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

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

Bibliometric Analysis of Ophthalmic Journals

Importance: The primary vehicle for reporting and testing advances in eye care is refereed ophthalmic journals, which can be characterized using targeted bibliometric analyses. Objective: To identify all ophthalmic journals and evaluate citation metrics relating to articles, journals, authors, institutions, and countries published therein. Design and Setting: A bibliometric analysis was undertaken of all ophthalmic journals included in the Scopus database (Elsevier). The search was restricted to all article types published in ophthalmic journals in English from inception through November 18, 2022. After excluding general medical journals, journals published in a language other than English, and spurious titles unrelated to the ophthalmic field, the Scopus database was found to list 335 ophthalmic journal titles that have published 471184 articles, constituting the data set for this analysis. The 20 most highly cited articles were identified. Rank-order lists by article count were assembled for journals, authors, institutions, and countries. Main Outcomes and Measures: An h-index for ophthalmic journal articles was derived from citations and article counts for each constituent of each category. Results: The h-index for ophthalmic journal articles was determined to be 494. The journal with the highest h-index was Ophthalmology (h-index, 297). The journal with the greatest number of articles was American Journal of Ophthalmology (38441 articles). The most highly cited article was by Quigley and Broman, 2006 (5147 citations), concerning the epidemiology of glaucoma. The author with the highest h-index for ophthalmic journal articles was Ronald Klein, MD (h-index, 126), and the most prolific was Carol L. Shields, MD (1400 articles). Johns Hopkins University (h-index, 215) was the institution with the highest h-index for ophthalmic journal articles, and Harvard University was the most prolific (10071 articles). The United States was the nation with the highest h-index for ophthalmic journal articles (h-index, 444) and was the most prolific (180017 articles). Conclusions and Relevance: In this study, the most highly cited articles published in ophthalmic journals were revealed, as well as the leading journals, authors, institutions, and countries. While excluding ophthalmology articles in general medical journals, this investigation affords a means of identifying highly cited authors, institutions, and countries which individuals or institutions can use as a guide regarding contributions to the field.</p

Controlling “chemical nose” biosensor characteristics by modulating gold nanoparticle shape and concentration

Verma, M. S., Chen, P. Z., Jones, L., & Gu, F. X. (2015). Controlling “chemical nose” biosensor characteristics by modulating gold nanoparticle shape and concentration. Sensing and Bio-Sensing Research, 5, 13–18. https://doi.org/10.1016/j.sbsr.2015.04.007Conventional lock-and-key biosensors often only detect a single pathogen because they incorporate biomolecules with high specificity. “Chemical nose” biosensors are overcoming this limitation and identifying multiple pathogens simultaneously by obtaining a unique set of responses for each pathogen of interest, but the number of pathogens that can be distinguished is limited by the number of responses obtained. Herein, we use a gold nanoparticle-based “chemical nose” to show that changing the shapes of nanoparticles can increase the number of responses available for analysis and expand the types of bacteria that can be identified. Using four shapes of nanoparticles (nanospheres, nanostars, nanocubes, and nanorods), we demonstrate that each shape provides a unique set of responses in the presence of different bacteria, which can be exploited for enhanced specificity of the biosensor. Additionally, the concentration of nanoparticles controls the detection limit of the biosensor, where a lower concentration provides better detection limit. Thus, here we lay a foundation for designing “chemical nose” biosensors and controlling their characteristics using gold nanoparticle morphology and concentration

Release of Ciprofloxacin and Moxifloxacin From Daily Disposable Contact Lenses From an In Vitro Eye Model

Bajgrowicz, M., Phan, C.-M., Subbaraman, L. N., & Jones, L. (2015). Release of Ciprofloxacin and Moxifloxacin From Daily Disposable Contact Lenses From an In Vitro Eye Model. Investigative Opthalmology & Visual Science, 56(4), 2234. https://doi.org/10.1167/iovs.15-16379Purpose.: To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and a novel in vitro eye model. Methods.: Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A, delefilcon A) were used. The lenses were incubated in drug solutions for 24 hours. After the incubation period, the lenses were placed in two release conditions: (1) a vial containing 4.8 mL PBS for 24 hours and (2) an in vitro eye model with a flow rate at 4.8 mL over 24 hours. Results.: Release in the vial for both drugs was rapid, reaching a plateau between 15 minutes and 2 hours for all lenses. In contrast, under physiological flow conditions, a constant and slow release was observed over 24 hours. The amounts of ciprofloxacin released from the lenses ranged between 49.6 ± 0.7 and 62.8 ± 0.3 μg per lens in the vial, and between 35.0 ± 7.0 and 109.0 ± 5.0 μg per lens in the eye model. Moxifloxacin release ranged from 24.0 ± 4.0 to 226.0 ± 2.0 μg per lens for the vial, and between 13.0 ± 2.0 and 151.0 ± 10.0 μg per lens in the eye model. In both systems and for both drugs, HEMA-based CLs released more drugs than other materials. Conclusions.: The parameters of the release system, in particular the volume and flow rate, have a significant influence on measured release profiles. Under physiological flow, release profiles are significantly slower and constant when compared with release in a vial

Branching and size of CTAB-coated gold nanostars control the colorimetric detection of bacteria

Rapid detection of pathogenic bacteria is challenging because conventional methods require long incubation times. Nanoparticles have the potential to detect pathogens before they can cause an infection. Gold nanostars have recently been used for colorimetric biosensors but they typically require surface modification with antibodies or aptamers for cellular detection. Here, CTAB-coated gold nanostars have been used to rapidly (<5 min) detect infective doses of a model Gram-positive pathogen Staphylococcus aureus by an instrument-free colorimetric method. Varying the amounts of gold nanoseed precursor and surfactant can tune the size and degree of branching of gold nanostars as studied here by transmission electron microscopy. The size and morphology of gold nanostars determine the degree and rate of color change in the presence of S. aureus. The optimal formulation achieved maximum color contrast in the presence of S. aureus and produced a selective response in comparison to polystyrene microparticles and liposomes. These gold nanostars were characterized using UV-Visible spectroscopy to monitor changes in their surface plasmon resonance peaks. The visual color change was also quantified over time by measuring the RGB components of the pixels in the digital images of gold nanostar solutions. CTAB-coated gold nanostars serve as a promising material for simple and rapid detection of pathogens.This work was financially supported by the Natural Sciences and Engineering Research Council of Canada (NSERC)and 20/20 NSERC Ophthalmic Materials Network.M. S. Verma is grateful for the NSERC Vanier Canada Graduate Scholarship.P. Z. Chen is thankful for the NSERC Undergraduate Student Research Award