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Peer-reviewed articles

2023

Phan,C. M., Ross,M., Fahmy,M., McEwen,B., Hofmann,I., Chan,V. Clark-Baba,C., Jones,L. Evaluating Viscosity and Tear Breakup Time of Contemporary Commercial Ocular Lubricants on an In Vitro Eye Model Translational Vision Science & Technology 2023;12(6):29 [ Show Abstract ]

Purpose: To evaluate the link between the viscosity of ophthalmic formulation and tear film stability using a novel in vitro eye model.

Methods: The viscosities and noninvasive tear breakup time (NIKBUT) of 13 commercial ocular lubricants were measured to evaluate the correlation between viscosity and NIKBUT. The complex viscosity of each lubricant was measured three times for each angular frequency (ranging from 0.1 to 100 rad/s) using the Discovery HR-2 hybrid rheometer. The NIKBUT measurements were performed eight times for each lubricant using an advanced eye model mounted on the OCULUS Keratograph 5M. A contact lens (CL; ACUVUE OASYS [etafilcon A]) or a collagen shield (CS) was used as the simulated corneal surface. Phosphate-buffered saline was used as a simulated fluid.

Results: The results showed a positive correlation between viscosity and NIKBUT at high shear rates (at 10 rad/s, r = 0.67) but not at low shear. This correlation was even better for viscosities between 0 and 100 mPa*s (r = 0.85). Most of the lubricants tested in this study also had shear-thinning properties. OPTASE INTENSE, I-DROP PUR GEL, I DROP MGD, OASIS TEARS PLUS, and I-DROP PUR had higher viscosity in comparison to other lubricants (P < 0.05). All of the formulations had a higher NIKBUT than the control (2.7 ± 1.2 seconds for CS and 5.4 ± 0.9 seconds for CL) without any lubricant (P < 0.05). I-DROP PUR GEL, OASIS TEARS PLUS, I-DROP MGD, REFRESH OPTIVE ADVANCED, and OPTASE INTENSE had the highest NIKBUT using this eye model.

Conclusions: The results show that the viscosity is correlated with NIKBUT, but further work is necessary to determine the underlying mechanisms.

2021

Chan,V. W. Y., Phan,C-M., Ngo,W., Jones,L. Lysozyme Deposition on Contact Lenses in an In Vitro Blink-Simulation Eye Model Versus a Static Vial Deposition Model Eye & Contact Lens 2021;47(7):388-393 [ Show Abstract ]

Purpose:
To evaluate active lysozyme deposition on daily disposable (DD) contact lenses (CL) using a novel in vitro blink model.

Methods:
Three conventional hydrogel DD CL materials (etafilcon A, omafilcon A, nelfilcon A) and three silicone hydrogel DD CL materials (delefilcon A, senofilcon A, somofilcon A) were tested. The device blink rate was set to 6 blinks/min with a tear flow rate of 1 μL/min using an artificial tear solution (ATS) containing lysozyme and other typical tear film components. After incubation at 2, 4, or 8 hr, lenses were removed, and lysozyme activity was measured. A separate experiment was conducted with lenses incubated in a static vial containing 480 μL of ATS.

Results:
Etafilcon A deposited significantly higher amounts of active lysozyme (402±102 μg/lens) than other lens materials after 8 hr (P<0.0001). Etafilcon A had a higher amount of active lysozyme using the blink model compared with the static vial (P=0.0435), whereas somofilcon A (P=0.0076) and senofilcon A (P=0.0019) had a higher amount of lysozyme activity in the vial compared with the blink model.

Conclusion:
The blink model can be tuned to provide quantitative data that closely mimics ex vivo studies and can be used to model deposition of lysozyme on CL materials.

