Artificial Tear Formulations Research Articles

Expert opinion on the prescription practice of artificial tear formulations for the management of dry eye disease in Indian settings: A questionnaire-based survey

Clinical studies suggested that Carboxymethyl cellulose (CMC) and Hyaluronic acid (HA) were equally effective in treating DED, other studies have shown that one treatment option outperforms the other.So, this study aimed to explore expert opinions on the use of artificial tear formulations for the effective treatment of dry eye disease (DED) in Indian settings, specifically focusing on prescribing practices for different severity levels of DED. The cross-sectional, questionnaire-based study in which data was collected through a multiple-response questionnaire. The questionnaire comprised 22 questions, covering various aspects such as the clinical characteristics of DED patients and the utilization of artificial tear formulations at different stages of the disease. Among the 54 respondents, 63% of them observed a higher prevalence of DED in individuals aged 25 to 40 years. Furthermore, 77.77% of respondents identified burning or stinging in the eyes as a significant symptom of aqueous deficiency in DED patients. As a first-line treatment for mild DED, 51.85% of participants recommended 0.5% Carboxymethyl cellulose (CMC) eye drops, while 44.44% suggested using combination eye drops containing polyethylene glycol and Propylene glycol (PEG-PG) for moderate DED cases. In the case of severe DED, the majority (68.52%) of respondents preferred prescribing sodium Hyaluronate (SH) eye drops.Experts have recommended the use of CMC eye drops to provide temporary relief from itchiness and pain caused by eye dryness, wind exposure or sun exposure. They have recommended the prescription of 0.5% CMC eye drops three times daily for mild DED patients.

Contralateral eye comparison of the efficacy and safety of two artificial tear formulations for corneal subbasal nerve fiber regeneration after photorefractive keratectomy

Background: Currently, artificial tears (ATs) are the first-line agents for managing dry eye disease (DED). This study compared the efficacy and safety of two different AT formulations, Systane® Hydration (SH) and Systane® Ultra (SU), on symptoms of DED and regeneration of the subbasal corneal nerve fiber length (CNFL) in photorefractive keratectomy (PRK)-treated eyes.
 Methods: This prospective contralateral comparative study recruited myopic eyes scheduled for PRK, and either SH or SU were administered for up to 3 months postoperatively. All participants underwent a standard comprehensive preoperative ophthalmological examination, in vivo confocal microscopy to evaluate the subbasal CNFL, and completed Ocular Surface Disease Index (OSDI) questionnaire for assessing dry eye symptoms. Image analysis software was used to calculate the subbasal CNFL (micrometer/mm2). Assessments were repeated at the 1- and 3-month follow-up visits. Pre- and postoperative subbasal CNFL and OSDI scores were compared to determine inter- and intra-group differences.
 Results: Fifty eyes of 25 participants were included in this study. The mean (standard deviation) age of the participants was 22.7 (3.8) years. The OSDI scores for both groups increased significantly at 1 month (both P<0.05), followed by a decrease at 3 months to values comparable to the preoperative scores (both P>0.05). Although OSDI scores were comparable at baseline and at the 1-month postoperative visit (both P>0.05), the SU-treated eyes had a significantly better OSDI score at the 3-month visit (P<0.05), despite being clinically insignificant. Preoperative subbasal CNFL differed significantly between the groups (P=0.001), yet the mean values at both postoperative visits were comparable (both P>0.05). In both groups, subbasal CNFL was significantly reduced at 1 month, followed by a significant increase at the 3-month postoperative visit compared to baseline (all P<0.05). No treatment-related complications were observed at the end of the study period.
 Conclusions: No significant difference was found between the preoperative and 3-month postoperative OSDI scores in the SH- or SU-treated eyes. Subbasal CNFL regeneration indicated a positive effect of both ATs, with a longer mean CNFL noted in the SH-treated eyes at the final visit. This suggests that SH may be a better option for improving corneal reinnervation after PRK. These observations must be verified in further trials with longer follow-up periods and larger sample sizes.

