Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents.

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m-1) and viscosity (2.69 ± 0.15 mPa s-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.

Recent advances and strategies for nanocarrier-mediated topical therapy and theranostic for posterior eye disease.

Posterior eye disorders, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, have a significant impact on human quality of life and are the primary cause of age-related retinal diseases among adults. There is a pressing need for innovative topical approaches to treat posterior eye disorders, as current methods often rely on invasive procedures with inherent risks. Limited success was attained in the realm of topical ophthalmic delivery through non-invasive means. Additionally, there exists a dearth of literature that delves into the potential of this approach for drug delivery and theranostic purposes, or that offers comprehensive design strategies for nanocarrier developers to surmount the significant physiological ocular barriers. This review offers a thorough and up-to-date state-of-the-art overview of 40 studies on therapeutic loaded nanocarriers and theranostic devices that, to the best of our knowledge, represent all successful works that reached posterior eye segments through a topical non-invasive administration. Most importantly, based on the successful literature studies, this review provides a comprehensive summary of the potential design strategies that can be implemented during nanocarrier development to overcome each ocular barrier.

Efficacy and safety of artificial tears containing Artemia salina extract with dinucleotides for dry eye.

CLINICAL RELEVANCE: This clinical trial was conducted as part of the marketing procedures for a medical device comprising artificial tears containing Artemia salina extract with dinucleotides. These molecules previously demonstrated secretagogue properties by enhancing the production of aqueous, mucinous, and lipidic components of the tears. BACKGROUND: After confirming the efficacy of artificial tears containing Artemia salina extract in an animal model, this study proceeded to evaluate their efficacy and safety on dry eye participants. METHODS: A randomised controlled clinical trial was performed on 36 dry eye participants (41.6 ± 20.6 years). Half of the participants were treated with saline solution as a placebo for four weeks, while the other half were treated with artificial tears containing Artemia salina, randomly assigned. After a wash-out period of two weeks, the treatments were crossed for another four weeks. Participants were assessed at baseline and after one week, two weeks, and four weeks. Efficacy variables were: eye dryness frequency (primary), eye comfort, visual satisfaction, tear secretion, tear break-up time, corneal staining, conjunctival staining, and conjunctival hyperaemia. Safety variables were: high- and low-contrast visual acuity, intraocular pressure, and eye fundus images analysis. RESULTS: Compared with the baseline, the saline solution showed no significant changes in any of the studied variables after four weeks of treatment (p ≥ 0.05). However, the topical instillation of the artificial tears with Artemia salina for four weeks significantly improved eye dryness frequency (p = 0.014) and corneal staining (p = 0.010). No systemic or ocular adverse events were reported during the clinical trial. CONCLUSION: The topical instillation of artificial tears containing Artemia salina in mild to moderate dry eye participants for four weeks slightly improved their symptoms related to eye dryness frequency and reduced corneal damage, with no undesirable side effects observed.

Accommodation response and spherical aberration during 1-Year of orthokeratology lens wear and after discontinuation.

BACKGROUND: To assess accommodation and spherical aberration changes during one year of orthokeratology lens wear and one month after lens cessation. METHODS: A prospective, randomized, longitudinal study was conducted on forty-seven young healthy subjects at the Optometry Clinic of the Complutense University of Madrid (Spain). Non-cycloplegic refraction, high and low uncorrected visual acuity, high and low best corrected visual acuity, accommodative lag, horizontal near phoria, corneal topography, and high-order aberrations were performed at baseline, 1-day, 1-week, 1-, 6- and 12-months of lens wear and after one month of wash out period. p < 0.05 was considered as statistically significant. RESULTS: Spherical equivalent refraction (SE) was -3.23 ± 1.57D at baseline and -0.36 ± 0.64D after 12-months of lens wear, while accommodative lag changed from 0.53 ± 0.39D to 0.15 ± 0.29D after one year of lens wear. No significant differences were found when comparing SE at baseline and after one month of lens cessation (p > 0.05). A high correlation was found between the accommodative lag at baseline and after 12 M of lens wear. 22 out of 25 subjects with exophoria at baseline showed a significant reduction in the deviation at 12-months (p < 0.05). Total spherical aberration increased during all visits due to the lens wear (p < 0.05) although internal spherical aberration showed a significant decrease for 1-week, 1-month and 12-month visits (p < 0,05). CONCLUSION: Orthokeratology lenses may change the accommodative response of the patient as a reduction on accommodative lag on exophoric patients and an overall increase on the internal spherical aberrations was found during treatment but return to nearly baseline values when cessation.

