Nichols,J. J., Morgan,P. M., Jones,L. W., Efron,N 21st century bibliometric analysis of the field of dry eye disease Clinical and Experimental Optometry 2021;104(5):639-640 [ Show Abstract ]

In 2012, the lead author of this paper (JJN) conducted a citation analysis of dry eye research to identify the leading papers, authors, institutions, countries and journals in the field. That analysis was essentially an historical overview of publications on this topic extending back over the past century. Because a strong and growing foundation of scientific literature is a fundamental component of evidenced-based clinical care of patients, the current work was conducted to update the research community on trends in the 21st century dry eye literature, and to compare this new literature with the prior analysis in the context of events or trends in the dry eye field.

Nichols,J. J., Willcox,M. D. P., Bron,A. J., Belmonte,C., Ciolino,J. B., Craig,J. P., Dogru,M., Foulks,G. N., Jones,L., Nelson,J. D., Nichols,K. K., Purslow,C., Schaumberg,D. A., Stapleton,F., Sullivan,D. A. The TFOS International Workshop on Contact Lens Discomfort: Executive summary Investigative Ophthalmology and Visual Science 2013;54(11):TFOS7-TFOS13

Nichols,K. K., Redfern,R. L., Jacob,J. T., Nelson,J. D., Fonn,D., Forstot,S. L., Huang,J. -F, Holden,B. A., Nichols,J. J. The TFOS International Workshop on Contact Lens Discomfort: Report of the definition and classification subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS14-TFOS19

Oh,S., McCanna,D., Subbaraman,L.N., Jones,L. Cytotoxic and inflammatory effects of contact lens solutions on human corneal epithelial cells in vitro Contact Lens and Anterior Eye 2018;41(3):282-289 [ Show Abstract ]

Purpose: To ascertain the effect that four contact lens (CL) multipurpose solutions (MPS) have on the viability and release of pro-inflammatory cytokines from human corneal epithelial cells (HCEC). Methods: HCEC were exposed to four different MPS at various concentrations for 18 hours. The cells were also exposed to phosphate buffer, borate buffer, and PHMB. The cell viability was evaluated using the alamarBlue assay. The release of pro-inflammatory cytokines was measured using a Multiplex electrochemiluminescent assay. Results: MPS-A, MPS-B and MPS-C all reduced cell metabolic activity p < 0.05 from control with MPS-A showing the greatest cytotoxic effect (maximum reduction, 90.6%). In contrast, MPS-D showed no significant reductions in cytotoxicity except at the highest concentration tested (19% reduction at 20% MPS concentration). Of the four cytokines evaluated MPS-C showed a substantial increase in the release of IL-1β, IL-6, IL-8, and TNF-α at higher concentrations when compared to control p < 0.05. At the 20% concentration of MPS-A and MPS-B the release of IL-1 β increased p 0.05. Exposing the cells to borate buffer and PHMB caused an increase in the release of TNF-α p < 0.05. Conclusions: This investigation demonstrates that at different concentration levels, several of the MPS tested showed a decrease in viability and an increase in the release of inflammatory cytokines from HCEC. The borate buffer component as well as PHMB appears to contribute to this pro-inflammatory reaction.

Omali,N. B., Heynen,M., Subbaraman,L. N., Papinski,D., Lakkis,C., Smith,S. L., Morgan,P. B., Berntsen,D. A., Nichols,J. J., Jones,L. W. Impact of lens care solutions on protein deposition on soft contact lenses Optometry and Vision Science 2016;93(8):963-972 [ Show Abstract ]

Purpose. To evaluate the effect of four contemporary lens care solutions on total protein, total lysozyme, and active lysozyme extracted from three contact lens materials. Methods. Adapted contact lens wearers were recruited at three sites, and all subjects were randomly assigned to daily wear of either etafilcon A, galyfilcon A, or senofilcon A for 2 weeks. Four lens care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and ClearCare) were used by each subject in random order with a new pair of lenses after a washout period between solutions of at least 4 days. After 2 weeks of daily wear, contact lenses were collected for analysis. Proteins were extracted from a subset of contact lenses (n = 568) and total protein, total lysozyme, and lysozyme activity were quantified using a modified Bradford assay, an enzyme-linked immunosorbent assay, and a micrococcal assay, respectively. Results. Higher levels of total protein were extracted from etafilcon A when used with Biotrue compared to other solutions (p = 0.0001). There were higher levels of total lysozyme extracted from galyfilcon A lenses when used with PureMoist than with Biotrue or Clear Care (p < 0.006). Higher total lysozyme was extracted from senofilcon A when used with RevitaLens OcuTec compared to Biotrue (p = 0.002). Lower lysozyme activity was recovered from senofilcon A lenses with RevitaLens OcuTec when compared to all other care solutions (all p < 0.004). When Biotrue, PureMoist, or RevitaLens OcuTec were used, higher total lysozyme was extracted from galyfilcon A compared to senofilcon A(p < 0.01). When RevitaLens OcuTec was used, higher levels of active lysozyme were extracted from galyfilcon A compared to senofilcon A (p = 0.02). Conclusions. The ability of lens care solutions to remove protein from lenses varies depending upon the care solution composition and also the polymeric make-up of the contact lens material. © Copyright 2016 American Academy of Optometry.

