose group showed statistically significant differences after treatment in TBUT, Schirmer test, the number of symptoms reported and the degree of improvement of subjective symptoms. However, there was no statistically significant difference between the high and low dose group after treatment in TBUT (9.42 +/- 2.87 sec, 9.54 +/- 1.58 sec, p=0.726), Schirmer test (19.98 +/- 4.05 mm, 19.65 +/- 5.02 mm, p=0.624), the number of symptoms reported (1.45 +/- 0.62, 1.53 +/- 0.52, p=0.304), as well as the degree of improvement of subjective symptoms (p=0.288). The high dose group (18 patients, 39.13%) reported side effects more frequently than did the low dose group (8 patients, 17.39%) (P=0.002). Low dose doxycycline (20 mg twice a day) therapy was effective in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy.
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To study the efficacy of topical application of alpha-linolenic acid (ALA) and linoleic acid (LA) for dry eye treatment. Formulations containing ALA, LA, combined ALA and LA, or vehicle alone, were applied to dry eyes induced in mice. Corneal fluorescein staining and the number and maturation of corneal CD11b(+) cells were determined by a masked observer in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva. Dry eye induction significantly increased corneal fluorescein staining; CD11b(+) cell number and major histocompatibility complex Class II expression; corneal IL-1alpha and tumor necrosis factor alpha (TNF-alpha) expression; and conjunctival IL-1alpha, TNF-alpha, interferon gamma, IL-2, IL-6, and IL-10 expression. Treatment with ALA significantly decreased corneal fluorescein staining compared with both vehicle and untreated controls. Additionally, ALA treatment was associated with a significant decrease in CD11b(+) cell number, expression of corneal IL-1alpha and TNF-alpha, and conjunctival TNF-alpha. Topical ALA treatment led to a significant decrease in dry eye signs and inflammatory changes at both cellular and molecular levels. Topical application of ALA omega-3 fatty acid may be a novel therapy to treat the clinical signs and inflammatory changes accompanying dry eye syndrome.
Article
Purpose: To develop a conceptual framework for analyzing the economic burden of dry eye and a preliminary assessment of key factors that contribute to that burden. Methods: The MEDLINE database was searched from 1966 to May 2003 combining the term “dry eye” with various economic terms. In addition, individual interviews with a panel of clinicians were conducted to provide additional insight on resource use. Results: Direct resource utilization among dry eye sufferers includes healthcare professional visits, nonpharmacological therapies, pharmacological treatments, and surgical procedures, with the latter 2 categories being the major cost drivers. Complementary and alternative medicine (CAM) therapies are a newly recognized component of the dry eye economic burden. There is wide variation in patterns of diagnosis and treatment, but current therapies are not universally effective. Given the prevalence of the condition, indirect costs may be large. Utilization of pharmacological therapies, especially those other than tear replacements, the extent of CAM use, cost of complications of surgical procedures, and indirect costs are unknown. The natural history and probability that patients will transition between therapies, based on underlying disease severity, need to be elucidated. Conclusions: Dry eye is a prevalent condition with the potential for a high economic burden; additional studies are needed to further characterize the economic impact.
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With the drastic expansion of internet usage, the demand of 10Gb/s transmission optoelectronic devices for local-area-network (LAN) and storage-area-network (SAN) are increasing. The key issues of these applications are to improve cost, manufacturability and reliability of optoelectronic devices in high speed transmission. The authors have demonstrated extremely low cost, high manufacturability and thermal stability optical fron-end for 10Gb/s Ethernet applications in this paper. High performance and high sensitivity of 10Gb/s transmitter optical sub-assembly (TOSA) and receiver optical sub-assembly (ROSA) with TO-Can packages are discussed and demonstrated to overcome the critical points in high speed applications, respectively. Moreover, 10km interconnection of 10Gb/s optical front-end without isolated elements inside are also proved to be error free at 10.3125Gb/s. In order to improve the signal integrity and manufacturability of 10Gb/s OSA in small form factor transceiver modules assembly, the authors also integrate high speed flex board and OSA package to extend the signal path, and to minimize the effect of crosstalk in modules. Furthermore, the integration of flex board and OSA package more release the difficulties in conjuunction OSA and electrical sub-assembly (ESA) in module to fulfill the request of 10Gb/s transeivers' Multi-Source Agreement (MSA). The performance of temperature stabilized TOSA over wide case temperature range is also experimented. The optical eye diagram of 10Gb/s TOSA developed in this study showing excellent eye quality passing 10Gb/s Ethernet mask test between 0°C to 85°C.