Chan,V. W. Y., Phan,C-M., Walther,H., Ngo,W., Jones,L. Effects of Temperature and Blinking on Contact Lens Dehydration of Contemporary Soft Lens Materials Using an In Vitro Blink Model Translational Vision Science & Technology 2021;10(8):11 [ Show Abstract ]

Purpose: The purpose of this studywas to evaluate the effects of temperature and blinking on contact lens (CL) dehydration using an in vitro blink model.

Methods: Three silicone hydrogel (delefilcon A, senofilcon A, and comfilcon A) and two conventional hydrogel (etafilcon A and omafilcon A) CL materials were evaluated at 1
and 16 hours. The water content (WC) of the CLs was measured using a gravimetric method. Lenses were incubated on a blink model, internally heated to achieve a clinically relevant surface temperature of 35°C. An artificial tear solution (ATS) was delivered to the blink model at 4.5 μL/min with a blink rate of 6 blinks/min. A comparison set of lenses were incubated in a vial containing either 2 mL of ATS or phosphate-buffered saline (PBS) at 35°C.

Results: Increasing temperature to 35°C resulted in a decrease in WC for all tested CLs over time (P ≤ 0.0052). For most CLs, there was no significant difference in WC over time between ATS or PBS in the vial (P > 0.05). With the vial system, WC decreased and plateaued over time. However, on the blink model, for most CLs, the WC significantly decreased after 1 hour but returned toward initial WC levels after 16 hours (P > 0.05).

Conclusions: The reduction in WC of CLs on the eye is likely due to both an increase in temperature and dehydration from air exposure and blinking.

Translational Relevance: This study showed that the novel, heated, in vitro blink model could be used to provide clinical insights into CL dehydration on the eye.

Yee,A., Chan,V., Heynen,M., Phan,C. M., Jones,L. Uptake and release of a multipurpose solution biocide (MAP-D) from hydrogel and silicone hydrogel contact lenses using a radiolabel methodology Eye & Contact Lens 2021;47(5):249-255 [ Show Abstract ]

Purpose:
The purpose of this study was to evaluate the uptake and release of radiolabelled myristamidopropyl dimethylamine (MAP-D) on reusable daily wear contact lenses (CLs) over 7 days.

Methods:
Three silicone hydrogel (SH) CL materials (lotrafilcon B, balafilcon A, senofilcon A) and two conventional hydrogel (CH) materials (etafilcon A, omafilcon A) were tested. A short-term (experiment 1, N=4) and a longer-term (experiment 2, N=3) study was conducted. In experiment 1, the CLs were incubated in 2 mL of phosphate buffered solution (PBS) containing 14C MAP-D (5 μg/mL) for 8 hrs. The release of 14C MAP-D was measured at t=0.25, 0.5, 1, 2, 4, 8, and 24 hr in PBS. In experiment 2, the CLs were incubated in the 14C MAP-D solution for 8 hrs followed by a 16-hr release in PBS. This cycle was repeated daily for 7 days. At the end of both experiments, lenses were extracted to determine the total uptake of MAP-D. The radioactivity was measured using a beta scintillation counter.

Results:
In experiment 1, all three SH lenses sorbed similar amounts of MAP-D (P=0.99), all of which were higher than the two CH materials (P<0.01). However, the CH materials released a greater amount of MAP-D than the SH materials (P<0.01). In experiment 2, the uptake of MAP-D in SH materials increased over 7 days, whereas the amount of MAP-D remained constant in the CH materials (P=0.99). Similar to experiment 1, the CH lenses released more MAP-D than SH lenses after 7 days (P<0.01).

Conclusion:
The SH materials absorbed greater amounts of MAP-D compared to CH materials. However, the CH materials released the greatest amount of MAP-D. Radioactive labelling of MAP-D offers a highly sensitive method of assessing the uptake and release profiles of biocides to CL materials.

Scientific Presentations

2023

Chan V, Drolle E, Phan CM, Hui A, Shi C, Subbaraman L, Wu J, Jones L. Evaluating the activity of lysozyme deposited on contemporary reusable silicone hydrogel contact lenses using an in vitro eye model The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, 2023 [ Show Abstract ][ PDF ]

Purpose: To evaluate lysozyme activity (LA) on five contemporary reusable silicone hydrogel contact lens (CL)materials over their proposed wear period using an advanced in vitro blink model.

