Carrageenan films as promising mucoadhesive ocular drug delivery systems.

Polymer mucoadhesive films being developed for use in ophthalmology represent a new tool for drug delivery and are considered an alternative to traditional dosage forms. Due to their mucoadhesive properties, carrageenans (CRGs) are widely used in various forms for drug delivery. In this study, films based on CRGs of various structural types (κ/ß, κ, x, and λ) for use in ophthalmology were studied. The films were loaded with the active substance echinochrome (ECH), a sea urchin pigment used in ophthalmology. Spectral data showed that ECH remained stable after its incorporation into the CRG films and did not oxidize for at least six months. Hydrophilic CRG films with a thickness of 10-12 µm were characterized in terms of their swelling and mucoadhesive properties. The rheological properties of solutions formed after film dissolution in artificial tears were also assessed. κ- and κ/ß-CRG films with ECH exhibited pseudoplastic behavior after rehydrating films with an artificial tear solution. The CRG-loaded films had different swelling characteristics depending on the structure of the CRG used. The films based on highly sulfated CRGs dissolved in artificial tears, while the films of low-sulfated κ/ß-CRG exhibited limited swelling. All studied ECH-loaded films exhibited mucoadhesive properties, which were evaluated by a texture analyzer using mucous tissue of the small intestine of the pig as a model. There was a slight prolongation of ECH release from CRG films in artificial tears. The effect of CRG/ECH on the epithelial cell lines of the outer shell of the human eye was investigated. At low concentrations, ECH in the composition of the CRG/ECH complex had no cytotoxic effect on corneal epithelial and conjunctival human cells. The use of ECH-containing films can prevent the drug from being immediately washed away by tears and help to retain it by increasing viscosity and having mucoadhesive properties.

Evaluation of the effect of artificial tears on corneal epithelial thickness changes after photorefractive keratectomy.

PURPOSE: This study aimed to evaluate the corneal epithelial thickness changes after photorefractive keratectomy (PRK) and the impact of long-term artificial tear usage on epithelial thickness changes in these patients. METHODS: This study was performed on 71 patients (142 eyes) without dry eye disease who received PRK for myopic refractive correction. The corneal epithelial thickness profile was obtained before, one, three, and six months after surgery using anterior segment optical coherence tomography. Patients were randomly divided into two groups: group A, who received preservative-free artificial tears post-surgery, and group B, who did not receive artificial tears. RESULTS: The epithelial thickness decreased universally in the first month and then increased in the 3- and 6-month follow-ups. Group A had a significantly thicker epithelium in central, paracentral, and midperipheral zones compared with group B in the 3-month follow-up. In the 6-month follow-up, no significant differences were detected between groups. At the last follow-up, the central, paracentral, and midperipheral zone epithelial thicknesses in all patients were significantly higher than preoperative values, but peripheral zone thickness only increased to preoperative values. CONCLUSIONS: Patients using artificial tears showed a faster thickening, especially in the central and paracentral zones, but there were no significant differences between the two groups in the final follow-up. Artificial tear usage may increase the rate of the epithelial remodeling process in post-PRK patients without significantly altering the final epithelial thickness profile. Further studies are warranted to evaluate the influence of different factors on epithelial remodeling.

A Critical Appraisal of the Physicochemical Properties and Biological Effects of Artificial Tear Ingredients and Formulations.

Dry eye disease is among the most prevalent diseases affecting the ocular surface. Artificial tears remain the cornerstone therapy for its management. There are currently a wide variety of marketed artificial tears available to choose from. These artificial tears differ significantly in their composition and formulation. This article reviews the physicochemical and biological properties of artificial tear components and how these characteristics determine their use and efficacy in the management of dry eye. Furthermore, this article also discusses the various formulations of artificial tears such as macro and nanoemulsion and the type of preservatives present in them.

Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease.

Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.

Commercially Available Eye Drops Containing Trehalose Protect Against Dry Conditions via Autophagy Induction.