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Einleitung: Das evaporative trockene Auge ist die häufigste Form der Benetzungsstörungen. Die vorliegende Studie dient der Evaluierung der Wirksamkeit zweier etablierter Behandlungsmöglichkeiten mit unterschiedlichem Wirkprinzip im direkten Vergleich. Patienten/Material und Methoden: 216 Patienten mit evaporativen trockenen Augen wurden in diese prospektive, randomisierte bizentrische Studie eingeschlossen. Sie wurden in zwei Behandlungsgruppen aufgeteilt und entweder mit einem Hyaluronsäure-Tränenersatzmittel (Vismed light) oder dem Phospholipid-Liposomen-Augenspray (Tears Again) jeweils über 3 Monate behandelt. Die Untersuchungen wurden zu Beginn der Studie (vor Wirkstoffgabe) sowie 4 und 12 Wochen nach Behandlungsbeginn durchgeführt und erfassten die objektiven Parameter LIPCOF, NIBUT, Schirmer-Test, Inspektion der Lider und die subjektive Patientenbeurteilung. Ergebnisse: Hinsichtlich des Lidkantenentzündungsgrades zeigten sich für beide Gruppen bedeutsame Verbesserungen (p < 0,001). Allerdings erfuhr die Augenspray-Gruppe bereits vier Wochen nach Behandlungsbeginn einen dreimal stärkeren Rückgang der Entzündung (p < 0,002), der auch nach 12 Wochen immer noch doppelt so groß war wie bei der Tränenersatzmittel-Gruppe. In Bezug auf die Tränenfilmaufreißzeit (NIBUT) unterschieden sich die Ergebnisse beider Gruppen im Gesamtverlauf hoch signifikant (p < 0,003) voneinander: die Tränenfilmaufreißzeit nahm in der Augenspray-Gruppe um mehr als das Doppelte zu wie in der Tränenersatzmittel-Gruppe. Auch bei dem Grad der Lidkanten-parallelen Falten (LIPCOF) zeigten beide Patientengruppen nach 12 Wochen Behandlungszeit eine signifikante Befundbesserung (p < 0,001), wobei sich in der Phospholipid-Liposomen-Gruppe eine deutlich größere Verbesserung zeigte (p < 0,02). Schlussfolgerungen: Die vorliegende Studie zeigt die klinische Überlegenheit des Phospholipid-Liposomen-Augensprays zur Behandlung des evaporativen trockenen Auges gegenüber der Therapie mit Hyaluronsäure-Tränenersatzmitteln. Besonders ausgeprägt ist das trockene Auge, wenn evaporatives trockenes Auge und Tränenflüssigkeitsmangel zusammen auftreten. Eine Kombination aus Phospholipid-Liposomen-Augenspray und konventionellen Tränenersatzmitteln ist daher in der Substitutionstherapie schwerer Verlaufsformen des trockenen Auges besonders empfehlenswert.
Article
Objective: To investigate the efficacy, safety, formulation tolerability, and optimal dosing of a novel cyclosporin A oil-in-water emulsion formulation for the treatment of moderate-to-severe dry eye disease.Design: Randomized, multicenter, double-masked, parallel-group, dose-response controlled trial.Participants: Total enrollment: 162 patients; cyclosporin A groups: 129 patients; vehicle group: 33 patients.Intervention: Patients instilled study medication (cyclosporin A ophthalmic emulsion 0.05%, 0.1%, 0.2%, or 0.4%, or vehicle) twice daily into both eyes for 12 weeks, followed by a 4-week posttreatment observation period.Main Outcome Measures: Efficacy: rose bengal staining, superficial punctate keratitis, Schirmer tear test, symptoms of ocular discomfort, and the Ocular Surface Disease Index (OSDI; a measure of symptom frequency and impact on vision-related functioning). Safety: biomicroscopy, cyclosporin A blood levels, conjunctival microbiology, intraocular pressure, visual acuity, and monitoring of adverse events.Results: In a subset of 90 patients with moderate-to-severe keratoconjunctivitis sicca, the most significant improvements with cyclosporin A treatment were in rose bengal staining, superficial punctate keratitis, sandy or gritty feeling, dryness, and itching, with improvements persisting into the posttreatment period in some treatment groups. There was also a decrease in OSDI scores, indicating a decrease in the effect of ocular symptoms on patients’ daily lives. There was no clear dose-response relationship, but cyclosporin A 0.1% produced the most consistent improvement in objective and subjective end points and cyclosporin A 0.05% gave the most consistent improvement in patient symptoms. The vehicle also performed well, perhaps because of its long residence time on the ocular surface. There were no significant adverse effects, no microbial overgrowth, and no increased risk of ocular infection in any treatment group. The highest cyclosporin A blood concentration detected was 0.16 ng/ml. All treatments were well tolerated by patients.Conclusions: Cyclosporin A ophthalmic emulsions, 0.05%, 0.1%, 0.2%, and 0.4%, were safe and well tolerated, significantly improved the ocular signs and symptoms of moderate-to-severe dry eye disease, and decreased the effect of the disease on vision-related functioning. Cyclosporin A 0.05% and 0.1% were deemed the most appropriate formulations for future clinical studies because no additional benefits were observed with the higher concentrations.