Omali,N. B., Lada,M., Lakkis,C., Morgan,P. B., Nichols,J. J., Subbaraman,L. N., Jones,L. W. Lipid Deposition on Contact Lenses when Using Contemporary Care Solutions Optometry and Vision Science 2017;94(9):919-927 [ Show Abstract ]

SIGNIFICANCE There remains only a small amount of data from human studies demonstrating the effect of contact lens/lens care solution combinations on the deposition of lipids. Therefore, information on the degree to which modern materials deposit lipids when used with contemporary care solutions would be valuable. PURPOSE The present study aims to determine the effect of lens care system combinations on levels of total lipid, cholesterol, and cholesteryl esters extracted from three different contact lenses (CLs) when used with four contemporary care systems. METHODS Experienced CL wearers were recruited to participate in this study. Combinations of three CLs (etafilcon A [ETA], galyfilcon A [GALY], and senofilcon A [SENO]) and four CL care solutions (Biotrue, ClearCare, OPTI-FREE PureMoist, and RevitaLens Ocutec) were investigated. A total of 791 CLs were analyzed. Subjects were randomized to one lens type and then used all four lens care solutions in random sequence for 10-14 days before the CLs were collected and analyzed for the amount of cholesterol, cholesteryl esters, and total lipids. RESULTS The mean range of cholesterol recovered across the different care solutions was 0.34-2.77 µg/lens, 3.48-4.29 µg/lens, and 4.75-6.20 µg/lens for ETA, SENO, and GALY lenses, respectively. Use of OPTI-FREE PureMoist with ETA lenses led to a significantly greater amount of cholesterol being recovered when compared to the use of the other solutions with ETA lenses (P .05). CONCLUSIONS This study did not demonstrate conclusively that any of the solution/CL combinations were superior to any of the other combinations when the amounts of lipid deposition were compared among the tested lenses. © Lippincott Williams & Wilkins.

Omali,N. B., Subbaraman,L. N., Coles-Brennan,C., Fadli,Z., Jones,L. W. Biological and clinical implications of lysozyme deposition on soft contact lenses Optometry and Vision Science 2015;92(7):750-757 [ Show Abstract ]

Within a few minutes of wear, contact lenses become rapidly coated with a variety of tear film components, including proteins, lipids, and mucins. Tears have a rich and complex composition, allowing a wide range of interactions and competitive processes, with the first event observed at the interface between a contact lens and tear fluid being protein adsorption. Protein adsorption on hydrogel contact lenses is a complex process involving a variety of factors relating to both the protein in question and the lens material. Among tear proteins, lysozyme is a major protein that has both antibacterial and anti-inflammatory functions. Contact lens materials that have high ionicity and high water content have an increased affinity to accumulate lysozyme during wear, when compared with other soft lens materials, notably silicone hydrogel lenses. This review provides an overview of tear film proteins, with a specific focus on lysozyme, and examines various factors that influence protein deposition on contact lenses. In addition, the impact of lysozyme deposition on various ocular physiological responses and bacterial adhesion to lenses and the interaction of lysozyme with other tear proteins are reviewed. This comprehensive review suggests that deposition of lysozyme on contact lens materials may provide a number of beneficial effects during contact lens wear. © 2015 American Academy of Optometry.

