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.

Perez, V. L., Chen, W., Craig, J. P., Dogru, M., Jones, L., Stapleton, F., Wolffsohn, J. S., Sullivan, D. A. TFOS DEWS III Editorial American Journal of Ophthalmology 2025;Online ahead of print [ Show Abstract ]

The Tear Film & Ocular Surface Society (TFOS), a non-profit organization, was created to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Since its incorporation in 2000, TFOS has launched numerous global initiatives. Perhaps the best-known are the TFOS Workshops, especially those related to dry eye disease (DED). DED afflicts hundreds of millions of people worldwide, is a leading cause of patient visits to eye care practitioners, and, if moderate or severe, is associated with significant pain, role limitations, low vitality and poor general health.

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., Hui,A., Shi,X., Zheng,Y., Subbaraman,L., Wu,J., Jones,L. The Impact of Comfort Eluting Agents and Replacement Frequency on Enhancing Contact Lens Performance Clinical Ophthalmology 2025;19(March 12):857-873 [ Show Abstract ]

This review explores the development and clinical implications of soft contact lenses designed to elute comfort agents, emphasizing their role in enhancing user experience and ocular health. As discomfort remains one of the primary reasons for discontinuation of lens wear, this concept aims to address this challenge by gradually releasing these agents over their period of use. This review also explores the effectiveness, safety, and user satisfaction associated with frequent replacement schedules of these lenses. Clinical trials demonstrate that lenses with eluting comfort agents significantly reduce dryness and irritation, leading to improved wear-time and overall comfort. The findings suggest that frequent replacement not only enhances lens hygiene but also maximizes the therapeutic benefits of the eluted agents, promoting a healthier ocular environment. The implications for practice highlight a shift towards more patient-centered approaches in contact lens design and management, aiming to improve adherence and satisfaction among users. This research paves the way for future innovations in contact lens technology, focusing on personalized solutions that cater to individual comfort needs.

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.

Phan,C. -M, Subbaraman,L., Jones,L. W. The use of contact lenses as biosensors Optometry and Vision Science 2016;93(4):419-425 [ Show Abstract ]

The tear film is a complex multilayer film consisting of various proteins, enzymes, and lipids and can express a number of biomarkers in cases of disease. The development of a contact lens sensor presents a noninvasive alternative for the detection and management of various diseases. Recent work has resulted in the commercialization of a device to monitor intraocular pressure for up to 24 h, and there are extensive efforts underway to develop a contact lens sensor capable of continuous glucose tear film monitoring to manage diabetes. This clinical perspective will highlight the major developments within this field and list some of the major challenges that still need to be addressed. © 2015 American Academy of Optometry.

Phan,C. -M, Subbaraman,L., Liu,S., Gu,F., Jones,L. In vitro uptake and release of natamycin Dex -b- PLA nanoparticles from model contact lens materials Journal of Biomaterials Science, Polymer Edition 2014;25(1):18-31 [ Show Abstract ]

Purpose: To evaluate the uptake and release of the antifungal agent natamycin encapsulated within poly(D,L-lactide)-dextran nanoparticles (Dex-b-PLA NPs) from model contact lens (CL) materials. Methods: Six model CL materials (gel 1:poly(hydroxyethyl methacrylate, pHEMA); gel 2:85% pHEMA: 15% [Tris(trimethylsiloxy)silyl]-propyl methacrylate (TRIS); gel 3: 75% pHEMA: 25% TRIS; gel 4: 85% N,N dimethylacrylamide (DMAA): 15% TRIS; gel 5:75% DMAA: 25% TRIS; and gel 6: DMAA) were prepared using a photoinitiation procedure. The gels were incubated in: (1) natamycin dissolved in deionized (DI) water and (2) natamycin encapsulated within Dex-b-PLA NPs in dimethylsulfoxide/DI water. Natamycin release from these materials was monitored using UV-visible spectrophotometry at 304 nm over 7 d. Results: Natamycin uptake by all model CL materials increased between 1 and 7 d (p < 0.001). The uptake of natamycin-NPs was higher than the uptake of the drug alone in DI water (p < 0.05). Drug release was higher in materials containing DMAA than pHEMA (p < 0.05). All gels loaded with natamycin-NPs also released more drug compared to gels soaked with natamycin in DI water (p < 0.001). After 1 h, CL materials loaded with natamycin alone released 28-82% of the total drug release. With the exception of gel 6, this burst released was reduced to 21-54% for CL materials loaded with natamycin-NPs. Conclusions: Model CL materials loaded with natamycin-Dex-b-PLA NPs were able to release natamycin for up to 12 h under infinite sink conditions. DMAA-TRIS materials may be more suitable for drug delivery of natamycin due to the higher drug release observed with these materials. © 2013 Taylor & Francis.

