Hall,B. J., Jones,L. W., Dixon,B. Silicone allergies and the eye: Fact or fiction? Eye and Contact Lens 2014;40(1):51-57 [ Show Abstract ]

OBJECTIVE: The purpose of this manuscript was to review the evidence concerning the role of an allergic reaction to silicone as the basis for the reported increase in contact lens-associated infiltrates in wearers of silicone hydrogel contact lenses. METHODS: A literature review was undertaken to investigate the antigenic properties of silicone and the causes of contact lens-associated inflammatory reactions. RESULTS: Immune cells cannot interact with silicone directly but can interact with antigens on these lenses. These antigens could be due to tear film deposits, microbial contamination, or components of care systems used with these lenses. CONCLUSIONS: Inflammatory reactions associated with silicone hydrogel contact lens wear are not caused by an allergic reaction to silicone alone. © 2013 Contact Lens Association of Ophthalmologists.

Hall,B., Forrest,J. A., Jones,L. A Review of Techniques to Measure Protein Sorption to Soft Contact Lenses Eye and Contact Lens 2017;43(5):276-286 [ Show Abstract ]

Purpose: To compare and critically evaluate a variety of techniques to measure the quantity and biological activity of protein sorption to contact lenses over short time periods. Methods: A literature review was undertaken investigating the major techniques to measure protein sorption to soft contact lens materials, with specific reference to measuring protein directly on lenses using in situ, ex situ, protein structural, and biological activity techniques. Results: The use of in situ techniques to measure protein quantity provides excellent sensitivity, but many are not directly applicable to contact lenses. Many ex situ techniques struggle to measure all sorbed proteins, and these measurements can have significant signal interference from the lens materials themselves. Techniques measuring the secondary and tertiary structures of sorbed proteins have exhibited only limited success. Conclusions: There are a wide variety of techniques to measure both the amount of protein and the biological activity of protein sorbed to soft contact lens materials. To measure the mass of protein sorbed to soft contact lenses (not just thin films) over short time periods, the method of choice should be I 125 radiolabeling. This technique is sensitive enough to measure small amounts of deposited protein, provided steps are taken to limit and measure any interaction of the iodine tracer with the materials. To measure the protein activity over short time periods, the method of choice should be to measure the biological function of sorbed proteins. This may require new methods or adaptations of existing ones. © 2017 Contact Lens Association of Ophthalmologists.

Hall,B., Heynen,M., Jones,L. W., Forrest,J. A. Analysis of Using I125 Radiolabeling for Quantifying Protein on Contact Lenses Current eye research 2016;41(4):456-465 [ Show Abstract ]

Purpose: To investigate the accuracy of I125 radiolabeling to quantitatively determine the deposition of protein onto various commercially available contact lens (CL) materials. Methods: Commercially available silicone hydrogel and conventional hydrogel CL materials were examined for times ranging from 10 s to 1 week. Adsorption of free I125 was measured directly for the CL. The use of dialyzing labeled proteins and/or using NaI to compete with free I125 uptake was investigated as ways to minimize effects due to free I125. Results: At all time points and with all lens materials, there was 0.3 µg/lens or greater of apparent mass attributable to free I125 uptake. Dialyzing labeled proteins significantly reduced free I125 uptake for all materials investigated. The benefit of using dialyzed protein was most prominent at shorter times, as free I125 is continuously generated over time. Using NaI can reduce free I125 uptake for some lens materials, but this is shown to directly affect protein deposition on some materials. Conclusions: Periodic replenishment of incubation solutions with freshly dialyzed labeled protein to limit free I125 generation is recommended, but the incorporation of NaI onto the buffer solution is not. Irrespective of the exact procedure to limit free I125 uptake, extra steps must be performed to quantify the amount of I125 adsorbed onto contact lens materials, to determine thresholds of confidence with respect to the actual protein deposition that occurs.