Article
Background: Most of the eye drops currently used replace only the aqueous phase of the tear film. But, due to the fact that, with approximately 80% of the patients with a dry eye, a distur- bance of the lipid phase is present, an approach for new treat- ment methods needed to be found. We examined a new therapy concept with an eye spray containing liposomes for the therapy of the "dry eye" in a long-term study. Goal: An examination of the effectiveness of a liposome eye spray (Tears again�, Optima Pharmaceutical GmbH, Germany) in patients with "dry eye" compared with a spray containing a balanced salt solution was carried out. Methods: Between August 2003 and May 2004a double-blind study with 382 patients was accomplished. The treatment group (V; n=191) was compared with the control group (K; n=191) for a period of 6 months regarding the follow- ing examination criteria: eyelid edge parallel conjunctival folds (LIPCOF),BREAK UPtime (BUT), Schirmer I test,best correctedvi- sual acuity, as well as slit lamp findings of the cornea and con- junctiva. Follow-up was after 4 weeks and 6 months. The statis- tical analysis was performed with the statistical program SPSS v.11.5. Results: The examined parameters such as LIPCOF, BUT and Schirmer were significantly better in the treatment group than in the control group. We found likewise significant im- provements of the inflammations of the edge of eyelid with a re- markable decrease of around 89.5%. Questioning of the patients resulted in, among other things, the belief that the liposome eye spray led altogether to a clear subjective improvement of the symptoms in 72% of the cases, although an initial burning sensa- tionwas mentioned after the application. All patients were of the opinion that application with a spray is more favourably and more pleasant than teardrops. Conclusion: The liposome tear Klinische Studie
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The aim of the DEWs Definition and Classification Subcommittee was to provide a contemporary definition of dry eye disease, supported within a comprehensive classification framework. A new definition of dry eye was developed to reflect current understanding of the disease, and the committee recommended a three-part classification system. The first part is etiopathogenic and illustrates the multiple causes of dry eye. The second is mechanistic and shows how each cause of dry eye may act through a common pathway. It is stressed that any form of dry eye can interact with and exacerbate other forms of dry eye, as part of a vicious circle. Finally, a scheme is presented, based on the severity of the dry eye disease, which is expected to provide a rational basis for therapy. these guidelines are not intended to override the clinical assessment and judgment of an expert clinician in individual cases, but they should prove helpful in the conduct of clinical practice and research.
Chapter
The GRADE approach, adopted by The Cochrane Collaboration, specifies four levels of quality (high, moderate, low and very low) where the highest quality rating is for a body of evidence based on randomized trials. Review authors can downgrade randomized trial evidence depending on the presence of five factors and upgrade the quality of evidence of observational studies depending on three factors. • Quality ratings are made separately for each outcome.
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Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease and spectroscopic behavior of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution. Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid, lipid-lipid interaction strength, and conformation and phase transition parameters were measured using Fourier transform infrared spectroscopy. In subjects with clinical evidence of MGD, changes in ordering of the lipids and resultant alteration of phase transition temperature were identified. Topical therapy with azithromycin relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Improvement in phase transition temperature of the meibomian gland lipid with the determined percent trans rotomer composition of the lipid strongly suggests that the ordering of the lipid molecules is altered in the disease state (MGD) and that azithromycin can improve that abnormal condition toward normal in a manner that correlates with clinical response to therapy.
Article
Most marketed artificial tears are substitutes for the aqueous layers of the tear film; therefore, frequent instillation of artificial tears is necessary. Newer gel-, cellulose-, and mineral oil-based formulations have been designed to overcome the disadvantages of current aqueous tear substitutes by offering prolonged retention times. The aim of this study was to compare the efficacy, safety, and local tolerance of artificial tears containing carbomer-based lipids or hydroxypropyl (HP)-guar gel in patients with dry eye syndrome. A 4-week, prospective, randomized, parallel-group, comparative, noninferiority study was conducted at the Taipei Medical University Hospital (Taipei, Taiwan) in patients with dry eye syndrome who were randomly assigned to 1 of 2 treatment groups: the carbomer-based lipid-containing (CBLC) gel group and the HP-guar gel group. The primary end point was global assessment of study treatment by the patients at weeks 2 and 4. All patients met the diagnostic criteria of impaired tear function and ocular surface abnormalities. Outcomes measured at baseline and 2 and 4 weeks included Schirmer's test values, tear breakup time (TBUT), and a patient subjective assessment of symptoms. Safety and tolerability were assessed by clinically significant changes in terms of incidence of adverse events and conducted by unmasked investigators. A total of 30 Taiwanese patients with dry eye syndrome were included and randomly assigned to the 2 treatment groups: the mean (SD) age was 40.37 (14.96) years in the CBLC gel group and 49.49 (12.20) years in the HP-guar gel group. At baseline, the mean (SD) Schirmer's test value was 4.53 (2.28) mm in the right eye and 5.13 (2.42) mm in the left eye in the CBLC gel group; 4.40 (2.16) mm in the right eye and 4.20 (1.78) mm in the left eye for the HP-guar gel group. The mean (SD) for both eyes was 4.83 (2.36) mm in the CBLC gel group and 4.30 (2.08) mm in the HP-guar gel group. There was no statistically significant difference between Schirmer's scores at baseline. Patients in both treatment groups experienced an improvement from baseline in symptoms and signs, Schirmer's test value, and TBUT at 2 and 4 weeks after treatment. The Schirmer's test score increased to a mean of 8.20 (4.49) mm in the right eye and 9.33 (4.94) mm in the left eye in the CBLC gel group after 2 weeks, and increased to 10.07 (5.56) mm in the right eye and 10.86 (5.58) mm in the left eye after 4 weeks. The increases in Schirmer's test score and TBUT were also observed in the HP-guar gel group. The Schirmer's test score increased to 5.13 (2.18) mm in the right eye and 5.60 (2.74) mm in the left eye after 2 weeks, and increased to 6.93 (3.37) mm in the right eye and 6.53 (3.16) mm in the left eye after 4 weeks. The increase in Schirmer's test values in both eyes was significantly greater at 2 and 4 weeks in the CBLC gel group than that in the HP-guar gel artificial tear group (all, P < 0.05). Subjective patient assessment was better with the CBLC group (excellent and good reported by 26.6% and 73.4%, respectively, of the CBLC gel group vs 13.4% and 33.4% of the HP-guar gel group at 4 weeks; both, P = 0.004). Both artificial tear formulations were effective in relieving dry eye syndrome in these patients. The tolerance of CBLC gel artificial tears was comparable to that of HP-guar gel artificial tears.
