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Peer-reviewed articles

2020

Drolle,E., Ngo,W., Leonenko,Z., Subbaraman,L., Jones,L. Nanoscale Characteristics of Ocular Lipid Thin Films Using Kelvin Probe Force Microscopy 2020;9(7):41 [ Show Abstract ]

Purpose: To describe the use of Kelvin probe force microscopy (KPFM) to investigate the electrical surface potential of human meibum and to demonstrate successful use of this instrument on both human meibum and a meibum model system (six-lipid stock [6LS]) to elucidate nanoscale surface chemistry and self-assembly characteristics.

Materials and Methods: 6LS and meibum were analyzed in this study. Mica-supported thin films were created using the Langmuir-Blodgett trough. Topography and electrical surface potential were quantified using simultaneous atomic force microscopy/KPFM imaging.

Results: Both lipid mixtures formed thin film patches on the surface of the mica substrate, with large aggregates resting atop. The 6LS had aggregate heights ranging from 41 to 153 nm. The range in surface potential was 33.0 to 125.9 mV. The meibum thin films at P = 5 mN/m had aggregates of 170 to 459 nm in height and surface poten- tial ranging from 15.9 to 76.1 mV, while thin films at P = 10 mN/m showed an aggregate size range of 147 to 407 nm and a surface potential range of 11.5 to 255.1 mV.

Conclusions: This study showed imaging of the differences in electrical surface poten- tial of meibum via KPFM and showed similarities in nanoscale topography. 6LS was also successfully analyzed, showing the capabilities of this method for use in both in vitro and ex vivo ocular research.

Translational Relevance: This study describes the use of KPFM for the study of ocular surface lipids for the first time and outlines possibilities for future studies to be carried out using this concept.

Luensmann,D., Omali,N. B., Suko,A., Drolle,E., Heynen,M., Subbaraman,L. S., Scales,C., Fadli,Z., Jones,L. Kinetic Deposition of Polar and Non-polar Lipids on Silicone Hydrogel Contact Lenses Current Eye Research 2020;Online ahead of print [ Show Abstract ]

Purpose: This study investigated kinetic lipid uptake to four silicone hydrogel (SiHy) lenses over a period of four weeks, using an in-vitro radiolabel method.

Methods: Four contemporary monthly replacement SiHy lenses (lotrafilcon B, senofilcon C, comfilcon A, samfilcon A) were incubated in three different solutions: 1) An artificial tear solution (ATS) containing 14C-labeled phosphatidylcholine (PC), 2) an ATS containing 14C-cholesteryl oleate (CO) and 3) an ATS containing four 14C-radiolabeled lipids (PC, phosphatidylethanolamine, CO, and cholesterol (total lipid)). After 16 hours, lipids were extracted twice from the lenses with chloroform:methanol and the radioactive counts determined the lipid quantities to simulate 1 day of wear. OPTI-FREE PureMoist (Alcon) was used to clean and disinfect the remaining lenses daily and the lipid quantities were further determined after 2 weeks and 4 weeks.

Results: The amount of total lipid increased for all lenses over time (p < .01). After four weeks, total lipid accumulated was 20.26 ± 0.15 µg/lens for senofilcon C, which was significantly higher (p < .01) than all other lens materials (samfilcon A - 17.84 ± 0.21; comfilcon A - 16.65 ± 0.12; lotrafilcon B - 7.41 ± 0.56 µg/lens). CO was highest on lotrafilcon B (1.26 ± 0.13 µg/lens) and senofilcon C attracted the most PC (3.95 ± 0.12 µg/lens) compared to the other materials.

Conclusion: The amount of both polar and non-polar lipid deposition on monthly replacement SiHy lenses increased over 4 weeks, with significant differences being seen between lens materials.