Methods: Five CL materials (lotrafilcon B, samfilcon A, comfilcon A, senofilcon A, and serafilcon A) were cycled daily for 16h on an eye model, followed by 8h of soaking in OPTI-FREE PureMoist, to mimic a typical wear cycle. An artificial tear solution containing physiologically representative proteins and lipids was delivered to the model at a rate of 1.2-2.1μl/min. The model includes an artificial eyelid that blinks at a rate of 6blinks/min, which was kept at room temperature and humidity above 50%. Serafilcon A and senofilcon A were tested over 14 days, whereas the other CLs were evaluated for 30 days. At specified time intervals, including after 1, 7, 14 and 30 days, CLs were removed from the model and lysozyme extracted using a solvent containing acetonitrile and trifluoroacetic acid. The LA from the extracts were then evaluated using a micrococcal absorbance assay.

Results: Overall, LA decreased over time, reaching non-detectable levels by day 30 (p<0.05). Serafilcon A (13.9 ± 7.8μg/lens), and samfilcon A (9.6 ± 2.3μg/lens), had the highest LA after 1 day, followed by comfilcon A (4.7 ± 1.8μg/lens), lotrafilcon B (3.3 ± 1.6μg/lens), and senofilcon A (2.2 ± 3.7μg/lens). By day 7, LA for the weekly replacement lens, serafilcon A, decreased to 0.5 ± 0.6μg/lens. By day 14, LA for the biweekly replacement lens, senofilcon A, decreased to 0.6 ± 0.7μg/lens. Lotrafilcon B, samfilcon A, and comfilcon A, all monthly replacement lenses, decreased in activity by day 30 (0.1 ± 0.2μg/lens, 0.5 ± 0.7μg/lens, 0.0 ±0.0μg/lens respectively).

Conclusions: Deposition of biologically active lysozyme has been proposed to be an important factor for biocompatible CL wear. A decline in activity over time as the deposited protein becomes denatured may impact overall CL performance and has been linked to reduced comfort. LA decreases over time and reaches near zero for all lens types by the end of their proposed wearing period, confirming that they should be replaced within their specified replacement intervals. Compared to simple in vitro vial models, using an advanced blink model for CL deposition testing aims to provide more physiologically relevant results prior to clinical testing.

Hui A, Heynen M, Chan V, Mirzapour P, Enstone D, Saad M, George M, Ngo W, Jones L. The impact of RGP care solutions on ISO measured lens parameters and the protein deposition on RGP lenses when managed with a hydrogen peroxide care solution Global Specialty Lens Symposium, Las Vegas, Jan 20, 2023 [ PDF ]

Phan C-M, Chan V, Walther H, Pereira da Mota A, Lorenzo CA, Jones L. Developing a High-throughput in vitro Eye Model for Evaluating Ocular Drug Delivery with Contact Lenses XXV Biennial Meeting of the International Society for Eye Research, Feb 21, 2023 [ Show Abstract ]

