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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Weeks,A., Subbaraman,L. N., Jones,L., Sheardown,H. The competing effects of hyaluronic and methacrylic acid in model contact lenses Journal of Biomaterials Science, Polymer Edition 2012;23(8):1021-1038 [ Show Abstract ]

The aim of this study was to determine the influence of hyaluronic acid (HA) on lysozyme sorption in model contact lenses containing varying amounts of methacrylic acid (MAA). One model conventional hydrogel (poly(2-hydroxyethyl methacrylate) (pHEMA)) and two model silicone hydrogels (pHEMA, methacryloxypropyltris(trimethylsiloxy)silane (pHEMA TRIS) and N,N-dimethylacrylamide, TRIS (DMAA TRIS)) lens materials were prepared with and without MAA at two different concentrations (1.7 and 5%). HA, along with dendrimers, was loaded into these model contact lens materials and then cross-linked with 1-ethyl-3-(3-dimethylamino propyl)-carbodiimide (EDC). Equilibrium water content (EWC), advancing water contact angle and lysozyme sorption on these lens materials were investigated. In the HA-containing materials, the presence (P < 0.05) and amount (P < 0.05) of MAA increased the EWC of the materials. For most materials, addition of MAA reduced the advancing contact angles (P < 0.05) and for all the materials, the addition of HA further improved hydrophilicity (P < 0.05). For the non-HA containing hydrogels, the presence (P < 0.05) and amount (P < 0.05) of MAA increased lysozyme sorption. The presence of HA decreased lysozyme sorption for all materials (P < 0.05). MAA appears to work synergistically with HA to increase the EWC in addition to improving the hydrophilicity of model pHEMA-based and silicone hydrogel contact lens materials. Hydrogel materials that contain HA have tremendous potential as hydrophilic, protein-resistant contact lens materials. © Koninklijke Brill NV, Leiden, 2012.

Weeks,A., Subbaraman,L. N., Jones,L., Sheardown,H. Physical entrapment of hyaluronic acid during synthesis results in extended release from model hydrogel and silicone hydrogel contact lens materials Eye and Contact Lens 2013;39(2):179-185 [ Show Abstract ]

OBJECTIVES:: This study was designed to assess the duration of hyaluronic acid (HA) release from model contact lens materials when HA was physically incorporated into the hydrogel during synthesis and to assess the effects of the HA release on lysozyme sorption. METHODS:: Model conventional and silicone hydrogel contact lens materials containing HA of various molecular weights as a releasable wetting agent were prepared. The HA was released into phosphate-buffered saline and MilliQ water, and the release was monitored using ultraviolet spectroscopy. Hyaluronic acid release was quantified by enzyme-linked immunosorbent assay. The effect of the releasable HA on lysozyme sorption to the materials was also analyzed using 125-I-labeled protein. RESULTS:: Hyaluronic acid loaded into the materials using this method could be released from conventional hydrogel materials for 21 days; the model silicone hydrogels showed release of more than 7 weeks. With one exception, the releasable HA decreased lysozyme sorption. CONCLUSIONS:: Hyaluronic acid physically incorporated into contact lens materials during synthesis may therefore be released for extended periods of time of up to 7 weeks. Hyaluronic acid release leads to decreased protein adsorption in general. This method has potential for modification of conventional and silicone hydrogel lenses with releasable HA as a wetting agent. © 2013 Lippincott Williams & Wilkins.

Willcox,M. D. P., Argüeso,P., Georgiev,G. A., Holopainen,J. M., Laurie,G. W., Millar,T. J., Papas,E. B., Rolland,J. P., Schmidt,T. A., Stahl,U., Suarez,T., Subbaraman,L. N., Uçakhan,O. Ö., Jones,L. TFOS DEWS II Tear Film Report Ocular Surface 2017;15(3):366-403 [ Show Abstract ]

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

Willcox,M. D. P., Walsh,K. Nichols,J. J., Morgan,P. B., Jones,L. W. The ocular surface, coronaviruses and COVID‐19 Clinical and Experimental Optometry 2020;103(4):418-424 [ Show Abstract ]

