Ocular compatibility of hydrogel contact lenses:deposition and clinical performance

Currently over 50 million people worldwide wear contact lenses, of which over 75% wear hydrogel lenses. Significant deposition occurs in approximately 80% of hydrogel lenses and many contact lens wearers cease wearing lenses due to problems associated with deposition. The contact lens field is not alone in encountering complications associated with interactions between the body and artificial devices. The widespread use of man-made materials to replace structures in the body has emphasised the importance of studies that examine the interactions between implantation materials and body tissues.This project used carefully controlled, randomized clinical studies to study the interactive effects of contact lens materials, care systems, replacement periods and patient differences. Of principal interest was the influence of these factors on material deposition and their subsequent impact on subjective performance. A range of novel and established analytical techniques were used to examine hydrogel lenses following carefully controlled clinical studies in which clinical performance was meticulously monitored. These studies established the inter-relationship between clinical performance and deposition to be evaluated. This project showed that significant differences exist between individuals in their ability to deposit hydrogel lenses, with approximately 20% of subjects displaying significant deposition irrespective of the lens material. Additionally, materials traditionally categorised together show markedly different spoilation characteristics, which are wholly attributable to their detailed chemical structure. For the first time the in vivo deposition kinetics of both protein and lipid in charged and uncharged polymers was demonstrated. In addition the importance of care systems in the deposition process was shown, clearly demonstrating the significance of the quality rather than the quantity of deposition in influencing subjective performance

Tidal and marine energy in the uk– identifying the future challenges for supply chain development

The purpose of this paper is to investigate the current technical and operational supply chain issues surrounding the development of tidal and marine energy production in the UK. The paper outlines the market and growth potential of tidal energy production in the UK before identifying the key supply chain themes surrounding tidal energy production including an analysis of the portability and transferability of current supply chain thinking and development from other renewable energy systems such as wind turbine technology towards the development of tidal energy supply chain systems. The paper closes by identifying the major challenges that the UK supply chain must overcome in order to develop a comprehensive and robust supply chain system

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

Mohammadi, S., Jones, L., & Gorbet, M. (2014). Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models. PLoS ONE, 9(9), e106653. https://doi.org/10.1371/journal.pone.0106653In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.The funding for this project was provided by a Collaborative Health Research Project grant (jointly funded by NSERC and CIHR)

Acetic and Acrylic Acid Molecular Imprinted Model Silicone Hydrogel Materials for Ciprofloxacin-HCl Delivery

Hui, A., Sheardown, H., & Jones, L. (2012). Acetic and Acrylic Acid Molecular Imprinted Model Silicone Hydrogel Materials for Ciprofloxacin-HCl Delivery. Materials, 5(12), 85–107. https://doi.org/10.3390/ma5010085Contact lenses, as an alternative drug delivery vehicle for the eye compared to eye drops, are desirable due to potential advantages in dosing regimen, bioavailability and patient tolerance/compliance. The challenge has been to engineer and develop these materials to sustain drug delivery to the eye for a long period of time. In this study, model silicone hydrogel materials were created using a molecular imprinting strategy to deliver the antibiotic ciprofloxacin. Acetic and acrylic acid were used as the functional monomers, to interact with the ciprofloxacin template to efficiently create recognition cavities within the final polymerized material. Synthesized materials were loaded with 9.06 mM, 0.10 mM and 0.025 mM solutions of ciprofloxacin, and the release of ciprofloxacin into an artificial tear solution was monitored over time. The materials were shown to release for periods varying from 3 to 14 days, dependent on the loading solution, functional monomer concentration and functional monomer:template ratio, with materials with greater monomer:template ratio (8:1 and 16:1 imprinted) tending to release for longer periods of time. Materials with a lower monomer:template ratio (4:1 imprinted) tended to release comparatively greater amounts of ciprofloxacin into solution, but the release was somewhat shorter. The total amount of drug released from the imprinted materials was sufficient to reach levels relevant to inhibit the growth of common ocular isolates of bacteria. This work is one of the first to demonstrate the feasibility of molecular imprinting in model silicone hydrogel-type materials.The authors would like to thank Lakshman Subbaraman for his help in making the materials and manuscript editing. AH is supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canadian Optometric Education Trust Fund (COETF) and a Vistakon® Research Grant and Ezell Fellowship, both administered by the American Optometric Foundation (AOF). This study is also supported by the NSERC 20/20 Network for the Development of Advanced Ophthalmic Materials