Article
Essential fatty acids (EFAs) play many important roles in human biology, affecting organ systems and cellular and intracellular function. Omega-3 and omega-6 EFAs are the precursors of eicosanoids, locally acting hormones involved in mediating inflammatory processes. It is largely via the production of these eicosanoids that the essential fatty acids influence human health and disease. In general, the omega-3 derived eicosanoids are anti-inflammatory while the n-6 pathway eicosanoids promote inflammation. To date, EFAs have been primarily studied with regard to systemic diseases, particularly cardiovascular disease. Currently, no dietary recommendations of EFAs for the prevention or treatment of eye disease exist. The majority of studies concerning EFAs and eye disease have focused on diseases of the retina. This article provides an overview of the current literature regarding EFAs and dry eye disease (DED). Eight studies were identified, including six randomized controlled trials. All the studies preliminarily confirmed that there is a relationship between EFA supplementation and improvement in DED. However, strong conclusions cannot be made yet because of limitations in the research reported. The role of essential fatty acids is an important topic that would benefit from a large, multicenter, randomized clinical trial powered to reach a conclusion regarding the efficacy of essential fatty acids in the treatment of dry eye disease.
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With the potential to address evaporative dry eye, a novel spray has been developed in which phospholipid liposomes are delivered to the tear film via the surface of the closed eyelid. This study evaluated the short-term effects of liposomal spray application on the lipid and stability characteristics of the pre-ocular tear film in normal eyes. Twenty-two subjects (12M, 10F) aged 35.1+/-7.1 years participated in this prospective, randomised, double-masked investigation in which the liposomal spray was applied to one eye, and an equal volume of saline spray (control) applied to the contralateral eye. Lipid layer grade (LLG), non-invasive tear film stability (NIBUT) and tear meniscus height (TMH) were evaluated at baseline, and at 30, 60, 90 and 135min post-application. Subjective reports of comfort were also compared. Treated and control eyes were not significantly different at baseline (p>0.05). Post-application, LLG increased significantly, at 30 and 60min, only in the treated eyes (p=0.005). NIBUT also increased significantly in the treated eyes only (p<0.001), at 30, 60 and 90min. TMH did not alter significantly (p>0.05). Comfort improved relative to baseline in 46% of treated and 18% of control eyes, at 30min post-application. Of those expressing a preference in comfort between the eyes, 68% preferred the liposomal spray. Consistent with subjective reports of improved comfort, statistically and clinically significant improvements in lipid layer thickness and tear film stability are observed in normal eyes for > or =1h after a single application of a phospholipid liposomal spray.
Article
Evaporative dry eye is the most common form of tear film dysfunction. The present trial aims to evaluate the efficacy of two established treatment options with different modes of action by comparison. 216 patients suffering from evaporative dry eye were included in this prospective, randomised two-centre trial. Divided into two treatment groups, patients either received treatment with hyaluronate artificial tears (Vismed light) or a phospholipid-liposome eye spray (Tears Again), each for three months. Tests (lid-parallel conjunctival folds [LIPCOF], non-invasive break-up time [NIBUT], Schirmer's test, inspection of lids and subjective assessment) were performed before as well as 4 and 12 weeks after initiation of this study. In the patients of the eye spray group there was a significantly greater reduction of the LIPCOF grade (p < 0.02) and the grade of inflammation of the lid margin (p < 0.002). With respect to the tear film break-up time (NIBUT) there was a significant difference between the results of both groups (p < 0.003). The improvement of the break-up time in patients of the eye spray group turned out to be more than twice as high as that in the artificial tears group. Both therapies improved evaporative dry eye, but patients on phospholipid-liposomal eye spray demonstrated greater clinical benefit from their therapy, particularly regarding the degree of inflammation of the lid margins as well as the grade of LIPCOF. When compared to hyaluronate artificial tears, NIBUT more than doubled in the phospholipid-liposome eye spray group. Clinical severity of dry eye is more pronounced when evaporative dry eye and aqueous tear deficiency coincide. A combination of the phospholipid-liposome eye spray and artificial tears appears to represent a considerable advancement in tear replacement therapy for severe cases of dry eye.