Hall,B., Jones,L. W., Forrest,J. A. Competitive effects from an artificial tear solution to protein adsorption Optometry and Vision Science 2015;92(7):781-789 [ Show Abstract ]

Purpose To compare the adsorption of lysozyme, lactoferrin, and albumin to various contact lens materials, between single-protein solutions and a multicomponent artificial tear solution (ATS). Additionally, extra steps were taken to distinguish loosely and tightly bound protein, the latter of which may be fully or partially denatured. Methods Using a previously described ATS, we measured the time-dependent adsorption of lys, lac, and alb onto one conventional hydrogel and four silicone hydrogel contact lens materials between the first minute and up to 1 week of protein interaction with the material surface. Proteins were quantified using I125 radiolabeling of each protein individually in ATS and buffered saline. Extra steps were taken to limit the amount of unbound I125 and to quantify the amount of reversibly bound protein. Results Comfilcon A, balafilcon A, and etafilcon A did not show any relevant competitive adsorption between the ATS components and lys, lac, or alb until after 1 week. Competitive adsorption effects for lys, lac, and alb were observed in as little as 1 minute on lotrafilcon B. Lotrafilcon B had no reversibly bound protein at any time points. The ionic materials balafilcon A and etafilcon A deposited significant amounts of reversibly bound lysozyme and lactoferrin in just 10 minutes. Senofilcon A apparent deposition was below our thresholds of confidence for this protein quantification method. Conclusions Both the competition between lys, lac, and alb and ATS components and the reversibility of these bound proteins is material specific. Coadsorption of lys, lac, and alb with ATS components can increase the reversibility of their adsorption. © 2015 American Academy of Optometry.

Hall,B., Jones,L., Forrest,J. A. Measuring the kinetics and activity of adsorbed proteins: In vitro lysozyme deposited onto hydrogel contact lenses over short time periods Journal of Biomedical Materials Research - Part A 2013;101 A(3):755-764 [ Show Abstract ]

A new process has been developed to determine the biological activity of an intact layer of lysozyme deposited onto a biomaterial surface. This process is applied to a number of common hydrogel contact lenses. The activity of the surface-adsorbed protein is measured using a standard micrococcal activity assay, with extra steps to distinguish between protein on the surface and protein in solution. This is in contrast to protein extraction work in which the activity of all adsorbed protein is measured. For ionic materials, which are known to deposit large amounts of protein, particularly positively charged proteins such as lysozyme, there is evidence for loosely bound protein re-entering the solution, thus making it impossible to truly separate out the surface-adsorbed protein. This optimized process provides the first quantification of the biological activity of an intact layer of surface-adsorbed protein at a hydrogel interface. © 2012 Wiley Periodicals, Inc.

Hall,B., Jones,L., Forrest,J. A. Kinetics of competitive adsorption between lysozyme and lactoferrin on silicone hydrogel contact lenses and the effect on lysozyme activity Current eye research 2015;40(6):622-631 [ Show Abstract ]

To determine the effect of competitive adsorption between lysozyme and lactoferrin on silicone hydrogel contact lenses and the effect on lysozyme activity. Methods: Three commercially available silicone hydrogel contact lens materials (senofilcon A, lotrafilcon B and balafilcon A) were examined, for time points ranging from 10s to 2h. Total protein deposition was determined by I125 radiolabeling of lysozyme and lactoferrin, while the activity of lysozyme was determined by a micrococcal activity assay. Results: Senofilcon A and balafilcon A did not show any relevant competitive adsorption between lysozyme and lactoferrin. Lotrafilcon B showed reduced protein deposition due to competitive adsorption for lactoferrin at all time points and lysozyme after 7.5min. Co-adsorption of lactoferrin and lysozyme decreased the activity of lysozyme in solution for senofilcon A and lotrafilcon B, but co-adsorption had no effect on the surface activity of lysozyme for all lens types investigated. Conclusions: Competition between lysozyme and lactoferrin is material specific. Co-adsorption of lysozyme and lactoferrin does not affect the activity of surface-bound lysozyme but can reduce the activity of subsequently desorbed lysozyme. © 2015 Informa Healthcare USA, Inc.

Hall,B., McCanna,D., Jones,L. Identification of coagulase-negative staphylococci in daily disposable contact lens wearers Letters in applied microbiology 2014;59(3):313-319 [ Show Abstract ]

This study aimed to identify and quantify the number of contaminating organisms on daily disposable (DD) soft contact lenses, which may be responsible for mild cases of keratitis that occur with this lens wear modality. Ten participants wore DD lenses, and 10 participants wore planned replacement (PR) lenses. Lenses were collected aseptically and analysed for microbial contamination. Colony-forming units (CFU) were recorded, and representative colonies were used for identification using the API identification system. The DD lenses evaluated in this study were contaminated with coagulase-negative staphylococcus (CNS), ranging from 1 to 653 CFU. PR lenses showed more diversity in the types of contaminating micro-organisms and consisted of CNS, Gram-negative bacteria (Pseudomonas), a yeast (Candida) and a mould (Aspergillus), ranging from 1 to 230 CFU. CNS was the only type of micro-organism found on DD contact lenses and therefore may be the cause of any form of keratitis observed in DD lens wearers. © 2014 The Society for Applied Microbiology.

