The Impact of Incubation Conditions on In Vitro Phosphatidylcholine Deposition on Contact Lens Materials.

SIGNIFICANCE: Previous in vitro measurements of contact lenses commonly investigate the impact of nonpolar tear film lipids (i.e., sterols). Polar lipids, however, are equally important stabilizing components of the tear film. This research explores and presents further knowledge about various aspects of polar lipid uptake that may impact contact lens performance. PURPOSE: This study evaluated the impact of incubation time, lipid concentration, and replenishment of an artificial tear solution (ATS) on the uptake of phosphatidylcholine (PC) onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials. METHODS: Four SHs and two CH lens materials (n = 4) were soaked in a complex ATS containing radioactive 14C-PC as a probe molecule. Phosphatidylcholine uptake was monitored at various incubation time points (1, 3, 7, 14, and 28 days), with different ATS lipid concentrations (0.5×, 1×, 2×) and with and without regular replenishment of the ATS. Phosphatidylcholine was extracted from the lenses, processed, and counted by a ß counter, and accumulated PC (µg/lens) was extrapolated from standard lipid calibration curves. RESULTS: All materials exhibited increasing PC deposition over time. Conventional hydrogel materials showed significantly lower PC uptake rates (P < .001) than any of the SH materials. Increasing lipid concentration in the ATS resulted in increased PC binding onto the contact lens materials (P < .001). Replenishing the ATS every other day, however, impacted the PC deposition differently, showing increased binding (P < .001) on CHs and reduced PC deposition for SH materials (P < .001). CONCLUSIONS: Length of incubation, lipid concentration in the ATS, and renewal of the incubation solution all influenced the amount of PC that sorbed onto various lens materials and therefore need to be considered when conducting future in vitro deposition studies.

Comparative study of lens solutions' ability to remove tear constituents.

PURPOSE: The purpose of this study was to use atomic force microscopy to compare and characterize the cleaning abilities of a hydrogen peroxide-based system (HPS) and a polyhexamethylene biguanide-containing multipurpose solution (MPS) at removing in vitro deposited tear film constituents, as well as to determine deposition patterns on various silicone hydrogel contact lenses. METHODS: Silicone hydrogel materials-balafilcon A (BA), lotrafilcon B (LB), and senofilcon A (SA)-were incubated for 1 week in an artificial tear solution (ATS) containing representative lipids, proteins, and salts from the tear film. Atomic force microscopy was used to resolve each lens before and after being cleaned overnight in HPS or MPS. Atomic force microscopy was used again to resolve HPS/MPS-cleaned lenses, which were reincubated in fresh ATS for 1 week, before and after an overnight clean in their respective cleaning solution. RESULTS: Atomic force microscopy imaging was able to characterize lens deposits with high resolution. Lenses incubated in ATS revealed distinct differences in their deposition pattern across lens materials. The surface of BA contained about 20-nm-high deposits, whereas deposit heights up to 150 nm completely occluded the surface of SA. Lotrafilcon B lenses revealed clusters of deposits up to 90 nm. The use of either lens solution left trace amounts of tear film constituents, although components from the MPS were seen adsorbed onto the surface after cleaning. Surface roughness (Ra) measurements revealed a significant difference between ATS-incubated and HPS/MPS-cleaned SA and LB lenses (p < 0.05). Ra between first incubated and HPS/MPS-cleaned reincubated SA and LB was also significant (p < 0.05). CONCLUSIONS: Unique variations in ATS deposition patterns were seen between lenses with atomic force microscopy. The application of both HPS and MPS removed most visible surface deposits.

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.

An Oral Polyphenol Formulation to Modulate the Ocular Surface Inflammatory Process and to Improve the Symptomatology Associated with Dry Eye Disease.

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer's test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 (p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.

Development of novel mucoadhesive hyaluronic acid derivate as lubricant for the treatment of dry eye syndrome.

BACKGROUND: Dry eye - a disease affecting between 4 and 34% of the population worldwide. Stressful conditions to ocular surface, contact lenses as well as systemic disease cause dry eye. Novel synthesized hyaluronic acid derivate was evaluated in terms of its potential as mucoadhesive and lubricant. Results & methodology: Hyaluronic acid was chemically modified with cysteine ethyl ester (hyaluronic acid-cysteine ethyl ester). Mucoadhesion, disintegration and water uptake capacity, moreover, safety as the hen's egg test for mucous membrane compatibility were evaluated. According to the results, hyaluronic acid-cysteine ethyl ester achieved 3.81-fold increased swelling capacity, 30.5-fold more improvement mucoadhesive properties and 9.72-fold higher stability of hyaluronic acid, which was achieved due to the chemical modification. SUMMARY: Thus, the promising results underpin further exploitation of this versatile polysaccharide for treating dry eye syndrome.