Omali,N. B., Subbaraman,L. N., Heynen,M., Fadli,Z., Coles-Brennan,C., Jones,L. W. In Vitro Effect of Lysozyme on Albumin Deposition to Hydrogel Contact Lens Materials Optometry and Vision Science 2017;94(11):1047-1051 [ Show Abstract ]

SIGNIFICANCE: Albumin deposition on contact lenses could be detrimental to contact lens (CL) wear because this may increase the risk of bacterial binding and reduce comfort. Lysozyme deposition on selected lens materials would reduce albumin deposition on lenses. PURPOSE: This study aims to determine if lysozyme deposition on CLs could act as a barrier against subsequent albumin adsorption, using an in vitro model. METHODS: Six hydrogel CL materials (etafilcon A, polymacon, nelfilcon A, omafilcon A, ocufilcon B, and nesofilcon A) were evaluated. Four CLs of each type were soaked in lysozyme solution for 16 hours at 37°C. Lysozyme-coated lenses were then placed in vials with 1.5 mL of artificial tear solution containing 125I-labeled albumin for 16 hours at 37°C with shaking. Four uncoated lenses of each type were used as controls. Lenses soaked in radiolabeled albumin were rinsed in a phosphate-buffered saline solution, and radioactive counts were measured directly on lenses using a gamma counter. Albumin uptake on lenses was measured using a calibration curve by plotting radioactive counts versus protein concentration. RESULTS: Results are reported as mean ± SD. Lysozyme-coated etafilcon A lenses exhibited lower levels of deposited albumin than uncoated etafilcon A lenses (58 ± 12 vs. 84 ± 5 ng/lens; P .05). Uncoated nesofilcon A lenses deposited the highest amount of albumin when compared with other uncoated lenses (P <.05). CONCLUSIONS: This study demonstrates that lysozyme deposited onto etafilcon A resists the deposition of albumin, which may potentially be beneficial to CL wearers. Copyright © 2017 American Academy of Optometry.

Omali,N. B., Subbaraman,L. N., Heynen,M., Lada,M., Canavan,K., Fadli,Z., Ngo,W., Jones,L. Lipid deposition on contact lenses in symptomatic and asymptomatic contact lens wearers Cont Lens Anterior Eye 2021;44(1):56-61 [ Show Abstract ]

Purpose
Lipid deposition on contact lenses (CL) has traditionally been believed to reduce comfort during CL wear. The purpose of this study was to quantify lipid deposition on CL in a group of symptomatic and asymptomatic adapted CL wearers.

Methods
This was a single-masked, randomized clinical trial. Only confirmed symptomatic (comfortable lens wear time (CWT) 10 h and minimal reduction in comfort over the course of the day) participants were recruited to participate in the study. Participants wore senofilcon A lenses in combination with a polyquaternium-based care solution (OPTI-FREE Replenish). Worn CL samples were collected on Day 14. Deposited lipid amounts from the lenses (including cholesteryl ester, cholesterol and triolein) were quantified using a liquid chromatography-mass spectrometry technique.

Results
Lipid deposition was significantly higher in CL extracts of asymptomatic wearers compared to the symptomatic wearers for all lipid types quantified, including cholesteryl ester (2.1 ± 0.6 vs 1.6 ± 0.5 log μg/lens), cholesterol (1.5 ± 0.3 vs 1.1 ± 0.3 log μg/lens) and triolein (0.3 ± 0.2 vs 0.1 ± 0.1 log μg/lens) (all p < 0.002). The amount of cholesteryl ester deposited was greatest (p = 0.0001), followed by cholesterol, then triolein, for both the asymptomatic and symptomatic groups (both p = 0.0001).

Conclusion
This study demonstrated that the asymptomatic group deposited a significantly greater amount of lipid on their CL. Although lipid levels measured are considered low to trigger any observable clinical deposition, they may influence other clinical outcomes, particularly comfort.

Omali,N.B., Subbaraman,L.N., Heynen,M., Ng,A., Coles-Brennan,C., Fadli,Z., Jones,L. Surface versus bulk activity of lysozyme deposited on hydrogel contact lens materials in vitro Contact Lens and Anterior Eye 2018;41(4):329-334 [ Show Abstract ]