Hall,B., Phan,C. -M, Subbaraman,L., Jones,L. W., Forrest,J. Extraction versus in Situ techniques for measuring surface-adsorbed lysozyme Optometry and Vision Science 2014;91(9):1062-1070 [ Show Abstract ]

PURPOSE: To compare two techniques for measuring the activity of lysozyme deposited onto hydrogel contact lens and to image the binding of Micrococcus lysodeikticus to contact lenses. METHODS: Using a previously described protein extraction technique and a recently developed in situ technique, we measured the time-dependent activity of adsorbed lysozyme on six different contact lens materials during the first minute and up to 1 week of interaction with the material surface. Total activity of extracted lysozyme, total in situ activity, and the activity of the outer surface layer of sorbed lysozyme were determined using the two different techniques. Micrococcal cellular interaction with surface-adsorbed lysozyme was imaged using confocal microscopy. RESULTS: The differences between total extracted activities, total in situ activities, and surface activities were both measurable and material specific. In most cases, total extracted activity is greater than total in situ activity, which, in turn, is greater than surface activity. After 1 week, etafilcon A had the highest extracted activity at 137 µg/lens, followed by omafilcon A, balafilcon A, comfilcon A, senofilcon A, and lotrafilcon B at 27.4, 2.85, 2.02, 0.46, and 0.27 µg/lens, respectively. Micrococcal cell adhesion was greatest on contact lenses with high contact angles, such as balafilcon A, omafilcon A, and senofilcon A and lowest on contact lenses with low contact angles, such as etafilcon A, comfilcon A, and lotrafilcon B. Subsequent removal/prevention of adhered micrococcal cells was greatest on balafilcon A, which had the highest surface activity, and lowest on lotrafilcon B, which had the lowest surface activity. CONCLUSIONS: This study has measured and made direct comparisons between two established techniques for measuring the activity of adsorbed lysozyme. The extraction technique determines the activity of underlying layers of lysozyme or lysozyme within the matrix of the material. Conversely, the in situ technique allows conclusions to be drawn about only the biologically relevant lysozyme including the activity of just the outer surface of adsorbed lysozyme. © American Academy of Optometry.

Haque,S., Fonn,D., Simpson,T., Jones,L. Corneal and epithelial thickness changes after 4 weeks of overnight corneal refractive therapy lens wear, measured with optical coherence tomography Eye and Contact Lens 2004;30(4):189-193 [ Show Abstract ]

Purpose. To investigate thickness changes of the total cornea and epithelium across the horizontal corneal meridian after 4 weeks of overnight corneal refractive therapy (CRT) rigid contact lens (Paragon Vision Sciences, Mesa, AZ) wear. Methods. Thirty subjects were fitted with CRT contact lenses (Dk/t = 67), which were worn overnight for 4 weeks. Corneal thickness was measured at nine locations along the horizontal meridian by using optical coherence tomography (OCT) before lens insertion in the evening. Corneal thickness was measured the next morning immediately after lens removal and 1, 3, 7, and 14 hours later. This was repeated on days 4, 10, and 28 of the study and then 3 days after discontinuing lens wear. Results. Twenty-three subjects completed the study. At lens removal on day 1, the central and paracentral cornea swelled by 4.9% and 6.2%, respectively (both P = 0.000). The central epithelium thinned by 7.3%, and the mid peripheral epithelium thickened by 13% (both P = 0.000). Corneal swelling recovered throughout the day, with most of the deswelling taking place within the first 3 hours after lens removal. Maximal central epithelial thinning reached 13.5% by day 4. Three days after the study completion, corneal and epithelial thickness had recovered to baseline values. Conclusions. This study shows that CRT lenses induce differential overnight swelling across the cornea, with rapid deswelling during the day. Central epithelial thinning and paracentral thickening occurs, with recovery 3 days after discontinuation of lens wear. © 2004 Contact Lens Association of Ophthalmologists, Inc.