Phan,C. -M, Walther,H., Gao,H., Rossy,J., Subbaraman,L. N., Jones,L. Development of an in Vitro ocular platform to test contact lenses Journal of Visualized Experiments 2016;2016(110):e53907 [ Show Abstract ]

Currently, in vitro evaluations of contact lenses (CLs) for drug delivery are typically performed in large volume vials,1-6 which fail to mimic physiological tear volumes.7 The traditional model also lacks the natural tear flow component and the blinking reflex, both of which are defining factors of the ocular environment. The development of a novel model is described in this study, which consists of a unique 2-piece design, eyeball and eyelid piece, capable of mimicking physiological tear volume. The models are created from 3-D printed molds (Polytetrafluoroethylene or Teflon molds), which can be used to generate eye models from various polymers, such as polydimethylsiloxane (PDMS) and agar. Further modifications to the eye pieces, such as the integration of an explanted human or animal cornea or human corneal construct, will permit for more complex in vitro ocular studies. A commercial microfluidic syringe pump is integrated with the platform to emulate physiological tear secretion. Air exposure and mechanical wear are achieved using two mechanical actuators, of which one moves the eyelid piece laterally, and the other moves the eyeballeyepiece circularly. The model has been used to evaluate CLs for drug delivery and deposition of tear components on CLs.

Phan,C. -M, Walther,H., Smith,R. W., Riederer,D., Lau,C., Lorenz,K. O., Subbaraman,L. N., Jones L. Determination of the release of PEG and HPMC from nelfilcon A daily disposable contact lenses using a novel in vitro eye model. J Biomater Sci Polym Ed 2018;29(17):2124-2136 [ Show Abstract ]

The traditional method to measure release of components from CLs is a vial containing a static volume of PBS (phosphate buffered saline). However, this model does not simulate physiologically relevant tear volume and natural tear flow, air exposure, and mechanical rubbing. These factors can significantly impact release kinetics. We have developed an in vitro eye model (OcuFlow) that simulates these parameters. The aim of the study was to measure the release of PEG (polyethylene glycol), and HPMC (hydroxypropyl methylcellulose) from a daily disposable hydrogel contact lens material (nelfilcon A; Dailies AquaComfort PLUS; DACP;) over 24 hrs using the OcuFlow platform. The elution of PEG and HPMC from DACP lenses was analyzed using LCMS (liquid chromatography mass spectrometry). The release of all wetting agents from the lenses followed a burst release pattern, which occurred within the first 1.5 hrs (P < 0.05). The release of PEG was greater than that of HPMC (P < 0.05). The amount of PEG and HPMC released at any given time was less than 1% of the amount in the blister pack solution. Our results suggest that HPMC and PEG are rapidly released from the CL.

Phan,C. -M, Weber,S., Mueller,J., Yee,A., Jones,L. A rapid extraction method to quantify drug uptake in contact lenses Translational Vision Science and Technology 2018;7(2):11 [ Show Abstract ]

Purpose: To develop a simple extraction procedure to quantify the uptake of four topical ocular pharmaceutical drugs into contact lenses (CLs). Methods: Four silicone hydrogel (SH) CLs (balafilcon A, senofilcon A, lotrafilcon B, comfilcon B) and four conventional hydrogel (CH) CLs (nesofilcon A, hilafilcon B, nelfilcon A, etafilcon A) were evaluated. The drugs studied were natamycin, moxifloxacin, timolol maleate, and ketotifen fumarate. For drug incubation, three CLs of each type were placed in 1 mL of 1 mg/mL drug-loading solution for 24 hours. The lenses were then extracted in 2 mL methanol for 2 hours. This process was repeated to obtain a total of three extraction cycles. Detection of natamycin, moxifloxacin, ketotifen fumarate, and timolol maleate were measured by absorbance at 305, 287, 297, and 295 nm, respectively. Results: The majority of the drugs were extracted after the first extraction cycle (P 0.05). Conclusions: This study provides a simple approach to determine drug uptake into CLs. This method can also be modified, such as changing the extraction time, extraction cycles, or extraction solvent to better suit other drugs and CL combinations. Translational Relevance: There is considerable interest in using CLs for ocular drug delivery. Accurately quantifying drug uptake on CLs has been a challenge. Hence, this study provides a simple method to quantify drug uptake in CLs. © 2018 The Authors.