Purpose: To determine and compare the levels of surface versus bulk active lysozyme deposited on several commercially available hydrogel contact lens materials. Methods: Hydrogel contact lens materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon and etafilcon A with polyvinylpyrrolidone (PVP)] were incubated in an artificial tear solution for 16 h. Total activity was determined using a standard turbidity assay. The surface activity of the deposited lysozyme was determined using a modified turbidity assay. The amount of active lysozyme present within the bulk of the lens material was calculated by determining the difference between the total and surface active lysozyme. Results: The etafilcon A materials showed the highest amount of total lysozyme activity (519 ± 8 μg/lens, average of Moist and Define), followed by the ocufilcon material (200 ± 5 μg/lens) and these two were significantly different from each other (p < 0.05). The amount of surface active lysozyme on etafilcon and ocufilcon lens materials was significantly higher than that found on all other lenses (p < 0.05). There was no active lysozyme quantified in the bulk of the nelfilcon material, as all of the active lysozyme was found on the surface (1.7 ± 0.3 μg/lens). In contrast, no active lysozyme was quantified on the surface of polymacon, with all of the active lysozyme found in the bulk of the lens material (0.6 ± 0.6 μg/lens). Conclusions: The surface and bulk activity of lysozyme deposited on contact lenses is material dependent. Lysozyme deposited on ionic, high water content lens materials such as etafilcon A show significantly higher surface and bulk activity than many other hydrogel lens materials.

Osae,E. A., Jones,L., Nichols,J. J. The impact of contact lenses on meibomian gland morphology Ocular Surface 2022;24(April):148-155 [ Show Abstract ]

Despite years of experience with contact lenses, controversy remains as to whether contact lenses adversely impact the meibomian glands (MG). This review summarizes the present body of evidence, showing that contact lens wear is associated with alterations in MG morphology (up to 80% higher gland atrophy compared to non-wearers) and qualitative changes in MG secretion. Key factors such as duration of contact lens wear, contact lens type (e.g., soft vs. rigid), edge design, and material modulus of elasticity are discussed in relation to the extent of MG morphological changes, the quality of MG secretion and other ocular surface parameters. Longitudinal studies of sufficient statistical power are needed to better understand how contact lens wear affects the MG, risk factors, and the clinical sequelae of these changes.

Otchere,H., Jones,L. W., Sorbara,L. Effect of Time on Scleral Lens Settling and Change in Corneal Clearance Optometry and Vision Science 2017;94(9):908-913 [ Show Abstract ]

SIGNIFICANCE With the increase in the use of scleral contact lenses among practitioners, questions regarding lens settling are gradually gaining attention. This is because current studies support the notion that scleral lenses settle back over time. More research is needed to understand the exact cause and the factors that underpin such phenomenon. PURPOSE The present study aims to assess the effect of time on topographic corneal clearance of three scleral contact lenses of varying sagittal depths. METHODS Three scleral contact lenses were fitted to 20 subjects with previous diagnosis of keratoconus (n = 18) or pellucid marginal degeneration (n = 2). The fit was based on corneal sagittal height measured with the Visante optical coherence tomographer (OCT) at 15 mm along the horizontal meridian. To select an appropriate lens from the diagnostic lens set, values of 325 μm (lens 1), 375 μm (lens 2), and 425 μm (lens 3) were randomly added in sequence to the corneal sagittal height. Subjects wore each lens for 1 hour. Corneal clearance was measured at 10-minute intervals for 1 hour using a custom ultra-long OCT. To assess change in clearance, central point and two mid-peripheral points (+3 mm and -3 mm) along an 8-mm chord were measured by taking differences at each time point up to 1 hour. Measurements were repeated for the two other lenses. RESULTS Mean central corneal clearance loss for all three lenses was 33.83 ± 48.40 μm. This was 26 ± 27 μm (13 ± 14 μm, +3 mm; 34 ± 37 μm, -3 mm), lens 1; 35 ± 59 μm (38 ± 61 μm, +3 mm; 52 ± 69 μm, -3 mm), lens 2; and 41 ± 54 μm (33 ± 26 μm, +3 mm; 52 ± 48 μm, -3 mm), lens 3, respectively. There was no significant difference (P = 0.06) at central and other locations for lens 1 (location and over time). There were significant differences for both lenses 2 and 3 (P <.001, P =.01, respectively) for all three locations and over time. CONCLUSIONS There is a likelihood of clearance loss after 1 hour of lens wear. This varies between subjects, initial lens-fit relationship, and over time.