Haque,S., Fonn,D., Simpson,T., Jones,L. Corneal refractive therapy with different lens materials, Part 1: Corneal, stromal, and epithelial thickness changes Optometry and Vision Science 2007;84(4):343-348 [ Show Abstract ]

PURPOSE. To assess the corneal swelling response to two myopic correction corneal refractive therapy (CRT) lenses of varying Dk/t values, worn for a single night. Change in thickness of the total cornea, stroma, and epithelium was measured across the horizontal meridian using optical coherence tomography (OCT). METHODS. In this double-masked, randomized study, twenty subjects wore a CRT design lens in each eye, manufactured from Menicon Z (MenZ; Dk/t = 91) and Equalens II (EqII; Dk/t = 47) materials. Baseline corneal thickness was measured centrally and at four points either side of the central cornea using OCT, the night before sleeping at the Centre for Contact Lens Research. The next morning, lenses were removed, and thickness measurements were repeated 1, 3, 6, and 12 h after removal. RESULTS. On lens removal, the MenZ eye had central and paracentral corneal swelling (mean ± SD) of 4.1 ± 2.0% and 5.6 ± 2.4%, and the EqII eye had 5.8 ± 2.6% and 7.0 ± 2.6%. These values were significantly different from baseline (ReANOVA; p 0.05). Stromal swelling values on lens removal were 5.7 ± 2.2% centrally and 5.5 ± 3.0% mid-peripherally (MenZ) and 7.7 ± 3.1% centrally and 6.6 ± 2.9% mid-peripherally (EqII) (all p < 0.001 from baseline). Central stromal swelling was different between eyes at lens removal (p < 0.001). Stromal thickness in both eyes returned to baseline values within 3 h. CONCLUSION. The higher-Dk/t MenZ material caused significantly less overnight corneal and stromal swelling than the Eqll material, which reinforces the need to prescribe lenses with high Dk/t for overnight wear. Neither central epithelial thinning nor paracentral thickening are significantly affected by Dk/t. © 2007 American Academy of Optometry.

Haque,S., Fonn,D., Simpson,T., Jones,L. Epithelial thickness changes from the induction of myopia with CRTH RGP contact lenses Investigative Ophthalmology and Visual Science 2008;49(8):3345-3350 [ Show Abstract ]

PURPOSE. To investigate changes in epithelial thickness after overnight wear of CRTH rigid gas-permeable (RGP) lenses (Paragon Vision Sciences, Mesa, AZ) for the correction of hyperopia. METHODS. Twenty subjects wore a +3.50 D hyperopia-correcting CRTH lens on one eye for a single night in an attempt to induce myopia (first study). The untreated eye served as the control. Corneal and epithelial thickness was measured at nine points across the horizontal meridian by OCT. Measurements were obtained the night before lens wear, immediately after lens removal the next morning, and 1, 3, 6, and 12 hours after removal. Measurements were obtained 28 hours later, to observe recovery. Then, the attempted hyperopic corrections of +1.50 and +3.50 D were evaluated, using CRTH lenses in both eyes of 20 subjects for a single night (second study). RESULTS. All values were compared to baseline unless otherwise stated. In the first study, the treated eye's central and midperipheral epithelial thickness increased by 21.5% ± 8.6% and 13.3% ± 7.6%, respectively, after lens removal (P < 0.001). The control eye's central epithelial thickness (CET) increased by 7.1% ± 6.0% (P < 0.05). In the second study, CET increased by 17.6% ± 8.5% (P < 0.001) in the +3.50 D-treated eye and by 13.3% ± 4.8% (P < 0.001) in the +1.50 D-treated eye. Midperipheral epithelial thickening was 5.9% ± 4.7% (P < 0.05) in the +3.50 D-treated eye and 6.0% ± 6.3% (P < 0.05) in the +1.50 D-treated eye. CONCLUSIONS. CRTH lenses, designed to correct hyperopia, when worn overnight, caused an increase in CET. The amount of epithelial change seemed to differ with modified lens design. Copyright © Association for Research in Vision and Ophthalmology.

