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.

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.

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.

Anti-inflammatory activity of CKC-containing cationic emulsion eye drop vehicles.

Purpose: Preservative-free cationic emulsion-based artificial tears (ATs) or drug vehicles are innovative eye drop formulations with tear film stabilization and drug delivery properties, and valuable in vivo anti-inflammatory and wound healing properties. These ATs have recently reached the market as ATs for the management of dry eye disease (DED) symptoms (i.e., Cationorm) or as a drug vehicle for cyclosporine (Ikervis). The aim of the present study was to explore the mechanism of action underlying the intrinsic anti-inflammatory and wound-healing efficacies harbored by the cationic emulsions of cetalkonium chloride (CE-CKC). Methods: The anti-inflammatory activity of two CE-CKC (0.002% and 0.005% CKC) emulsions was evaluated by assessing the expression of proinflammatory genes and the secretion of various markers in the following human cell types stressed by different agents: peripheral blood mononuclear cells (PBMCs; stimulation with anti-CD3/anti-CD28 or lipopolysaccharide (LPS)), CD4+ T lymphocytes (TCD4; stimulation with anti-CD3/anti-CD28), and a human corneal epithelial cell line (HCE-2; stimulation with LPS). The cells were incubated for 30 min with a 10% dilution of CE-CKC emulsions and then cultured without the emulsions for 24 h or 72 h in the presence of the various challenging agents. The supernatant was collected, and the secreted markers quantitated with flow cytometry or an enzyme-linked immunosorbent assay (ELISA). Gene expression of inflammatory markers was evaluated only in the PBMCs and HCE-2 cells stimulated with LPS. The in vitro protein kinase C (PKC) binding assay for IC50 determination was performed using standard procedures. Results: The CE-CKC emulsions decreased inflammatory gene expression in LPS-stimulated PBMCs (IFN-γ, IL-17A, CXCL-9, and TNFα) and LPS-stimulated HCE-2 cells (THBS1 and CCL2). Both CE-CKC emulsions inhibited the secretion of IL-17 (from anti-CD3/anti-CD28-stimulated TCD4), TNFα, IFN-γ, and IL-2 (from anti-CD3-/anti-CD28-stimulated PBMCs), and IL-6 and IL-8 (from LPS-stimulated HCE-2). The in vitro PKC binding assay revealed that CKC, the cationic agent, is a specific PKCα inhibitor. In addition, tyloxapol, another excipient, showed some anti-inflammatory activity on IL-6 and IL-8 in the LPS-stimulated HCE-2 cells. Conclusions: This study indicates that the CE-CKC emulsions are able to directly modulate the secretion and expression of proinflammatory cytokines and chemokines. The results also suggest that CKC and tyloxapol are pharmacologically active excipients with potentially beneficial effects in vivo. These data shed new light on the efficacy observed on the DED signs of these CE-CKC emulsions in clinical trials.

Higher-Order Aberrations After Cyclopentolate, Tropicamide, and Artificial Tear Drops Application in Normal Eyes.

PURPOSE: To determine the effect of cyclopentolate, tropicamide, and artificial tear drops on higher-order aberrations (HOAs) in normal eyes with OPD-Scan III (Nidek Inc., Tokyo, Japan). METHODS: In this study, 189 eyes of individuals aged 20 to 35 years were selected as samples. Inclusion criteria were a corrected visual acuity of 20/20 or better, a minimum size of about 5 mm for the pupil in the dark, hyperopia and myopia less than 5 D, and astigmatism less than 2 D. Moreover, participants with pathological eye problems, a history of intraocular surgery, and ocular diseases affecting the accommodation, pupil size, and corneal surface were excluded. Higher-order aberrations of the participants were assessed by the OPD-Scan III before and after cyclopentolate (Colircuss), tropicamide (Mydrax 0.5%), and artificial tears (Tearlose) drop instillation. RESULTS: After instilling cyclopentolate drops, the mean of the total root mean square (RMS) increased from 4.580 to 6.335 D, total spherical aberration increased from 0.155 to 0.381 D, and total coma increased from 0.195 to 0.369 D; the increases were significant for total RMS and total spherical aberration, but a significant relationship was not seen with total coma. After tropicamide, the mean aberrations of total RMS increased from 4.301 to 4.568 D, total spherical aberration increased from 0.146 to 0.160 D, and total coma increased from 0.213 to 0.230 D; the increase was only significant for total coma. On the other hand, after artificial tears, the average of all aberrations decreased in a nonsignificant manner. CONCLUSION: Most changes of mean aberrations were related to cyclopentolate drops. Tropicamide and artificial tears had the second and third rank according to their effect on mean errors. As a result, it seems that ocular accommodation is the most important impact on HOA than pupil size. However, the pupil size is the second factor for HOAs.

Novel Artificial Tears Containing Cross-Linked Hyaluronic Acid: An In Vitro Re-Epithelialization Study.