Purpose: Evaluation of marketed eye drops with or without trehalose, a nonreducing natural osmoprotector disaccharide, in autophagy modulation and its role in cell survival during desiccation. Methods: Eye drops containing either sodium hyaluronate (SH) (Hyabak®, Thea, France) or a combination of SH with trehalose (Thealose Duo®, Thea, France) were compared with control conditions to evaluate the ability to modulate autophagy in human epithelial cells in vitro. Autophagy was monitored using LC3, a marker of the autophagic machinery, by fluorescence microscopy and immunoblot analysis. Control and autophagy-deficient cells treated with eye drops were exposed to desiccation to mimic dry eyes and cell survival was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Trehalose, a known autophagy inducer was used as a positive control. Results: Artificial tears containing SH with and without trehalose induce a complete autophagic flux, as indicated by an increase in the number of autophagosomes and autolysosomes, and the accumulation of the lipidated form of LC3 associated with complete autophagy. In addition, there was a synergistic effect of SH for autophagy induction when combined with trehalose, compared with each of the components alone. Survival of cells treated with both eye drops and exposed to desiccation was decreased in autophagy-deficient cells, demonstrating the essential role of autophagy on eye drop protection. Conclusions: Autophagic flux is induced by SH-containing eye drops, and this phenomenon is enhanced in combination with trehalose. We also demonstrated that autophagy induction is involved in the osmoprotective effects of both trehalose and SH-containing eye drops, to maintain epithelial cell homeostasis in dry conditions.

Preclinical Development of Artificial Tears Based on an Extract of Artemia Salina Containing Dinucleotides in Rabbits.

PURPOSE: To evaluate the preclinical efficacy of eye drops based on an extract of Artemia salina on the ocular surface of rabbits. Tear secretion, tear break-up time and corneal staining were measured. MATERIAL AND METHODS: A preclinical and short-term prospective study was performed. Twenty New Zealand white rabbits were divided into five groups, with four rabbits per group, each receiving a different concentration of Artemia salina. In each rabbit, an extract of Artemia salina (2%, 4%, 6%, 8% or 10%) was randomly instilled in one eye and saline solution (negative control) in the other eye. Tear secretion, tear break-up time and corneal staining were measured before and after the instillation of five drops per eye (one drop per hour) on the same day. RESULTS: In tear secretion, there was an increase of 43.88 ± 6.73% with 4% Artemia salina in comparison with its baseline measurement (P = .049). The rest of the groups did not show differences (P ≥ 0.05). For tear break-up time, none of the groups showed differences (P ≥ 0.05), while for corneal staining score, there was an improvement of 0.88 ± 0.83 with 4% Artemia salina (P = .038) and a deterioration of 0.50 ± 0.83 with control solution (P = .008). CONCLUSIONS: Short-term instillation of eye drops with 4% Artemia salina produced both stimulation of tear secretion and a slight improvement of physiological corneal staining. Besides, all the doses of up to 10% Artemia salina did not produce undesirable side effects on the ocular surface. Therefore, these eye drops are presented as a possible new treatment for dry eye due to their secretagogue properties and ocular surface regeneration.

Formulation of hyaluronan grafted with dodecanoic acid as a potential ophthalmic treatment.

This work concerns the chemical modification of medium molecular weight hyaluronan for ophthalmic applications. The synthesis of amphiphilic HA with dodecanoyl moities was carried out under mild aqueous conditions. Perfect control of the degree of substitution was obtained by varying the molar ratio of activated fatty acid used in the reaction feed. Moreover, the preparation of the derivatives was optimized to achieve the desired degree of substitution (DS = 9.0 ± 0.2 %). The prepared hyaluronan derivatives were water-soluble and exhibited self-associating properties (amphiphilicity). The structure of the prepared derivatives was elucidated by NMR spectroscopy, rheology, turbidity, SEC-MALLS, and gas chromatography (GC). The hydrophobic moieties increase the solution viscosity by physical crosslinking. Low concentration of HAC12 is needed to prepare highly viscous solutions with potential use for ophthalmic applications. Amphiphilic HA kept the biocompatibility of hyaluronan. The degree of substitution and Mw of the amphiphilic HA controls the sterilization by filtration. The protection against desiccation was tested using human keratinocytes (HaCaT) cells lines.

Effect of Artificial Tear Formulations on the Metabolic Activity of Human Corneal Epithelial Cells after Exposure to Desiccation.