The ocular surface has been suggested as a site of infection with Coronavirus‐2 (SARS‐CoV‐2) responsible for the coronavirus disease‐19 (COVID‐19). This review examines the evidence for this hypothesis, and its implications for clinical practice. Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), responsible for the COVID‐19 pandemic, is transmitted by person‐to‐person contact, via airborne droplets, or through contact with contaminated surfaces. SARS‐CoV‐2 binds to angiotensin converting enzyme‐2 (ACE2) to facilitate infection in humans. This review sets out to evaluate evidence for the ocular surface as a route of infection. A literature search in this area was conducted on 15 April 2020 using the Scopus database. In total, 287 results were returned and reviewed. There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface. Evidence from animal studies is limited, with a single study suggesting viral particles on the eye can travel to the lung, resulting in very mild infection. Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID‐19, along with isolated cases of conjunctivitis as a presenting sign. Coronaviruses have been rarely isolated from tears or conjunctival swabs. The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection. Additionally, hypotheses that the virus could travel from the nasopharynx or through the conjunctival capillaries to the ocular surface during infection are probably incorrect. Conjunctivitis and isolation of the virus from the ocular surface occur only rarely, and overwhelmingly in patients with confirmed COVID‐19. Necessary precautions to prevent person‐to‐person transmission should be employed in clinical practice throughout the pandemic, and patients should be reminded to maintain good hygiene practices.

Willcox,M., Keir,N., Maseedupallu,V., Masoudi,S., McDermott,A., Mobeen,R., Purslow,C., Santodomingo-Rubio,J., Tavazzi,S., Zeri,F., Jones,L. W. CLEAR - Contact lens wettability, cleaning, disinfection and interactions with tears Contact Lens Anterior Eye 2021;44(2):157-191 [ Show Abstract ]

Contact lens materials have undergone significant changes over the past 20 years, particularly with respect to the introduction of silicone hydrogel materials. Whilst this development addressed hypoxic issues, other important areas relating to contact lens success, notably comfort, require further research.

Contact lens wettability remains a crucially important part of biocompatibility. Contact lenses can be made more wettable by incorporation of surfactants into blister packs, internal wetting agents, surface treatments or care solutions. However, there remains no clear association between contact lens wettability and comfort, making it challenging to determine the potential for these approaches to be of significant clinical benefit. Most contact lenses are used on a daily wear, reusable basis, which requires them to be disinfected when not worn. The ideal disinfecting solution would also improve comfort during wear. However, balancing these requirements with other factors, including biocompatibility, remains a challenge. Soft lens materials invariably take up and subsequently release certain components of disinfecting solutions onto the ocular surface. This may affect tear film stability and the normal ocular microbiome, and further research is needed in this area to determine whether this has any affect on comfort. Finally, contact lens materials sorb components of the tear film, and these interactions are complex and may change the biochemistry of the tear film, which in turn may affect their comfort.

In conclusion, the interaction between lens materials, tear film and disinfection solution plays an important role in the biocompatibility of lenses. However, the exact role and whether this can be altered to improve biocompatibility and comfort during wear remains debatable. This report summarises the best available evidence to examine this complex relationship and the opportunities for practitioners to enhance in-eye comfort of contemporary lenses, along with providing suggestions for areas of study that may provide further information on this topic.

Wolffsohn,J. S., Arita,R., Chalmers,R., Djalilian,A., Dogru,M., Dumbleton,K., Gupta,P. K., Karpecki,P., Lazreg,S., Pult,H., Sullivan,B. D., Tomlinson,A., Tong,L., Villani,E., Yoon,K. C., Jones,L., Craig,J. P. TFOS DEWS II Diagnostic Methodology report Ocular Surface 2017;15(3):539-574 [ Show Abstract ]

The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

Wolffsohn,J. S., Berkow,D., Chan,K. Y., Chaurasiya,S. K., Fadel,D., Haddad,M., Imane, T., Jones,L., Sheppard,A. L., Vianya-Estopa,M., Walsh,K., Woods,J., Zeri,F., Morgan,P. B. BCLA CLEAR Presbyopia: Evaluation and diagnosis Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

It is important to be able to measure the range of clear focus in clinical practice to advise on presbyopia correction techniques and to optimise the correction power. Both subjective and objective techniques are necessary: subjective techniques (such as patient reported outcome questionnaires and defocus curves) assess the impact of presbyopia on a patient and how the combination of residual objective accommodation and their natural DoF work for them; objective techniques (such as autorefraction, corneal topography and lens imaging) allow the clinician to understand how well a technique is working optically and whether it is the right choice or how adjustments can be made to optimise performance. Techniques to assess visual performance and adverse effects must be carefully conducted to gain a reliable end-point, considering the target size, contrast and illumination. Objective techniques are generally more reliable, can help to explain unexpected subjective results and imaging can be a powerful communication tool with patients. A clear diagnosis, excluding factors such as binocular vision issues or digital eye strain that can also cause similar symptoms, is critical for the patient to understand and adapt to presbyopia. Some corrective options are more permanent, such as implanted inlays / intraocular lenses or laser refractive surgery, so the optics can be trialled with contact lenses in advance (including differences between the eyes) to better communicate with the patient how the optics will work for them so they can make an informed choice.

