A Trans-Atlantic Perspective on Stagnation in Clinical Translation of Antimicrobial Strategies for the Control of Biomaterial-Implant-Associated Infection.

Current regulatory requirements impede clinical translation and market introduction of many new antimicrobial combination implants and devices, causing unnecessary patient suffering, doctor frustration, and costs to healthcare payers. Regulatory requirements of antimicrobial combination implants and devices should be thoroughly revisited and their approval allowed based on enrichment of benefit demonstrations from high-risk patient groups and populations or device components to facilitate their clinical translation. Biomaterial implant and devices equipped with antimicrobial strategies and approved based on enrichment claims should be mandatorily enrolled in global registry studies supervised by regulatory agencies for a minimum five-year period or until statistically validated evidence for noninferiority or superiority of claims is demonstrated. With these recommendations, this trans-Atlantic consortium of academicians and clinicians takes its responsibility to actively seek to relieve the factors that stagnate downward clinical translation and availability of antimicrobial combination implants and devices. Improved dialogue between the various key players involved in the current translational blockade, which include patients, academicians and doctors, policymakers, regulatory agencies, manufacturers, and healthcare payers, is urgently needed.

Fibrous Catalyst-Enhanced Acanthamoeba Disinfection by Hydrogen Peroxide.

SIGNIFICANCE: Hydrogen peroxide (H2O2) disinfection systems are contact-lens-patient problem solvers. The current one-step, criterion-standard version has been widely used since the mid-1980s, without any significant improvement. This work identifies a potential next-generation, one-step H2O2, not based on the solution formulation but rather on a case-based peroxide catalyst. PURPOSE: One-step H2O2 systems are widely used for contact lens disinfection. However, antimicrobial efficacy can be limited because of the rapid neutralization of the peroxide from the catalytic component of the systems. We studied whether the addition of an iron-containing catalyst bound to a nonfunctional propylene:polyacryonitrile fabric matrix could enhance the antimicrobial efficacy of these one-step H2O2 systems. METHODS: Bausch + Lomb PeroxiClear and AOSept Plus (both based on 3% H2O2 with a platinum-neutralizing disc) were the test systems. These were tested with and without the presence of the catalyst fabric using Acanthamoeba cysts as the challenge organism. After 6 hours' disinfection, the number of viable cysts was determined. In other studies, the experiments were also conducted with biofilm formed by Stenotrophomonas maltophilia and Elizabethkingia meningoseptica bacteria. RESULTS: Both control systems gave approximately 1-log10 kill of Acanthamoeba cysts compared with 3.0-log10 kill in the presence of the catalyst (P < .001). In the biofilm studies, no viable bacteria were recovered following disinfection in the presence of the catalyst compared with ≥3.0-log10 kill when it was omitted. In 30 rounds' recurrent usage, the experiments, in which the AOSept Plus system was subjected to 30 rounds of H2O2 neutralization with or without the presence of catalytic fabric, showed no loss in enhanced biocidal efficacy of the material. The catalytic fabric was also shown to not retard or increase the rate of H2O2 neutralization. CONCLUSIONS: We have demonstrated the catalyst significantly increases the efficacy of one-step H2O2 disinfection systems using highly resistant Acanthamoeba cysts and bacterial biofilm. Incorporating the catalyst into the design of these one-step H2O2 disinfection systems could improve the antimicrobial efficacy and provide a greater margin of safety for contact lens users.

1. History, evolution, and evolving standards of contact lens care.

Contact lenses and lens care regimens are an important part of eyecare practices and vital to lens-wearing patients. New contact lens materials and cleaning options continue to come to market and affect how patients wear and care for their lenses. In this section we look at how the contact lens and lens solution revolution started, how it has evolved over the last 40 years, and how standards have evolved and impacted these new offerings.

Creating antimicrobial surfaces and materials for contact lenses and lens cases.

Contact lenses are a safe and effective mode of vision correction used by more than 100 million people worldwide, yet some adverse responses to microbial contamination of contact lenses still occur. Various medical devices, including contact lens cases, currently use antimicrobial agents to eliminate or reduce microbial contamination at the surface. The application of antimicrobial surface technologies to contact lenses and lens cases is being explored. This article describes agents that hold promise for antimicrobial surfaces for contact lenses or lens cases.

Corneal oxygen distribution with contact lens wear.