In Vitro Evaluation of Soft Contact Lens Wettability With a Nonmodified Commercial Videokeratoscope.

PURPOSE: To evaluate a new in vitro technique for measuring soft contact lens wettability using a nonmodified commercial videokeratoscope, the Medmont E300. To this end, the capability of different artificial tears containing hyaluronic acid (HA) to improve soft contact lens wettability in vitro was investigated. METHODS: An experimental in vitro study was conducted to assess the wetting properties of three artificial tears containing different concentrations of HA (0.1%, 0.2%, and 0.3%) on soft contact lenses. A saline solution was used as the control. For each solution, 15 hydrogel (Ocufilcon D) contact lenses and 15 silicone-hydrogel (Somofilcon A) contact lenses were evaluated. The in vitro wettability of the lenses was measured using the Medmont E300 with a self-developed technique, which involved measuring the tear film surface quality (TFSQ) mean, TFSQ area, TFSQ central, and TFSQ inferior. RESULTS: Compared with the saline solution, all the concentration of HA (0.1%, 0.2%, and 0.3%) improved the in vitro wettability of both soft contact lenses by decreasing their TFSQ mean and TFSQ area ( P <0.05). Regression models revealed an exponential relationship between contact lens wettability and the concentration of HA for both soft contact lenses ( R >0.5, P <0.05). Furthermore, the hydrogel contact lens presented a wetter surface than the silicone-hydrogel contact lens ( P <0.05). CONCLUSIONS: The measurement of in vitro wettability of soft contact lenses with a nonmodified Medmont E300 seems to be a useful technique to evaluate the wetting properties of contact lens products.

Visual quality assessment and comparison of two multifocal scleral lens designs.

PURPOSE: To analyze the visual quality of a new multifocal scleral lens with a customized decentred optic zone compared to a conventional design by measuring visual acuity, contrast sensitivity function, stereopsis, subjective vision and comfort after one month of wear. METHODS: Nineteen presbyopic subjects were fitted with two multifocal scleral lens designs: a conventional multifocal and a customized decentred optical zone design. All subjects wore both scleral lens designs for one month with a two-week washout period. The main variables evaluated included high and low-contrast visual acuity under photopic and mesopic light conditions, binocular defocus curves, contrast sensitivity function and a visual analogue scale (VAS) for subjective vision and comfort. RESULTS: Comparing the two scleral lens designs, statistically significant differences in visual acuity were found, highlighting the improvement in more than one chart line (6 letters) for low contrast near tests under photopic light conditions with the decentred optics lens design. VAS questionnaire scores also showed a significant improvement in distance and overall subjective vision with the decentred optics lenses. Contrast sensitivity function showed an improvement with decentred multifocal lenses at all spatial frequencies measured, being statistically significant for 12 cycles per degree. No differences in stereoacuity were found. CONCLUSION: Multifocal scleral lenses with a customized decentred optical zone proved to be a promising refractive correction in presbyopic subjects after one month of wear, offering good comfort and visual quality under photopic and mesopic light conditions.

Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability.

Contact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.

Visual Quality Assessment and Comparison of Monofocal and Multifocal Scleral Lens Designs: A Pilot Study.

PURPOSE: To compare visual quality, contrast sensitivity, stereopsis, subjective vision, and comfort between monofocal and multifocal scleral lens (SL) designs. METHODS: An experimental, cross over and short-term pilot study has been performed. Nineteen presbyopic patients (51.9±3.8 years) with regular corneas participated voluntarily in the study and Onefit MED monofocal and multifocal SL designs were fitted bilaterally. Subjective vision and comfort, contrast sensitivity function, stereopsis, high- and low-contrast visual acuity (VA) at 4 m and 40 cm under photopic and mesopic conditions, and defocus curves were measured. Data analysis was performed with nonparametric tests. P<0.05 was considered as statistically significant. RESULTS: Mean addition power of the prescribed lenses was 1.72±0.38 diopters. Multifocal design showed a statistically significant improvement for intermediate and near vision in the defocus curve under photopic and mesopic conditions (P<0.05), however, worsening in stereopsis (P<0.05) and contrast sensitivity for high spatial frequencies (P<0.05). Distance visual acuity (VA) showed significantly lower values under mesopic conditions for high- and low-contrast tests (P<0.05), and on low-contrast test under photopic conditions (P<0.001) with the multifocal design. CONCLUSION: Multifocal SLs showed better visual performance at intermediate and near distances without compromising distance vision under photopic conditions for a high-contrast test when compared with monofocal design.