Phan,C. M., Chan,V. W. Y., Drolle,E., Hui,A., Ngo,W., Bose,S., Shows,A., Liang,S., Sharma,B., Subbaraman,L., Zheng,Y., Shi,X., Wu,J., Jones,L. Evaluating the in vitro wettability and coefficient of friction of a novel and contemporary reusable silicone hydrogel contact lens materials using an in vitro blink model Contact Lens Anterior Eye 2024;47(2):102129 [ Show Abstract ]

Purpose
To evaluate the in vitro wettability and coefficient of friction of a novel amphiphilic polymeric surfactant (APS), poly(oxyethylene)–co-poly(oxybutylene) (PEO-PBO) releasing silicone hydrogel (SiHy) contact lens material (serafilcon A), compared to other reusable SiHy lens materials.

Methods
The release of fluorescently-labelled nitrobenzoxadiazole (NBD)-PEO-PBO was evaluated from serafilcon A over 7 days in a vial. The wettability and coefficient of friction of serafilcon A and three contemporary SiHy contact lens materials (senofilcon A; samfilcon A; comfilcon A) were evaluated using an in vitro blink model over their recommended wearing period; t = 0, 1, 7, 14 days for all lens types and t = 30 days for samfilcon A and comfilcon A (n = 4). Sessile drop contact angles were determined and in vitro non-invasive keratographic break-up time (NIKBUT) measurements were assessed on a blink model via the OCULUS Keratograph 5 M. The coefficient of friction was measured using a nano tribometer.

Results
The relative fluorescence of NBD-PEO-PBO decreased in serafilcon A by approximately 18 % after 7 days. The amount of NBD-PEO-PBO released on day 7 was 50 % less than the amount released on day 1 (6.5±1.0 vs 3.4±0.5 µg/lens). The reduction in PEO-PBO in the lens also coincided with an increase in contact angles for serafilcon A after 7 days (p 0.05). The other contact lens materials had stable contact angles and NIKBUT over their recommended wearing period (p > 0.05), with the exception of samfilcon A, which had an increase in contact angle after 14 days as compared to t = 0 (p < 0.05). Senofilcon A and samfilcon A also showed an increase in coefficient of friction at 14 and 30 days, respectively, compared to their blister pack values (p < 0.05).

Conclusion
The results indicate that serafilcon A gradually depletes its reserve of PEO-PBO over 1 week, but this decrease did not significantly change the lens performance in vitro during this time frame.

Phan,C. M., Qiao,H., Yee,A., Jones,L. Deposition of Fluorescently Tagged Lysozyme on Contact Lenses in a Physiological Blink Model Eye & Contact Lens 2021;47(2):127-133 [ Show Abstract ]

PURPOSE: To visualize the deposition of fluorescein isothiocyanate (FITC) lysozyme on daily disposable contact lenses (CLs) using a novel blink model.

METHODS: Three daily disposable conventional hydrogel CLs (etafilcon A, omafilcon A, and nelfilcon A) and three silicone hydrogel CLs (delefilcon A, senofilcon A, and somofilcon A) were evaluated in the study. The CLs were mounted onto a novel blink model and exposed to an artificial tear solution containing FITC lysozyme for 2 and 10 hr. The flow rate and blink speed were set to 1 μL/min and 6 blinks/min, respectively. After the incubation period, a 5-mm-diameter disc was punched out from the center of the lens and mounted on a microscope slide. The slides were imaged using the Zeiss 510 Meta confocal laser scanning microscope, which scanned the lens from the front to the back surface at 5-μm increments.

RESULTS: There was an increase in deposition of FITC lysozyme for all lens types with increasing incubation time (P0.05). The conventional hydrogel CLs deposited higher amounts of FITC lysozyme than the silicone hydrogel CLs (P<0.001), with etafilcon A depositing the highest at all time points (P<0.05). Interestingly, at the 2-hr incubation time, most CLs showed a higher amount of deposition at the front surface than the back surface of the lens. In particular, etafilcon A showed preferred deposition at the front surface at all time points.

CONCLUSION: The results suggest that there is differential deposition at the front surface of the CL, which is exposed to the prelens tear film, compared with the back surface of the CL, which is exposed to the postlens tear film. Therefore, it may be beneficial to design CL materials with differing surface properties for the front and back surfaces of the CL to enhance interactions with the tear film and ocular surface.