Haque,S., Simpson,T., Jones,L. Corneal and epithelial thickness in keratoconus: A comparison of ultrasonic pachymetry, Orbscan II, and optical coherence tomography Journal of Refractive Surgery 2006;22(5):486-493 [ Show Abstract ]

PURPOSE: To compare corneal thickness measurements in individuals with keratoconus using optical coherence tomography (OCT), Orbscan II, and ultrasonic pachymetry and to measure epithelial and stromal thickness in these individuals using OCT. METHODS: Twenty individuals with keratoconus and 20 controls (without keratoconus) were enrolled. The Orbscan II was used to locate the steepest area of the cornea, which was taken to represent the cone apex. Each instrument was used to obtain four total corneal thickness measurements-from the cone apex, corneal center, mid-nasal, and mid-temporal cornea. Optical coherence tomography scans were analyzed to provide epithelial and stromal thickness readings. RESULTS: In individuals with keratoconus, mean central corneal thickness (CCT) measured by ultrasonic pachymetry, Orbscan, and OCT was 494.2±50.0 μm, 438.6±47.7 μm, and 433.5±39.7 μm, respectively. The central keratoconic cornea was 57.7 μm thinner than the normal cornea (post-hoc P.05). CONCLUSIONS: Ultrasonic pachymetry produced the highest corneal thickness readings in the center and apex, compared to Orbscan II and OCT. Centrally, the total cornea, epithelium, and stroma were thinner in individuals with keratoconus than in normal individuals.

Henderson,L., Bond,D., Simpson,T. The association between eye color and corneal sensitivity measured using a Belmonte esthesiometer Optometry and Vision Science 2005;82(7):629-632 [ Show Abstract ]

Purpose. The purpose of this study is to determine the association between corneal sensitivity measured using a pneumatic esthesiometer and eye color quantified objectively. Methods. Twenty subjects had ocular surface sensitivity measured using a Belmonte esthesiometer. An ascending method of limits followed by the method of constant stimuli were used to estimate 1) cold detection thresholds, 2) discomfort detection thresholds (both using pneumatic stimuli at 20°C, 3) mechanical detection thresholds using pneumatic stimuli at 50°C (ocular surface temperature approximately 33°C), and 4) percent CO2 chemical detection thresholds using 50°C pneumatic stimuli at flow rates set at half of each subject's pneumatic detection threshold (therefore detected by the chemical content and not the mechanical content). Eye color was estimated 1) clinically by two observers ranking the color (light to dark) of digital images of each subject's iris, 2) photometrically by measuring iris luminance, and 3) using chromaticity obtained from a Photo Research 650 spectroradiometer with controlled illumination. Correlation and linear and nonlinear regression analyses were used to examine relationships between variables. Results. There were no associations between eye color (determined clinically or objectively) for mechanical and chemical detection thresholds (best r2 = 0.15, all p > 0.05). There was a significant linear association between 20° detection thresholds and eye color (r2 = 0.39), which was substantially improved with a two-line function (part level and part increasing linearly, r2 = 0.65). Conclusions. We were generally unable to demonstrate the relationship between eye color and sensitivity reported previously using a Cochet-Bonnet esthesiometer. However, for a subset of subjects with palest irises, there appears to be a linear association between eye color and sensitivity to cooling stimuli. Copyright © 2005 American Academy of Optometry.

Heynen,M., Babaei Omali,N., Fadli,Z., Coles-Brennan,C., Subbaraman,L. N., Jones,L. Selectivity and localization of lysozyme uptake in contemporary hydrogel contact lens materials Journal of Biomaterials Science, Polymer Edition 2017;28(13):1351-1364 [ Show Abstract ]

The purpose of this study was to investigate the early and selective uptake of lysozyme and the location of deposited lysozyme on contemporary hydrogel contact lens (CL) materials after exposure to an artificial tear solution (ATS) for 16 h. Seven different hydrogel CL materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon B, etafilcon A (Acuvue Moist), and etafilcon A (Acuvue Define)] were incubated in an ATS for various times. Total protein deposition was determined using a modified Bradford technique. Lysozyme, lactoferrin, and albumin deposition on CLs were determined using 125I-radiolabeling method. A confocal laser scanning microscopy (CLSM) technique was utilized to map the location of lysozyme uptake in an asymmetric environment. All lens materials had significant amounts of lysozyme after 1 min of exposure to ATS. After 16 h of incubation, higher levels of total protein deposited on the two etafilcon A-based lenses (Moist and Define), followed by ocufilcon B and both were significantly higher than all other CLs tested (p = 0.0001). The two etafilcon A materials (Moist and Define) also deposited the highest amounts of lysozyme (514.8 ± 28.4 and 527.1 ± 14.7 µg/lens respectively) when compared to other test CLs (p = 0.0001). The CLSM technique revealed that the non-ionic CLs tended to have symmetric distribution of lysozyme throughout the lens materials, while the ionic CLs had an asymmetric distribution, with the highest concentration of lysozyme on and near the exposed surface. The quantity and nature of proteins deposited on CLs varies, depending upon the chemical composition of the material. Among the various lenses tested, etafilcon A deposited the highest amount of total protein, most of it represented by lysozyme, which was largely located near the surface of the lens. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Heynen,M., Lorentz,H., Srinivasan,S., Jones,L. Quantification of non-polar lipid deposits on senofilcon A contact lenses Optometry and Vision Science 2011;88(10):1172-1179