Anterior, Posterior, and Thickness Cornea Differences after Scleral Lens Wear in Post-LASIK Subjects for One Year.

The aim of this study is to analyze the anterior and posterior corneal surface shape and the corneal thickness difference outcomes between before and after scleral lens (ScCL) wear in post-LASIK ectasia subjects for one year. Twenty eyes with post-LASIK ectasia wearing scleral lenses were evaluated in a visit before contact lens and after 1, 6, and 12 months. The study variables analyzed included the apex, nasal, temporal, inferior, and superior corneal thickness; the anterior and posterior surface corneal at corneal diameters of 8, 6, 4, and 2 mm, and high-contrast visual acuity. A statistically significant increment of corneal thickness (p < 0.05) was observed in the inferior area after 6 months and in the superior area in the 12-month follow-up after wearing ScCLs. The anterior corneal curvature presented a flattening and a statistically significant steepening (p < 0.05) in the central and peripheral radii, respectively, after one year. The posterior corneal curvature showed a significant (p < 0.05) steepening, which mainly affected the central region after one year. Despite these changes, high-contrast visual acuity with ScCL correction remained at the same values. The prolonged use of scleral lenses in post-LASIK subjects showed significant changes in the corneal curvature and thickness. These outcomes recommend more detailed and periodic topographic and vision quality checks to monitor the wear in ScCL patients.

Dipyridamole activates adenosine A2B receptor and AMPK/cAMP signaling and promotes myogenic differentiation of myoblastic C2C12 cells.

Introduction: Sarcopenia is defined as a loss of muscle mass and strength. ATP homeostasis is crucial during myogenesis. We determined how the purinergic system modulates myogenesis using dipyridamole (blocks adenosine taken up by the cells) and tenofovir (inhibits ATP release) in a myoblast cell line. Methods: C2C12 cells were differentiated in the presence/absence of tenofovir/dipyridamole, with/without the A2B selective inhibitor PSB-603. Extra-/intracellular nucleotides were examined via HPLC. The expression of muscle differentiation proteins (Pax7, Mif5, MyoD, MyoG, and MHC), PKA/CREB, adenosine receptors (A1, A2A, A2B, and A3), ATP-channel pannexin-1 and the P2X7 receptor was analyzed via WB and RT-PCR. cAMP and AMPK activation was measured. Results: Tenofovir increased intracellular ATP and reduced extracellular adenosine, decreasing Pax7 expression and increasing MHC expression prematurely. Dipyridamole increased intracellular AMP and extracellular adenosine, counteracting the premature myogenesis promoted by tenofovir. All adenosine receptors were expressed during differentiation with dipyridamole, increasing A2B expression. Tenofovir maintained inactive AMPK and decreased cAMP levels, as well as PKAα and pCREB expression, which were recovered with dipyridamole. Discussion: Adenosine and ATP act as mediators in muscle myogenesis. The blockade of ATP release by tenofovir promotes premature myogenesis, with dipyridamole counteracting the premature differentiation promoted by tenofovir via the adenosine A2B receptor and cAMP/AMPK pathways. Therefore, dipyridamole might be of interest as a therapeutic approach in sarcopenia.

New Biomarker Combination Related to Oxidative Stress and Inflammation in Primary Open-Angle Glaucoma.

Glaucoma is a multifactorial neurodegenerative disease and the second leading cause of blindness. Detection of clinically relevant biomarkers would aid better diagnoses and monitoring during treatment. In glaucoma, the protein composition of aqueous humor (AH) is relevant for the discovery of biomarkers. This study analyzes AH protein concentrations of putative biomarkers in patients with primary open-angle glaucoma (POAG) compared to a control group. Biomarkers were selected from known oxidative-stress and inflammatory pathways. Osteopontin (OPN), matrix metalloproteinase 9 (MMP-9), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and interleukin-10 (IL-10) were measured using the ELISA technique. Thirty-two patients were recruited to the study, including sixteen control and sixteen glaucoma patients. The glaucoma group consisted of patients diagnosed with glaucoma. In both groups, the aqueous humor sample was obtained during cataract surgery. A significant increase in OPN, MMP-9, TNF-alpha, and IL-10 was observed in the POAG aqueous humor, compared to the control group (p < 0.05). Of note, the AH of POAG patients contained 5.6 ± 1.2-fold more OPN compared to that of control patients. Different expression profiles of oxidative stress-related and inflammatory biomarkers were observed between patients with POAG and controls. This confirms the reported involvement of inflammatory and oxidative stress pathways in POAG pathophysiology. In the future, several, targeted AH proteins may be used to generate a potential biomarker expression profile of this disease, aiding diagnoses and disease progression monitoring. This approach highlights the importance of biomarkers in the future. Biomarkers provide a way to measure disease progression and response to treatment. In the future, biomarkers will play a more critical role in the toolkit of ophthalmology healthcare professionals as the field moves towards personalized medicine and precision healthcare.