Categorization of Marketed Artificial Tear Formulations Based on Their Ingredients: A Rational Approach for Their Use.

Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and preservatives. The currently marketed artificial tears can be grouped into four categories based on their active ingredients. The artificial tears also contain biologically active chemicals listed as inactive ingredients, which have osmoprotectant, humectant, and tear film lipid layer or mucous layer mimicking properties. Most artificial tears contain vanishing type preservatives such as purite or sodium perborate and safer quaternary compound polyquaternium-1. The majority of these artificial tear formulations are also available as preservative-free single dose unit. The study provides a formulary of artificial tears based on active ingredients, biologically active excipients, and the preservative-free option. The formulary should assist healthcare providers in making a stepwise and rational selection of appropriate artificial tears for patients suffering from dry eye disease.

“Keratrop” eye drops efficacy in dry eye syndrome treatment in diabetic patients

Significance. Prevalence of diabetes mellitus (DM) is increasing worldwide. People with diabetes are at higher risk to dry eye syndrome (DES). The increasing dependence of society on computers, air conditioning, and visual workload, etc. results in an increase in the manifestations of DES in diabetic patients. A significant part of the socially active population with diabetes requires prescription of drugs aimed at correcting disorders associated with both hyperglycemia and dry eyes. Conservative treatment of DES in case of diabetes includes prescription of artificial tears, metabolic, immunocorrecting, hormonal, antiallergic therapies as well as treatment of meibomian gland dysfunction (MGD). The tear substitutes, however, cannot always satisfy the needs of doctors and patients due to the imperfections of their formulas. Therefore, more and more new drugs are introduced to the market that require a comprehensive assessment.Purpose. To evaluate the clinical efficacy of Keratrop eye drops – a new artificial tear formulation – in dry eye syndrome treatment in patients with diabetes mellitus (DM).Methods. The study included 65 patients (130 eyes) with dry eye syndrome stages I and II associated with mild and moderate diabetes. These were adult patients of both sexes who had not previously received artificial tears as treatment and were undergoing either inpatient or domiciliary care. All studied patients provided a written informed consent and were divided into 2 groups by random sampling. The main group (35 patients) was receiving Keratrop instillations 2 times a day during 14 days, in the course of antidiabetic treatment. Instillations of “artificial tear” were not prescribed to patients of the control group (30 patients), and they only received antidiabetic treatment prescribed by the endocrinologist. Before and after treatment, all patients underwent standard ophthalmic examinations, meibography imaging, tear film assessment and filled in OSDI questionnaires.Results. The study showed that during treatment, in patients of the experimental group – with both I and II dry eye syndrome stages – a significant decrease in subjective and objective manifestations was observed, along with an improvement in the tear film stability. In the control group, positive dynamics was observed only in patients with the first stage of dry eye syndrome.Conclusion. Dry eye syndrome treatment in patients with diabetes should be comprehensive and must include both basic antidiabetic therapy and instillation of tear substitutes.