Article
Disturbances of the lipid composition can, like mucin or fluid deficiency, cause 'dry eye'. The substitution of the lipids of the tear fluid has previously been unsatisfactory since eye ointments containing fats can lead to a considerable deterioration of the visual acuity due to the film of ointment resulting from an irregular spreading behavior. We proposed the introduction of physiological lipids that are normally present in tear fluid, such as phospholipids, saturated and unsaturated fatty acids and triglycerides, to provide lipid-containing eye drops. These best correspond to 'natural tears' and, due to the small size of the lipid particles, avoid a disturbance of the spreading behavior of the lipid layer. With lipid-containing eye drops of this kind, we carried out the following examinations: inquiry of patients' symptoms based on a standardized interview; Schirmer test under local anesthesia; break-up time (BUT); biomicroscopic evaluation of the lipid film, and stability tests as pH, gas chromatographic analysis of the fatty acid pattern and thin-layer chromatographic analysis of the lipid pattern. Schirmer test, BUT measurement and questioning about symptoms were undertaken after 1 week and then again after 3 weeks of treatment. All three parameters finally showed an improvement with a high statistical significance (p less than 0.001). The stability tests have shown that pH, lipid particle size, fatty acid and lipid composition of the examined lipid-containing eye drops were nearly unchanged till 4 months after preparation.
Article
The effect on tear evaporation of two artificial tear solutions is compared with that of an equal volume of saline instilled into the eye. Changes in tear evaporation rates (TER) were measured with a modified Servomed Evaporimeter in a cross-over study of nine subjects. Initial increases in TER were found with all three solutions; however, slight evidence exists for a faster return to baseline with artificial tear solutions.
Article
The existence of the tear film is well known but its structure is less well understood. It is unwise to consider the tear film in isolation from blinking. Blinking has a profound influence upon the structure, stability, and function of the tear film. Many glands from different sites contribute to the clear fluid that bathes the surface of the eye. Chemically tears are very similar to dilute blood, with a reduced protein content. (The pH of tears approximates to that of blood plasma but it has a slightly greater osmotic pressure.) The film covers the exposed surface of the eye and provides an optically smooth interface with the atmosphere. Lacrimation is well known throughout the animal kingdom, but crying with sorrow and laughter are probably confined to man. This is probably an adjunct to the vast range of facial expressions available to man. The parasympathetic nerve fibers that are secretomotor to the lacrimal gland are distributed for much of their course with the facial nerve, the motor nerve of facial expression.
Article
Corneal fluorescein staining is widely used in clinical practice and research, but little information exists on the distribution of staining in a large group of asymptomatic contact lens wearers. This cross-sectional study took place at 3 centers, and investigated the pattern of corneal fluorescein staining in both eyes of 98 hydrogel contact lens wearers. We also investigated the strategies used by three experienced clinicians to grade corneal staining. Overall corneal staining was graded using a scale from 0 to 4 in one-half steps, and five corneal zones, superior, inferior, nasal, temporal, and central, were also graded. The average overall staining grade for both eyes of our subjects was 0.50, with an average of 0.57 for the right eye and 0.44 for the left. This difference between the eyes was statistically significant (p = 0.011). In addition, a comparison of the zones within each eye showed a significant difference (p = 0.0001) among the zones. Corneal staining between the two eyes was also positively and significantly correlated (r = 0.58; p = 0.0001). Grading strategies among clinical investigators were significantly different (p = 0.0001), indicating a potential source of bias in multi-centered studies. The difference in corneal staining between the eyes may represent a source of systematic bias, and could be due to grading the right eye before the left. The correlation in corneal staining between the eyes indicates that the two eyes of a subject cannot serve as independent data points. One-third of the subjects who participated in this study had notable corneal staining. This finding underlines the importance of regularly checking corneal staining in clinical practice.
Article
Previous work on rabbits has demonstrated a four-fold increase in tear evaporation when the tear lipid layer is removed. However, in vitro work has suggested that the lipid layer does not play a role in retarding evaporation of the aqueous layer. The importance of the lipid layer in human tear film stability and evaporation was determined in the current study by measurement of these parameters in the same individuals. The left eyes of 161 normal and dry eye subjects (72 males, 89 females), with an age range of 13 to 85 years, were examined. Tear evaporation was derived from the vapor pressure gradient measured with a modified Servomed evaporimeter. Lipid layer structure and noninvasive break-up time (NIBUT) were assessed clinically, by specular reflection, with the Keeler Tearscope. Lipid layer structure was categorized into marmoreal (open and closed meshwork), flow, amorphous, and colored fringe (normal and abnormal) patterns. These observed patterns reflect lipid layer thickness. Ambient temperature and relative humidity remained fairly constant throughout the experiment. Tear evaporation rate was found to vary significantly with different lipid layer patterns. Eyes with no visible lipid layer, or exhibiting an abnormal colored fringe pattern (with clumping of lipid amidst areas of little or no lipid cover), demonstrated a significantly higher rate of evaporation of the tear film (p < 0.001). There were no significant differences amongst the remainder of the patterns. The NIBUT was also found to vary significantly with lipid layer pattern (p < 0.001), with the absent or abnormal colored fringe lipid patterns exhibiting the poorest stability. Where the human lipid layer is absent, or is not confluent, and the tear film is unstable, tear evaporation is increased four-fold. However, where there is a stable, intact lipid layer, regardless of lipid thickness, tear evaporation is retarded.
Article
Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed. A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication. All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication. Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.