Wolffsohn,J. S., Calossi,A., Cho,P., Gifford,K., Jones,L., Jones,D., Guthrie,S., Li,M., Lipener,C., Logan,N. S., Malet,F., Peixoto-de-Matos,S. C., González-Méijome,J. M., Nichols,J. J., Orr,J. B., Santodomingo-Rubido,J., Schaefer,T., Thite,N., van der Worp,E., Tarutta,E., Iomdina,E., Ali,B. M., Villa-Collar,C., Abesamis-Dichoso,C., Chen,C., Pult,H., Blaser,P., Parra Sandra Johanna,G., Iqbal,F., Ramos,R., Carrillo Orihuela,G., Boychev,N. Global trends in myopia management attitudes and strategies in clinical practice – 2019 Update Cont Lens Anterior Eye 2020;43(1):9-17 [ Show Abstract ]

Purpose: A survey in 2015 identified a high level of eye care practitioner concern about myopia with a reported moderately high level of activity, but the vast majority still prescribed single vision interventions to young myopes. This research aimed to update these findings 4 years later. Methods: A self-administrated, internet-based questionnaire was distributed in eight languages, through professional bodies to eye care practitioners globally. The questions examined: awareness of increasing myopia prevalence, perceived efficacy of available strategies and adoption levels of such strategies, and reasons for not adopting specific strategies. Results: Of the 1336 respondents, concern was highest (9.0 ± 1.6; p < 0.001) in Asia and lowest (7.6 ± 2.2; p < 0.001) in Australasia. Practitioners from Asia also considered their clinical practice of myopia control to be the most active (7.7 ± 2.3; p < 0.001), the North American practitioners being the least active (6.3 ± 2.9; p < 0.001). Orthokeratology was perceived to be the most effective method of myopia control, followed by pharmaceutical approaches and approved myopia control soft contact lenses (p < 0.001). Although significant intra-regional differences existed, overall, most practitioners did not consider single-vision distance under-correction to be an effective strategy for attenuating myopia progression (79.6 %), but prescribed single vision spectacles or contact lenses as the primary mode of correction for myopic patients (63.6 ± 21.8 %). The main justifications for their reluctance to prescribe alternatives to single vision refractive corrections were increased cost (20.6 %) and inadequate information (17.6 %). Conclusions: While practitioner concern about myopia and the reported level of activity have increased over the last 4 years, the vast majority of eye care clinicians still prescribe single vision interventions to young myopes. With recent global consensus evidence-based guidelines having been published, it is hoped that this will inform the practice of myopia management in future.

Wolffsohn,J. S., Calossi,A., Cho,P., Gifford,K., Jones,L., Li,M., Lipener,C., Logan,N. S, Malet,F., Matos,S., Meijome,J. M. G., Nichols,J .J., Orr, J.B., Santodomingo-Rubido,J., Schaefer,T., Thite,N., van der Worp,E., Zvirgzdina, M. Global trends in myopia management attitudes and strategies in clinical practice. Contact Lens and Anterior Eye 2016;39(2):106-116

Wolffsohn,J. S., Dhallu,S., Aujla,M., Laughton,D., Tempany,K., Powell,D., Gifford,K., Gifford,P., Wan,K., Cho,P, Stahl,U., Woods,J. International multi-centre study of potential benefits of ultraviolet radiation protection using contact lenses Contact Lens Anterior Eye 2022;45(6):101593 [ Show Abstract ]

Purpose
To examine the effects of long-term ultraviolet radiation (UVR) blocking wearing contact lenses on ocular surface health, eye focus and macular pigment.

Method
210 pre-presbyopic patients were recruited from Birmingham UK, Brisbane Australia, Hong Kong China, Houston USA and Waterloo Canada (n = 42 at each site). All patients had worn contact lenses for ≥ 5 years, half (test group) of a material incorporating a UVR-blocking filter. Ocular health was assessed using slit-lamp biomicroscopy and UV autofluorescence. Accommodation was measured subjectively with a push-up test and overcoming lens-induced defocus. Objective stimulus response and dynamic measures of the accommodative response were quantified with an open-field aberrometer. Macular pigment optical density (MPOD) was assessed using heterochromatic flicker photometry (MPS II).