Evaluation of 18 artificial tears based on viscosity and pH

Introduction: Different polymers used in artificial tear formulations influence their physical properties, such as viscosity and pH, hence affecting their bioavailability. There is limited data available from manufacturers specifying the physical properties of artificial tears, even though these data can contribute to their efficacyand effectiveness.
 Purpose: The aim of this study was to evaluate 18 artificial tears available in the Malaysian market based on their physical properties.
 Methodology: Viscosity and pH of 18 artificial tears were evaluated using rheometer and compact pH-meter, respectively, at standard room temperature (25°C). The amount of fluid used for both tests of each artificial tear was standardised using micropipette. The Kruskal-Wallis test was employed to compare the viscosity median between the three groups (low, medium, and high viscosity) of artificial tears, while the independent t-test was used to compare the pH between preservative and non-preservative artificial tears. A p-value of 0.05 was set as the level of significance.
 Results: The mean viscosity for all 18 artificial tears was 12.05 cP ± 10.21 within a range of 0.55 cP to 34.49 cP. There was a significant difference observed in viscosity between low- (n = 7), median- (n = 8), and high- (n = 3) viscosity groups, χ2(2) = 14.474, p = 0.001. The mean pH for all 18 artificial tears was 7.21 ± 0.43, with a range of 6.19 to 7.85. pH for preservative artificial tears was slightly alkaline compared to non-preservative artificial tears (7.26 ± 0.47 vs 7.14 ± 0.38, respectively).
 Conclusion: Rheological findings indicated that different formulations of artificial tears have different viscosities, with most artificial tears falling within the recommended values. There was no difference in terms of pH between preservative and non-preservative artificial tears.

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.

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

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

Assessment of Phosphate and Osmolarity Levels in Chronically Administered Eye Drops

Objectives:To assess phosphate and osmolarity levels of chronically administered eye drops commercially available in Turkey.Materials and Methods:A total of 53 topical eye drops including 18 antiglaucoma drugs, 4 nonsteroidal anti-inflammatory drugs (NSAIDs), 10 corticosteroids, 7 antihistaminics, and 14 artificial tears identified using the Vademecum Modern Medications Guideline (2018) were included in the study. Phosphate levels were assessed using Roche Cobas C501 analyzer (Roche Diagnostics GmbH, Mannheim, Germany) and the respective kits. Osmolarity was assessed using Vescor Vapro 5600 vapor pressure osmometer (Sanova Medical Systems, Vienna, Austria). Mean phosphate and osmolarity levels were obtained after averaging three measurements. Eye drops were categorized as isoosmolar, hypoosmolar and hyperosmolar based on physiologic tear osmolarity range (296.5±9.8 mOsm/L).Results:The highest phosphate concentration was found in the antiglaucoma group (20.3±35.4 mmol/L), followed by antihistaminics (17.3±17.9 mmol/L), corticosteroids (15.2±19.1 mmol/L), artificial tears (0.8±1.0), and NSAIDs (0.04±0.08). Percentage of medications in the hyperosmolar category was highest in the NSAI group (75%), followed by antihistaminics (43%), corticosteroids (20%), and antiglaucoma drugs (19%). Nearly all of the artificial tear formulations were in the hypoosmolar (71%) or isoosmolar (21%) categories.Conclusion:Approximately 40% of glaucoma medications and approximately 60% of corticosteroid and antihistaminic medications had a phosphate concentration higher than the physiologic tear phosphate level (1.45 mmol/L).

Development and Validation of A Fast, Simple And Specific Stability Indicating RP-HPLC Method for Determination of Dexpanthenol in Eye Gel Formulation.

In this study a simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of Dexpanthenol in an artificial tear formulation. The chromatographic separation was performed on a HPLC C18 column (25.0 cm ´4.6 mm, 5 mm) using a mixture of 0.037 M monobasic potassium phosphate in water (adjusted with 0.1% (v/v) phosphoric acid to a pH of 3.2) and methanol (90:10). The flow rate was set at 1.5 mL/min and Dexpanthenol concentration was determined at λmax = 205 nm. The HPLC analysis method was validated in terms of linearity, precision, accuracy, specificity, and sensitivity according to International Conference on Harmonization (ICH) guidelines. The results indicated that the retention time was 8 min and no interferences were observed from the formulation excipients and stress degradation products. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 10 - 100 μg/mL; the regression coefficient was 0.996 and the linear regression equation was y = 20.011 x + 146.83. This HPLC method was precise and accurate in the range of 10 – 100 μg/mL. Also, the dexpanthenol concentration in artificial tear formulation was determined by this HPLC method, which was in accordance with the label claimed. This validated HPLC method could be used for routine analysis, quality control and the stability of analysis of eye gel containing dexpanthenol formulations.

