Essential fatty acids for dry eye:a review

Purpose Dry eye is a common complaint often encountered in optometric practice. However, it is a difficult condition to treat as clinical signs do not always correlate with patient symptoms. Essential fatty acids (EFA), particularly omega-3 EFA, may be effective in dealing with the underlying causes. Methods A literature review was carried out on the PubMed, ScienceDirect and Ovid databases. Searches included keywords such as ‘dry eye’, ‘essential fatty acids’ and ‘nutrition’ to find articles relating to the treatment of dry eye syndrome (DES) with omega-3 EFAs. Results Omega-3 and -6 EFAs need to be consumed together within a reasonable ratio to be effective. Currently, typical diets in developed countries lack omega-3 EFA and this results in an overexposure to omega-6. Omega-3 supplementation has an anti-inflammatory effect, inhibiting creation of omega-6 prostaglandin precursors. Omega-3 EFAs also demonstrate anti-inflammatory action in the lacrimal gland preventing apoptosis of the secretory epithelial cells. Supplementation clears meibomitis, allowing a thinner, more elastic lipid layer to protect the tear film and cornea. Conclusion Dietary supplementation of omega-3 EFA has already proven to be effective in coronary heart disease and arthritis. Safety is not a concern as it works synergistically with omega-6 in the body. Evidence suggests that supplementation with omega-3 EFA may be beneficial in the treatment and prevention of DES.

Mild wear in dry and lubricated sliding systems

A vertical pin on horizontal disc machine has been used to conduct a series of experiments in air under dry and lubricating sliding conditions. For dry sliding low load and speed combinations were chosen to correspond to the mild wear region below the Welsh T1 transition. Lubricated tests were conducted under flooded conditions using Esso Technical White Oil alone and with a 0.1% stearic acid additive, for load and speed ranges that produced substantial amounts of asperity contact and thus a boundary lubricated regime of wear. The test material in all cases was AISI 52100 steel, for unlubricated sliding subjected to loads from 5 to 50 N and a range of speeds from 10-3 to 1.0 ms-1, and for lubricated sliding loads of 50 to 123 N and for speeds of 10-2 to 1.0 ms-1. Unlubricated wear debris was found to be a mixture of -Fe_2O_3 and -Fe. Unlubricated wear was found to occur via a thin film logarithmic oxide growth followed by agglomeration into thicker oxide plateaux 2 to 10 m in thickness. Lubricated wear occurred via thick film diffusion controlled oxide growth producing homogeneous oxide plateaux 0.1 to 0.2 m in thickness. X-ray photoelectron spectroscopy identified the presence of a surface film on pins worn in White Oil with stearic acid, which is thought to be iron stearate. A model has been developed for unlubricated wear based upon the postulated growth of thin film oxides by a logarithmic rate law. The importance of sliding geometry and environment to the dominant wear mechanism has been illustrated.

Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions

A dry matrix application for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was used to profile the distribution of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate, monohydrochloride (BDNC, SSR180711) in rat brain tissue sections. Matrix application involved applying layers of finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA) to the surface of tissue sections thaw mounted onto MALDI targets. It was not possible to detect the drug when applying matrix in a standard aqueous-organic solvent solution. The drug was detected at higher concentrations in specific regions of the brain, particularly the white matter of the cerebellum. Pseudomultiple reaction monitoring imaging was used to validate that the observed distribution was the target compound. The semiquantitative data obtained from signal intensities in the imaging was confirmed by laser microdissection of specific regions of the brain directed by the imaging, followed by hydrophilic interaction chromatography in combination with a quantitative high-resolution mass spectrometry method. This study illustrates that a dry matrix coating is a valuable and complementary matrix application method for analysis of small polar drugs and metabolites that can be used for semiquantitative analysis.

The development of a testing procedure for dry friction brakes

A description of the background to testing friction materials for automotive brakes explains the need for a rapid, inexpensive means of assessing their behaviour in a way which is both accurate and meaningful. Various methods of controlling inertia dynamometers to simulate road vehicles are rejected in favour of programming by means of a commercially available XY plotter. Investigation of brake service conditions is used to set up test schedules, and a dynamometer programming unit built to enable service conditions on vehicles to be simulated on a full scale dynamometer. A technique is developed by which accelerated testing can be achieved without operating under overload conditions, saving time and cost without sacrificing validity. The development of programming by XY plotter is described, with a method of operating one XY plotter to programme the machine, monitor its own behaviour, and plot its own results in logical sequence. Commissioning trials are described and the generation of reproducible results in frictional behaviour and material durability is discussed. Teclmiques are developed to cross check the operation of the machine in retrospect, and retrospectively correct results in the event of malfunctions. Sensitivity errors in the measuring circuits are displayed between calibrations, whilst leaving the recorded results almost unaffected by error. Typical results of brake lining tests are used to demonstrate the range of performance parameters which can be studied by use of the machine. Successful test investigations completed on the machine are reported, including comments on behaviour of cast iron drums and discs. The machine shows that materials can repeat their complex friction/ temperature/speed/pressure relationships at a reproducibility of the order of +-0.003u and +~ 0.0002 in. thickness loss during wear tests. Discussion of practical and academic implications completes the report with recommendations for further work in both fields.