Otchere,H., Jones,L., Sorbara,L. The Impact of Scleral Contact Lens Vault on Visual Acuity and Comfort. Eye and Contact Lens 2018;44(Suppl 2):S54-S59 [ Show Abstract ]

PURPOSE: To assess how varying degrees of corneal clearance of scleral contact lenses (ScCL) impact visual acuity (VA) and comfort in patients with corneal ectasia.
METHOD: Three ScCL were fitted to 20 subjects with previous diagnosis of either keratoconus (n=18) or pellucid marginal degeneration (n=2). Fitting of ScCL was based on corneal sagittal height (CSH) measured with Visante OCT at a 15-mm chord on the horizontal meridian. To select the ScCL from the diagnostic lens set, values of 325, 375, and 425 μm were randomly added in sequence to CSH. Subjects wore ScCL for 1 hr. Central corneal clearance (CCC) and topographic corneal clearance (TCC) along the vertical meridian were assessed using an ultralong optical coherence tomographer. High-contrast VA (HCVA) and low-contrast VA (LCVA) were measured using a logarithm of the minimum angle of resolution VA chart, and comfort ratings were obtained with a standard comfort scale (0-100).
RESULTS: Mean CSH in the horizontal meridian was 3.78±0.53 (range: 3.33-4.17) mm at a 15-mm chord. Mean CCC was 190±100 μm (TCC: 160±94 μm at +3 mm and 180±94 μm at -3 mm), 360±120 μm (TCC: 260±100 μm at +3 mm and 330±110 μm at -3 mm), and 450±170 μm (TCC: 320±120 μm at +3 mm and 400±120 μm at -3 mm) for each lens (P=0.001). Mean HCVA for lenses 1, 2, and 3 were 0.05±0.12, 0.07±0.11, and 0.11±0.08 respectively, which were significantly different (P=0.02). Tukey post hoc analysis showed that this difference was only significant between lenses 1 and 3 (P=0.01). Similar findings were found for LCVA. Comfort ratings for lenses 1, 2, and 3 were 74.9±9.2, 79.7±11.6, and 78.6±10.8, respectively (P=0.24).
CONCLUSION: The CSH is an effective method of determining the appropriate lens/cornea relationship. Lens 2 (+375 μm) gave the best combination of acuity and comfort ratings. Evaluation of the fluorescein pattern must be balanced with VA and comfort ratings for successful fitting in a clinical setting.

Papas,E. B., Ciolino,J. B., Jacobs,D., Miller,W. S., Pult,H., Sahin,A., Srinivasan,S., Tauber,J., Wolffsohn,J. S., Nelson,J. D. The TFOS International Workshop on Contact Lens Discomfort: Report of the management and therapy subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS183-TFOS203

Papas,E. B., Decenzo-Verbeten,T., Fonn,D., Holden,B. A., Kollbaum,P. S., Situ,P., Tan,J., Woods,C. Utility of short-term evaluation of presbyopic contact lens performance Eye and Contact Lens 2009;35(3):144-148 [ Show Abstract ]

OBJECTIVES: To establish if evaluations of multifocal contact lens performance conducted at dispensing are representative of behavior after a moderate adaptation period. METHODS: Eighty-eight presbyopic subjects, across four clinical sites, wore each of four multifocal soft contact lenses (ACUVUE BIFOCAL, Focus Progressives, Proclear Multifocal, and SofLens Multifocal) for 4 days of daily wear. Comprehensive performance assessments were conducted at dispensing and after 4 days wear and included the following objective metrics: LogMAR acuity (contrast, 90% and 10%; illumination, 250 and 10 cd/m; distance, 6 m, 100 cm, and 40 cm), stereopsis (RANDOT), reading critical print size and maximum speed and range of clear vision at near. Subjective assessments were made, with 100-point numerical rating scales, of comfort, ghosting (distance, near), visual quality (distance, intermediate, and near), and the appearance of haloes. At two sites, subjects (n = 39) also rated visual fluctuation (distance, intermediate, and near), facial recognition, and overall satisfaction. RESULTS: Among the objective variables, significant differences (paired t test, P<0.05) between dispensing and 4 days were found only for range of clear vision at near (2.9 ± 2.0 cm; mean difference ± standard deviation) and high contrast near acuity in low illumination (-0.013 ± 0.011 LogMAR). With the exception of insertion comfort, all subjective variables showed significant decrements over the same period. Overall satisfaction declined by an average of 10.9 ± 5.1 points. CONCLUSIONS: Early assessment is relatively unrepresentative of performance later on during multifocal contact lens wear. Acuity based measures of vision remain substantially unchanged over the medium term, apparently because these metrics are insensitive indicators of performance compared with subjective alternatives. © 2009 Lippincott Williams & Wilkins.