Heynen,M., Ng,A., Martell,E., Subbaraman,L. N., Jones,L. Activity of Deposited Lysozyme on Contemporary Soft Contact Lenses Exposed to Differing Lens Care Systems Clinical Ophthalmology 2021;15(April):1727-1733 [ Show Abstract ]

Purpose: The amount of protein deposition on soft contact lenses and to what extent the proteins are denatured may have an impact on comfortable wearing times of contact lenses. The purpose of this study was to evaluate the effects of two lens care systems on total protein and the quantity and activity of lysozyme deposited on worn senofilcon A, silicone hydrogel contact lenses.

Participants and Methods: Thirty symptomatic soft contact lens wearers were enrolled into a 4-week prospective, randomized, bilateral eye, daily-wear, crossover, double-masked study. Participants were fitted with biweekly senofilcon A lenses and were assigned either a polyquaternium-1 and myristamidopropyl dimethylamine-containing system (OPTI-FREE RepleniSH) or a peroxide-based system (CLEAR CARE). After each wear period, proteins were extracted from the lenses and analyzed for total protein, total lysozyme quantity and activity.

Results: The use of either the peroxide-based system or the polyquaternium-1 and myristamidopropyl dimethylamine-containing system resulted in no difference (P> 0.05) to the amount of total protein deposited on the lenses (6.7 ± 2.8 micrograms/lens versus 7.3 ± 2.8 micrograms/lens, respectively) or to the amount of denatured lysozyme deposits (0.8 ± 0.7 versus 0.9 ± 0.7 micrograms/lens), respectively. The total amount of lysozyme deposited on the lenses was significantly lower when using the peroxide-based system (1.3 ± 0.9 micrograms/lens) compared to the polyquaternium-1 and myristamidopropyl dimethylamine-containing system (1.7 ± 1.0 micrograms/lens) (P=0.02).

Conclusion: The inactivation of lysozyme deposited on senofilcon A lenses when disinfected with the peroxide-based or the polyquaternium-1 and myristamidopropyl dimethylamine-containing systems were neither statistically nor clinically significant and the overall amounts of denatured lysozyme recovered from the lenses were low (< 1 microgram/lens).

Holland,E. J., Darvish,M., Nichols,K. K., Jones,L., Karpecki,P. M. Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review Ocul Surf 2019;17:412-423 [ Show Abstract ]

Dry eye disease (DED) is a multifactorial and complex disease of the ocular surface, with a high prevalence in adults. We systematically reviewed efficacy and safety data from published articles reporting results from prospective, controlled trials of topical ophthalmic drugs for DED. PubMed was searched from January 1997 to October 2017. Twenty-six unique trials investigating 13 ophthalmic drugs were identified, including trials of the approved drugs cyclosporine A, cyclosporine A cationic emulsion, diquafosol, rebamipide and lifitegrast. All identified studies provided level 1 evidence. None of the large (N > 100) studies demonstrated statistical significance of primary endpoints for both a sign and a symptom endpoint versus a control treatment in the same published trial. Publications on lifitegrast reported statistical superiority in a symptom or sign endpoint versus the control group in a large (N > 200), multicenter trial, with results repeated in trials of similar design. The most common adverse events associated with the approved drugs related to ocular discomfort upon instillation, especially burning/stinging and ocular irritation. The trial design and endpoints used across the studies varied considerably, highlighting the importance of standardization in clinical trials for DED. Recent advances in drug delivery and improved understanding of DED should contribute to new ophthalmic drug approvals.