Increased ocular dopamine levels in rabbits after blue light stimulation of the optic nerve head.

The purpose was to quantify ocular dopamine in rabbits after stimulation of the optic nerve head with short-wavelength (blue) light to activate melanopsin expressed in the axons of intrinsically photosensitive retinal ganglion cells (ipRGCs). Dopamine levels in tears, aqueous humor, vitreous body, and retina (including choroid) were quantified after blue light stimulation of the optic nerve head of 15 rabbits with an optical fiber for 1 min, 10 min, or no stimulation (n = 5, each group). The left eye of all rabbits was operated on to introduce the optical fiber and stimulate the optic nerve, while the contralateral eye served as internal control. One minute of blue light stimulation significantly increased dopamine concentration in the vitreous body of the treated eyes compared to the contralateral ones (P = 0.015). Stimulation for 10 min significantly increased dopamine concentration in the vitreous body, as well as the aqueous humor (P < 0.05). Therefore, using an optical fiber approach to stimulate the optic nerve head with blue light significantly increased dopamine concentration in the aqueous humor and the vitreous body. This likely reflects an upregulation of retinal dopamine synthesis that could be attributed to ipRGC activation. However, the data provided in this study fell short of establishing a definitive link between dopamine release and ipRGC activation, mainly due to the lack of evidence supporting the expression of the melanopsin photopigment in the optic nerve.

Effects of physical activity/exercise on tear film characteristics and dry eye associated symptoms: A literature review.

PURPOSE: To conduct a review of the literature in order to identify the potential association between physical activity or exercise and the objective signs and/or subjective symptoms of dry-eye disease. METHODS: A review of PubMed and Web of Science databases was performed, according to the PRISMA guidelines. The papers included in the review addressed the relationship of physical activity or exercise with dry-eye associated signs (changes in tear volume, osmolarity or biochemical composition) and/or subjective symptoms. RESULTS: A total of 16 papers were included. In eight, the changes in tear film volume, osmolarity and/or biochemical composition were studied after a single, acute bout of aerobic exercise. In another eight, changes in dry-eye associated symptoms were studied in relation to the habitual practice of physical activity or to prescribed exercise programmes. Acute responses of the tear film to exercise included: a) an increase of tear volume, without an increase of the tear break-up time; b) a trend to increase tear osmolarity, although within its physiological range; and c) a reduced concentration of several cytokines, and other molecular markers of inflammation or oxidative stress. Long-term exposure to physical activity or exercise programmes was associated with relief of dry-eye associated symptoms and a trend to increased tear break-up time. CONCLUSIONS: Despite a high heterogeneity in the studied population, study designs and methods, the current body of evidence suggests a potential role for physical activity as a modulatory stimulus for the proper functioning of the tear film and/or the relief of dry-eye symptoms.

Accuracy and precision of automated subjective refraction in young hyperopes under cycloplegia.