Artificial lipid-containing tear formulations are developed to reduce tear evaporation by the restoration of a deficient tear lipid layer. Artificial tear formulations that prevent cell desiccation will result in ocular surface protection and the maintenance of cell metabolic activity. During dehydration, cells undergo the process of loss of metabolic activity and subsequently cell death. This work describes a method for assessing the efficacy of artificial tear formulations. The metabolic dye (i.e., alamarBlue) changes from a low fluorescent molecule resazurin to a fluorescent molecule resorufin in viable cells. The biological performance of an artificial tear formulation is measured as the ability of the formulation to (a) maintain cell viability and (b) provide cell protection from desiccation. Growth media and saline are used as controls for the cell viability/desiccation tests. Cells are incubated with test solutions for 30 min and then desiccated for 0 or 5 min at 37 °C and 45% relative humidity. Cell metabolic activity after initial exposure and after cell desiccation is then determined. The results show the comparative effects of eye drop formulations on cell metabolic activity and desiccation protection. This method can be used to test dry eye formulations that are designed to treat individuals with evaporative dry eye.

Nanoscale poly(acrylic acid)-based hydrogels prepared via a green single-step approach for application as low-viscosity biomimetic fluid tears.

The present work reports a nanotechnology strategy to prepare a low-viscosity poly(acrylic acid) (PAAc)-based tear substitute with enhanced efficacy and compliance. Specifically, nanogels composed of PAAc and polyvinylpyrrolidone (PVP) were prepared by adapting an ionizing radiation method. For this purpose, different aqueous systems: PVP/PAAc nanoparticulate complexes, PVP/acrylic acid (AAc), N-vinylpyrrolidone (N-VP)/PAAc, and N-VP/AAc were exposed to gamma rays. The dynamic light scattering technique showed that stable nanogels are only produced in a relatively high yield from the PVP/AAc system. Nanogel formation was driven by the hydrogen-bonding complexation between PVP and PAAc (formed in situ) as well as the radiation-induced cross-linking. Transparency, viscosity and mucoadhesiveness of emerged nanogels were optimized by controlling the feed composition and irradiation dose. Furthermore, neutralized nanogels were topically applied in a dry eye model and compared with a PAAc-based commercial tear substitute, namely Vidisic® Gel. The results of Schirmer's test and tear break-up time demonstrated that nanogels prepared from AAc-rich feed solutions at 20 kGy enhanced markedly the dry eye conditions. The histopathological analysis also ensured the competence of PAAc-rich nanogels to completely return the corneal epithelium to its normal state.

Adhesion of Pseudomonas aeruginosa, Achromobacter xylosoxidans, Delftia acidovorans, Stenotrophomonas maltophilia to contact lenses under the influence of an artificial tear solution.

Corneal infection is a devastating sight-threatening complication that is associated with contact lens (CL) wear, commonly caused by Pseudomonas aeruginosa. Lately, Achromobacter xylosoxidans, Delftia acidovorans, and Stenotrophomonas maltophilia have been associated with corneal infection. This study investigated the adhesion of these emerging pathogens to CLs, under the influence of an artificial tear solution (ATS) containing a variety of components commonly found in human tears. Two different CL materials, etafilcon A and senofilcon A, either soaked in an ATS or phosphate buffered saline, were exposed to the bacteria. Bacterial adhesion was investigated using a radio-labeling technique (total counts) and plate count method (viable counts). The findings from this study revealed that in addition to P. aeruginosa, among the emerging pathogens evaluated, A. xylosoxidans showed an increased propensity for adherence to both CL materials and S. maltophilia showed lower viability. ATS influenced the viable counts more than the total counts on CLs.

Innovative bulls eye drop applicator for self-instillation of eye drops.