PURPOSE: Since 1991, multilayer mathematical in vivo oxygenation models have been created to predict normal corneal oxygenation with contact lens wear. From these models, there have been assertions that most hydrogel contact lenses allow 97%-98% of normal corneal oxygenation compared to no contact lens wear. In light of hydrogel lens-induced neovascularization and limbal hyperemia, to clinicians, this finding seems counterintuitive. This work seeks to validate or refute those preexisting models and estimate the impact of contact lens wear on the oxygen distribution profile across the cornea. To this end, to estimate the impact of contact lens wear on the 3-dimensional (3-D) oxygen distribution profile within the cornea as a function of the oxygen permeability of the contact lens, a two-dimensional axisymetric finite element analysis (FEA) model was constructed for contact lenses, on the cornea, both having varying thickness profiles. METHODS: A two dimensional (2-D) axi-symetric finite element analysis (FEA) model of a -3.00 D contact lens on eye was constructed. The model included the varying thickness profiles of the contact lens and cornea. By symmetry, this 2-D model is equivalent to a full 3-D model. The oxygen permeability, material thickness profile, and oxygen consumption coefficients from Brennan (Optometry and Vision Science, June 2005) were used for this validation. Several different oxygen consumption profiles were also considered. Oxygen partial pressure, flux, and consumption profiles were generated. RESULTS: Profiles of the oxygen partial pressure, flux, and consumption were generated from the central cornea to the limbal junction. CONCLUSION: This FEA model reproduced Brennan 8-layer model (BEL model) results at the central cornea. However, BEL model parameters yielded regions of oxygen deficiency in the corneal periphery, even in the open eye with no contact lens. If the BEL model cannot account for oxygenation across the whole cornea, it may be incorrect or incomplete. This assertion calls into question any conclusions from the BEL model regarding the minimum contact lens transmissibility needed to fully oxygenate the eye.

The elution of poly (vinyl alcohol) from a contact lens: the realization of a time release moisturizing agent/artificial tear.

The use of a contact lens as a polymeric delivery vehicle is presented. Specifically, the elution of nonfunctionalized poly (vinyl alcohol) (PVA) from nelfilcon A hydrogel lenses is presented as a model of delivering polymeric active agents to the eye. High molecular weight nonfunctionalized PVA is added to the lens matrix for later release into the tears. This is made possible by photo crosslinking a macromer species in lieu of monomeric polymerization. Consistent near zero order release of 0.062% (wt/wt) was demonstrated in vitro over a 20-h period. The result is a new contact lens device based on the slow release of PVA. In vivo results demonstrate that this product improves the wearing comfort of this type of contact lens and acts as a model basis for drug delivery.

Clinical performance of daily disposable soft contact lenses using sustained release technology.

PURPOSE: Polyvinyl alcohol (PVA) is a successful tear film stabiliser and is widely used in comfort drops and some soft contact lens materials. A PVA-containing lens, nelfilcon A has been modified to include additional (non-functional) PVA in order to provide improved comfort. This study aims to examine the clinical performance of this nelfilcon A lens with AquaRelease (AquaRelease). METHODS: Two contralateral, investigator masked, open label, subjective and objective evaluations were conducted. The first examined the effect of adding increased molecular weight PVA to nelfilcon A (n=5), and the second compared this AquaRelease lens to ocufilcon B (n=34). The principal measures were non-invasive break-up time (NIBUT) and subjective comfort, which were assessed at the beginning and end of a week of daily wear, and three times throughout 1 day at 8, 12 and 16 h. RESULTS: All subjects successfully completed the daily wearing schedule of 16h. On initial insertion, subjective comfort and NIBUT improved for AquaRelease than original nelfilcon A lenses (p<0.05). Initial comfort was better for AquaRelease compared to ocufilcon B lenses (p=0.01); however, NIBUT was not statistically different (11.7+/-15.6s versus 8.4+/-6.8s; p=0.26). Subjective comfort decreased with time (p<0.001), but there was no significant difference between AquaRelease and ocufilcon B lenses (p=0.16). NIBUT was not significantly affected by time (p=0.56) or between lenses (p=0.33). At the end of a weeks' wear, subjective initial, end-of-day, overall comfort and vision were rated significantly better with AquaRelease than ocufilcon B (p<0.01). CONCLUSIONS: Release of additional non-functionalised PVA from the nelfilcon A lenses appears to enhance comfortable contact lens wear.