Verma,M. S., Chen,P. Z., Jones,L., Gu,F. X. "Chemical nose" for the visual identification of emerging ocular pathogens using gold nanostars Biosensors and Bioelectronics 2014;61:386-390 [ Show Abstract ]

Ocular pathogens can cause serious damages in the eye leading to severe vision loss and even blindness if left untreated. Identification of pathogens is crucial for administering the appropriate antibiotics in order to gain effective control over ocular infection. Herein, we report a gold nanostar based "chemical nose" for visually identifying ocular pathogens. Using a spectrophotometer and nanostars of different sizes and degrees of branching, we show that the "chemical nose" is capable of identifying the following clinically relevant ocular pathogens with an accuracy of 99%: S. aureus, A. xylosoxidans, D. acidovorans and S. maltophilia. The differential colorimetric response is due to electrostatic aggregation of cationic gold nanostars around bacteria without the use of biomolecule ligands such as aptamers or antibodies. Transmission electron microscopy confirms that the number of gold nanostars aggregated around each bacterium correlates closely with the colorimetric response. Thus, gold nanostars serve as a promising platform for rapid visual identification of ocular pathogens with application in point-of-care diagnostics. © 2014 Elsevier B.V.

Verma,M. S., Chen,P. Z., Jones,L., Gu,F. X. Controlling "chemical nose" biosensor characteristics by modulating gold nanoparticle shape and concentration Sensing and Bio-Sensing Research 2015;513-18 [ Show Abstract ]

Conventional 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. © 2015 The Authors.

Verma,M. S., Rogowski,J. L., Jones,L., Gu,F. X. Colorimetric biosensing of pathogens using gold nanoparticles Biotechnology Advances 2015;33(6):666-680 [ Show Abstract ]

Rapid detection of pathogens is crucial to minimize adverse health impacts of nosocomial, foodborne, and waterborne diseases. Gold nanoparticles are extremely successful at detecting pathogens due to their ability to provide a simple and rapid color change when their environment is altered. Here, we review general strategies of implementing gold nanoparticles in colorimetric biosensors. First, we highlight how gold nanoparticles have improved conventional genomic analysis methods by lowering detection limits while reducing assay times. Then, we focus on emerging point-of-care technologies that aim at pathogen detection using simpler assays. These advances will facilitate the implementation of gold nanoparticle-based biosensors in diverse environments throughout the world and help prevent the spread of infectious diseases. © 2015 Elsevier Inc.

Verma,M. S., Tsuji,J. M., Hall,B., Chen,P. Z., Forrest,J., Jones,L., Gu,F. X. Towards point-of-care detection of polymicrobial infections: Rapid colorimetric response using a portable spectrophotometer Sensing and Bio-Sensing Research 2016;1015-19 [ Show Abstract ]

Infectious diseases spread rapidly because current diagnostic methods are slow, expensive, and require technical expertise. Biosensors have recently been used as devices that can be deployed at the point-of-care for rapid and accurate diagnosis. Here, we show that a “chemical nose” biosensor based on gold nanoparticles can be coupled with a portable spectrophotometer to detect monomicrobial and polymicrobial solutions of pathogenic bacteria within 2 min of data collection. The design presented here exploits the rapid kinetics of gold nanoparticle aggregation around bacteria, which leads to a dramatic color change. The “chemical nose” produces unique signals based on the surface characteristics of the bacteria—such as the presence of extracellular polymeric substances, distribution of charged lipids, and localization of proteins—and hence provides a versatile platform for detection. We present a biosensor design that can easily be translated to the point-of-care because of its rapid response and simple output. © 2016 The Authors

Verma,M. S., Wei,S. -C, Rogowski,J. L., Tsuji,J. M., Chen,P. Z., Lin,C. -W, Jones,L., Gu,F. X. Interactions between bacterial surface and nanoparticles govern the performance of "chemical nose" biosensors Biosensors and Bioelectronics 2016;83:115-125 [ Show Abstract ]

Rapid and portable diagnosis of pathogenic bacteria can save lives lost from infectious diseases. Biosensors based on a "chemical nose" approach are attracting interest because they are versatile but the governing interactions between bacteria and the biosensors are poorly understood. Here, we use a "chemical nose" biosensor based on gold nanoparticles to explore the role of extracellular polymeric substances in bacteria-nanoparticle interactions. We employ simulations using Maxwell-Garnett theory to show how the type and extent of aggregation of nanoparticles influence their colorimetric response to bacteria. Using eight different species of Gram-positive and Gram-negative bacteria, we demonstrate that this "chemical nose" can detect and identify bacteria over two orders of magnitude of concentration (89% accuracy). Additionally, the "chemical nose" differentiates between binary and tertiary mixtures of the three most common hospital-isolated pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (100% accuracy). We demonstrate that the complex interactions between nanoparticles and bacterial surface determine the colorimetric response of gold nanoparticles and thus, govern the performance of "chemical nose" biosensors. © 2016 Elsevier B.V.