Evaluation of an enhanced viscosity artificial tear for moderate to severe dry eye disease: A multicenter, double-masked, randomized 30-day study

PurposeIn a randomized, controlled clinical trial, two lubricant artificial tear formulations with enhanced viscosity were compared: an investigational product at the time, containing carboxymethylcellulose 1.0% and glycerin 0.9% (CMC-GLY) with osmoprotectants, and a standard formula containing carboxymethylcellulose 1.0% alone (CMC). MethodsThis double-masked study recruited patients with moderate to severe dry eye at 10 US centers. After a 7-day run-in with CMC 0.5% (Refresh Tears) patients were randomized to use either CMC-GLY or CMC as needed, but at least 2 times daily for 30 days. Patients were stratified by Ocular Surface Disease Index© (OSDI) score into moderate (23–32) and severe (> 32–65) subgroups. Assessments included OSDI (primary efficacy variable), corneal and conjunctival staining, tear break-up time (TBUT), symptom surveys, and safety variables. Study visits were days 1 (baseline/randomization), 7, and 30. ResultsA total of 188 patients (94 CMC-GLY, 94 CMC) were enrolled. The severe subgroup had 67 CMC-GLY and 65 CMC patients. OSDI scores progressively improved and were similar at day 30 between treatment groups. At day 7, only the CMC-GLY group demonstrated significant improvements from baseline in OSDI score (all patients p < 0.001, severe p < 0.001), corneal staining (p = 0.004), and TBUT (p < 0.001). Between-group dose frequency for CMC-GLY was lower at day 7 (p = 0.031). Other efficacy results were similar between groups. The most commonly reported adverse event in both groups was blurred vision. ConclusionsOverall, the CMC-GLY artificial tear formulation was as effective as the CMC formulation. CMC-GLY demonstrated improvements at an earlier stage (day 7). Both artificial tear formulations were safe and well tolerated, with no treatment-related serious adverse events. These results support the use of the CMC-GLY artificial tear formulation as an effective treatment to reduce the symptoms and signs of dry eye disease.

Efficacy and safety of dual-polymer hydroxypropyl guar- and hyaluronic acid-containing lubricant eyedrops for the management of dry-eye disease: a randomized double-masked clinical study.

BackgroundAn artificial-tear formulation containing the dual polymers hydroxypropyl guar (HPG) and hyaluronic acid (HA) is approved for the treatment of dry-eye disease (DED). The present study compared the efficacy and safety of the HPG-HA dual-polymer formulation vs a sodium hyaluronate (SH)-containing artificial-tear formulation in patients with DED.MethodsIn a prospective, 6-week, multicenter, double-masked, parallel-group study, patients with DED aged ≥18 years and total ocular surface staining (TOSS) score ≥4 and ≤9 were randomized (1:1) to receive either HPG-HA or SH four times a day for 42 days. Changes from baseline in TOSS (primary end point), impact of dry eye on everyday life (IDEEL) treatment-satisfaction scores (effectiveness and inconvenience), and tear-film breakup time (TFBUT) at day 42 were assessed using a fixed-sequence testing strategy. Noninferiority was assessed on the primary end point based on the upper limit of two-sided 95% CIs for mean treatment difference (HPG-HA or SH) <2 units.ResultsIn total, 99 patients were randomized (HPG-HA, n= 50; SH, n= 49). At day 42, the least square (LS) mean ± SE change from baseline in TOSS was −1.16±0.24 and −0.92±0.23 in the HPG-HA and SH groups, respectively, and the treatment difference was −0.24±0.33 (95% CI −0.90 to 0.42). Noninfe-riority was demonstrated as the upper limit of the 95% CI was <2 units. LS mean change from baseline at day 42 for HPG-HA vs SH was −3.18 (P=0.4817) in IDEEL treatment-effectiveness scores, −12.56 (P=0.0001) in treatment-inconvenience scores, and 0.30 seconds (P=0.5789) in TFBUT.ConclusionThe HPG-HA dual-polymer formulation was noninferior to the SH lubricant eye-drops for improvement in ocular surface staining in DED. HPG-HA did not show improvement over SH in IDEEL treatment-satisfaction scores. No new safety findings were reported.