Composition of incubation solution impacts in vitro protein uptake to silicone hydrogel contact lenses

Jadi, S., Heynen, M., Luensmann, D., & Jones, L. (2012). Composition of incubation solution impacts in vitro protein uptake to silicone hydrogel contact lenses. Molecular Vision, 18, 337–347.Purpose: To determine the impact of incubation solution composition on protein deposition to silicone hydrogel (SH) contact lenses using a simplistic and a complex model of the tear film. Methods: Three SH materials – senofilcon A (SA), lotrafilcon B (LB), and balafilcon A (BA) – were incubated in two different solutions; Solution A was a simplistic augmented buffered saline solution containing a single protein, whereas Solution B was a complex artificial tear solution (ATS), containing the augmented buffered saline solution in addition to proteins, lipids, and mucins (pH=7.4). The proteins of interest (lysozyme, lactoferrin, albumin) were radiolabeled with Iodine-125 (2% protein of interest) and the accumulation of the conjugated protein to the lens materials was determined after 1, 7, 14, and 28 days of incubation. Protein deposition was measured using a gamma counter and the raw data were translated into absolute amounts (µg/lens) via extrapolation from standards. Results: After 28 days, lysozyme uptake was significantly lower on BA lenses when incubated in Solution A (33.7 μg) compared to Solution B (56.2 μg), p0.05. LB lenses also deposited similar amounts of lysozyme for both solutions (Solution A: 5.0 μg, Solution B: 4.7 μg, p>0.05). After 28 days, BA lenses accumulated approximately twice the amount of lactoferrin than the other lens materials, with 30.3 μg depositing when exposed to Solution A and 22.0 μg with Solution B. The difference between the two solutions was statistically significant (p0.05). After 28 days, albumin deposition onto BA lenses was significantly greater when lenses were incubated in Solution B (1.7 μg) compared to Solution A (0.9 μg), p0.05). LB lenses incubated in Solution A deposited more albumin compared to Solution B (0.9 μg versus 0.6 μg), p=0.003. Discussion: Protein deposition onto SH materials varied when contact lenses were incubated in either a complex ATS compared to a single protein solution. More lysozyme accumulated onto BA lenses incubated in a complex analog of the human tear film, whereas lactoferrin deposited onto SA lenses independent of incubation solution composition. To better mimic the ex vivo environment, future studies should use more appropriate analogs of the tear film.This study was funded by the Centre for Contact Lens Research (CCLR) at the University of Waterloo and by the Canadian Optometric Education Trust Fund (COETF)

In Vitro and In Vivo Evaluation of Novel Ciprofloxacin-Releasing Silicone Hydrogel Contact Lenses

Hui, A., Willcox, M., & Jones, L. (2014). In Vitro and In Vivo Evaluation of Novel Ciprofloxacin-Releasing Silicone Hydrogel Contact Lenses. Investigative Opthalmology & Visual Science, 55(8), 4896. https://doi.org/10.1167/iovs.14-14855Purpose.: The purpose of this study was to evaluate ciprofloxacin-releasing silicone hydrogel contact lens materials in vitro and in vivo for the treatment of microbial keratitis. Methods.: Model silicone hydrogel contact lens materials were manufactured using a molecular imprinting technique to modify ciprofloxacin release kinetics. Various contact lens properties, including light transmission and surface wettability, were determined, and the in vitro ciprofloxacin release kinetics elucidated using fluorescence spectrophotometry. The materials then were evaluated for their ability to inhibit Pseudomonas aeruginosa growth in vitro and in an in vivo rabbit model of microbial keratitis. Results.: Synthesized lenses had similar material properties to commercial contact lens materials. There was a decrease in light transmission in the shorter wavelengths due to incorporation of the antibiotic, but over 80% light transmission between 400 and 700 nm. Modified materials released for more than 8 hours, significantly longer than unmodified controls (P 0.05), which is significantly less than corneas treated with unmodified control lenses or those that received no treatment at all (P < 0.05). Conclusions.: These novel contact lenses designed for the extended release of ciprofloxacin may be beneficial to supplement or augment future treatments of sight-threatening microbial keratitis.Supported by the Natural Science and Engineering Research Council of Canada (NSERC)20/20 Network for the Development of Advanced Ophthalmic Materialsand by an NSERC Alexander Graham Bell Doctoral Scholarshipthe Ezell Fellowship from the American Optometric Foundationand the Endeavour Research Grant from the Australian Government (AH)