PURPOSE: To report the role of Bulls eye drop applicator device in self-instillation of eye drops and in prevention of wastage of medicine. METHODS: A small pocket sized device "Bulls eye drop applicator" was developed, which is a simple, handy, mirror-based attachment which can be attached to any eye drop bottle to help in accurate self-instillation of the drops in the eye. The prototype of this device was tried in ten volunteer subjects (Group 1) and 15 patients (Group 2); they were asked to use lubricating eye drops (5 ml bottle) in one eye without the device (N) and in the other eye with the device (M). The numbers of attempts for the application of eye drops were noted and the residual eye drops in the returned bottles were measured for quantitative assessment. RESULTS: Ten volunteers and 11/15 patients completed the study. At the completion of the study, there were a total of 232 applications of eye drops in the Group 1 N (without device) and 1 M (with device). To achieve these 232 applications, there were 330 attempts without the device and 266 attempts of instillation were needed with the device (P < 0.0001). In Group 2, there were a total of 544 applications of eye drops; to achieve this, there were 879 attempts in Group 2 N and 685 attempts of instillation in Group 2 M (p < 0.0001). The cumulative quantity of residual drops in the returned bottles collected from Group 2 N was 5.1 ml and it was 19.7 ml in Group 2 M (p = 0.001). CONCLUSIONS: The number of attempts of instillation reduced significantly with the use of the eye drop applicator device. The use of eye drops applicator device reduced the wastage of drops from 42.2% to 14.6% in Group 1 N Vs Group 1 M and saving of about 35.7 % in Group 2 M compared to Group 2 N.

Assessing the effectiveness of OTC Advertising on artificial tear drops from an experiential marketing perspective.

Introduction: It is acknowledged that leading pharmaceutical companies lately spend more on marketing than they are investing in research and technology development. Romania registers one of the largest market growths in the pharmaceutical industry from Central and Eastern Europe, and it is one of the main investors on the advertising market. The rapid changes in the pharmaceutical landscape have demanded for organizations to re-evaluate their infrastructure and the information delivery methods, as well as cut through the clutter and build competitive advantages by using effective advertising. The dry eye is a commonly disease encountered worldwide, which is treated with the help of over-the-counter (OTC) artificial tear drops. Aim: The aim of this study was twofold: to determine the profile of the Romanian consumer who uses artificial tear drops and to assess the components of experiential marketing used in a TV advertisement, which have the highest influence on the consumer's perception of effective advertising. Material and method: We selected a TV advertisement that used the magical concept of the artificial tear drops in the shape of water in a desert area, suggesting an eye irritation. The instrument for data collection was a self-administered questionnaire based on the watched advertising spot about the OTC artificial tear drops. The sample was made up of 384 participants and the sampling method was the snowball technique. Moreover, a model using Structural Equation was validated in order to assess the established relationships between the experiential marketing components and the effectiveness of the OTC artificial tear drops advertising. Findings: The findings showed that the demographic profile of the OTC artificial tear drops consumer is a female, with the mean age of 39 years, who graduated from university, with an average income of 2500 RON (Romanian currency), single, and with an office job. The mean number of hours spent in front of a computer per day was 10. The structural equation model revealed that the component think experience has the highest direct influence on the consumer's perception of an advertisement about OTC artificial tear drops as being effective. Discussion: The pharmaceutical market is different from other markets in that the decision maker is not the purchaser except for the OTC drugs that do not require a receipt from a physician. Think experience focuses on rational decision-making and problem solving but in a creative way.

Effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes: a systematic review / Eficácia do uso de colírios sem preservativos comparados com colírios com preservativos no tratamento do olho seco: uma revisão sistemática

ABSTRACT This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). Online databases were searched (LILACS, EMBASE, MEDLINE, and CENTRAL) from inception to April 2018; references from included papers were also searched. The following keywords were used: lubricants OR artificial tears OR artificial tears, lubricants AND dry eye OR dry eye syndrome OR syndromes, dry eye OR dry eyes. Among the 2028 electronic search results, 29 full papers were retrieved and four were considered relevant. The number of participants from these studies ranged from 15 to 76. Meta-analysis was possible for the following outcomes: score of symptoms according to the Ocular Surface Disease Index - Allergan (OSDI), tear secretion rate using the Schirmer test, tear evaporation rate using the tear film breakup time test, burning, foreign body sensation, and photophobia. No statistically significant difference was observed between the two groups, and no side effects were attributed to the interventions. Evidence proving that preservative-free artificial tears are more effective than preserved artificial tears is lacking.