Vincent,S. J., Cho,P., Yin Chan,K., Fadel,D., Ghorbani-Mojarrad,N., González-Méijome,J. M., Johnson,L., Michaud,L., Simard,P., Jones,L. CLEAR - Orthokeratology Contact Lens Anterior Eye 2021;44(2):240-269 [ Show Abstract ]

Orthokeratology (ortho-k) is the process of deliberately reshaping the anterior cornea by utilising specialty contact lenses to temporarily and reversibly reduce refractive error after lens removal. Modern ortho-k utilises reverse geometry lens designs, made with highly oxygen permeable rigid materials, worn overnight to reshape the anterior cornea and provide temporary correction of refractive error. More recently, ortho-k has been extensively used to slow the progression of myopia in children.

This report reviews the practice of ortho-k, including its history, mechanisms of refractive and ocular changes, current use in the correction of myopia, astigmatism, hyperopia, and presbyopia, and standard of care. Suitable candidates for ortho-k are described, along with the fitting process, factors impacting success, and the potential options for using newer lens designs. Ocular changes associated with ortho-k, such as alterations in corneal thickness, development of microcysts, pigmented arcs, and fibrillary lines are reviewed. The safety of ortho-k is extensively reviewed, along with an overview of non-compliant behaviours and appropriate disinfection regimens. Finally, the role of ortho-k in myopia management for children is discussed in terms of efficacy, safety, and potential mechanisms of myopia control, including the impact of factors such as initial fitting age, baseline refractive error, the role of peripheral defocus, higher order aberrations, pupil size, and treatment zone size.

von Ahrenschildt,A., Hanneberg,L., Robich,M., Jones-Jordan,L., Marx,S., Sickenberger,W., Powell,D., Kwan,J. T., Wong,S., Srinivasan,S., Jones,L., Pucker,A. D. Morphological characteristics of Meibomian Glands and their Influence on Dry Eye disease in contact lens wearers Ocular Surface 2022;24(April):93-99 [ Show Abstract ]

Purpose:
Meibomian glands (MG) are now easily imaged via clinical meibography machines. The purpose of this work was to explore the utility of the known MG morphology metrics for predicting dry eye disease (DED) in contact lens (CL) wearers.

Methods:
Successful and previous CL wearers were recruited. DED was diagnosed if the participant's worst eye had a reduced tear meniscus height (TMH) of <0.2 mm or non-invasive tear break-up time (NITBUT) of [removed]5.0. Meibography was performed and images were subjectively graded by two examiners for the following MG characteristics: distorted, tortuous, hooked, abnormal gap, overlapping, fluffy areas, tadpoling, thinned, thickened, ghost, no extension to lid margin, shortened and dropout (atrophy). DED diagnostic ability of each metric was determined with receiver operating characteristic (ROC) analysis.

Results:
A total of 112 participants were recruited, with 18.8% having DED and 60.7% being female. The only MG morphology metrics that were marginally predictive of DED were thickened upper eyelid MGs (p = 0.046), thickened mean upper plus lower eyelid MGs (p = 0.007), and atrophy of upper eyelid MGs (p = 0.043); however, none of these metrics reached a meaningful area under the curve in ROC analysis (all <0.70).

Conclusion:
While abnormal MG morphology is likely suggestive of DED in CL wearers, none of the MG morphology metrics evaluated alone in this study had clinically meaningful predictive value for detecting DED in this group of current and previous CL wearers.

Wallerstein,A., Jackson,W.B., Chambers,J., Moezzi,A., Lin,H., Simmons,P.A Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose Clinical Ophthalmology 2018;12:839-848 [ Show Abstract ]

Purpose: To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK).
Methods: This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer’s test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled.
Results: A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer’s test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated.
Conclusion: CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK.