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.

Phan,C. M., Shukla,M., Walther,H., Heynen,M., Suh,D., Jones,L. Development of an In Vitro Blink Model for Ophthalmic Drug Delivery Pharmaceutics 2021;13(Article 300):1-10 [ Show Abstract ]

Purpose: The purpose of this study was to develop an advanced in vitro blink model that
can be used to examine the release of a wide variety of components (for example, topical ophthalmic
drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using
computer-aided design software and printed using a stereolithography 3D printer. The eyelid and
eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated
tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each
blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The
flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and
senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye
model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min.
Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation,
nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL)
than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau
profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was
sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05).
Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye
model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure
the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink
mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better
results than a simple, static vial incubation model.

Phan,C. M., Subbaraman,L., Jones,L. Uptake and release of polyvinyl alcohol from hydrogel daily disposable contact lenses Optom Vis Sci 2019;96(3):180-186 [ Show Abstract ]

SIGNIFICANCE:
Polyvinyl alcohol is a wetting agent that could reduce the symptoms of dry eye and contact lens discomfort. Currently, only one lens type, nelfilcon A (DAILIES AquaComfort Plus), releases polyvinyl alcohol. The concept of releasing this agent from contact lenses could be applied to other lens materials.

PURPOSE:
The purpose of this study was to measure the release of polyvinyl alcohol from commercially available hydrogel daily disposable contact lenses using refractive index and iodine-borate methods.

METHODS:
Etafilcon A, omafilcon A, and nelfilcon A were soaked in phosphate-buffered saline and 0.2% trifluoroacetic acid/acetonitile for 24 hours to remove residual blister pack components. The lenses were then incubated in a 10-mg/mL solution of polyvinyl alcohol for 24 hours. After the incubation period, the lenses were placed in 2 mL of phosphate-buffered saline. At specified time intervals, t = 0.5, 1, 2, 4, 8, 12, and 24 hours, the samples were evaluated using refractive index and an iodine-borate assay. Polyvinyl alcohol uptake was determined by extracting the lenses with methanol for 24 hours.

RESULTS:
There were no differences in the uptake of polyvinyl alcohol between lens types (P > .05). The release of this wetting agent for all lens types followed a burst-plateau profile after the first 30 minutes (P > .05). Nelfilcon A had a slightly higher release of polyvinyl alcohol (P .05).

CONCLUSIONS:
The results suggest that the contact lenses tested in this study have similar efficiency in delivering polyvinyl alcohol.

Phan,C. M., Walther,H., Qiao,H., Shinde,R., Jones,L. Development of an eye model with a physiological blink mechanism Translational Vision Science & Technology 2019;8(5):Article 1 [ Show Abstract ]

Purpose: To develop an eye model with a physiological blink mechanism.

Methods: All parts of the eye model were designed using computer-aided design software. The eyelid consisted of a unique 3D printed structure containing teeth to physically secure a flexible membrane. Both the eyeball and eyelid membrane were synthesized using polyvinyl alcohol (PVA). Four molecular weights of PVA (89–98, 85–124, 130, and 146–186 kDa) were tested at a range of concentrations between 5% and 30% weight/volume. The wettability and water content of these materials were compared with the bovine cornea and sclera. The model was connected to a microfluidic pump, which delivers artificial tear solution (ATS) to the eyelid. A corneal topographer was used to evaluate the tear break-up and tear film regeneration.

Results: The eyelid flexes and slides across the eyeball during each blink, which ensures direct contact between the two surfaces. When loaded with an ATS, this mechanism evenly spreads the solution over the eyeball to generate an artificial tear film. The artificial tear film in this eye model had a tear break-up time (TBUT) of 5.13 ± 0.09 seconds at 1.4 μL/min flow rate, 6 blinks/min, and <25% humidity.

Conclusions: This model simulates a physiological blink actuation and an artificial tear film layer. Future studies will examine variations in flow rates and ATS composition to simulate clinical values of TBUT.

Translational Relevance: The eye model could be used to study in vitro TBUT, tear deposition, and simple drug delivery.