Purpose: To develop a high-throughput in vitro eye model for evaluating ocular drug delivery with contact lenses (CLs).
Method: The eye model was designed using CAD software and manufactured using a combination of fabrication methods, including moulding, CNC machining, laser cutting, and 3D printing. The model consists of an eyeball, an upper and lower eyelid, and a collection tray to collect flow-through fluid. The portion of the upper eyelid that comes into contact with the eyeball is moulded with a highly wettable and durable polyvinyl alcohol hydrogel. The centre of the eyeball is designed with a 300 µm thick, 15 mm diameter cut-out that allows for a contact lens to be mounted. Simulated tear fluids can be delivered through an inlet located on the upper eyelid using a pump. During each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The blink distance, speed and rate are actuated using a motor controlled by an Arduino board and software. The release of a red dye from two CLs (etafilcon A and senofilcon A) and the release of two drugs (resveratrol and pravastatin sodium) from drug-loaded CLs were evaluated using the model and compared to the traditional vial testing method. Phosphate buffered saline (PBS) was used as the simulated tear fluid and infused into the model at 5 µL/min, at a blink rate of 1 blink/10 s.
Results: The fluid flows from the inlet, spreads across the eye, accumulates in the lower eyelid and then flows into the collection tray via gravity. During this process, approximately 25% of the fluid originally injected into the model was lost due to evaporation, nonspecific absorption, and residual dead volume. Overall, the release of the dye and drugs from the CLs was higher in a vial compared with the eye model. Interestingly, the drug release profiles from the drug-loaded CLs on the eye model were similar to in vivo results previously collected from a rabbit study, although the total amount of drugs released was significantly less. 9 or 24 CLs can be tested with one syringe or peristaltic pump, respectively.
Conclusion: The current eye model developed from this study could be used to measure the release of ophthalmic drugs or comfort agents from CLs in a high-throughput manner. However, further work is required to fine-tune the parameters of the model, such as the composition of the tear fluid, blink rate, tear flow rates, and temperature, to better simulate in vivo conditions.

2022

Chan V, Phan CM, Walther H, Ngo W, Jones L. Effects of temperature and blinking on contact lens dehydration using an in vitro blink model 10th Canadian Optometry School Research Conference, Montréal, Canada, Dec 3, 2022

Chan VWY, Phan CM, Walther H, Jones L. Fabrication of an in vitro eye model for practicing corneal foreign body removal 10th Canadian Optometry School Research Conference, Montréal, Canada, Dec 3, 2022

Phan CM, Chan V, Drolle E, Shi C, Subbaraman L, Wu J, Jones L. Evaluating the in vitro wettability of contemporary reusable soft contact lenses using an in vitro blink model American Academy of Optometry, San Diego, 2022 [ Show Abstract ][ PDF ]

Purpose: To evaluate the in vitro wettability of four contemporary reusable soft contact lens materials (serafilcon A, senofilcon A, senofilcon C, lotrafilcon B, comfilcon A) over a 14-day simulated wearing period using a novel, physiologically relevant in vitro eye model.

Methods: The 14-day wearing period was simulated using an in vitro blink model (OcuBlink). A tear mimic solution containing relevant proteins and lipids was delivered to the eye model at a rate of 1.25 -2.25 µL/min. A tear film was created over the lens via an artificial eyelid that slid across an eyeball surface at 6 blinks/minute, with a lens in-situ, at room temperature and humidity above 50%. For each cycling day, the lenses were incubated on the eye model for 16 hours, followed by a 10 second rub-rinse each side with OPTI-FREE PureMoist Solution, and then incubated overnight for 8 hours in the same solution. Lens wettability was quantified at t = 0 (straight from blister pack), 1, 7, and 14 days via two methods, (1) sessile drop contact angle (CA) and (2) non-invasive keratographic tear-break-up time (NIKBUT), n = 4 for each lens type. Contact angles were measured using the Optical Contact Analyzer (DataPhysics, Germany). NIKBUT measurements were assessed on the OcuBlink via the OCULUS Keratograph 5M (OCULUS, Germany).

Results: At t = 0, comfilcon A (24.0 ± 5.3°) had the lowest contact angle, followed by lotrafilcon B (29.6 ± 6.5°), serafilcon A (67.7 ± 16.0°), senofilcon C (89.2 ± 6.0°), and senofilcon A (92.0 ± 3.1°). All contact lens materials had similar CA out of the blister pack compared to 7 days (p >0.05). There was a slight increase in CA between 7-14 days for serafilcon A and lotrafilcon B, but this was not statistically significant (p>0.05). The NIKBUT for all contact lens materials ranged between 4 – 9 seconds, and there were no significant differences between NIKBUT within the same lens type at any time point (p>0.05). NIKBUT at t = 0 was highest for serafilcon A (8.3 ± 1.7 s) (p<0.05), followed by lotrafilcon B (6.3 ± 1.4 s), comfilcon A (6.1 ± 1.5 s), senofilcon A (5.6 ± 1.1 s), and senofilcon C (5.5 ± 0.8 s).

