Statins are receiving increasing attention in the ophthalmic field. Their activity as 3-hydroxy-3-methylglutaryl–CoA (HMG–CoA) reductase inhibitors is clinically used to regulate cholesterol levels and leads to pleiotropic effects, which may help in the management of diabetes-related ocular pathologies. This work aims to design bioinspired contact lenses (CLs) with an affinity for atorvastatin by mimicking the active site of HMG–CoA reductase. Sets of imprinted and nonimprinted 2-hydroxyethyl methacrylate (HEMA) hydrogels were synthesized, varying the contents in functional monomers that bear chemical groups that resemble those present in HMG–CoA reductase, namely, ethylene glycol phenyl ether methacrylate (EGPEM), 2-aminoethyl methacrylate hydrochloride (AEMA), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). The hydrogels were characterized in terms of suitability as CLs (solvent uptake, light transmission, mechanical properties, and biocompatibility) and capability to load and release atorvastatin. Three sterilization protocols (steam heat, gamma radiation, and high hydrostatic pressure) were implemented and their effects on hydrogel properties were evaluated. Copolymerization of AEMA and, particularly, APMA endowed the hydrogels with a high affinity for atorvastatin (up to 11 mg/g; KN/W > 200). Only high hydrostatic pressure sterilization preserved atorvastatin stability and hydrogel performance. Permeability studies through the porcine cornea and sclera tissues revealed that the amount of atorvastatin accumulated in the cornea and sclera could be effective to treat ocular surface diseases.
(1) Background: The purpose of this study was to synthesize melatonin-eluting contact lenses (CLs) and evaluate both the ocular kinetics of the released melatonin and its effect on tear volume and intraocular pressure. (2) Methods: In vitro, melatonin-eluting CLs were synthesized by using non-functionalized (HEMA) and functionalized (HEMA/APMA) monomers. In vivo, a short-term prospective and randomized study was performed on 15 rabbits divided into two groups: 12 rabbits wearing functionalized CLs and 3 rabbits without CLs as a control. The melatonin levels in tears, aqueous humor, vitreous body and retina, tear volume, and intraocular pressure were measured for 8 h. (3) Results: In vitro, both monomers did not show differences in terms of melatonin loading and release (p ≥ 0.05). In vivo, the melatonin concentration was elevated in tears and aqueous humor after 2 and 4 h of wearing CLs, respectively (p < 0.05). Additionally, the CLs increased tear volume for 2 h (p < 0.05). (4) Conclusions: The melatonin-eluting CLs released their content over the ocular surface for at least 2 h, which was associated with a secretagogue effect on tear volume. However, the increased amount of melatonin found in the aqueous humor had no effect on intraocular pressure.
This study aimed to evaluate the effects of two months of orthokeratology (OK) treatment in the accommodative response of young adult myopes. Twenty eyes (21.8 ± 1.8 years) were fitted with the Paragon CRT® 100 LENS to treat myopia between −1.00 and −2.00 D. Low- and high-contrast visual acuity (LCDVA and HCDVA), central objective refraction, light disturbance (LD), and objective accommodative response (using the Grand Seiko WAM-5500 open-field autorefractometer coupled with a Badal system) were measured at baseline (BL) before lens wear and after 1, 15, 30, and 60 nights of OK. Refractive error correction was achieved during the first fifty days of OK lens wear, with minimal changes afterwards. LD analysis showed a transient increase followed by a reduction to baseline levels over the first 30 nights of treatment. The accommodative response was lower than expected for all target vergences in all visits (BL: 0.61 D at 1.00 D to 0.96 D at 5.00 D; 60 N: 0.36 D at 1.00 D to 0.79 D at 5.00 D). On average, the accommodative lag decreases over time with OK lens wear. However, these differences were not statistically significant (p > 0.050, repeated-measures ANOVA and Friedman test). This shows that overnight OK treatment does not affect objectively measured the accommodative response of young, low myopic eyes after two months of treatment stabilization.
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.
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