Walline,J. J., Holden,B. A., Bullimore,M. A., Rah,M. J., Asbell,P. A., Barr,J. T., Caroline,P. J., Cavanagh,H. D., Despotidis,N., Desmond,F., Koffler,B. H., Reeder,K., Swarbrick,H. A., Wohl,L. G. The current state of corneal reshaping Eye and Contact Lens 2005;31(5):209-214 [ Show Abstract ]

Purpose. The application of contact lenses to alter the shape of the cornea and temporarily reduce or eliminate myopia is known as orthokeratology, corneal refractive therapy, or corneal reshaping. It was first introduced in the 1960s, but high oxygen permeable materials and more sophisticated designs allow patients to wear contact lenses only during sleep, while dramatically improving the predictability and rate of myopia reduction. Many studies have shown that most corneal reshaping patients achieve uncorrected visual acuity of 20/25 or better that lasts all day long in one to two weeks of nighttime wear. 1-3 Treatment is primarily effective through central epithelial thinning and midperipheral epithelial and stromal thickening. Much remains to be learned about corneal reshaping contact lenses and their effects on the cornea. Methods. The authors reviewed existing knowledge and determined what needs to be learned in order to provide patients with appropriate informed consent prior to corneal reshaping contact lens wear. Results. While corneal reshaping contact lenses are effective at temporarily reducing or eliminating myopia, claims about the progress of myopia being controlled with corneal reshaping contact lenses should not be made until further studies are published in peer-reviewed literature. The incidence and prevalence of microbial keratitis related to corneal reshaping contact lens wear is not known. Any overnight wear of contact lenses increases the risk of infection, but it is not known whether the risks of microbial keratitis are greater for corneal reshaping overnight contact lens wearers than other form of overnight contact lens wear. It is also not known whether the risk of microbial keratitis is greater for children than adults, but we must determine if children are at greater risk than adults because many children are wearing corneal reshaping contact lenses. Conclusions. Finally, it is recommended that ongoing education be provided to practitioners and staff regarding safety, informed consent, and prevention of potential problems, with special emphasis on the critical need to properly and thoroughly disinfect lenses that will be worn overnight. © 2005 Contact Lens Association of Ophthalmologists, Inc.

Walsh,K., Jones,L. The use of preservatives in dry eye drops Clinical Ophthalmology 2019;13:1409-1425 [ Show Abstract ]

Topical ocular preparations are widely recommended by health care professionals, or chosen by patients, to help manage dry eye disease (DED). The chronic and progressive nature of DED may result in the administration of topical products several times a day, over a period of many years. Given DED is a condition that by definition affects the ocular surface, it is important to understand how the repeated use of eye drops may impact the ocular surface, influence clinical signs, affect symptoms, and impact the overall disease process of dry eye. The component in topical preparations with the greatest potential to adversely affect the ocular surface is the preservative. This paper reviews the literature in relation to the use of preservatives in formulations for dry eye. The ocular effects of benzalkonium chloride (BAK) are summarised and compared to the performance of alternative preservatives and preservative-free formulations. Use of preserved and preservative-free drops in relation to the management of varying stages of DED is discussed.

Walsh,K., Jones,L., Moody,K. Addressing common myths and misconceptions in soft contact lens practice Clinical and Experimental Optometry 2022;105(5):459-473 [ Show Abstract ]

Advances in contact lens technology over the past 50 years since the commercialisation of the first soft lenses in 1971 have been incredible, with significant changes in contact lens materials, frequency of replacement, care systems and lens designs occurring. However, despite the widespread availability of contact lenses, penetration rates for those who need vision correction remain in the low single digits and many practitioners seem to hold on to concepts around the potential value of contact lenses that appear based in the dim and distant past and are certainly no longer valid today. This review addresses 10 common ‘myths and misconceptions’ around soft contact lenses using an evidence-based approach that can hopefully dispel some of these incorrect assumptions.

Walther,H., Phan,C. -M., Subbaraman,L. N., Jones,L. Differential deposition of fluorescently tagged cholesterol on commercial contact lenses using a novel in vitro eye model Translational Vision Science and Technology 2018;7(2):18 [ Show Abstract ]

Purpose: We evaluate the differences in lipid uptake and penetration in daily disposable (DD) contact lenses (CL) using a conventional “in-vial” method compared to a novel in vitro eye model. Methods: The penetration of fluorescently labelled 22-(N-(7-Nitrobenz-2-Oxa-1,3- Diazol-4-yl)Amino)-23,24-Bisnor-5-Cholen-3beta-Ol (NBD)–cholesterol on three silicone hydrogel (SH) and four conventional hydrogel (CH) DD CLs were investigated. CLs were incubated for 4 and 12 hours in a vial, containing 3.5 mL artificial tear solution (ATS), or were mounted on an in vitro eye-blink platform designed to simulate physiologic tear flow (2 mL/24 hours), tear volume and “simulated” blinking. Subsequently, CLs were analyzed using laser scanning confocal microscopy and ImageJ. Results: Penetration depth and fluorescence intensities of NBD-cholesterol varied between the incubation methods as well as lens materials. Using the traditional vial incubation method, NBD-cholesterol uptake occurred equally on both sides of all lens materials. However, using our eye-blink model, cholesterol penetration was observed primarily on the anterior surface of the CLs. In general, SH lenses showed higher intensities of NBD-cholesterol than CH materials. Conclusions: The traditional “in-vial” incubation method exposes the CLs to an excessively high amount of ATS, which results in an overestimation for cholesterol deposition. Our model, which incorporates important ocular factors, such as intermittent air exposure, small tear volume, and physiological tear flow between blinks, provides a more natural environment for in vitro lens incubation. Translational Relevance: In vitro measurements of CLs are a common approach to predict their interactions and performance on the eye. Traditional methods, however, are rudimentary. Therefore, this study presents a novel in vitro model to evaluate CLs, which consequently will enhance elucidations of the interactions between CLs and the eye.