Phan,C. M., Walther,H., Riederer,D., Lau,C., Lorentz,H., Subbaraman,L., Jones,L. Analysis of polyvinyl alcohol release from commercially available daily disposable contact lenses using an in vitro eye model J Biomed Mater Res B Appl Biomater 2019;107(5):1662-1668 [ Show Abstract ]

The purpose of this work was to determine the release of polyvinyl alcohol (PVA) from etafilcon A, omafilcon A, and nelfilcon A daily disposable hydrogel contact lenses using a novel in vitro model. PVA is an ocular lubricant that can be found in multiple formulations of artificial tears. Nelfilcon A innately contains PVA, so only the release of PVA from this lens was evaluated. Etafilcon A and omafilcon A lenses were incubated in a PBS solution containing PVA. The release of PVA was evaluated using a novel in vitro blink platform with Milli-Q water and PBS under various blink conditions and flow rates. Nelfilcon A lenses significantly released more PVA than other lenses at 0.5 and 1.5 h in both PBS and Milli-Q water (p 0.05). All tested groups and lenses showed a burst release within the first 4.5 h and rapidly plateaued thereafter. The current study demonstrates that releasable PVA (whether through uptake or through being inherently available from the material) is loosely bound on hydrogel lenses, and the majority is released within 4.5 h.

Phan,C. M., Wulff,D., Thacker,M., Hui,A. Drug releasing contact lenses and their application to disease presentations
Clinical and Experimental Optometry 2025;Online ahead of print [ Show Abstract ]

Eye drops, the most common method for anterior segment treatment, face challenges of inefficiency, with less than 7% instilled drugs typically reaching target tissues of interest. The advent of contact lens drug delivery systems offers a paradigm shift, enhancing drug residence time and bioavailability on the ocular surface. This review focuses on the considerations and challenges in developing contact lenses for drug delivery, particularly for managing four categories of ocular diseases: anterior segment infections, dry eye disease, ocular allergies, and glaucoma. Each disease category requires tailored therapeutic approaches, and the technical intricacies of drug-releasing contact lenses must address concerns related to lens properties, drug release duration, and safety. The aim of this review is to provide insights into the therapeutic needs of ocular diseases and offer a comprehensive overview of the progress made in this innovative approach. The emergence of a commercially available ketotifen fumarate-releasing lens serves as a testament to the feasibility and potential benefits of this innovative approach, paving the way for further refinement and targeted applications in ocular therapeutics.

Phan,C.-M., Ho,B., Hui,A., Walther,H., Zhen,Y., Subbaraman,L., Shi,X., Wu,J., Jones,L. Evaluating the initial and end-of-day wettability of contemporary daily disposable contact lenses using various in vitro methods Optometry and Vision Science 2025;Online ahead of print [ Show Abstract ]

SIGNIFICANCE:
Contact lens wettability is potentially correlated with friction, which is linked to lens comfort. However, measuring wettability can be highly variable. This study assessed wettability using three techniques for a more accurate profile.

PURPOSE:
To evaluate the wettability of contemporary daily disposable contact lenses after 16 hours on an in vitro model using the sessile drop, captive bubble, and a novel in vitro noninvasive keratograph breakup time (NIKBUT) method.

METHODS:
The wettability of six contemporary silicone hydrogel contact lens materials (verofilcon A, delefilcon A, senofilcon A, kalifilcon A, stenfilcon A, and somofilcon A) and two conventional hydrogel materials (nesofilcon A and etafilcon A) were evaluated using an in vitro blink model at t = 0 and 16 hours. The blink rates of the eye model were 20 blinks per minute. Sessile drop and captive bubble angles were analyzed using the Optical Contact Analyzer. NIKBUT was assessed on a blink model in combination with the OCULUS Keratograph 5M.

RESULTS:
There were no significant differences in wettability for any lens types between 0 and 16 hours when assessed using the captive bubble or NIKBUT methods (p>0.05). For the sessile drop method, verofilcon A had the lowest contact angle values (36.5 ± 2.9°), and all lenses except for etafilcon A had similar wettability after 16 hours. All the lenses had similar wettability when assessed using the captive bubble method, suggesting that they had similar wettability under optimal wetting conditions. For NIKBUT, delefilcon A had the longest NIKBUT values (9.0 ± 1.0 s) after 16 hours.

CONCLUSIONS:
The sessile drop technique produced the most measurable differences in wettability between different lens types, whereas the captive bubble technique was not able to provide any measurable differences between lenses. NIKBUT measurements may provide a better measure of on-eye wettability, but variability in the results using the current eye model still needs to be addressed in future studies for improved repeatability. Although the contact lenses showed different contact angles and NIKBUT results, their in vitro wettability did not significantly change over the 16 hours of simulated wear in terms of the captive bubble or NIKBUT values.