Papas,E., Wolffsohn,J. S., Jones,L. Innovation in contact lenses: Basic research and clinical science Journal of Optometry 2010;3(3):123-124

Pereira-da-Mota,A. F., Phan,C-M., Concheiro,A., Jones,L., Alvarez-Lorenzo,C. Testing drug release from medicated contact lenses: The missing link to predict in vivo performance Journal of Controlled Release 2022;343(March):672-702 [ Show Abstract ]

Contact lenses (CLs) offer a wide variety of advantages as ocular drug-releasing platforms, but the feasibility of medicated CL development is constrained by numerous scientific, technological, and regulatory challenges. One main difficulty is the setting of release rate specifications for each drug, since at present there are no standardized in vitro release models that can appropriately predict the performance of drug-eluting CLs once placed onto the eye. CL-adapted release tests may provide knowledge on how the drug release pattern should perform in vivo to trigger and maintain the therapeutic effects for both anterior and posterior ocular tissues. Moreover, in vitro release tests are valuable tools for quality assessment during production and to investigate the effect of a change in composition or process variables. This review aims to shed light on biorelevant ways of evaluating in vitro drug release from CLs and the feasibility of establishing in vitro-in vivo correlations (IVIVC) to predict in vivo performance. First, general guidelines and Pharmacopeia release tests for topical ophthalmic formulations as well as in vitro release tests implemented for drug-CLs in the last two decades are analyzed. Then, development of an appropriate method to investigate IVIVC is attempted from the few papers simultaneously reporting in vitro release profiles and either in vivo release or therapeutic response. Finally, key points to be considered for in vitro testing drug release from a medicated CL are suggested to pave the way to the clinical arena.

Pereira-da-Mota,A. F., Vivero-Lopez, M., Garg,P., Phan,C-M., Concheiro,A., Jones,L., Alvarez-Lorenzo,C. In vitro–in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model Drug Delivery and Translational Research 2023;13(4):1116-1127 [ Show Abstract ]

There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studies.

Peterson,R. C., Fonn,D., Woods,C. A., Jones,L. Impact of a rub and rinse on solution-induced corneal staining Optometry and Vision Science 2010;87(12):1030-1036 [ Show Abstract ]

Purpose.: To investigate whether the inclusion of a rub and rinse step before contact lens disinfection has an impact on solution-induced corneal staining. Methods.: This was a prospective, double-masked, single investigator study. Twenty participants were recruited for two visits, where balafilcon-A lenses were worn bilaterally for 2 h. Each pair of lenses was prepared using two different methodologies. The "control" lens was transferred from the blister pack directly into a storage case containing polyhexamethylene biguanide-based lens care solution. The contralateral "test" lens was rubbed and simultaneously rinsed using the same polyhexamethylene biguanide-based care solution, for either 60 s (visit 1) or 20 s (visit 2). Both lenses were then soaked in the solution overnight. After baseline corneal staining assessments, the lenses were inserted following a randomized contralateral model. After 2 h, lenses were removed, corneal staining was regraded, and comfort scores were obtained. Results.: Rubbed and rinsed test lenses induced significantly less corneal staining than control lenses for all participants during visit 1 (mean ± SD: 516 ± 843 vs. 2170 ± 902; p 0.05). Conclusions.: Corneal staining induced after 2 h of lens wear with the combination of balafilcon-A and polyhexamethylene biguanide-based lens care solution can be significantly reduced by including a rub and rinse step before overnight soaking. Further work is required to establish the longevity of this effect during the monthly wearing cycle. Copyright © 2010 American Academy of Optometry.

Phan,C. -M, Bajgrowicz-Cieslak,M., Subbaraman,L. N., Jones,L. Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing Transl Vis Sci Technol. 2016;5(6):3 [ Show Abstract ]

PURPOSE: The aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model.
METHODS: Four commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device.
RESULTS: Overall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05).
CONCLUSIONS: Moxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased.
TRANSLATIONAL RELEVANCE: Results suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials.