RESUMO Esta revisão sistemática teve como objetivo avaliar a eficácia do uso de lágrimas artificiais sem conservantes em comparação com lubrificantes preservados no tratamento do olho seco na Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). As bases de dados online foram pesquisadas (LILACS, EMBASE, MEDLINE e CENTRAL) desde o início até abril de 2018; referências de artigos incluídos também foram pesquisadas. Foram utilizados os seguintes descritores: lubrificantes OU lágrimas artificiais OU lágrimas artificiais, lubrificantes E olho seco OU síndrome do olho seco OU síndromes, olho seco OU olhos secos. Dos 2028 resultados de busca eletrônica, 29 artigos completos foram recuperados, e quatro foram considerados relevantes. O número de participantes desses estudos variou de 15 e 76. A meta-análise foi possível para as seguintes variáveis: escore de desfecho dos sintomas de acordo com o Índice de Doença da Superfície Ocular - Allergan (OSDI), taxa de secreção lacrimal pelo teste de Schirmer, taxa de evaporação lacrimal usando o teste de tempo de ruptura do filme lacrimal, queimação, sensação de corpo estranho e fotofobia. Nenhuma diferença estatisticamente significativa foi observada entre os dois grupos, e nenhum efeito adverso foi atribuído às intervenções. Evidências provando que as lágrimas artificiais sem conservantes são mais eficazes do que as lágrimas artificiais preservadas estão faltando.

Effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes: a systematic review.

This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). Online databases were searched (LILACS, EMBASE, MEDLINE, and CENTRAL) from inception to April 2018; references from included papers were also searched. The following keywords were used: lubricants OR artificial tears OR artificial tears, lubricants AND dry eye OR dry eye syndrome OR syndromes, dry eye OR dry eyes. Among the 2028 electronic search results, 29 full papers were retrieved and four were considered relevant. The number of participants from these studies ranged from 15 to 76. Meta-analysis was possible for the following outcomes: score of symptoms according to the Ocular Surface Disease Index - Allergan (OSDI), tear secretion rate using the Schirmer test, tear evaporation rate using the tear film breakup time test, burning, foreign body sensation, and photophobia. No statistically significant difference was observed between the two groups, and no side effects were attributed to the interventions. Evidence proving that preservative-free artificial tears are more effective than preserved artificial tears is lacking.

Improvement of ferning patterns of lubricant eye drops mixed with various electrolytes and carboxymethylcellulose.

PURPOSE: To investigate the effect of the addition of electrolytes, basic tear solution (BTS), and sodium carboxymethylcellulose (SCMS) on the tear ferning (TF) patterns of Blink Contact Soothing Eye Drops® and Refresh Plus Tears®. METHOD: Samples of Blink Contact Soothing Eye Drops® and Refresh Plus Tears® (10 µL) were mixed with different volumes (3-30 µL) of several electrolytes, namely sodium chloride, potassium chloride, calcium chloride, magnesium chloride hexahydrate, sodium hydrogen carbonate, and sodium dihydrogen phosphate, BTS, and SCMS. Samples (1 µL) of the mixtures were dried on a glass slide at room temperature and the TF patterns were inspected using a light microscope, graded using the Masmali five-point grading scale and compared to the corresponding TF grades of the artificial tears. RESULTS: The TF grades of Blink Contact Soothing Eye Drops® and Refresh Plus Tears® improved from 1.2 and 1.5, respectively to 0.2 when calcium chloride was used as the electrolyte. Improvements in TF grades were also observed when other electrolytes (e.g., sodium dihydrogen phosphate), BTS, and SCMS were used. CONCLUSION: The tear ferning test can be used to evaluate the effect of the addition of electrolytes to an artificial tear in-vitro. The TF patterns of artificial tear solutions such as Blink Contact Soothing Eye Drops® and Refresh Plus Tears® can be improved with the addition of various concentrations of electrolytes, BTS, and SCMS, however further research is still needed to understand the clinical relevance of TF patterns with respect to the management of dry eye symptoms and their potential role in the development of new artificial tears.

Tear-film-oriented diagnosis for dry eye.