Comparison of the clinical efficacy of preserved and preservative-free hydroxypropyl methylcellulose-dextran-containing eyedrops / Comparación de la eficacia clínica de los colirios con conservantes y los colirios con contenido de hidroxipropil metilcelulosa-dextran sin conservantes

Purpose: This study aimed to compare the efficacy of two sustained-release formulation of artificial tear drops. Patients and methods: This is a randomized patient-masked clinical trial, a total 88 patients into two group A (n=41; with single dose of artificial tear, containing dextran 70, 1mg/ml and hypromellose, 3mg/ml hydroxypropyl methylcellulose (HPMC) and group B (n=47; with multidose of artificial tear, containing 0.3g HPMC and 0.1g of dextran 70, with 0.01% benzalkonium chloride (BAK) as preservative) were completed the study. The ocular surface disease index (OSDI) questionnaire, tear break up time (TBUT), corneal and conjunctival staining and Schirmer test, were performed. Repeated measures ANOVA was used to assess the differences among the two products. A p-value less than 0.05 was considered significant. Results: The mean of age of the participants in the Group A and B was 44.08±6.29 (range, 33-58 years) years and 45.83 ± 8.42 (31-60 years), respectively. In comparing two groups before the intervention, the OSDI scores, the TBUT scores, the conjunctival and corneal staining scores and the Schirmer scores did not show statistically significant differences (p=0.339, p=0.640, p=0.334, p=0.807 and p=0.676, respectively). After 4 weeks, the OSDI scores, conjunctival and corneal staining scores showed improvement in compare to those before the intervention (p<0.001). But, the differences for the Schirmer test score and TBUT score was not significant (p=0.115, p=0.013, respectively). Conclusion: Our outcomes indicated that improvement occurred with use of both products but there was no statistically significant difference between them (AU)

Objetivo: El objetivo de este estudio fue comparar la eficacia de dos fórmulas de lágrimas artificiales de liberación sostenida. Pacientes y Métodos: Ensayo clínico aleatorizado y enmascarado para el paciente, se incluyó a un total de 88 pacientes distribuidos en dos grupos: el grupo A (n=41; con una dosis única de lágrima artificial con contenido de Dextran 70,1mg/ml e hipromelosa, 3mg/ml hidroxipropil metilcelulosa (HPMC), y el grupo B (n=47; con multidosis de lágrima artificial, con contenido de 0,3g HPMC y 0,1g de Dextran 70, y 0,01% de cloruro de benzalconio (BAK) como conservante). Se realizaron las siguientes pruebas: cuestionario del índice de enfermedad de la superficie ocular (OSDI), tear break-up time (TBUT), tinción corneal y conjuntival y prueba de Schirmer. Para el análisis estadístico se utilizó ANOVA para mediciones repetidas, a fin de evaluar las diferencias entre los dos productos. Se consideró significativo un valor p inferior a 0,05. Resultados: La media de edad de los participantes de los grupos A y B fue de 44,08±6,29 (rango de 33 a 58 años) y 45,83 ± 8,42 (de 31 a 60 años), respectivamente. Al comparar los dos grupos antes de la intervención, las puntuaciones OSDI, TBUT, las de tinción conjuntival y corneal, y las de la prueba de Schirmer no reflejaron diferencias estadísticamente significativas (p=0,339, p=0,640, p=0,334, p=0,807 y p=0,676, respectivamente). Transcurridas cuatro semanas, las puntuaciones OSDI y las de tinción conjuntival y corneal reflejaron una mejora en comparación a las puntuaciones anteriores a la intervención (p<0,001). Pero las diferencias en cuanto a las puntuaciones de la prueba de Schirmer y TBUT no fueron significativas (p=0,115, p=0,013, respectivamente). Conclusión: Nuestros resultados indican que se produjo una mejora con el uso de ambos productos, pero que no se produjo una diferencia estadísticamente significativa entre ambos (AU)