Dynamics of a Gel-Based Artificial Tear Film with an Emphasis on Dry Disease Treatment Applications

This paper discusses the spreading of gel-based ophthalmic formulation on the cornea surface assumed to be flat. We show that gel-based formulations exhibit rheological behaviors that the Herschel–Bulkley model can describe. The continuity and momentum equations are solved numerically using the monofluid formulation and the volume-of-fluid (VOF) method. We investigated the influence of the rheological properties, namely the consistency, the yield stress, and the flow behavior index, on the spreading of a gel-based artificial tear over the cornea surface. We propose optimal values of these properties for efficient gel-based artificial tears.

Acupuncture at a Single Acupoint, BL1 (Jingming), Compared to Artificial Tears in Moderate to Severe Dry Eye Disease: A Randomized Controlled Trial

BackgroundThe global incidence of dry eye disease (DED) is very high. DED seriously affects the quality of life of patients; however, the current curative effect of medicine for moderate to severe DED is poor. This randomized clinical trial was planned to investigate the effect of acupuncture compared with artificial tears on moderate to severe DED.MethodsA randomized clinical trial was performed at 2 hospitals in China. 120 DED patients were randomly equally divided into an acupuncture and an artificial tear group. Either acupuncture or artificial tears was performed for an 8-week period, and a 32-week follow-up was performed. The primary outcome measure was the Schirmer-I test (SIT) value. The secondary outcome measures included the numerical rating scale (NRS) for improvement in ocular symptoms, the ocular surface disease index (OSDI), the tear-film break-up time (TBUT), corneal fluorescein staining (CFS), and acupuncture acceptability. Adverse events also were monitored and documented.ResultsFor the primary outcome, the mean changes in the SIT values were significantly different between the acupuncture (5.75 [2.53‒9.75]) and artificial tear (0.52 [-1.18‒2.46]) groups at week 8 (P = 0.01). The OSDI decreased by -16.14 (-35.40‒16.30) and − 7.65 (-19.25‒15.05) from baseline to week 8 in the acupuncture and artificial tear groups, respectively (P < 0.05). A significant decrease was found in the NRS score for eye dryness, eye pain, and blurred vision in the acupuncture group, as compared to the artificial tear group. However, the change in the average symptom NRS score, TBUT, and CFS did not differ significantly at week 8. Five cases experienced acupuncture-related adverse events.ConclusionsThis randomized clinical trial found that acupuncture at a single acupoint, BL1, significantly promoted tear secretion and improved multiple eye discomfort symptoms. Acupuncture showed greater benefits than artificial tears for moderate to severe DED. However, the study findings warrant verification.Trial registrationRegistration number: ChiCTR1800015831. Name of trial registry: Efficacy and safety of acupuncture in the treatment of moderate to severe dry eye disease: a randomized controlled trial.

Features of the Clinical Course and Treatment of Dry Eye Syndrome in the Setting of Chronic Conjunctivitis in the South Aral Sea Region

Background. Currently, the health status of the population in the Aral Sea region should be considered with reference to long-term effects of environmental pollution – air, soil and drinking water containing toxic salts. As per results of the analysis of primary eye diseases in the Southern Aral Sea region, it was revealed that the main cause of conjunctivitis were chemical and physical exogenous irritation factors, such as dust, smoke and exposure to salt and sand storms that create a favorable environment for infection and development of secondary Dry Eye Syndrome. Purpose. To optimize treatment of secondary Dry Eye Syndrome (DES) in patients with chronic conjunctivitis in the South Aral Sea region. Materials and Methods. The research included 62 patients (120 eyes) with chronic conjunctivitis, aged 35–62 years, who had been observed in an outpatient clinic for the last 3 years, with signs of DES. All studied patients were divided into 2 groups by random sampling after preliminary adequate antibacterial and anti-inflammatory therapy. The control group (20 patients, 40 eyes) was instilled with Tsinosol antiseptic (composition: zinc sulphate, boric acid, Aseptic) – 2 drops 3 times a day, during 30 days. Patients of the main group (42 patients, 80 eyes) were instilled with Tsinosol antiseptic (2 drops 3 times a day) and Keratrop artificial tear (AT) eye drops (composition: sodium carmellose, glycerin, levocarnitine, erythrol, firma Aseptica) – 2 drops 3 times a day, during a month. All patients underwent standard ophthalmological tests, and special tests were carried out to verify DES, including Schirmer, Norn and Jones tests. Lower lacrimal meniscus height and the severity of the conjunctival fold were also determined. Results. Studies have shown that in the main group, both subjective and objective signs of the disease significantly decreased compared with the baseline and with the respective parameters of the control group, and a significant improvement in the stability of the tear film was noted. Conclusion. To optimize the therapy of secondary DES, it is necessary to include artificial tear eye drops in the treatment regimen in general, and consider using Keratrop eye drops in particular.