PURPOSE: To assess the agreement between the Eye Refract, an instrument to perform subjective automated refraction, and the traditional subjective refraction, as the gold standard, in young hyperopes under noncycloplegic and cycloplegic conditions. METHODS: A cross-section and randomized study was carried out, involving 42 participants (18.2 ± 7.7 years, range 6 to 31 years). Only one eye was chosen for the analysis, randomly. An optometrist conducted the refraction with the Eye Refract, while another different optometrist conducted the traditional subjective refraction. Spherical equivalent (M), cylindrical components (J0 and J45), and corrected distance visual acuity (CDVA) were compared between both refraction methods under noncycloplegic and cycloplegic conditions. A Bland-Altman analysis was performed to assess the agreement (accuracy and precision) between both refraction methods. RESULTS: Without cycloplegia, the Eye Refract showed significantly lower values of hyperopia than the traditional subjective refraction (p < 0.009), the mean difference (accuracy) and its 95% limits of agreement (precision) being -0.31 (+0.85, -1.47) D. Conversely, there were no statistical differences between both refraction methods under cycloplegic conditions (p ≥ 0.05). Regarding J0 and J45, both refraction methods manifested no significant differences between them under noncycloplegic and cycloplegic conditions (p ≥ 0.05). Finally, the Eye Refract significantly improved CDVA (0.04 ± 0.01 logMAR) compared with the traditional subjective refraction without cycloplegia (p = 0.01). CONCLUSIONS: The Eye Refract is presented as a useful instrument to determine the refractive error in young hyperopes, the use of cycloplegia being necessary to obtain accurate and precise spherical refraction.

Oxidative Stress in the Anterior Ocular Diseases: Diagnostic and Treatment.

The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases.

Improvement of Soft Contact Lens Wettability After the Instillation of Hyaluronic Acid Eye Drops.

PURPOSE: To evaluate the effect of the topical instillation of hyaluronic acid eye drops with different viscosity on soft contact lens wettability and comfort. METHODS: A randomized and participant-masked study was performed, involving 20 participants (25.4±2.6 years). One eye wore hydrogel (ocufilcon D) contact lenses, and another eye wore silicone-hydrogel (somofilcon A) contact lenses. The in vivo wettability tear film surface quality (TFSQ) index and comfort were measured before and after the instillation of different eye drops: saline solution (control) and 0.1%, 0.2%, and 0.3% hyaluronic acid. RESULTS: Compared with saline solution, the instillation of 0.1%, 0.2%, and 0.3% hyaluronic acid improved the in vivo wettability of the hydrogel contact lenses by decreasing their TFSQ mean for 5, 10, and 30 min, respectively ( P <0.05). During silicone-hydrogel contact lens wear, the hyaluronic acid did not affect wettability because there were no changes in TFSQ mean ( P ≥0.05), but the 0.3% hyaluronic acid produced a decrease in comfort for the first 3 min ( P <0.05). CONCLUSIONS: The instillation of hyaluronic acid eye drops increased the in vivo wettability of the hydrogel contact lens, and the duration of this effect was directly related to its concentration and viscosity.

Dual-Mode Gold Nanoparticle-Based Method for Early Detection of Acanthamoeba.

Acanthamoeba keratitis is an aggressive and rapidly progressing ocular pathology whose main risk factor is the use of contact lenses. An early and differential diagnosis is considered the main factor to prevent the progression and improve the prognosis of the pathology. However, current diagnosis techniques require time, complex and costly materials making an early diagnosis challenging. Thus, there is a need for fast, accessible, and accurate methods for Acanthamoeba detection by practitioners for timely and suitable treatment and even for contact lens user as preventive diagnosis. Here, we developed a dual-mode colorimetric-based method for fast, visual, and accurate detection of Acanthamoeba using gold nanoparticles (AuNPs). For this strategy, AuNPs were functionalized with thiolated probes and the presence of target Acanthamoeba genomic sequences, produce a colorimetric change from red to purple. This approach allows the detection of 0.02 and 0.009 µM of the unamplified Acanthamoeba genome by the naked eye in less than 20 min and by color analysis using a smartphone. Additionally, real samples were successfully analyzed showing the potential of the technology considering the lack of point-of-care tools that are mostly needed.

Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior.