Hrynchak,P., Hutchings,N., Jones,D., Simpson,T. A comparison of cup-to-disc ratio evaluation in normal subjects using stereo biomicroscopy and digital imaging of the optic nerve head Ophthalmic and Physiological Optics 2003;23(1):51-59 [ Show Abstract ]

The cup-to-disc (CD) ratio evaluated using stereoscopic biomicroscopy was compared with that evaluated by viewing a non-stereo digital image of the optic nerve head. Twenty normal subjects (mean age 26 +/- 4 years) were evaluated by two observers. The average CD ratio was 0.29 with a range of 0-0.80. The intra-class correlations between the observers ranged from 0.82 to 0.96, when comparing horizontal and vertical CD ratios for both evaluation techniques. The mean CD ratio was significantly smaller when viewing the digital image (0.25 +/- 0.01) compared with stereoscopic observation (0.33 +/- 0.03, p < 0.0001). Although the mean differences between the two techniques were small, the percentage of CD ratios that differed by >or=0.2 were between 5 and 25% of evaluations. Caution should be exercised when using stereoscopic and non-stereo digital evaluations of CD ratio interchangeably to assess longitudinal progression in a multi-clinician setting.

Hrynchak,P., Simpson,T. Optical coherence tomography: An introduction to the technique and its use Optometry and Vision Science 2000;77(7):347-356 [ Show Abstract ]

This report describes the new optical imaging technique of optical coherence tomography (OCT). OCT is capable of high-resolution, micrometer-scale, cross-sectional imaging of biological tissue. The OCT for ophthalmic application uses 843-nm, near-infrared light, which produces a longitudinal resolution of 10 to 20 μm and a penetration depth of a few millimeters. The scans are displayed in a false color representation scale on which warm colors represent areas of high optical reflectivity and cool colors represent areas of minimal or no reflectivity. A cross-sectional view similar to a histology section is obtained. The cornea, iris, and lens may be visualized as well as the retina and optic nerve. OCT has been used to investigate several ocular diseases. These include macular disease, genetic retinal disease, retinal detachment and retinoschisis, choroidal tumors, optic nerve disorders, and glaucoma.

Hui,A., Bajgrowicz-Cieslak,M., Phan,C. -M, Jones,L. In vitro release of two anti-muscarinic drugs from soft contact lenses Clinical Ophthalmology 2017;11:1657-1665 [ Show Abstract ]

The purpose of this study was to investigate the release of the anti-myopia drugs atropine sulfate and pirenzepine dihydrochloride from commercially available soft contact lenses. Standard ultraviolet (UV) absorbance-concentration curves were generated for atropine and pirenzepine. Ten commercially available contact lenses, including four multifocal lenses, were loaded by soaking in atropine or pirenzepine solutions at two different concentrations (10 mg/mL and 1 mg/mL). The release of the drugs into phosphate-buffered saline was determined over the course of 24hours at 34°C using UV absorbance. Materials with surface charge released the greatest amount of atropine when loaded with either concentration when compared to the other lens types (p<0.05), releasing upward of 1.026±0.035mg/lens and 0.979±0.024mg/lens from etafilcon A and ocufilcon A, respectively. There were no significant differences in the amount of atropine or pirenzepine released from the multifocal and non-multifocal lenses made from the same lens materials. Narafilcon A material demonstrated prolonged release of up to 8 hours when loaded with pirenzepine, although the overall dose delivered from the lens into the solution was among the lowest of the materials investigated. The rest of the lenses reached a plateau within 2 hours of release, suggesting that they were unable to sustain drug release into the solution for long periods of time. Given that no single method of myopia control has yet shown itself to be completely effective in preventing myopia progression, a combination of optical and pharmaceutical devices comprising a drug delivering contact lens presents a novel solution that warrants further investigation. © 2017 Hui et al.

Hui,A., Boone,A., Jones,L. Uptake and release of ciprofloxacin-HCl from conventional and silicone hydrogel contact lens materials. Eye & contact lens 2008;34(5):266-271 [ Show Abstract ]