Results
The two groups of participants were matched for age, sex, race, body-mass-index, diet, lifestyle, UVR exposure, refractive error and visual acuity. Limbal (p = 0.035), but not bulbar conjunctival redness (p = 0.903) was lower in eyes that had worn UVR-blocking contact lenses compared to controls. The subjective (8.0 ± 3.7D vs 7.3 ± 3.3D; p = 0.125) and objective (F = 1.255, p = 0.285) accommodative response was higher in the test group, but the differences did not reach significance. However, the accommodative latency was shorter in eyes that had worn UVR-blocking contact lenses (p = 0.003). There was no significant different in MPOD with UVR filtration (p = 0.869).

Conclusions
Blocking the transmission of UVR is beneficial in maintaining the eye’s ability to focus, suggesting that presbyopia maybe delayed in long-term UVR-blocking contact lenses wearers. These lenses also provide protection to the critical limbal region.

Wolffsohn,J. S., Dumbleton,K., Huntjens,B., Kandel,H., Koh,S., Kunnen,C. M. E., Nagra,M., Pult,H., Sulley,A. L., Vianya-Estopa,M., Walsh,K., Wong,S., Stapleton,F. CLEAR - Evidence-based contact lens practice Contact Lens Anterior Eye 2021;44(2):368-397 [ Show Abstract ]

Evidence-based contact lens -->practice involves finding, appraising and applying research findings as the basis for patient management decisions. These decisions should be informed by the strength of the research study designs that address the question, as well as by the experience of the practitioner and the preferences and environment of the patient. This reports reviews and summarises the published research evidence that is available to inform soft and rigid contact lens history and symptoms taking, anterior eye health examination (including the optimised use of ophthalmic dyes, grading scales, imaging techniques and lid eversion), considerations for contact lens selection (including the ocular surface measurements required to select the most appropriate lens parameter, lens modality and material selection), evaluation of lens fit, prescribing (teaching self-application and removal, adaptation, care regimen and cleaning instructions, as well as -->minimising risks of lens wear through encouraging compliance) and an aftercare routine.

Wolffsohn,J. S., Flitcroft,D. I., Gifford,K. L., Jong,M., Jones,L., Klaver,C. C. W., Logan,N. S., Naidoo,K., Resnikoff,S., Sankaridurg,P., Smith,E. L. 3rd, Troilo,D., Wildsoet,C. F. IMI - Myopia Control Reports Overview and Introduction Invest Ophthalmol Vis Sci 2019;60(3):M1-M19 [ Show Abstract ]

With the growing prevalence of myopia, already at epidemic levels in some countries, there is an urgent need for new management approaches. However, with the increasing number of research publications on the topic of myopia control, there is also a clear necessity for agreement and guidance on key issues, including on how myopia should be defined and how interventions, validated by well-conducted clinical trials, should be appropriately and ethically applied. The International Myopia Institute (IMI) reports the critical review and synthesis of the research evidence to date, from animal models, genetics, clinical studies, and randomized controlled trials, by more than 85 multidisciplinary experts in the field, as the basis for the recommendations contained therein. As background to the need for myopia control, the risk factors for myopia onset and progression are reviewed. The seven generated reports are summarized: (1) Defining and Classifying Myopia, (2) Experimental Models of Emmetropization and Myopia, (3) Myopia Genetics, (4) Interventions for Myopia Onset and Progression, (5) Clinical Myopia Control Trials and Instrumentation, (6) Industry Guidelines and Ethical Considerations for Myopia Control, and (7) Clinical Myopia Management Guidelines.

Wolffsohn,J. S., Kollbaum,P. S., Berntsen,D. A., Atchison,D. A., Benavente,A., Bradley,A., Buckhurst,H., Collins,M., Fujikado,T., Hiraoka,T., Hirota,M., Jones,D., Logan,N. S., Lundström,L., Torii,H., Read,S. A., Naidoo,K. IMI - Clinical Myopia Control Trials and Instrumentation Report Invest Ophthalmol Vis Sci 2019;60(3):M132-M160 [ Show Abstract ]

The evidence-basis based on existing myopia control trials along with the supporting academic literature were reviewed; this informed recommendations on the outcomes suggested from clinical trials aimed at slowing myopia progression to show the effectiveness of treatments and the impact on patients. These outcomes were classified as primary (refractive error and/or axial length), secondary (patient reported outcomes and treatment compliance), and exploratory (peripheral refraction, accommodative changes, ocular alignment, pupil size, outdoor activity/lighting levels, anterior and posterior segment imaging, and tissue biomechanics). The currently available instrumentation, which the literature has shown to best achieve the primary and secondary outcomes, was reviewed and critiqued. Issues relating to study design and patient selection were also identified. These findings and consensus from the International Myopia Institute members led to final recommendations to inform future instrumentation development and to guide clinical trial protocols.