Tear-film (TF) stability protects the ocular surface epithelium from desiccation and is ensured via cooperation between the ocular surface components including constituents of the TF and ocular surface epithelium. Thus, when those components are insufficient or impaired, the TF breakup that initiates dry eye occurs. Recently, new, commercially available eye drops have appeared in Japan that enable TF stabilization via targeted supplementation of deficient ocular surface components. Hence, a new layer-by-layer diagnosis and treatment concept for dry eye, termed tear-film-oriented diagnosis and tear-film-oriented therapy (TFOD and TFOT, respectively), have emerged and become widely accepted in Asian countries and beyond. TFOD is a diagnostic method for dry eye based on the TF dynamics and breakup patterns (BUPs), through which dry-eye subtypes, including aqueous-deficient dry eye, decreased-wettability dry eye, and increased-evaporation dry eye, are diagnosed. BUPs and/or each diagnosed dry-eye subtype can, in a layer-by-layer fashion, reveal the insufficient ocular surface components responsible for the TF breakup. Using these data, the optimal topical TFOT to treat dry eye can be proposed by addressing the TF breakup via the supplementation of the insufficient components. In Japan, TF breakup is now regarded as a visible core mechanism of dry eye, and abnormal breakup time (ie, ≤ 5 seconds) and symptoms are currently considered part of the diagnostic criteria for dry eye. In this review, the importance of TF instability as a core manifestation of dry eye, the molecular mechanism of TF breakup, the concept of TFOD, and the methods for implementing TFOD for TFOT are introduced.

Effects of 5% sodium chloride ophthalmic ointment on thickness and morphology of the normal canine cornea.

OBJECTIVE: To determine the effect of 5% sodium chloride ophthalmic ointment (5% NaCl) on thickness and morphology of the normal canine cornea using ultrasonic pachymetry (USP), in vivo confocal microscopy (IVCM), and Fourier-domain optical coherence tomography (FD-OCT). METHODS: Five healthy laboratory Beagles received ophthalmic examinations including USP, IVCM, and FD-OCT prior to and at fixed intervals following treatment. The right and left eyes were treated with 5% NaCl and artificial tears ophthalmic ointment (AT), respectively, every 2 hours for 4 treatments/d (days 2-9), and then hourly for 7 treatments/d (day 10). Treatment groups were statistically compared using mixed-effects linear regression. RESULTS: Treatment with 5% NaCl resulted in a 12 µm decrease in corneal thickness from baseline (P < .001), while there was no significant difference in corneal thickness between values obtained at baseline and following treatment with AT (P = .82). Epithelial cell density significantly increased from baseline (530 ± 52 cells/mm2 ) to 577 ± 43 and 567 ± 15 cells/mm2 with 5% NaCl and AT, respectively (P = .003 and .005, respectively). However, keratocyte cell density in the anterior and posterior stroma and endothelial cell density did not significantly differ following treatment with 5% NaCl or AT ointment (P > .05). CONCLUSIONS: Short-term topical treatment with 5% NaCl decreased corneal thickness in normal dogs with no observable changes in corneal morphology or signs of ocular toxicity.

Preclinical Evaluation of a New Hydroxypropyl-Guar Phospholipid Nanoemulsion-Based Artificial Tear Formulation in Models of Corneal Epithelium.

PURPOSE: To evaluate the effect of hydroxypropyl-guar anionic phospholipid nanoemulsion (HP-guar nanoemulsion), a new artificial tear formulation for treatment of dry eye disease (DED), in corneal epithelium models. METHODS: Cultured human corneal epithelial cells were used to assess (1) hydration protection and hydration retention protection against desiccation, and (2) cell recovery after benzalkonium chloride (BAC) damage. Corneal epithelium permeability was measured by 5,6-carboxyfluorescein (CF) uptake in intact rabbit eyes. Lubricity was determined using simulated blinking in bovine pericardium-pericardium tribological experiments; elastic filament strength was measured using an extensional rheometer. Comparator arms included vehicle/control and the microemulsion [Systane® Balance (SYSB)]. RESULTS: Cell hydration protection was 39.5%, 7.1%, and -0.1%, and surface hydration retention was 32.6%, 11.0%, and -1.2% with HP-guar nanoemulsion, SYSB, and vehicle, respectively, after desiccation. After 48 h, cell recovery from BAC exposure (relative fluorescence units ± SD) was faster with HP-guar nanoemulsion treatment (2.66 ± 0.2) than SYSB (2.76 ± 0.2) and vehicle (3.11 ± 0.4). The CF permeability (ng CF/g) decreased in rabbit cornea treated with HP-guar nanoemulsion (9.6 ± 2.3) than those with SYSB (13.12 ± 2.8) or BAC-exposed cornea (22.6 ± 5.1). HP-guar nanoemulsion demonstrated greater lubricity and polymer filament break-up time than SYSB and vehicle. In all assessments, HP-guar nanoemulsion showed significant improvement versus vehicle/control (P < 0.05); outcomes were better with HP-guar nanoemulsion versus microemulsion. CONCLUSIONS: The HP-guar nanoemulsion promotes greater moisture retention, protection, improved cell barrier function, and increased elastic filament strength in corneal epithelium models. The potential clinical benefits of HP-guar nanoemulsion needs to be evaluated in patients with DED, in future studies.