Conclusion: Lenses with a very low CA did not translate into significantly higher NIKBUT. For some lens materials, notably serafilcon A, there was an increase in CA after 7 days of in vitro testing, which warrants further investigation.

2020

Chan V, Phan CM, Jones L. Evaluating lysozyme deposition on contemporary daily disposable contact lenses in a novel in vitro blink model The Association for Research in Vision and Ophthalmology, 2020 [ Show Abstract ][ PDF ]

Purpose : To evaluate total lysozyme deposition on daily disposable (DD) contact lenses (CL) using a novel in vitro eye-blink model.

Methods : Three conventional hydrogel (CH) DD CL materials (etafilcon A, omafilcon A, nelfilcon A) and three silicone hydrogel (SH) DD CL materials (delefilcon A, senofilcon A, somofilcon A) were tested. The lenses were removed from their blister packs and placed directly on the eye model. An artificial tear solution (ATS) was flown over the lenses at a flow rate of 1 µl/min. The blink rate was set to 6 blinks per minute and the model was incubated at room temperature (23-26°C) and >45% humidity. After exposure periods of 2, 4 or 8 hours the lenses were removed and the lysozyme was extracted using acetonitrile: 0.2% trifluoroacetic acid (n=3). A separate experiment was conducted with lenses incubated in a vial containing 480 µL of ATS on an orbital shaker at 60 rpm for 8 hours (n=3). The lysozyme activity was measured using a spectrophotometric assay.

Results : Etafilcon A had the highest amount of active lysozyme absorption at all time points (p>0.001). After 8 hours, a cumulative total of 402 ± 102µg/lens of active lysozyme was absorbed on etafilcon A. Delefilcon A had the highest cumulative amount of active lysozyme (26 ± 1µg/lens) for SH materials (p<0.05). Nelfilcon A, senofilcon A and somofilcon A had the lowest amount of lysozyme activity (p0.05). The amount of active lysozyme sorption for certain lens types was different when measured using the eye-blink model as compared to a vial (p<0.05). Etafilcon A had a higher amount of active lysozyme when incubated on the blink model as compared to the vial (p<0.05), whereas somofilcon A and senofilcon A had a higher amount of lysozyme activity in the vial compared to the eye model (p0.05).

Conclusions : The in vitro eye-blink model provides quantitative data that is close to that determined from ex vivo studies and is an excellent model to assess the deposition of lysozyme on DD CL materials.

This is a 2020 ARVO Annual Meeting abstract.

2019

Walther H, Chan V, Phan CM, Jones L. Modelling non-invasive tear break-up times of soft lenses using a sophisticated in vitroblink platform Invest Ophthalmol Vis Sci 2019;60, E-abstract 6328 [ Show Abstract ][ PDF ]

Purpose : To evaluate the feasibility of a novel in vitro eye model to determine the pre-lens non-invasive tear breakup times (NIBUT) of two daily disposable (DD) contact lenses (CLs).

Methods : An artificial eyeball synthesized from polyvinyl alcohol (15% w/t, 89-98 kDa) was used on a novel in vitroeye model (OcuBlink), incorporating a blink and constant tear flow. A flat black disc was incorporated into the eyeball for contrast. The OcuBlink’s flexible eyelid design ensures contact with the eyeball, thereby enabling an even spread of the tear solution over the front of the CL. The blink interval was set to 10 seconds, and the flow rate of an artificial tear solution was set to 1.4 µL/min. A silicone hydrogel (SH; delefilcon A), and conventional hydrogel (CH; nelfilcon A) DD were placed over the corneal section and the NIBUT was evaluated after 1 h of blinking. A corneal topographer (Atlas, Zeiss Canada) was used to illuminate the lens surfaces and capture changes of the placido ring images. The humidity during the experiment was between 22-23%.