Article
To compare the efficacy and safety of cyclosporin A ([CsA] 0.05% and 0.1% ophthalmic emulsions) to vehicle in patients with moderate to severe dry eye disease. Multicenter, randomized, double-masked, parallel-group, 6-month, vehicle-controlled. A total of 877 patients with defined moderate to severe dry eye disease (292 to 293 in each treatment group). Two identical clinical trials; patients were treated twice daily with either CsA, 0.05% or 0.1%, or vehicle. The results of these two trials were combined for analysis. Efficacy: corneal and interpalpebral dye staining, Schirmer tear test (with and without anesthesia), tear break-up time, Ocular Surface Disease Index (OSDI), facial expression, patient subjective rating scale, symptoms of dry eye, investigator's evaluation of global response to treatment, treatment success, and daily use of artificial tears. Safety: occurrence of adverse events, best-corrected visual acuity, intraocular pressure, biomicroscopy, and blood trough CsA concentrations. Treatment with CsA, 0.05% or 0.1%, gave significantly (P < or = 0.05) greater improvements than vehicle in two objective signs of dry eye disease (corneal staining and categorized Schirmer values). CsA 0.05% treatment also gave significantly greater improvements (P < 0.05) in three subjective measures of dry eye disease (blurred vision, need for concomitant artificial tears, and the physician's evaluation of global response to treatment). There was no dose-response effect. Both CsA treatments exhibited an excellent safety profile, and there were no significant topical or systemic adverse safety findings. The novel ophthalmic formulations CsA 0.05% and 0.1% were safe and effective in the treatment of moderate to severe dry eye disease yielding improvements in both objective and subjective measures. Topical CsA represents a new pharmacologically based treatment for dry eye disease that may provide significant patient benefits.
Article
To investigate the efficacy, safety, formulation tolerability, and optimal dosing of a novel cyclosporin A oil-in-water emulsion formulation for the treatment of moderate-to-severe dry eye disease. Randomized, multicenter, double-masked, parallel-group, dose-response controlled trial. Total enrollment: 162 patients; cyclosporin A groups: 129 patients; vehicle group: 33 patients. Patients instilled study medication (cyclosporin A ophthalmic emulsion 0.05%, 0.1%, 0.2%, or 0.4%, or vehicle) twice daily into both eyes for 12 weeks, followed by a 4-week posttreatment observation period. Efficacy: rose bengal staining, superficial punctate keratitis, Schirmer tear test, symptoms of ocular discomfort, and the Ocular Surface Disease Index (OSDI; a measure of symptom frequency and impact on vision-related functioning). Safety: biomicroscopy, cyclosporin A blood levels, conjunctival microbiology, intraocular pressure, visual acuity, and monitoring of adverse events. In a subset of 90 patients with moderate-to-severe keratoconjunctivitis sicca, the most significant improvements with cyclosporin A treatment were in rose bengal staining, superficial punctate keratitis, sandy or gritty feeling, dryness, and itching, with improvements persisting into the posttreatment period in some treatment groups. There was also a decrease in OSDI scores, indicating a decrease in the effect of ocular symptoms on patients' daily lives. There was no clear dose-response relationship, but cyclosporin A 0.1% produced the most consistent improvement in objective and subjective end points and cyclosporin A 0.05% gave the most consistent improvement in patient symptoms. The vehicle also performed well, perhaps because of its long residence time on the ocular surface. There were no significant adverse effects, no microbial overgrowth, and no increased risk of ocular infection in any treatment group. The highest cyclosporin A blood concentration detected was 0.16 ng/ml. All treatments were well tolerated by patients. Cyclosporin A ophthalmic emulsions, 0.05%, 0.1%, 0.2%, and 0.4%, were safe and well tolerated, significantly improved the ocular signs and symptoms of moderate-to-severe dry eye disease, and decreased the effect of the disease on vision-related functioning. Cyclosporin A 0.05% and 0.1% were deemed the most appropriate formulations for future clinical studies because no additional benefits were observed with the higher concentrations.
Article
We developed low-concentration homogenized castor oil eye drops for the treatment of patients with noninflamed obstructive meibomian gland dysfunction (MGD), a major cause of lipid-deficiency dry eye, and assessed the safety, stability, and efficacy of the eye drops. Randomized, double-masked, placebo-controlled crossover clinical trial. Forty eyes of 20 patients with noninflamed MGD. After a preliminary study of eye drops containing castor oil, 2% castor oil and 5% polyoxyethylene castor oil (emulsifier) were mixed to formulate homogenized oil eye drops. The patients were assigned randomly to receive oil eye drops or placebo six times daily for 2 periods of 2 weeks each. At the end of each treatment period, we assessed symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal scores, tear break-up time (BUT), and meibomian gland orifice obstruction. Safety and stability tests were also performed. Symptom scores, tear interference grade, tear evaporation test results, rose bengal scores, tear BUT, and orifice obstruction scores after the oil eye drop period showed significant improvement compared with the results after the placebo period. No complications attributable to the eye drops were observed. The oil eye drops were stable when stored at 4 degrees C. The results indicate that castor oil eye drops are effective and safe in the treatment of MGD. The possible mechanisms of this treatment are improvement of tear stability as a result of lipid spreading, ease of meibum expression, prevention of tear evaporation, and the lubricating effect of the oil eye drops.