Characterisation and surface-profiling techniques for composite particles produced by dry powder coating in pharmaceutical drug delivery

The production of composite particles using dry powder coating is a one-step, environmentally friendly, process for the fabrication of particles with targeted properties and favourable functionalities. Diverse functionalities, such flowability enhancement, content uniformity, and dissolution, can be developed from dry particle coating. In this review, we discuss the particle functionalities that can be tailored and the selection of characterisation techniques relevant to understanding their molecular basis. We address key features in the powder blend sampling process and explore the relevant characterisation techniques, focussing on the functionality delivered by dry coating and on surface profiling that explores the dynamics and surface characteristics of the composite blends. Dry particle coating is a solvent- and heat-free process that can be used to develop functionalised particles. However, assessment of the resultant functionality requires careful selection of sensitive analytical techniques that can distinguish particle surface changes within nano and/or micrometre ranges.

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.

Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers

This study investigated optimizing the formulation parameters for encapsulation of a model mucinolytic enzyme, a-chymotrypsin (a-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-?-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. a-CH or DNase I loaded microparticles were prepared via spray drying from double emulsion (w(1)/o/w(2)) utilizing chloroform (CHF) as the organic solvent, l-leucine as a dispersibility enhancer and an internal aqueous phase (w(1)) containing PEG4500 or Pluronic(®) F-68 (PLF68). a-CH released from microparticles was investigated for bioactivity using the azocasein assay and the mucinolytic activity was assessed utilizing the degradation of mucin suspension assay. The chemical structure of PEG-co-(PGA-co-PDL) was characterized by (1)H NMR and FT-IR with both analyses confirming PEG incorporated into the polymer backbone, and any unreacted units removed. Optimum formulation a-CH-CHF/PLF68, 1% produced the highest bioactivity, enzyme encapsulation (20.08±3.91%), loading (22.31±4.34µg/mg), FPF (fine particle fraction) (37.63±0.97%); FPD (fine particle dose) (179.88±9.43µg), MMAD (mass median aerodynamic diameter) (2.95±1.61µm), and the mucinolytic activity was equal to the native non-encapsulated enzyme up to 5h. DNase I-CHF/PLF68, 1% resulted in enzyme encapsulation (17.44±3.11%), loading (19.31±3.27µg/mg) and activity (81.9±2.7%). The results indicate PEG-co-(PGA-co-PDL) can be considered as a potential biodegradable polymer carrier for dry powder inhalation of macromolecules for treatment of local pulmonary diseases.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects

Purpose: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Methods: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60. min. The aberration data were analyzed over a 5. mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Results: Hypromellose drops caused an increase in total higher order aberrations (p= <0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p= <0.01, dry eyes p= 0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60. min. Differences in comfort levels failed to reach statistical significance. Conclusion: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. © 2013 British Contact Lens Association.

Report of the inaugural meeting of the TFOS i2 = initiating innovation Series:targeting the unmet need for dry eye treatment

On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i2 = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i2 meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i2 meeting.

Management of allergic conjunctivitis and dry eye

Ocular allergy is a common eye condition encountered in clinical practice. However, little is known how seasonal allergic conjunctivitis (SAC), the most common subtype, is managed in clinical practice. Further, dry eye, another common eye condition, may be misdiagnosed as SAC and vice-versa as they share similar signs and symptoms. In addition, despite the frequent recommendation of non-pharmacological treatments for SAC, evidenceto support their use has not been identified in the scientific literature. The aim of this thesis was therefore to determine the actual diagnosis and management of SAC and dry eye in clinical practice and investigate the efficacy of non-pharmacological treatments for these conditions. The diagnostic and management strategies for SAC and dry eye employed by pharmacy staff are found to be inconsistent with current guidelines and scientific evidence based upon a mystery shopper design. Cluster analysis of tear film metrics in normal and dry eye patients identified several clinically relevant groups of patients that may allow for targeted treatment recommendations. Using a novel environmental chamber model of SAC, the use of artificial tears and cold compresses, either alone or combined is an effective treatment modality for acute and symptomatic SAC, on a par with topical anti-allergic medication, and has been demonstrated for the first time. In addition, eyelid warming therapy with a simple, readily available, seed filled device is an effective method of treating meibomian gland dysfunction (MGD) related evaporative dry eye, perhaps the most common dry eye subtype. A greater focus on ophthalmology must be implemented as part of the formal education and training of pharmacy staff, while greater professional communication between community pharmacists, optometrists and the population they serve is required. Artificial tears and cold compresses may be considered as front line agents for acute SAC by pharmacy staff and optometrists, to whom pharmacological treatment options are limited.