Walther,H., Lorentz,H., Heynen,M., Kay,L., Jones,L. W. Factors that influence in vitro cholesterol deposition on contact lenses Optometry and Vision Science 2013;90(10):1057-1065 [ Show Abstract ]

PURPOSE: The purpose of this study was to analyze the impact that incubation time, lipid concentration, and solution replenishment have on silicone hydrogel (SiHy) and conventional hydrogel (CH) contact lens cholesterol deposition via in vitro radiochemical experiments. METHODS: Four SiHy (senofilcon A, lotrafilcon B, comfilcon A, balafilcon A) and two CH (etafilcon A and omafilcon A) contact lenses were incubated in an artificial tear solution (ATS) that contained major tear film proteins, lipids, salts, salts, and a trace amount of radioactive C-cholesterol. Lenses were incubated for various incubation times (1, 3, 7, 14, or 28 days), with three concentrations of lipid (0.5×, 1×, 2× tear film concentration) and with or without solution replenishment to assess each variable's impact on cholesterol deposition. After incubation, the lenses were extracted using 2:1 chloroform:methanol, extracts were analyzed in a beta counter and masses (micrograms per lens) were extrapolated from standard curves. RESULTS: Within the SiHy materials, balafilcon A deposited the greatest amount of cholesterol (p replenishing > 1× > 0.5×. CONCLUSIONS: Overall, SiHy lenses deposit significantly more cholesterol than CH lens materials, and the mass of lipid deposited is dependent on the contact lens material, length of incubation, concentration of lipids in the ATS, and the replenishment of ATS. Copyright © 2013 American Academy of Optometry.

Walther,H., Lorentz,H., Heynen,M., Kay,L., Jones,L. W. The Impact of Incubation Conditions on in Vitro Phosphatidylcholine Deposition on Contact Lens Materials Optometry & Vision Science 2021;98(4):341-349 [ Show Abstract ]

SIGNIFICANCE: Previous in vitro measurements of contact lenses commonly investigate the impact of nonpolar
tear film lipids (i.e., sterols). Polar lipids, however, are equally important stabilizing components of the tear film.
This research explores and presents further knowledge about various aspects of polar lipid uptake that may impact
contact lens performance.

PURPOSE: This study evaluated the impact of incubation time, lipid concentration, and replenishment of an artificial
tear solution (ATS) on the uptake of phosphatidylcholine (PC) onto conventional hydrogel (CH) and silicone
hydrogel (SH) contact lens materials.

METHODS: Four SHs and two CH lens materials (n = 4) were soaked in a complex ATS containing radioactive
14C-PC as a probe molecule. Phosphatidylcholine uptake was monitored at various incubation time points (1, 3,
7, 14, and 28 days), with different ATS lipid concentrations (0.5, 1, 2) and with and without regular replenishment
of the ATS. Phosphatidylcholine was extracted from the lenses, processed, and counted by a β counter,
and accumulated PC (μg/lens) was extrapolated from standard lipid calibration curves.

RESULTS: All materials exhibited increasing PC deposition over time. Conventional hydrogel materials showed significantly lower PC uptake rates (P < .001) than any of the SH materials. Increasing lipid concentration in the ATS
resulted in increased PC binding onto the contact lens materials (P < .001). Replenishing the ATS every other day,
however, impacted the PC deposition differently, showing increased binding (P < .001) on CHs and reduced PC
deposition for SH materials (P < .001).

CONCLUSIONS: Length of incubation, lipid concentration in the ATS, and renewal of the incubation solution all
influenced the amount of PC that sorbed onto various lens materials and therefore need to be considered when
conducting future in vitro deposition studies.