Design of advanced contact lenses (CLs) demands materials that are safe and comfortable for the wearers and that preserve the normal eye microbiota, avoiding chronic inflammation and biofilm development. This work aimed to combine the natural antibiofouling phosphorylcholine and the antioxidant and prebiotic resveratrol as integral components of CLs that may have the additional performance of preventing oxidative-stress related eye diseases. Different from previous uses of 2-methacryloyloxyethyl phosphorylcholine (MPC) as coating, we explored the feasibility of adding MPC at high proportions as a comonomer of 2-hydroxyethyl methacrylate (HEMA)-based hydrogels while still allowing for the loading of the hydrophobic resveratrol. Homogeneous distribution of MPC along the hydrogel depth (confirmed by Raman spectroscopy) notably increased solvent uptake and the proportion of free water while it decreased Young's modulus. Relevantly, MPC did not hinder the uptake of resveratrol by CLs (>10 mg/g), which indeed showed network/water partition coefficients of >100. Protocols for CLs sterilization and loading of resveratrol under aseptic conditions were implemented, and the effects of tear proteins on resveratrol release rate were investigated. CLs sustained resveratrol release for more than 24 h in vitro, and sorption of albumin onto the hydrogel, although attenuated by MPC, slowed down the release. The combination of MPC and resveratrol reduced P. aeruginosa and S. aureus growth as tested in a novel hydrogel disk-agar interface biofilm growth setup. The developed CLs showed excellent anti-inflammatory properties and biocompatibility in in ovo and rabbit tests and provided higher and more prolonged levels of resveratrol in tear fluid, which favored resveratrol biodistribution in anterior and posterior eye segments compared to eye drops. Correlations between the release profiles of resveratrol in vitro and in vivo were assessed. Relevantly, the CLs preserved the antioxidant properties of resveratrol during the entire 8 h of wearing. In sum, CLs prepared with high proportion in MPC may help address safety and comfort requirements while having drug releasing capabilities.

Pluronic®/casein micelles for ophthalmic delivery of resveratrol: In vitro, ex vivo, and in vivo tests.

Ocular health may strongly benefit from the supply of antioxidant agents that counteract free radicals and reactive oxygen species responsible for long-term eye diseases. Additionally, natural antioxidants like resveratrol can inhibit bacteria growth and restore natural microbiota. However, their use is hindered by limited solubility, fast degradation, and low ocular permeability. This work aimed to overcome these limitations by preparing single and mixed micelles of Pluronic® F127 and casein that serve as resveratrol nanocarriers. Single and mixed (0.1 % casein) micelles (0.0 to -17.0 mV; 2.4 to 32.7 nm) increased 50-fold resveratrol solubility, remained stable for one month at 4 °C, withstood fast dilution, underwent sol-to-gel transitions in the 23.9-27.1 °C range, and exhibited potent antioxidant properties. All formulations successfully passed the HET-CAM assay but showed Pluronic®-casein dose-dependent toxicity in the zebrafish embryo model. Resveratrol-loaded single and mixed micelles (10-15 mM Pluronic® F127) displayed antimicrobial activity against S. aureus and P. aeruginosa. The micelles favored resveratrol accumulation in cornea and sclera, but mixed micelles showed larger lag times and provided lower amount of resveratrol permeated through sclera. In vivo (rabbit) tests confirmed the safety of resveratrol-loaded single micelles and their capability to supply resveratrol to anterior and posterior eye segments.

Corneal Confocal Analysis after Scleral Lens Wear in Keratoconus Patients: A Pilot Study.

SIGNIFICANCE: Scleral lenses rely on the scleroconjunctival region without bearing the cornea, which could improve the symptoms and modify the corneal nerve plexus morphology. PURPOSE: This study aimed to evaluate symptoms and changes in corneal nerve plexus morphology and density of Langerhans cells in keratoconus patients with and without intrastromal corneal ring before and after scleral lens wear. METHODS: Sixteen scleral lens wearers with keratoconus were recruited for this short-term experimental pilot study. Subjects were divided into two groups: keratoconus group and intrastromal corneal ring segment group. All subjects were examined in two visits: baseline (before scleral lens wear) and after 6 months of scleral lens wear, after lens removal. The Schirmer I test, the Ocular Surface Disease Index, tear breakup time, and in vivo confocal microscopy were evaluated. RESULTS: The mean age was 42.33 ± 11.27 years. A significant decrease in tear breakup time was found in the total group ( P = .01, Wilcoxon) compared with baseline. Ocular Surface Disease Index score had decreased after 6 months of scleral lens wear in the keratoconus with intrastromal corneal ring segment subgroup ( P = .03, Wilcoxon) and in the total group ( P = .001, Wilcoxon). No statistical changes in nerve density, tortuosity, and ramification were found for either the total group or the subgroup. However, the mean nerve length was higher in all groups, especially in the keratoconus subgroup ( P = .03, Wilcoxon) after 6 months of scleral lens wear. Regarding optical density, the total group showed a significant increase after 6 months of wearing ( P = .02, Wilcoxon). Finally, Langerhans cell density was not statistically different in any group. CONCLUSIONS: These results suggest that scleral lens wearing improves the symptoms and increased the mean length nerves after 6 months of wear use in keratoconus patients.