Article
Warm-compress therapy applied to the skin of the closed eyelids has been recommended as a treatment for meibomian gland dysfunction (MGD). Previous studies have evaluated the effects of warm-compress therapy on tear-film fluorescein break-up time and tear evaporation rate. The purpose of this study was to determine if tear-film lipid layer thickness (TFLLT) was altered following 5, 15, and 30 minutes of warm, moist compress therapy. Twenty patients with a diagnosis of dry eye associated with MGD and a baseline TFLLT of <or= 90 nm (baseline difference between experimental and control eyes <or= 25 nm) were studied. The skin of the closed eyelids of one eye of each subject was treated for a total of 30 minutes with a compress saturated with warm (40.0 +/- 2.0 degrees C) water used as a compress; and the skin of the closed eyelids of the contralateral control eye was treated for a total of 30 minutes with a compress saturated with room-temperature (24.0 degrees C +/- 1.0 degrees C) water used as a compress. The subjects' eyes were randomized into experimental and control eyes. TFLLT was measured at the following time points: 5, 15, and 30 minutes during the 30-minute treatment period, and after 5 minutes following the 30-minute treatment period. The mean baseline TFLLT of the experimental eye prior to treatment with a warm, moist compress was 57.8 +/- 12.9 (standard error) nm; after 5 minutes of treatment, TFLLT was 105.8 +/- 23.7 nm; after 15 minutes of treatment, 117.8 +/- 26.4 nm; after 30 minutes of treatment, 121.5 +/- 27.1 nm; and after 5 minutes following the 30-minute treatment, 96.0 +/- 21.5 nm. The mean baseline TFLLT of the control eye prior to treatment with a room temperature, moist compress was 63.0 +/- 14.1 nm; after 5 minutes of treatment, TFLLT was 63.8 +/- 14.3 nm; after 15 minutes of treatment, 62.3 +/- 13.9 nm; after 30 minutes of treatment, 64.5 +/- 14.4 nm; and after 5 minutes following the 30-minute treatment period, 58.5 +/- 13.1 nm. Using a paired-data t-test, the results demonstrated a significant increase in mean TFLLT in the experimental eye after 5 minutes (P < 0.001), 15 minutes (P < 0.001), and 30 minutes (P < 0.001) of treatment, and after 5 minutes following the 30-minute treatment period (P < 0.001) when compared to baseline TFLLT. In comparison, there was no significant increase in TFLLT of the control eye after 5 minutes (P = 0.79), 15 minutes (P = 0.77), and 30 minutes (P = 0.81) of treatment, and after 5 minutes following the 30-minute treatment period (P = 0.20) when compared to baseline TFLLT. Warm, moist compress therapy applied to the skin of the closed eyelids increases TFLLT for subjects with MGD by more than 80%, 5 minutes after initiating treatment and an additional 20% after 15 minutes of treatment. This study supports clinical experience and previous reports on warm, moist compress therapy as an effective treatment for meibomian gland dysfunction.
Article
To describe the epidemiology of dry eye in an elderly Chinese population in Taipei, Taiwan. A population-based cross-sectional study. The Shihpai Eye Study was a population-based survey of eye diseases in the elderly (> or =65 years) in Shihpai, Taipei, Taiwan. Noninstitutionalized residents, as of July 1999, were identified by using the official household registration database. A total of 2045 subjects were selected, and 1361 (66.6%) people participated in the study. Among them, 822 (60.4%) were men. Trained interviewers administered a standardized questionnaire pertaining to dry-eye symptoms. Objective examinations of dry eye included tear film breakup time, Schirmer test, fluorescein stain of the cornea, and anatomic assessment of the meibomian glands via slit-lamp biomicroscopy. Frequency of dry-eye symptoms and positive dry-eye tests. In this population, 33.7% (459/1361) were symptomatic, defined as reporting 1 or more dry-eye symptoms often or all of the time. Women were more likely to report frequent symptoms of dry eye (odds ratio, 1.49; 95% confidence interval, 1.19-1.87). Among those who were symptomatic, 78.9% (362/459) had a low tear film breakup time (< or =10 seconds), 62.5% (287/459) had a low Schirmer test result (< or =5 mm), and 61.7% (283/459) had abnormal anatomic features of the meibomian glands. Furthermore, 85.4% (392/459) were symptomatic and had either a low Schirmer score or an abnormal meibomian gland assessment. Of those symptomatic, 49.9% (229/459) indicated that they had visited an eye doctor, 5.4% (25/459) responded that they had been diagnosed with dry eye, and 47.5% (218/459) reported current use of eyedrops. This is the first report of population-based data of dry eye that includes symptoms and signs in elderly Asians. The prevalence of dry eye, although varied according to definition, is relatively higher in this study than that reported for whites. Further studies are needed to determine whether this is due to racial or environmental factors.
Article
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. Comparative, nonrandomized interventional study. Five normal subjects and 10 aqueous tear deficiency (ATD) patients with or without lipid tear deficiency were enrolled prospectively. 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. Symptoms, pattern, thickness, and spread time of the tear film. 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). 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.
Article
The majority of dry eye symptoms are due to a chronic inflammation of the lacrimal functional unit resulting in a loss of tear film integrity and normal function. This leads to a reduction in the ability of the ocular surface to respond to environmental challenges. The underlying cause of tear film dysfunction is the alteration of tear aqueous, mucin, and lipid components. This may result from a systemic autoimmune disease or a local autoimmune event. A lack of systemic androgen support to the lacrimal gland has been shown to be a facilitative factor in the initiation of this type of pathophysiology. Tear secretion is controlled by the lacrimal functional unit consisting of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland and the interconnecting innervation. If any portion of this functional unit is compromised, lacrimal gland support to the ocular surface is impeded. Factors such as neurogenic inflammation and T cell involvement in the disease pathogenesis as well as newly developed animal models of ocular surface inflammation are discussed.