Walther,H., Subbaraman,L, N., Jones,L. Efficacy of Contact Lens Care Solutions in Removing Cholesterol Deposits From Silicone Hydrogel Contact Lenses. Eye & Contact Lens 2019;45(2):105-111 [ Show Abstract ]

PURPOSE: To determine the efficacy of multipurpose solutions (MPSs) on the removal of cholesterol deposits from silicone hydrogel (SH) contact lens materials using an in vitro model.
MATERIALS AND METHODS: Five SH lens materials: senofilcon A, comfilcon A, balafilcon A, lotrafilcon A, and lotrafilcon B were removed from the blister pack (n=4 for each lens type), incubated for 7 days at 37°C in an artificial tear solution containing C radiolabeled cholesterol. Thereafter, lenses were stored in a preserved saline solution control (Sensitive Eyes Saline Plus) or cleaned with 1 of the 5 MPSs incorporating different preservatives (POLYQUAD/ALDOX, polyquaternium-1/alexidine, polyquaternium-1/PHMB, and 2 based on PHMB alone) using a rub and rinse technique, according to the manufacturer's recommendations, and stored in the MPS for a minimum of 6 hr. Lenses were then extracted with 2:1 chloroform:methanol, analyzed in a beta counter, and μg/lens of cholesterol was determined.
RESULTS: Balafilcon A and senofilcon A lens materials showed the highest amounts of accumulated cholesterol (0.93±0.02 μg/lens; 0.95±0.01 μg/lens, respectively), whereas lotrafilcon A and lotrafilcon B deposited the lowest amounts (0.37±0.03 μg/lens; 0.47±0.12 μg/lens, respectively). For all lens materials, the MPS preserved with POLYQUAD/ALDOX removed more deposited cholesterol than any other test solution; however, the amount of removed cholesterol contamination from the individual contact lenses was only statistically significant for balafilcon A and senofilcon A (P=0.006 and P=0.042, respectively). Sensitive eyes and the other evaluated MPSs showed no significant effect on cholesterol removal (P>0.05).
CONCLUSION: Cholesterol-removal efficacy varies depending on the combination of lens material and solution. Only 1 MPS showed a statistically significant reduction of cholesterol deposit for only 2 of the 5 tested lens materials.

Walther,H., Subbaraman,L. N., Jones,L. Novel in vitro method to determine pre-lens tear break-up time of hydrogel and silicone hydrogel contact lenses Cont Lens Anterior Eye 2019;42(2):178-184 [ Show Abstract ]

PURPOSE:
To develop an in vitro model to determine pre-lens non-invasive break-up time (NIBUT) and to subsequently use this method to compare the NIBUT over contemporary daily disposable (DD) contact lenses (CL).
METHODS:
Three silicone hydrogel (SH) and two conventional hydrogel (CH) DD CLs were incubated in an artificial tear solution (ATS). A model blink cell (MBC) was utilised to mimic intermittent air exposure. CLs were repeatedly submerged for 3 seconds (s) and exposed to air for 10 s over periods of 2, 6, 12, and 16 hours (h). NIBUTs (n = 4) were determined out of the blister pack (T0) and at the end of each incubation period.
RESULTS:
Overall, nesofilcon A showed the longest NIBUTs (p < 0.001). At T0, CHs revealed significantly longer NIBUTs (p ≤ 0.001) than SHs. After 2 h, nesofilcon A showed the longest NIBUT, however, this was only statistically significant compared with delefilcon A (p ≤ 0.001). After 6 h, nesofilcon A NIBUT was significantly longer than all other CLs (p ≤ 0.001). Etafilcon A showed a significantly longer NIBUT (p ≤ 0.001) after 12 h and delefilcon A had the longest NIBUT (p ≤ 0.001) after 16 h. Statistically significant (p ≤ 0.05) changes of NIBUT within the lens materials varied between time points. After 16 h, all CLs showed significant reductions in NIBUTs (p ≤ 0.001) in comparison to T0.
CONCLUSION:
NIBUT values reduced gradually over time and varying levels of deposition impacted measured pre-lens NIBUTs. While NIBUT of CH materials are longer immediately out of the blister pack, after tear film exposure, the NIBUTs obtained using this methodology became very similar.

Walther,H., Subbaraman,L., Jones,L. W. In vitro cholesterol deposition on daily disposable contact lens materials Optometry and Vision Science 2016;93(1):36-41 [ Show Abstract ]