Chitosan-modified dry powder formulations for pulmonary gene delivery

Spray-drying is an effective process for preparing micron-dimensioned particles for pulmonary delivery. Previously, we have demonstrated enhanced dispersibility and fine particle fraction of spray-dried nonviral gene delivery formulations using amino acids or absorption enhancers as dispersibility-enhancing excipients. In this study, we investigate the use of the cationic polymer chitosan as a readily available and biocompatible dispersibility enhancer. Lactose-lipid:polycation:pDNA (LPD) powders were prepared by spray-drying and post-mixed with chitosan or spray-dried chitosan. In addition, the water-soluble chitosan derivative, trimethyl chitosan, was added to the lactose-LPD formulation before spray-drying. Spray-dried chitosan particles, displaying an irregular surface morphology and diameter of less than 2 mu m, readily adsorbed to lactose-LPD particles following mixing. In contrast with the smooth spherical surface of lactose-LPD particles, spray-dried trimethyl chitosan-lactose-LPD particles demonstrated increased surface roughness and a unimodal particle size distribution (mean diameter 3.4 mu m), compared with the multimodal distribution for unmodified lactose-LPD powders (mean diameter 23.7 mu m). The emitted dose and in vitro deposition of chitosan-modified powders was significantly greater than that of unmodified powders. Moreover, the inclusion of chitosan mediated an enhanced level of reporter gene expression. In summary, chitosan enhances the dispersibility and in vitro pulmonary deposition performance of spray-dried powders.

Randomised masked clinical trial of the MGDRx eyebag for the treatment of meibomian gland dysfunction-related evaporative dry eye

Background/aims To investigate the efficacy and safety of the MGDRx EyeBag (The Eyebag Company, Halifax, UK) eyelid warming device. Methods Twenty-five patients with confirmed meibomian gland dysfunction (MGD)-related evaporative dry eye were enrolled into a randomised, single masked, contralateral clinical trial. Test eyes received a heated device; control eyes a non-heated device for 5 min twice a day for 2 weeks. Efficacy (ocular symptomology, noninvasive break-up time, lipid layer thickness, osmolarity, meibomian gland dropout and function) and safety (visual acuity, corneal topography, conjunctival hyperaemia and staining) measurements were taken at baseline and follow-up. Subsequent patient device usage and ocular comfort was ascertained at 6 months. Results Differences between test and control eyes at baseline were not statistically signi ficant for all measurements ( p>0.05). After 2 weeks, statistically significant improvements occurred in all efficacy measurements in test eyes ( p<0.05). Visual acuity and corneal topography were unaffected (p>0.05). All patients maintained higher ocular comfort after 6 months ( p<0.05), although the bene fit was greater in those who continued usage 1-8 times a month (p<0.001). Conclusions The MGDRx EyeBag is a safe and effective device for the treatment of MGD-related evaporative dry eye. Subjective benefit lasts at least 6 months, aided by occasional retreatment. Trial registration number NCT01870180.

Management of dry eye in UK pharmacies

Purpose - To investigate the ability of pharmacy staff in the United Kingdom (UK) to diagnose and treat dry eye. Methods - A mystery shopper technique to simulate a patient with presumed dry eye was used in 50 pharmacy practices in major towns and cities across the UK. Pharmacies were unaware of their involvement in the study. With the exception of a predetermined opening statement to initiate the consultation, no further information was volunteered. Questions asked, diagnoses given, management strategy advised and staff type was recorded immediately after the consultation. Results - The mean number of questions was 4.5 (SD 1.7; range 1–10). The most common question was the duration of symptoms (56%) and the least common was whether the patient had a history of headaches (2%). All pharmacy staff gave a diagnosis, but the majority were incorrect (58%), with only 42% correctly identifying dry eye. Treatment was advised by 92% of pharmacy staff, with the remaining 8% advising referral directly to the patient's GP or optometrist. Dry eye treatments involved topical ocular lubrication via eye drops (90%) and lipid based sprays (10%). However, only 10% gave administration advice, 10% gave dosage advice, 9% asked about contact lens wear, and none offered follow up although 15% also advised GP or optometrist referral. Conclusions - There is a need for improved ophthalmological training amongst pharmacists and pharmacy staff and establishment of cross referral relationships between pharmacies and optometry practices.