Infrared Imaging of Meibomian Glands and Evaluation of the Lipid Layer in Sjogren's Syndrome Patients and Nondry Eye Controls

Menzies, K. L., Srinivasan, S., Prokopich, C. L., & Jones, L. (2015). Infrared Imaging of Meibomian Glands and Evaluation of the Lipid Layer in Sjogren’s Syndrome Patients and Nondry Eye Controls. Investigative Ophthalmology & Visual Science, 56(2), 836–841. https://doi.org/10.1167/iovs.14-13864Purpose.: The purpose of this study was to evaluate meibomian gland dropout and lipid layer thickness (LLT) in patients with and without Sjögren's syndrome dry eye (SS). Methods.: We recruited 11 participants with SS (males/females [M/F], 1:10; mean age = 56.0 ± 9.1 years) and 10 control subjects without dry eye (M/F, 3:7; mean age = 58.5 ± 4.7 years). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The LLT was assessed using the Tearscope Plus based on the appearance of the lipid layer. Noninvasive tear break-up time (NITBUT) also was measured. The lower and upper lids were everted, and the meibomian glands were imaged using the infrared camera of the Keratograph 4. A meibomian gland dropout score due to gland loss was obtained. Statistical analysis was conducted using the Mann-Whitney U test and correlations were determined using Spearman rank correlations. Results.: Of the SS participants, 100% reported ocular and oral dryness symptoms in the AECC questionnaire. The SS group recorded a higher OSDI score (median = 48.00, interquartile range [IQR] 23.0–56.2 vs. 2.1, IQR 0.0–2.6; P < 0.001), reduced LLT (median [IQR] = 15.0 [15.0–15.0] vs. 60.0 [45.0–100.0] nm; P = 0.001), and lower NITBUT (median [IQR] = 3.7 [2.5–4.2] vs. 9.5 [6.4–17.6] sec; P < 0.001) compared to the controls. Digital meibomian gland dropout score (% dropout) was significantly higher for the SS group (16.0% [IQR 12.1–40.0%] vs. 6.7% [IQR 1.5–12.7%]; P = 0.01). Subjective meibomian gland dropout score (0–6 score) was significantly higher for the SS group (median [IQR] = 1.5 [1.0–4.0] vs. 1.0 [0.0–1.25]; P = 0.03). Conclusions.: Patients with SS showed higher meibomian gland dropout scores and reduced LLT and NITBUT, which likely contribute to the severe dry eye symptoms reported by SS subjects

Impression Cytology of the Lid Wiper Area

Muntz, A., van Doorn, K., Subbaraman, L. N., & Jones, L. W. (2016). Impression Cytology of the Lid Wiper Area. Journal of Visualized Experiments, (114). https://doi.org/10.3791/54261Few reports on the cellular anatomy of the lid wiper (LW) area of the inner eyelid exist and only one report makes use of cytological methods. The optimization of a method of collecting, staining and imaging cells from the LW region using impression cytology (IC) is described in this study. Cells are collected from the inner surface of the upper eyelid of human subjects using hydrophilic polytetrafluoroethylene (PTFE) membranes, and stained with cytological dyes to reveal the presence of goblet cells, mucins, cell nuclei and various degrees of pre- and para-keratinization. Immunocytochemical dyes show cell esterase activity and compromised cell membranes by the use of a confocal scanning laser microscope. Up to 100 microscopic digital images are captured for each sample and stitched into a high-resolution, large scale image of the entire IC span. We demonstrate a higher sensitivity of IC than reported before, appropriate for identifying cellular morphologies and metabolic activity in the LW area. To our knowledge, this is the first time this selection of fluorescent dyes was used to image LW IC membranes. This protocol will be effective in future studies to reveal undocumented details of the LW area, such as assessing cellular particularities of contact lens wearers or patients with dry eye or lid wiper epitheliopathy