Purpose. The goal of this study was to analyze how various incubation times affect the uptake of cholesterol on silicone hydrogel (SH) and conventional hydrogel (CH) daily disposable (DD) contact lens materials using an in vitro radiochemical detectionmethod. Methods. Three SH (somofilcon A, delefilcon A, and narafilcon A) and four CH (etafilcon A, nesofilcon A, ocufilcon A, and nelfilcon A) contact lenses were incubated in an artificial tear solution that contained major tear film components and a portion of radioactive 14C-cholesterol. Lenses (N = 4) were incubated for four incubation times (2, 6, 12, or 16 h) to assess the effects on cholesterol deposition. Subsequent to the incubation, the lenses were extracted using 2:1 chloroform:methanol, and the extracts were analyzed in a beta counter and (in nanograms per lens) extrapolated from standard curves. Results. In general, cholesterol deposited statistically significantly more on SH lenses than CHs (p e 0.033), with the exception of somofilcon A and nesolfilcon A materials (p = 0.067). Within the SH materials, narafilcon A accumulated the largest quantity of cholesterol (p G 0.05) and somofilcon A the lowest (p G 0.05). The uptake of cholesterol ranged from 22.63 T 2.98 ng/lens to 97.94 T 4.18 ng/lens for all lens materials. The accumulation of cholesterol was shown to be continuous throughout the 16 h of incubation, without reaching a plateau (p G 0.001). Conclusions. For the periods thatDDlens materials are worn, cholesterol deposits significantlymore ontoSHcontact lenses than CHs. This could have implications for wearers who have higher levels of lipid in their tears that are fitted with SH DD materials. Copyright © American Academy of Optometry.

Wang,J., Fonn,D., Simpson,T. L. Topographical thickness of the epithelium and total cornea after hydrogel and PMMA contact lens wear with eye closure Investigative Ophthalmology and Visual Science 2003;44(3):1070-1074 [ Show Abstract ]

PURPOSE. To determine changes in topographical thickness of the epithelium and total cornea after hydrogel (2-hydroxyethyl methacrylate; HEMA or soft lens) and PMMA rigid contact lens wear with eyes closed, as measured by optical coherence tomography (OCT). METHODS. Epithelial and total corneal thickness in 18 neophyte eyes was measured with OCT at intervals of 10° across a 10-mm zone of the horizontal meridian of the cornea, before and after 3 hours of soft and rigid contact lens wear with the eye closed. These measurements were repeated 20 minutes after removal of the lenses. RESULTS. Lens type, time, and location were found to be significant main influences (P < 0.0001) on corneal swelling in patched eyes, by three-way ANOVA, and there was a significant three-way interaction among lens type, time, and location (F(16,272) = 1.78, P = 0.033). However, there was no significant main effect and interaction of epithelial thickness (F(16, 272) = 0.33, P = 0.99). Immediately after removal of the lenses, total corneal thickness in the horizontal meridian was significantly greater with both soft and PMMA lenses (P < 0.001) at each location with each lens, compared with the baseline measurements. With both lenses, the increase in actual thickness and percentage of corneal swelling at the center was greater than at each peripheral point (excluding the first 10° points; P < 0.005). HEMA lenses caused greater corneal swelling than the PMMA lenses at each location immediately after removal of the lenses (P < 0.005). CONCLUSIONS. This study shows that corneal swelling is dependent on lens type and corneal location when eyes are closed, but epithelial thickness across the horizontal corneal meridian does not change during lens wear with eyes closed. OCT is an efficient method of measuring topographical corneal and epithelial thickness in response to contact lens wear.

Wang,J., Fonn,D., Simpson,T. L., Jones,L. Relation between optical coherence tomography and optical pachymetry measurements of corneal swelling induced by hypoxia American Journal of Ophthalmology 2002;134(1):93-98 [ Show Abstract ]

PURPOSE: To determine the relation between optical coherence tomography (OCT) and optical pachymetry (OP) measurements of corneal swelling induced by hypoxia. DESIGN: Experimental study. METHODS: One randomly selected eye of 20 noncontact lens wearers (10 males and 10 females, age 35.6 ± 9.6 years) was patched during 3 hours of soft contact lens (SCL) wear while the contralateral eye acted as control. Central corneal thickness of both eyes was measured before and after SCL wear using OCT and OP in randomized order. RESULTS: Baseline central corneal thickness was 523.6 ± 33.0 μm (mean ± standard deviation [SD]) measured with OCT and 490.6 ± 25.5 μm with OP. Immediately after contact lens removal, corneal thickness measured with OCT increased by 13.8 ± 2.3% compared with 12.1 ± 1.8% (paired t test: P < .001) measured with OP. Thereafter, corneal thickness decreased at the rate of 5.6% per hour for OCT and 5.4% per hour for OP. The difference in thickness between instruments before lens insertion, which was 33 μm compared with the difference after lens removal (edematous cornea), which ranged from 46 to 41 μm. The difference between instruments decreased during the corneal deswelling period after lens removal. The correlation coefficient between OCT and OP was 0.914 before lens insertion and 0.932 after lens removal. CONCLUSION: This study has demonstrated the difference of corneal thickness measured with OCT and OP. Although both instruments are correlated highly in all conditions tested, OCT may overestimate corneal thickness in normal and edematous corneas. © 2002 by Elsevier Science Inc. All rights reserved.