Novel in vitro method to determine pre-lens tear break-up time of hydrogel and silicone hydrogel contact lenses.

PURPOSE: To develop an in vitro model to determine pre-lens non-invasive break-up time (NIBUT) and to subsequently use this method to compare the NIBUT over contemporary daily disposable (DD) contact lenses (CL). METHODS: Three silicone hydrogel (SH) and two conventional hydrogel (CH) DD CLs were incubated in an artificial tear solution (ATS). A model blink cell (MBC) was utilised to mimic intermittent air exposure. CLs were repeatedly submerged for 3 seconds (s) and exposed to air for 10 s over periods of 2, 6, 12, and 16 hours (h). NIBUTs (n = 4) were determined out of the blister pack (T0) and at the end of each incubation period. RESULTS: Overall, nesofilcon A showed the longest NIBUTs (p < 0.001). At T0, CHs revealed significantly longer NIBUTs (p ≤ 0.001) than SHs. After 2 h, nesofilcon A showed the longest NIBUT, however, this was only statistically significant compared with delefilcon A (p ≤ 0.001). After 6 h, nesofilcon A NIBUT was significantly longer than all other CLs (p ≤ 0.001). Etafilcon A showed a significantly longer NIBUT (p ≤ 0.001) after 12 h and delefilcon A had the longest NIBUT (p ≤ 0.001) after 16 h. Statistically significant (p ≤ 0.05) changes of NIBUT within the lens materials varied between time points. After 16 h, all CLs showed significant reductions in NIBUTs (p ≤ 0.001) in comparison to T0. CONCLUSION: NIBUT values reduced gradually over time and varying levels of deposition impacted measured pre-lens NIBUTs. While NIBUT of CH materials are longer immediately out of the blister pack, after tear film exposure, the NIBUTs obtained using this methodology became very similar.

The impact of dry eye disease treatment on patient satisfaction and quality of life: A review.

Several aspects of the quality of life (QoL) and treatment satisfaction of patients with dry eye disease (DED) may be underestimated. Ocular symptoms, which are assessed by validated patient-reported questionnaires and may include stinging, burning, itchiness, grittiness, dryness and discomfort, reduce QoL by affecting daily activities and work productivity. Self-reported symptoms do not always correlate with post-treatment improvements in clinical measures such as tear film break-up time, inflammation and osmolarity. Thus, treatments may improve clinical ocular features without improving symptoms that affect daily life. This review explores 1500 abstracts from congress presentations and peer-reviewed journals for QoL and treatment satisfaction data on the use of active lubricants, osmoprotectants, secretagogues, and immunomodulators present in topical formulations for DED treatment, and validated symptom questionnaires. Patient-reported symptoms of DED are generally improved after treatment with topical formulations for tear replacement, tear stimulation or anti-inflammatory therapy compared with baseline or a control treatment. However, more data are required to compare the performance of active ingredients. It is fundamental to diagnose patients with DED accurately, recognising the major cause behind their dry eyes. Studies are also necessary to identify how patient satisfaction and QoL may be improved through long-term use of topical preparations. We conclude that careful and thorough consideration of patient-reported symptoms should be integrated into DED management to help tailor treatment to patient needs.