The Effect of Three Eye Care Methods on the Severity of Lagophthalmos in Intensive Care Patients: A Randomized Controlled Clinical Trial

Background. Patients admitted to intensive care units are exposed to a variety of eye injuries such as lagophthalmos, which can lead to blindness. There is conflicting evidence regarding the effectiveness of different eye protection methods, and evaluations are ongoing. Therefore, this study was performed to compare the effect of “polyethylene cover,” “polyethylene cover plus artificial tear drops,” and “polyethylene cover plus Lubratex eye ointment” on the severity of lagophthalmos. Methods. A total of 156 patients connected to ventilators were included in this clinical trial using the convenience sampling method. They were randomly divided into three groups: “polyethylene cover,” polyethylene cover plus artificial tear drops,” and “polyethylene cover plus Lubratex eye ointment.” In each group, one eye was regarded as control and the other eye as intervention. The control eye received routine interventions, including washing with normal saline. The eyes were examined daily by an ophthalmologist for 5 days for the occurrence of lagophthalmos. Results. There was no statistically significant difference in the severity of lagophthalmos among the three groups “polyethylene cover,” “polyethylene cover plus artificial tear drop,” and “polyethylene cover plus Lubratex eye ointment.” However, clinically the severity of lagophthalmos was lower in the “polyethylene cover plus artificial tear drops” group than in the other two groups. Conclusion. The results showed that the combination of polyethylene cover and artificial tears drops can be clinically effective in reducing the severity of lagophthalmos. Therefore, the use of this method is recommended for patients admitted to the intensive care unit. Similar studies are recommended.

Effect of a Novel Multi-Ingredient Formulation on Management of Dry Eye Discomfort in a Randomized, Double-Blind, Placebo-Controlled Human Clinical Study

Objectives Dry eye is a chronic condition associated with insufficient tear production and faster tear evaporation and commonly accompanied by inflammation that may lead to ocular surface damage. We have developed a multi-ingredient formulation containing lutein, zeaxanthin, curcumin, and vitamin D3 to address conditions associated with dry eye. The objective of this study was to evaluate the efficacy and safety of our formulation in subjects with mild to moderate dry eye symptoms. Methods This was a randomized, double-blind, parallel, placebo-controlled study. Sixty subjects with mild to moderate DES were randomly assigned in a 1 : 1 ratio to the test or placebo groups. Subjects consumed one capsule of the test or placebo product every morning through the study duration of 56 days. The test product comprised 20 mg lutein, 4 mg zeaxanthin, 200 mg curcuminoids, and 600 IU vitamin D3 in form of a capsule. The placebo product contained soybean oil. Changes in tear volume by Schirmer's test and severity of dry eye discomfort measured by Ocular Surface Disease Index (OSDI) score, changes in Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear film break up time (TBUT), corneal & conjunctival staining, tear osmolarity, Matrix Metalloproteinases (MMP)-9 levels in tear fluid, and artificial tear usage were evaluated. Results Thirty subjects in Test and 29 in Placebo group completed study. We observed statistically significant (P &lt; 0.05) improvements in tear volume, TBUT, and a reduction in dry eye discomfort as measured by OSDI and SPEED scores from baseline to day 56 in the Test group. Mean corneal & conjunctival staining scores, tear osmolarity and tear MMP-9 levels also showed significant improvements (P &lt; 0.05) when compared to Placebo on day 56. Artificial tear usage & frequency of usage were significantly reduced (P &lt; 0.05) in test group as compared to Placebo. Products were well tolerated without any adverse events. Conclusions Our multi-ingredient formulation demonstrated significant improvement in dry eye conditions including eye hydration and moisture, tear stability and quality, and overall improvements in eye comfort. Funding Sources OmniActive Health Technologies

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.

Development of an In Vitro Blink Model for Ophthalmic Drug Delivery

Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model.

Formulation Considerations for the Management of Dry Eye Disease

Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.