OBJECTIVES: To investigate the uptake and release characteristics of the antibiotic ciprofloxacin-HCl in conventional and silicone hydrogel lenses, and evaluate their potential as therapeutic drug delivery devices. METHODS: Nine differing soft contact lens materials were soaked in a 0.3% ciprofloxacin-HCl solution at 34 degrees C. The uptake of the drug into the lenses was measured by the change in concentration over 24 hours using fluorescence spectrophotometry. The lenses were then placed in a buffered saline solution, and the release of the drug from the lenses was also measured using spectrophotometry. RESULTS: The release of drug varied from 0.016 +/- 0.004 mg/lens for lotrafilcon A lenses to 0.42 +/- 0.03 mg/lens for etafilcon A lenses, with an average of 0.133 mg/lens. The 3 conventional lenses used in the study released a statistically significantly different amount of drug when compared with the silicone hydrogels. The release of drug was very rapid, with drug release reaching a plateau after no more than 10 minutes for the majority of the lenses. The majority of the lenses were able to release enough drug to achieve minimum inhibitory concentration 90 for most resistant ocular pathogens. Ciprofloxacin was found to heavily precipitate on the etafilcon A lenses during the release phase at physiologic pH. CONCLUSION: While balafilcon A released the most drug from the silicone hydrogel materials, all materials released the drug too quickly to be effective as drug delivery devices.

Hui,A., Sheardown,H., Jones,L. Acetic and acrylic acid molecular imprinted model silicone hydrogel materials for ciprofloxacin-HCL delivery 2012;5(1):85-107 [ Show Abstract ]

Contact 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.

Hui,A., Willcox,M., Jones,L. In vitro and in vivo evaluation of novel ciprofloxacin-releasing silicone hydrogel contact lenses Investigative Ophthalmology and Visual Science 2014;55(8):4896-4904 [ Show Abstract ]

PURPOSE. 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. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

Huynh,C. B., Nagaarudkumaran,N., Kalyaanamoorthy,S., Ngo,W. In Silico and In Vitro Approach for Validating the Inhibition of Matrix Metalloproteinase-9 by Quercetin Eye & Contact Lens 2023;49(5):193-198 [ Show Abstract ]

Purpose:
To validate the mechanism and inhibitory activity of quercetin against matrix metalloproteinase-9 (MMP-9) using a hybrid in silico and in vitro approach.

Methods:
The structure of MMP-9 was obtained from the Protein Data Bank, and the active site was identified using previous annotations from the Universal Protein Resource. The structure of quercetin was obtained from ZINC15. Molecular docking was performed to quantify the binding affinity of quercetin to the active site of MMP-9. The inhibitory effect of various concentrations of quercetin (0.0025, 0.025, 0.25, 1.0, and 1.5 mM) on MMP-9 was quantified using a commercially available fluorometric assay. The cytotoxicity of quercetin to immortalized human corneal epithelial cells (HCECs) was quantified by obtaining the metabolic activities of the cells exposed to various concentrations of quercetin for 24 hr.

Results:
Quercetin interacts with MMP-9 by binding within the active site pocket and interacting with residues LEU 188, ALA 189, GLU 227, and MET 247. The binding affinity predicted by molecular docking was −9.9 kcal/mol. All concentrations of quercetin demonstrated significant inhibition of MMP-9 enzyme activity (all P0.99).

Conclusions:
Quercetin inhibited MMP-9 in a dose-dependent manner and was well-tolerated by HCECs, suggesting a potential role in therapy for diseases with upregulated MMP-9 as part of its pathogenesis.

Huynh,C. B., Ngo,W. Quantifying the Effect of Spectacle Frame Dimensions on Wind-Induced Ocular Plane Evaporation Using an in Vitro Model Eye & Contact Lens 2021;47(347):351 [ Show Abstract ]

Purpose: To quantify the effect of spectacle frame dimensions on wind-induced ocular plane evaporation.

Methods: A drop of 0.5 μL water was pipetted onto an eye of a mannequin head. The face was fitted with a spectacle frame. A fan positioned 10 cm away directed air (185 CFM) toward the face and the time required for the drop to evaporate was recorded. This procedure was repeated with 31 different frames to obtain evaporation times for various eye sizes, vertical heights, vertex distances, temperature, and humidity. This was also repeated 30 times without spectacle wear to obtain evaporation times for various temperature and humidity conditions.

Results: Spectacle wear increased evaporation times compared with nonspectacle wear, in both high (>35%) and low humidity (<30%) conditions (both P<0.01). Humidity was correlated with evaporation time, regardless of spectacle and nonspectacle wear (both P<0.01). Evaporation time did not correlate with spectacle eye size, vertical height, or vertex distance (all P≥0.21).

Conclusion: This study showed that spectacle wear guarded against wind-induced evaporation at the ocular plane compared with nonspectacle wear. However, once spectacles were worn, eye size, vertical height, and vertex distance were not correlated with evaporation times. Humidity drove evaporation independent of spectacle wear.