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

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. 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)]. 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. 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.

Efficacy of polyethylene glycol-propylene glycol-based lubricant eye drops in reducing squamous metaplasia in patients with dry eye disease.

PurposeSquamous metaplasia in dry eye disease (DED) manifesting as the loss of conjunctival goblet cells results in reduced mucin secretion and tear film instability. The objective of this study was to evaluate the efficacy of a polyethylene glycol–propylene glycol/hydroxypropyl-guar (PEG-PG/HP-guar) artificial tear formulation in reducing the squamous metaplasia in patients with DED using conjunctival impression cytology (CIC).MethodsIn this Phase IV, single-arm, open-label study, DED patients (aged ≥18 years) with a corneal staining sum score ≥3 and tear film break-up time (TFBUT) <7 s self-administered the PEG-PG/HP-guar artificial tears, 3 times a day for a period of 90 days. The primary end point was the change from baseline in goblet cell density (Nelson’s CIC grading score) over the treatment period. Other end points were change in the corneal and conjunctival staining scores, and TFBUT. Statistical evaluation was performed using a paired t-test.ResultsIn total, 49 patients (n=98 eyes) completed the study. Compared with baseline, there was a significant reduction in the mean CIC scores (ie, improvement in goblet cell density) at Days 30, 60, and 90 (1.6±0.5 vs 1.2±0.5, 0.9±0.5, and 0.8±0.5; P<0.0001). At Day 90, 22% of eyes demonstrated squamous metaplasia Grade 0 (ie, normal epithelium). Similar improvements were observed in the corneal staining scores (5.7 vs 3.1, 1.1, and 0.5; P<0.0001), conjunctival staining scores (5.5 vs 3.6, 1.6, and 0.9; P<0.0001), and TFBUT (4.8 vs 5.8, 6.3, and 6.8 s; P<0.0001) at Days 30, 60, and 90, respectively.ConclusionIn this study, treatment with PEG-PG/HP-guar artificial tears for 90 days decreased CIC score, reduced corneal and conjunctival staining, and increased TFBUT in patients with DED. These results suggest that PEG-PG/HP-guar artificial tears can improve the ocular surface health and reverse the changes induced by squamous metaplasia in DED.

Novel liposomal artificial tear formulation containing gellan gum for dry eye disease treatment

Novel liposomal artificial tear formulation containing gellan gum for dry eye disease treatment

Novel Nano-Liposome Formulation for Dry Eyes with Components Similar to the Preocular Tear Film.

Dry eye is commonly treated with artificial tears; however, developing artificial tears similar to natural tears is difficult due to the complex nature of tears. We characterized and evaluated a novel artificial tear formulation with components similar to the lipid and aqueous constituents of natural tears. Nano-liposomes, composed in part of phosphatidylcholine, were dispersed in an aqueous solution of bioadhesive sodium hyaluronate. Liposome size, zeta potential, and physicochemical properties of the fresh and stored (4 °C) liposomal formulation were analyzed. In vitro tolerance was tested using human corneal and conjunctival cell lines by exposures of 15 min to 4 h. The tolerance of the liposomal formulation was evaluated in animals (rabbits). The average liposome size was 186.3 ± 7.0 nm, and the zeta potential was negative. The osmolarity of the formulation was 198.6 ± 1.7 mOsm, with a surface tension of 36.5 ± 0.4 mN/m and viscosity of 3.05 ± 0.02 mPa·s. Viability values in the human corneal and conjunctival cell lines were always >80%, even after liposomal formulation storage for 8 weeks. Discomfort and clinical signs after instillation in rabbit eyes were absent. The new formulation, based on phosphatidylcholine-liposomes dispersed in sodium hyaluronate has suitable components and characteristics, including high in vitro cell viability and good in vivo tolerance, to serve as a tear substitute.