Results : A stable artificial tear film layer was formed over the artificial eyeball and the CLs. This layer was regenerated after each blink. The NIBUTs for delfilcon A, nelfilcon A, and the artificial eyeball were 7.55 ± 1.59 seconds, 8.16 ± 0.81 seconds, and 5.13 ± 0.09 seconds respectively. There were no significant differences between the two lens types (p>0.05), and between nelfilcon A and the artificial eyeball (p>0.05). However, delfilcon A had a longer NIBUT than the artificial eyeball (p<0.05).

Conclusions : The measured NIBUT values over the artificial eyeball and CLs are similar to those found in vivo. The OcuBlink simulates the blink motion and physiological tear flow rates, and could be used to measure in vitro pre-lens NIBUT values for various CLs.

Yee A, Chan V, Heynen M, Jones L. A radioactive labelling technique for evaluating the uptake and release of myristamidopropyl dimethylamine (MAP-D) from contact lenses Invest Ophthalmol Vis Sci 2019;E-abstract 6370 [ Show Abstract ][ PDF ]

Purpose: The uptake and subsequent release of biocides from contact lens (CL) materials is of relevance as it has been linked with outbreaks of microbial keratitis and potential cytotoxic responses. Previous uptake and release studies of myristamidopropyl dimethylamine (MAP-D; ALDOX®) have used light-scattering techniques, which are time consuming and have relatively low sensitivity. The purpose of this study was to develop a radioactive labelling technique in order to improve the accuracy and sensitivity of biocide uptake and release to CL materials.

Methods: Four soft CL materials (lotrafilcon A, balafilcon A, senofilcon A, etafilcon A) were tested (N=4). Radioactive (14C) MAP-D was purchased from Moravek Inc. (California, USA). The lenses were incubated in PBS (ISO 18369-3) solution containing radioactive MAP-D (5µg/mL) for 8 hours. After the incubation period of 8 hours, the lenses were placed into the release condition. The release of MAP-D was assessed over 24 hours in 2 mL of PBS. Aliquots were removed at 0.25, 0.5, 1, 2, 4, 8, and 24 hour time points and added to scintillation fluor (PerkinElmer, USA). The samples were counted for their radioactive signal (CPM) using the LS6500 Beckman Coulter liquid scintillation beta counter (Beckman Coulter, ON, CA). The CPM was converted to µg of MAP-D based on a standard curve.

Results: After the incubation period of 8 hours, the uptake of MAP-D by etafilcon A (2.78±0.19µg) was significantly different than lotrafilcon A (4.69±0.1µg, p<0.01), balafilcon A (4.55±0.31µg, p<0.01), and senofilcon A (4.35±0.13µg, p<0.01). The total amount of MAP-D released by etafilcon A (1.41±0.09µg) was significantly greater than lotrafilcon A (0.27±0.02µg, p<0.01), balafilcon A (0.23±0.04µg, p<0.01), and senofilcon A (0.21±0.01µg, p<0.01). The results demonstrate that the uptake of MAP-D was higher for all silicone hydrogel (SH) lenses and lower for the conventional hydrogel lens. The release profile of etafilcon A was greater than the SH lenses, with a burst release of 0.33µg at 0.25 hr.

Conclusions: Radioactive labelling of MAP-D offers a highly sensitive, accurate way of assessing the uptake and release profiles of biocides to CL materials. Future studies using this methodology will investigate the profiles for other biocides, such as polyhexamethylene biguanide (PHMB), a common biocide used in CL solutions.

Professional Publications

2022

Chan V. Fast forward to the future - drugs & the ocular surface Contact Lens Spectrum 2022;37, June: 11