Phan,C. -M, Bajgrowicz,M., Gao,H., Subbaraman,L. N., Jones,L. W. Release of fluconazole from contact lenses using a novel in vitro eye model Optometry and Vision Science 2016;93(4):387-394 [ Show Abstract ]

Purpose. Rapid drug release followed by a plateau phase is a common observation with drug delivery from contact lenses (CLs) when evaluated in a vial. The aim of this study was to compare the release of fluconazole from seven commercially available daily disposable CLs using a conventional vial-based method with a novel in vitro eye model. Methods. An eye model was created using two 3-dimensional printed molds, which were filled with polydimethylsiloxane to obtain an inexpensive model that would mimic the eyeball and eyelid. The model was integrated with a microfluidic syringe pump, and the flow-through was collected in a 12-well microliter plate. Four commercial daily disposable conventional hydrogels (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three silicone hydrogels (somofilcon A, narafilcon A, delefilcon A) were evaluated. These CLs were incubated with fluconazole for 24 h. The drug release was measured in a vial containing 4.8 mL of phosphate-buffered saline and in the polydimethylsiloxane eye model with a 4.8-mL tear flow across 24 h. Results. Overall, conventional hydrogel CLs had a higher uptake and release of fluconazole than silicone hydrogel CLs (p < 0.05). A higher drug release was observed in the vial condition compared with the eye model (p < 0.001). In the vial system, the drugs were rapidly released from the CL within the first 2 h, followed by a plateau phase. In contrast, drug release in the eye model under low tear volume was sustained and did not reach a plateau across 24 h (p < 0.05). Conclusions. Rapid drug release results from using a vial as the release system. Under low tear volume at physiological tear flow, commercial CLs can maintain a sustained drug release profile for up to 24 h. However, eyes with fungal keratitis may have increased tearing, which would significantly accelerate drug release. © 2015 American Academy of Optometry.

Phan,C. -M, Bajgrowicz,M., McCanna,D. J., Subbaraman,L. N., Jones,L. Effects of Antifungal Soaked Silicone Hydrogel Contact Lenses on Candida albicans in an Agar Eye Model Eye and Contact Lens 2016;42(5):313-317 [ Show Abstract ]

Purpose: To evaluate the effects of two commercial silicone hydrogel contact lenses (CLs) soaked with natamycin (NA) or fluconazole (FL) on the growth of Candida albicans in an in vitro eye model. Methods: Three-D printed molds were used as a cast for making eye-shaped models comprising potato dextrose agar. Senofilcon A (SA) and lotrafilcon B (LB) CLs were incubated with either 2 mL of NA or FL at a concentration of 1 mg/mL for 24 hr. To simulate a fungal infection, the eye models were coated with C. albicans. The drug-soaked lenses were placed on top of the eye models. Seven experimental conditions were examined: (1) NA-SA, (2) NA-LB, (3) FL-SA, (4) FL-LB, (5) SA, (6) LB, and (7) control - no lens. At specified time points (t1, 8, 16, 24, 48 hr), the agar eyes from each experimental condition were removed from the incubator and photographed. The yeast cells from the 24 and 48 hr time point were also analyzed using light microscopy. Results: At 24 and 48 hr, there was considerable growth observed for all conditions except for the NA-SA and NA-LB conditions. When observed under the microscope at 24 and 48 hr, the morphology of the yeast cells in the FL-SA and SA condition were similar to that of the control (oval shaped). There was limited hyphae growth observed for LB and significant visible hyphae growth for the NA-LB group. For NA-SA, NA-LB, and FL-LB groups, the cells were significantly smaller compared with the control. Conclusions: For NA-SA and NA-LB, there was limited growth of C. albicans observed on the eye models even after 48 hr. Under the microscope, the cell morphology differ noticeably between each testing condition, and is dependent on drug-lens combinations. © 2015 Contact Lens Association of Ophthalmologists.

Phan,C. -M, Subbaraman,L. N., Jones,L. In vitro uptake and release of natamycin from conventional and silicone hydrogel contact lens materials Eye and Contact Lens 2013;39(2):162-168 [ Show Abstract ]

OBJECTIVES:: To investigate the uptake and release of the antifungal ocular drug, natamycin from commercially available conventional hydrogel (CH) and silicone hydrogel (SH) contact lens (CL) materials and to evaluate the effectiveness of this delivery method. METHODS:: Five commercial SH CLs (balafilcon A, comfilcon A, galyfilcon A, senofilcon A, and lotrafilcon B) and four CH CLs (etafilcon A, omafilcon A, polymacon, vifilcon A) were examined in this study. These lenses were incubated with natamycin solubilized in dimethyl sulfoxide, and the release of the drug from these lenses, in Unisol 4 pH 7.4 at 32±1 C, was determined using UV-visible spectrophotometry at 305 nm over 24 hours. RESULTS:: There was a significant uptake of natamycin between 0 hour and 24 hours (P0.05). There was a significant difference in release between all the SH materials (P0.05). There was a significant difference in release between all the SH materials (P0.05). There was a significant difference in release between all the SH materials (P0.05). Overall, the release of natamycin was higher in CH than SH lenses (P<0.001). CONCLUSIONS:: All CLs released clinically relevant concentrations of natamycin within 30 minutes, but this release reached a plateau after approximately 1 hour. Further CL material development will be necessary to produce a slow and sustained drug releasing device for the delivery of natamycin. © 2013 Lippincott Williams & Wilkins.