Dry eye syndrome is a common disease which can damage the corneal epithelium. It is treated with eye drops to stimulate tear production and hydrate the corneal surface. The most prescribed artificial tear remedies contain hyaluronic acid (HA), which enhances epithelial wound healing, improving tissue health. To the best of our knowledge, only a few recent studies have investigated cross-linked HA (HA-CL) in eye drops for human applications. This work consists in an in vitro evaluation of the re-epithelialization ability of two different preparations containing a recently synthetized HA cross-linked with urea: 0.02% (w/v) HA-CL (solution 1, S1), and 0.4% (w/v) HA-CL (solution 2, S2). The study was conducted on both 2D human corneal cells (HCEpiC) and 3D reconstructed tissues of human corneal epithelium (HCE). Viability by 3(4,5-dimethylthiazol-2)2,5-diphenyltetrazolium bromide (MTT) test, pro-inflammatory cytokine release (interleukin-8, IL-8) by ELISA, and morphology by hematoxylin and eosin (HE) staining were evaluated. In addition, to understand the molecular basis of the re-epithelialization properties, cyclin D1 levels were assessed by western blot. The results showed no cellular toxicity, a slight decrease in IL-8 release, and restoration of epithelium integrity when the wounded 3D model was treated with S1 and S2. In parallel, cyclin D1 levels increased in cells treated with both S1 and S2.

[Potential for use of hydroxypropyl guar in tear substitute therapy]. / Vozmozhnosti primeneniya gidroksipropilguara v slezozamestitel'noi terapii.

Of the large number of polymers used in artificial tear formulations, natural polysaccharides - hydroxypropyl guar, sodium hyaluronate, chondroitin sulfate, dextran, etc., are gaining more and more popularity. Hydroxypropyl guar stands out through its ability to form a long-lasting structured matrix adhered to the damaged ocular surface and ensuring good wettability of the latter and regeneration of epithelial cells. At that, the viscosity of hydroxypropyl guar increases with increasing tear pH (which, in turn, correlates with the severity of xerosis) and further prolongs the moisturizing effect. According to experimental studies, the in vitro protective activity of hydroxypropyl guar surpasses that of sodium hyaluronate, which is widely used. Thus, corneal epithelial cell cultures were more tolerant to drying and pericardial leaflets showed lower friction coefficient, if pretreated with hydroxypropyl guar and not hyaluronic acid. Subsequent clinical studies showed that Systane Ultra was more effective in patients with dry eye syndrome than a carboxymethylcellulose and glycerol-containing drug. It has been also proved that Systane Balance provides a greater increase in thickness of the tear film lipid layer and in overall stability of the tear film as compared to SootheXP, which has a similar lipid composition. The present review also covers potential utility of other artificial tear formulations that, besides the moisturizing effect, are able to reduce the tear film osmolarity, prevent further oxidative stress, and abate the inflammatory process.

Histopathological changes on the ocular surface of New Zealand white rabbits after instillation of a fixed combination of 0.09 % xanthan gum and 0.1 % chondroitin sulfate.

The aim of this study was to evaluate the histopathological changes in a model of New Zealand white rabbits after the ocular instillation of a fixed combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate for 15 days. This was a preclinical study which compared the previously described combination with placebo on an animal model of sixteen New Zealand white rabbits. The intervention consisted of the instillation of one drop of a fixed combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate on the right eye of each rabbit 6 times per day (every 2 h) in a 12-hour period for 15 days. The left eyes were used as control. Assessments on the anterior and posterior segment, ocular signs, and specific ocular surface characteristics were conducted at days 0, 1, 2, 4, 7, 10, and 15. Histopathological studies of the corneal and conjunctival epithelium were performed at the end of the intervention. No significant changes were observed during the assessments of the anterior and posterior segments. No differences in the number of goblet cells between groups were reported. The histopathological study of the corneal basement membrane's thickness, stromal, and conjunctival epithelium did not show significant changes between groups. The use of a fixed-dose combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate on the ocular surface of New Zealand white rabbits every 2 h for 15 days causes no histopathological changes in anterior/posterior segments, nor a decrease in the number of goblet cells compared with placebo.

[Development of new magistral method for the preparation of artificial tears]. / Korszeru tartósítási módszer fejlesztése magisztrálisan eloállítható mukönnyhöz.

Nowadays, large part of the population in Hungary is affected by the dry eye disease or symptom. Most of these magistral pharmaceuticals (FoNo VI) compared to the industrial products have disadvantages. They are not compatible with contact lenses, because of the preservatives and after opening they can be used only for seven days. In our experiments we used sodium-perborate as preservative, which could be a solution for the problems mentioned above. Our results indicate that the sodium-perborate sterilized the solution and resists against microbiological contamination. Its preservative effect maintained for more than four weeks. Our further purpose is to develop a new pharmacy drug preparation method to find an effective solution for the microbiological stability-related problems of artificial tears.

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.

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.

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.

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.

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.

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.

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.

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.

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.