Wang,J., Fonn,D., Simpson,T. L., Jones,L. The measurement of corneal epithelial thickness in response to hypoxia using optical coherence tomography American Journal of Ophthalmology 2002;133(3):315-319 [ Show Abstract ]

PURPOSE: To determine if corneal epithelial thickness increases in association with corneal edema induced by wearing soft contact lenses during eye closure. DESIGN: Experimental study. METHODS: One eye (randomly selected) of twenty noncontact lens wearers (10 males and 10 females, age 35.6 ± 9.6 years) was patched during 3 hours of soft contact lens (SCL) wear and the contralateral eye acted as a control. Corneal and epithelial thickness of both eyes was measured before and after SCL wear using optical coherence tomography (OCT). RESULTS: Immediately after contact lens removal, total corneal thickness was increased significantly by 13.8 ± 2.3% (mean ± SD) compared with baseline (P .05, paired t test). Immediately after contact lens removal, corneal epithelial thickness was increased by 1.7 ± 4.8%, but this change was not statistically significant (P > .05, paired t test). Following contact lens removal, epithelial thickness changed significantly (Repeated measure analysis of variance [Re-ANOVA]: F(7,133) = 4.91, pH-F < 0.001) over the next 100 minutes with thinning recorded at 60, 80, and 100 minutes (P < .05, paired t test). There was no significant change over time in epithelial thickness of the control eyes (Re-ANOVA: F(4, 76) = 0.91, pH-F = 0.464). CONCLUSION: OCT demonstrated that corneal epithelial thickness does not increase in response to hypoxia from SCL wear and eye closure, in contrast to a significant increase in total corneal thickness. © 2002 by Elsevier Science Inc. All rights reserved.

Wang,J., Fonn,D., Simpson,T. L., Jones,L. Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography Investigative Ophthalmology and Visual Science 2003;44(6):2524-2528 [ Show Abstract ]

PURPOSE. To demonstrate the feasibility of indirectly measuring the precorneal tear film thickness and pre- and postlens tear film (PLTF) thickness using optical coherence tomography (OCT). METHODS. Central corneal thickness (C1) which includes the tear film (T) of both eyes of 40 non-contact lens wearers was measured using OCT after calibration. The mean age of the 40 subjects was 31.2 ± 9.3 years with a mean horizontal K-reading of 7.87 mm. Rigid contact lenses with base curves 0.3- to 0.5-mm steeper than the flattest K of the eye were fitted to measure real corneal thickness (C2), independently of the postlens tear film. T was calculated by T = C1 - C2. To measure pre- and postlens tear film thickness, Focus Night & Day and Acuvue lenses (Vistakon, Johnson & Johnson Vision Care, Jacksonville, FL) were fitted on both eyes. Central soft lens thickness (L1), which includes the prelens tear film (P), was measured by OCT in situ and in saline in a wet cell (L2). P was calculated by P = L1 - L2. Thickness of the central cornea plus the postlens tear film (C3) was measured during lens wearing. Postlens tear film (PLTF) was calculated by PLTF = C3 - C2. RESULTS. The mean ± SD precorneal tear film thickness was 3.3 ± 1.5 μm (range, 0-6.9) before lens insertion and 4.7 ± 2.3 μm (range, 0.7-11.0) after lens fitting, which was significantly thicker (paired t-test: P < 0.01). The prelens tear film thickness was 3.9 ± 2.6 and 3.6 ± 2.1 μm (mean ± SD; paired t-test: P = 0.52) and the postlens tear film thickness was 4.5 ± 2.3 and 4.7 ± 3.1 μm (paired t-test: P = 0.08) on and under Focus Night & Day and Acuvue lenses, respectively. Post hoc tests showed that precorneal (baseline) and prelens tear films were equivalent, and each was different (thinner; Tukey honestly significant difference P < 0.05) from the postlens tear film. CONCLUSIONS. OCT can noninvasively measure the thickness of the precorneal and prelens tear film as well as the postlens tear film. The thickness of the normal precorneal tear film is approximately 3 μm and becomes thicker after lens fitting. The postlens tear film is thicker than the precorneal and prelens tear films with soft contact lenses. The thickness of both preand postlens tear films appears to be independent of the investigated lens types.

Watson,S. L., Jones,L. W., Stapleton,F., Hinds,M., Ng,A.Y., Tan,J, Alster,Y., Bosworth,C., Rafaeli,O., DePuy,V, Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: A vehicle-controlled, randomized clinical trial The Ocular Surface 2023;29(July):537-546 [ Show Abstract ]

Purpose
Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD.