Phan,C. -M, Subbaraman,L. N., Jones,L. In vitro drug release of natamycin from ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin-functionalized contact lens materials Journal of Biomaterials Science, Polymer Edition 2014;25(17):1907-1919 [ Show Abstract ]

Purpose: The antifungal agent natamycin can effectively form inclusion complexes with beta-cyclodextrin (ß-CD) and 2-hydroxypropyl-ß-cyclodextrin (HP-ßCD) to improve the water solubility of natamycin by 16-fold and 152-fold, respectively (Koontz, J. Agric. Food. Chem. 2003). The purpose of this study was to develop contact lens materials functionalized with methacrylated ß-CD (MßCD) and methacrylated HP-ßCD (MHP-ßCD), and to evaluate their ability to deliver natamycin in vitro. Methods: Model conventional hydrogel (CH) materials were synthesized by adding varying amounts of MßCD and MHP-ßCD (0, 0.22, 0.44, 0.65, 0.87, 1.08% of total monomer weight) to a monomer solution containing 2-hydroxyethyl methacrylate (HEMA). Model silicone hydrogel (SH) materials were synthesized by adding similar concentrations of MßCD and MHP-ßCD to N,N-dimethylacrylamide (DMAA)/10% 3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS). The gels were cured with UV light, washed with ethanol and then, hydrated for 24 h (h). The model materials were then incubated with 2 mL of 100 g/mL of natamycin in phosphate buffered saline (PBS) pH 7.4 for 48 h at room temperature. The release of natamycin from these materials in 2 mL of PBS, pH 7.4 at 32 ± 2 °C was monitored using UV-vis spectrophotometry at 304 nm over 24 h. Results: For both CH and SH materials, functionalization with MßCD and MHP-ßCD improved the total amount of drugs released up to a threshold loading concentration, after which further addition of methacrylated CDs decreased the amount of drugs released (p < 0.05). The addition of CDs did not extend the drug release duration; the release of natamycin by all model materials reached a plateau after 12 h (p < 0.05). Overall, DMAA/10% TRIS materials released significantly more drug than HEMA materials (p < 0.05). The addition of MHP-ßCD had a higher improvement in drug release than MßCD for both HEMA and DMAA/10% TRIS gels (p < 0.05). Conclusions: A high loading concentration of methacrylated CDs decreases overall drug delivery efficiency, which likely results from an unfavorable arrangement of the CDs within the polymer network leading to reduced binding of natamycin to the CDs. HEMA and DMAA/10% TRIS materials functionalized with MHP-ßCD are more effective than those functionalized with MßCD to deliver natamycin.

Phan,C. -M, Subbaraman,L., Jones,L. Contact lenses for antifungal ocular drug delivery: A review Expert Opinion on Drug Delivery 2014;11(4):537-546 [ Show Abstract ]

Introduction: Fungal keratitis, a potentially blinding disease, has been difficult to treat due to the limited number of approved antifungal drugs and the taxing dosing regimen. Thus, the development of a contact lens (CL) as an antifungal drug delivery platform has the potential to improve the treatment of fungal keratitis. A CL can serve as a drug reservoir to continuously release drugs to the cornea, while limiting drug loss through tears, blinking, drainage and non-specific absorption. Areas covered: This review will provide a summary of currently available methods for delivering antifungal drugs from commercial and model CLs, including vitamin E coating, impregnated drug films, cyclodextrin-functionalized hydrogels, polyelectrolyte hydrogels and molecular imprinting. This review will also highlight some of the main factors that influence antifungal drug delivery with CLs. Expert opinion: Several novel CL materials have been developed, capable of extended drug release profiles with a wide range of antifungal drugs lasting from 8 h to as long as 21 days. However, there are factors, such as first-order release kinetics, effectiveness of continuous drug release, microbial resistance, ocular toxicity and potential complications from inserting a CL in an infected eye, that still need to be addressed before commercial applications can be realized. © Informa UK, Ltd.