Novel liposome-based and in situ gelling artificial tear formulation for dry eye disease treatment.

Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film. Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a human epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits. Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33 °C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa s within the shear rate interval of 200-1000 s-1 at 33 °C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits. The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease.

Evaluation of a new artificial tear formulation for the management of tear film stability and visual function in patients with dry eye.

PurposeArtificial tears are the first line of therapy for dry eye disease (DED) and are also the most frequently used treatment approach for this common condition. Despite this, there are few published studies that directly compare the effectiveness of different drop preparations, especially those formulated specifically for dry eye. In this study, we tested a new artificial tear product, Rohto® Dry-Aid™, for its ability to relieve the signs and symptoms of DED. The study used a second drop, Systane® Ultra, as a positive comparator.Materials and methodsThis was a prospective, single-center, open-label, parallel-group study comparing the effects of the two products when used continuously over ~30 days (Clinical Trials registration number NCT03183089). Subjects were randomly assigned to one of the two test groups and were monitored 2 and 4 weeks after enrollment. Efficacy endpoints included ocular staining, visual function, and ocular discomfort.ResultsTreatment groups had similar ocular staining and ocular comfort scores, and both showed statistically significant ocular discomfort score improvement. Subjects in the Rohto group reported significant improvements in visual tasking activities such as watching television and driving at night. There was also a tendency for diary symptom scores to worsen from morning to evening in the Systane group, but not in the Rohto group; this trend was not significant, but warrants further study.ConclusionThe two products, Rohto Dry-Aid and Systane Ultra, elicited comparable effects on the signs and symptoms of DED. While both products are designed to provide long-lasting relief, subjects in the Rohto group experienced a superior relief from discomfort associated with visual tasking activities and daily diaries, indicating that the Rohto drops may provide a longer duration of symptomatic relief over the course of the day.

Investigating the potential benefits of a new artificial tear formulation combining two polymers.

PurposeArtificial tear formulations typically contain a water-soluble polymer to enhance residence time, moisture retention, and binding to the mucin coat of the ocular surface, which facilitate corneal healing. This study investigated the potential advantages of combining carboxymethylcellulose (CMC) and hyaluronic acid (HA) polymers in a single formulation.Materials and methodsIndividual CMC and HA solutions were prepared and tested for bulk viscosity in comparison to a solution that combined CMC and HA. Rheometry determined the differences between solutions at increasing shear rates, simulating eye movement and blinking.ResultsThe bulk viscosity of the individual 0.5% CMC and 0.1% HA solutions was 2.5 and 5.7 cP, respectively. The viscosity of the combined solution (13.1 cP) was 60% higher than predicted by additive effects. Rheometry revealed shear rates between 10/second (open eye) and 10,000/second (blinking eye). At these rates, viscosity ranged from 2.7 to 3.5 cP for 0.5% CMC, 2.8 to 6.8 cP for 0.1% HA, and 5.2 to 15.3 cP for the 0.5% CMC–0.1% HA combination. Low-shear viscosity of the CMC–HA combination increased 48% over the sum of the individual solutions, but high-shear viscosity remained virtually unchanged. Data from CMC and HA solutions at higher concentrations were consistent with these results.ConclusionCombining CMC and HA polymers produced a synergistic increase in low-shear viscosity (which cannot be fully explained by simple molecular entanglement), while the high-shear viscoelasticity of the combined solution remained unaffected. These data suggest that CMC–HA combinations have properties that may be used to formulate artificial tears that optimize ocular retention (through higher low-shear viscosity), while minimizing blur and stickiness during blinking (through lower high-shear viscosity).

Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease

Eye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a standard HA eye drop.

Potential for use of hydroxypropyl guar in tear substitute therapy

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.