Qiao,H., Luensmann,D., Heynen,M., Drolle,E., Subbaraman,L. N., Scales,C., Riederer,D., Fadli,Z., Jones,L. In Vitro Evaluation of the Location of Cholesteryl Ester Deposits on Monthly Replacement Silicone Hydrogel Contact Lens Materials Clinical Ophthalmology 2020;142821-2828 [ Show Abstract ]

Purpose: The deposition profile of cholesteryl ester on the surface and throughout the matrix of silicone hydrogel contact lens (CL) materials was determined under conditions that mimic a daily wear regimen.

Methods: In this in vitro study, four SiHy CL materials (senofilcon C, lotrafilcon B, comfilcon A and samfilcon A) were incubated in an artificial tear solution (ATS) for up to 30 days. CL incubation was alternated between the ATS (16 hours) and a multipurpose care regimen (8 hours). The ATS included fluorescently tagged cholesteryl ester (5-cholesten-3ß-ol 6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]caproate; CE-NBD) and confocal laser scanning microscopy visualized the distribution of the lipid through the CLs.

Results: The distribution of CE-NBD was homogenous from the anterior to posterior surface in senofilcon C and comfilcon A, at all time points. For lotrafilcon B and samfilcon A, CE-NBD localization was heterogeneous, with greater amounts on the surfaces on Day 1 and Day 14 compared to the lens matrix; however, differences in concentration between the surface and bulk diminished by Day 30.

Conclusion: The distribution of the non-polar lipid CE-NBD varied with lens material chemistry. While some lens materials deposited the lipid primarily on the surface after 16 hours of exposure, all materials exhibited a homogenous distribution after one month.

Keywords: lipid distribution, silicone hydrogel contact lenses, cholesteryl ester, artificial tear solution

Yamasaki,K., Drolle,E., Nakagawa,H., Hisamuare,R., Ngo,W., Jones,L. W. Impact of a low molecular weight hyaluronic acid derivative on contact lens wettability Cont Lens Anterior Eye 2020;Online ahead of print [ Show Abstract ]

Purpose
To investigate the interaction of a novel low molecular weight hyaluronic acid derivative containing hydrophobic groups with soft contact lenses and its effect on lens hydrophilicity compared with a conventional form of hyaluronic acid.

Methods
This investigation studied the uptake of fluorescently-labelled hyaluronic acid and a low molecular weight hyaluronic acid derivative to four types of contact lenses using fluorescent microscopy and confocal laser scanning microscopy. Further, the four lens types were used to compare efficacy in improving hydrophilicity, as well as maintenance of contact angle measurements, in commercially available multipurpose solutions that contained either hyaluronic acid, the low molecular weight hyaluronic acid derivative, or an alternative wetting agent.

Results
The low molecular weight hyaluronic acid derivative was found to sorb more readily to silicone hydrogel lenses and exhibit a greater accumulation over time than conventional hyaluronic acid. Multipurpose solutions containing the low molecular weight hyaluronic acid derivative showed an increase in lens hydrophilicity through decreases in contact angle measurements when compared with those obtained from lenses treated with multipurpose solutions containing conventional hyaluronic acid or alternative wetting agents. This increase in lens hydrophilicity associated with the low molecular weight hyaluronic acid derivative was also maintained over multiple cycles in phosphate buffered saline, while alternative solutions with conventional hyaluronic acid did not.

Conclusion
Overall, lens treatment using a low molecular weight hyaluronic acid derivative-based solution lead to improved in vitro lens hydrophilicity.

2015

Hagedorn,S., Drolle,E., Lorentz,H., Srinivasan,S., Leonenko,Z., Jones,L. Atomic force microscopy and Langmuir-Blodgett monolayer technique to assess contact lens deposits and human meibum extracts Journal of Optometry 2015;8(3):187-199 [ Show Abstract ]