Methods
A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs).

Results
AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug).

Conclusions
Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated.

Weeks,A., Boone,A., Luensmann,D., Jones,L., Sheardown,H. The effects of hyaluronic acid incorporated as a wetting agent on lysozyme denaturation in model contact lens materials Journal of Biomaterials Applications 2013;28(3):323-333 [ Show Abstract ]

Conventional and silicone hydrogels as models for contact lenses were prepared to determine the effect of the presence of hyaluronic acid on lysozyme sorption and denaturation. Hyaluronic acid was loaded into poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) hydrogels, which served as models for conventional and silicone hydrogel contact lens materials. The hyaluronic acid was cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide in the presence of dendrimers. Active lysozyme was quantified using a Micrococcus lysodeikticus assay while total lysozyme was determined using 125-I radiolabeled protein. To examine the location of hyaluronic acid in the gels, 6-aminofluorescein labeled hyaluronic acid was incorporated into the gels using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry and the gels were examined using confocal laser scanning microscopy. Hyaluronic acid incorporation significantly reduced lysozyme sorption in poly(2-hydroxyethyl methacrylate) (p < 0.00001) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) (p < 0.001) hydrogels, with the modified materials sorbing only 20% and 16% that of the control, respectively. More importantly, hyaluronic acid also decreased lysozyme denaturation in poly(2-hydroxyethyl methacrylate) (p < 0.005) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) (p < 0.02) hydrogels. The confocal laser scanning microscopy results showed that the hyaluronic acid distribution was dependent on both the material type and the molecular weight of hyaluronic acid. This study demonstrates that hyaluronic acid incorporated as a wetting agent has the potential to reduce lysozyme sorption and denaturation in contact lens applications. The distribution of hyaluronic acid within hydrogels appears to affect denaturation, with more surface mobile, lower molecular weight hyaluronic acid being more effective in preventing denaturation. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Weeks,A., Luensmann,D.,Boone,A, Jones,L., Sheardown,H. Hyaluronic acid as an internal wetting agent in model DMAA/TRIS contact lenses 2011 1-10 [ Show Abstract ]

Model silicone hydrogel contact lenses, comprised of N,N-dimethylacrylamide and methacryloxypropyltris (trimethylsiloxy) silane, were fabricated and hyaluronic acid (HA) was incorporated as an internal wetting agent using a dendrimer-based method. HA and dendrimers were loaded into the silicone hydrogels and cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. The presence and location of HA in the hydrogels was confirmed using X-ray photoelectron spectroscopy and confocal laser scanning microscopy, respectively. The effects of the presence of HA on the silicone hydrogels on hydrophilicity, swelling behavior, transparency, and lysozyme sorption and denaturation were evaluated. The results showed that HA increased the hydrophilicity and the equilibrium water content of the hydrogels without affecting transparency. HA also significantly decreased the amount of lysozyme sorption (p < 0.002). HA had no effect on lysozyme denaturation in hydrogels containing 0% and 1.7% methacrylic acid (MAA) (by weight) but when the amount of MAA was increased to 5%, the level of lysozyme denaturation was significantly lower compared to control materials. These results suggest that HA has great potential to be used as a wetting agent in silicone hydrogel contact lenses to improve wettability and to decrease lysozyme sorption and denaturation.

Weeks,A., Morrison,D., Alauzun,J. G., Brook,M. A., Jones,L., Sheardown,H. Photocrosslinkable hyaluronic acid as an internal wetting agent in model conventional and silicone hydrogel contact lenses Journal of Biomedical Materials Research - Part A 2012;100 A(8):1972-1982 [ Show Abstract ]

Photocrosslinkable methacrylated hyaluronic acid (HA) was prepared and incorporated into model conventional and silicone hydrogel contact lenses as an internal wetting agent. The molecular weight of the HA, the degree of methacrylation as well as the amount (0.25 to 1.0 wt %) incorporated were varied. The HA-containing hydrogels were analyzed using a variety of techniques including water contact angles, equilibrium water content (EWC), and lysozyme sorption. The presence of HA could be detected in the materials using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopya - attenuated total reflectance. The materials containing methacrylated HA had improved hydrophilicity and reduced lysozyme sorption. Effects of modified HA on EWC were dependent upon the materials but generally increased water uptake. Increased mobility of the HA associated with a lower molecular weight and lower degree of methacrylation was found to be more effective in improving hydrophilicity and decreasing lysozyme sorption than the less mobile HA. All results found suggest that photocrosslinkable HA has significant potential in contact lens applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012. Copyright © 2011 Wiley Periodicals, Inc.