Article
Most of the eye drops currently used replace only the aqueous phase of the tear film. But, due to the fact that, with approximately 80 % of the patients with a dry eye, a disturbance of the lipid phase is present, an approach for new treatment methods needed to be found. We examined a new therapy concept with an eye spray containing liposomes for the therapy of the "dry eye" in a long-term study. An examination of the effectiveness of a liposome eye spray (TEARS AGAIN, Optima Pharmaceutical GmbH, Germany) in patients with "dry eye" compared with a spray containing a balanced salt solution was carried out. Between August 2003 and May 2004 a double-blind study with 382 patients was accomplished. The treatment group (V; n = 191) was compared with the control group (K; n = 191) for a period of 6 months regarding the following examination criteria: eyelid edge parallel conjunctival folds (LIPCOF), BREAK UP time (BUT), Schirmer I test, best corrected visual acuity, as well as slit lamp findings of the cornea and conjunctiva. Follow-up was after 4 weeks and 6 months. The statistical analysis was performed with the statistical program SPSS v.11.5. The examined parameters such as LIPCOF, BUT and Schirmer were significantly better in the treatment group than in the control group. We found likewise significant improvements of the inflammations of the edge of eyelid with a remarkable decrease of around 89.5 %. Questioning of the patients resulted in, among other things, the belief that the liposome eye spray led altogether to a clear subjective improvement of the symptoms in 72 % of the cases, although an initial burning sensation was mentioned after the application. All patients were of the opinion that application with a spray is more favourably and more pleasant than teardrops. The liposome tear substitute shows statistically significant advantages against a balanced salt solution. This new liposome eye spray represents a new, revolutionary and effective procedure in the therapy of the "dry eye". Considering the disturbance of the lipid phase in 80 % of the patients, TEARS AGAIN ought to be a first choice treatment.
Article
To develop a conceptual framework for analyzing the economic burden of dry eye and a preliminary assessment of key factors that contribute to that burden. The MEDLINE database was searched from 1966 to May 2003 combining the term "dry eye" with various economic terms. In addition, individual interviews with a panel of clinicians were conducted to provide additional insight on resource use. Direct resource utilization among dry eye sufferers includes healthcare professional visits, nonpharmacological therapies, pharmacological treatments, and surgical procedures, with the latter 2 categories being the major cost drivers. Complementary and alternative medicine (CAM) therapies are a newly recognized component of the dry eye economic burden. There is wide variation in patterns of diagnosis and treatment, but current therapies are not universally effective. Given the prevalence of the condition, indirect costs may be large. Utilization of pharmacological therapies, especially those other than tear replacements, the extent of CAM use, cost of complications of surgical procedures, and indirect costs are unknown. The natural history and probability that patients will transition between therapies, based on underlying disease severity, need to be elucidated. Dry eye is a prevalent condition with the potential for a high economic burden; additional studies are needed to further characterize the economic impact.
Article
As tear secretion and tear clearance decrease in the dry eye, an inflammatory response is initiated on the ocular surface that appears to involve both soluble and cellular mediators. Although the traditional approach to treating dry eye is to hydrate and lubricate the ocular surface with artificial tears, symptoms and/or sight-threatening corneal disease may persist in some patients on such aqueous enhancement therapies. In these patients, treatment with anti-inflammatory agents, such as cyclosporin A, corticosteroids, tetracyclines, or autologous serum, may be considered. Results of studies investigating the use of these agents are discussed. During treatment, patients should be conscientiously monitored for adverse effects.
Article
To determine the effect of an oil-in-water emulsion eye drop compared with a conventional dry eye supplement (hypromellose) on tear physiology in dry eye. A randomized parallel, longitudinal, and investigator-masked study of the efficacy of 1.25% castor oil emulsion and 0.32% hypromellose solution was carried out. A total of 53 patients with mild to moderate dry eye (27 in emulsion group and 26 in hypromellose group) were recruited for the study. Patients were enrolled if they reported at least 2 symptoms on a McMonnies Dry Eye Questionnaire together with 1 of the following screening tests: noninvasive tear breakup time (5-10 seconds) and Schirmer test without anesthesia (2-5 mm in 5 minutes). Patients were instructed to use the test solutions 3 times a day for 30 days. Tear production, evaporation, lipid layer structure, and osmolality were measured before and 30 days after use of the drops. A statistically significant decrease was seen after 1 month in tear evaporation rates with both emulsion (7.25 +/- 5.43 g/m2/h) and hypromellose (2.02 +/- 4.75 g/m2/h). However, the decrease with emulsion was significantly greater than with hypromellose (P < 0.001). Lipid layer structure improved from day 1 to day 30 of the study with the emulsion but not with the hypermellose. No significant changes were seen in tear production and osmolality with either of the drops. The oil-water emulsion was more effective in reducing tear evaporation than hypromellose after repeated application over a 1-month period. This finding signifies the potential of the emulsion in the management of evaporative dry eye.