Purpose The purpose of this exploratory study was to investigate the differences in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface topography between participants with and without meibomian gland dysfunction (MGD). Methods Meibum study: Meibum was collected from all participants and studied via Langmuir-Blodgett (LB) deposition with subsequent Atomic Force Microscopy (AFM) visualization and surface roughness analysis. CL Study: Participants with and without MGD wore both etafilcon A and balafilcon A CLs in two different phases. CL lipid deposits were extracted and analyzed using pressure-area isotherms with the LB trough and CL surface topographies and roughness values were visualized using AFM. Results Meibum study: Non-MGD participant meibum samples showed larger, circular aggregates with lower surface roughness, whereas meibum samples from participants with MGD showed more lipid aggregates, greater size variability and higher surface roughness. CL Study: Worn CLs from participants with MGD had a few large tear film deposits with lower surface roughness, whereas non-MGD participant-worn lenses had many small lens deposits with higher surface roughness. Balafilcon A pore depths were shallower in MGD participant worn lenses when compared to non-MGD participant lenses. Isotherms of CL lipid extracts from MGD and non-MGD participants showed a seamless rise in surface pressure as area decreased; however, extracts from the two different lens materials produced different isotherms. Conclusions MGD and non-MGD participant-worn CL deposition were found to differ in type, amount, and pattern of lens deposits. Lipids from MGD participants deposited irregularly whereas lipids from non-MGD participants showed more uniformity. © 2014 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

2014

Cheung,S., Lorentz,H., Drolle,E., Leonenko,Z., Jones,L. W. Comparative study of lens solutions' ability to remove tear constituents Optometry and Vision Science 2014;91(9):1045-1061 [ Show Abstract ]

PURPOSE: The purpose of this study was to use atomic force microscopy to compare and characterize the cleaning abilities of a hydrogen peroxide-based system (HPS) and a polyhexamethylene biguanide-containing multipurpose solution (MPS) at removing in vitro deposited tear film constituents, as well as to determine deposition patterns on various silicone hydrogel contact lenses. METHODS: Silicone hydrogel materials - balafilcon A (BA), lotrafilcon B (LB), and senofilcon A (SA) - were incubated for 1 week in an artificial tear solution (ATS) containing representative lipids, proteins, and salts from the tear film. Atomic force microscopy was used to resolve each lens before and after being cleaned overnight in HPS or MPS. Atomic force microscopy was used again to resolve HPS/MPS-cleaned lenses, which were reincubated in fresh ATS for 1 week, before and after an overnight clean in their respective cleaning solution. RESULTS: Atomic force microscopy imaging was able to characterize lens deposits with high resolution. Lenses incubated in ATS revealed distinct differences in their deposition pattern across lens materials. The surface of BA contained about 20-nm-high deposits, whereas deposit heights up to 150 nm completely occluded the surface of SA. Lotrafilcon B lenses revealed clusters of deposits up to 90 nm. The use of either lens solution left trace amounts of tear film constituents, although components from the MPS were seen adsorbed onto the surface after cleaning. Surface roughness (Ra) measurements revealed a significant difference between ATS-incubated and HPS/MPS-cleaned SA and LB lenses (p < 0.05). Ra between first incubated and HPS/MPS-cleaned reincubated SA and LB was also significant (p < 0.05). CONCLUSIONS: Unique variations in ATS deposition patterns were seen between lenses with atomic force microscopy. The application of both HPS and MPS removed most visible surface deposits. © American Academy of Optometry.

Scientific Presentations

2017

Drolle E, Leonenko Z, Subbaraman L, Jones L. Nanoscale Differences in Meibum Thin Films from Dry Eye and Non-Dry Eye Individuals ISCLR, Portland, Oregon, USA, 2017

Drolle E, Leonenko Z, Subbaraman L, Jones L. Nanoscale comparison of meibum and an in vitro lipid model Invest Ophthalmol Vis Sci 2017;E-Abstract 2250

2013

Cheung S, Lorentz H, Drolle E, Leonenko Z, Jones L. Contact lens solution efficacy at removing in vitro tear film constituents from silicone hydrogel contact lenses: An atomic force microscopy study Optom Vis Sci 2013;90: E-Abstract 135010

Cheung S, Lorentz H, Drolle E, Leonenko Z, Jones L. Contact lens solution efficacy at removing in vitro tear film constituents from silicone hydrogel contact lenses: An atomic force microscopy study Canadian Optometry Schools Research Conference, Waterloo, Canada, 2013