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. At this time no specific clinical outcome instrument can be recommended on the basis of an evidence-based review of the literature, but the CLDEQ-8 best approaches the most validated measure 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,CM, Hui,A., Subbaraman,L., Jones,L. Insights to Using Contact Lenses for Drug Delivery Clin Exp Pharmacol 2014;3(145):2161-1459 [ Show Abstract ]

There has been considerable interest in the potential application of contact lenses for ocular drug delivery. This short communication provides an overview of the challenges faced by delivering drugs using contact lenses, highlights the solutions to limitations that have already been achieved, and describes the barriers that remain before commercial application can be realized.

Potvin,R. J., Doughty,M. J., Fonn,D. Tarsal conjunctival morphometry of asymptomatic soft contact lens wearers and non-lens wearers International Contact Lens Clinic 1994;21(11-12):225-231 [ Show Abstract ]

Soft contact lens wear is known to induce changes in the tarsal conjunctiva; qualitative grading is the current standard for recording such changes. This project was designed to investigate the usefulness of quantitatively assessing the morphometry of the tarsal conjunctiva, through a comparison of eight asymptomatic long-term soft contact lens wearers and eight nonwearers. The right tarsal plates were photographed after staining with fluorescein. A subjective assessment and grading of the fluorescein-highlighted tarsal plates was not able to distinguish the wearers and nonwearers. However, morphometry of the fluorescein-highlighted features across zone 1 of each tarsal plate revealed two basic patterns to the histograms of the areas of these features in both contact lens wearers and nonwearers. The analyses suggest that there are at least two types of "features" highlighted by fluorescein, evident in both wearers and nonwearers. Asymptomatic long-term soft lenswear appears to reduce the size of "small features" and increase the size and variability of "large features". These differences could be shown to be statistically significant. Further refinement of these quantitative assessment techniques should be useful in defining contact lens wear-related changes in the tarsal conjunctiva. © 1994.

Potvin,R. J., Fonn,D., Sorbara,L. Comparison of polycarbonate and steel test surfaces for videokeratography Journal of Refractive Surgery 1995;11(2):89-91 [ Show Abstract ]

BACKGROUND: Assessing video imaging systems for measuring corneal topography often requires test surfaces. Steel bearings have been employed, but manufacturers caution that high reflectance (>90%) relative to the eye (<10%) may compromise test findings. The differences between steel and polycarbonate test surfaces are quantified in this study. METHODS: Images of a steel and a polycarbonate sphere of known radius of curvature were obtained with the Tomey/Computed Anatomy Topographic Modeling System (TMS, Cambridge, Mass). Analysis was performed on the raw video data files and the resultant surface curvature estimates. RESULTS: The raw video images differed sufficiently to affect image processing. Polycarbonate yielded consistently better images. Many steel images (approximately 25%) contained data points that could not be processed; calculated surface contour was more variable for these. Differences were less obvious when these images were removed from the pool. CONCLUSIONS: Results support the manufacturer's caution against the use of steel surfaces for testing or calibration of the TMS instrument. Problems appear due to the fundamental differences in the intensity distributions of video images captured from high- and low-reflectance surfaces.

Pritchard,N., Fonn,D. Dehydration, lens movement and dryness ratings of hydrogel contact lenses Ophthalmic and Physiological Optics 1995;15(4):281-286 [ Show Abstract ]

Previous studies have shown that soft lenses dehydrate during lens wear. The purpose of this study was to determine the dehydration time course of 38% water content non-ionic Medalist(®), 58% ionic Acuvue(®) and 74% non-ionic Permaflex(®) lenses, and the relationship between dehydration and in vivo diameter, movement and symptoms of dryness. Nineteen subjects randomly wore three pairs of lenses, each for 7 h. Lens movement and diameter were measured in vivo and hydration after lens removal at 1, 3 and 7 h. Dryness was rated by the subjects using a visual analogue scale. A separate experiment was conducted to measure hydration changes after 7 continuous hours of lens wear. The water content of all three lens types decreased significantly over 7 h with Acuvue decreasing more than the Permaflex and Medalist(®) lenses in the interrupted and continuous experiments (ANOVA P < 0.05). Dehydration of Acuvue was significantly greater in the 7 h continuous experiment (9.0 ± 2.6% H2O, ANOVA P = 0.0062) compared to the interrupted experiment. Hydration levels measured for Acuvue lenses on subjects for control purposes at 0, 1, 3 and 7 h showed no difference over time (ANOVA P = 0.0711). Movement of Permaflex lenses decreased 0.60 ± 0.57 mm (ANOVA P = 0.0005) over 7 h and the in vivo diameter of Acuvue lenses decreased by 0.12 ± 0.16 mm (ANOVA P = 0.0569). Dryness ratings increased significantly and equally for all three lenses over 7 h (ANOVA P = 0.9833). No correlation was found between lens dehydration, movement, diameter and dryness with the exception of a weak significant (r = 0.5, P < 0.05) correlation between dehydration and dryness for Permaflex. The results of the study suggest that dehydration of soft lenses over a 7 h period does not significantly affect the clinical performance (dryness and movement) of the three lens types.

Pritchard,N., Fonn,D. Post-lens tear debris during extended wear of hydrogels Canadian Journal of Optometry 1998;60(2):87-91 [ Show Abstract ]

Debris entrapment after overnight wear of hydrogel lenses has been implicated as a cause of adverse ocular responses. We conducted two short-term pilot studies to determine if post-lens debris is related to the duration of lens wear, lens binding after overnight wear, movement of the lens prior to sleep or lens type. Debris and lens movement patterns upon waking were examined after one night (1N), one day and one night (1D+N) and one week of extended wear (6N). Three lens types were used on 10 subjects for the 1N experiment, and one lens type was used on 6 different subjects for the 1D+N and 6N experiment. Debris did appear to increase with duration of wear and was observed in approximately 60% of subjects after 1N. The appearance of debris observed ranged from light grey streaks to small clumped patches. Acuvue was bound more frequently than Medalist and NewVue. Movement was re-established after approximately 4 minutes of eye opening; however, the lenses appeared more adherent after 6N of overnight wear than after 1N or 1D+N. Debris dissipated after approximately 15 minutes (range 9 to 24 minutes) following eye opening. No statistical association was made between debris, lens binding, movement and lens type in this small group of subjects. These experiments demonstrated that debris appears to increase with duration of wear, may be associated with lens binding in a larger group and is quite difficult to view and quantify.

Pritchard,N., Fonn,D., Weed,K. Ocular and subjective responses to frequent replacement of daily wear soft contact lenses CLAO Journal 1996;22(1):53-59 [ Show Abstract ]

Purpose: A significant number of soft contact lens wearers develop complications as a result of lens contamination. We conducted a single-blind 2 year clinical trial to determine if scheduled frequent replacement of lenses decreases complications. Methods: One hundred nineteen non-contact lens wearers were fit with soft contact lenses and randomly assigned to 1 or 3 month replacement schedules or a non-replacement (control) group. All subjects were fit with 0.04 mm thick HEMA (water content: 38%) lenses to be worn on a daily wear basis only. A single multipurpose solution was prescribed for cleaning and disinfection. Results: The 2-year results showed a significantly greater number of subjects in the non-replacement group exhibited microcysts, infiltrates, clinically significant corneal staining, and limbal and bulbar injection. As a result of lens deposition and damage, approximately twice the number of unscheduled lens replacements per subject were necessary in the non-replacement group compared with the 1 and 3 month replacement groups. Overall subject satisfaction with lens wear decreased in the non-replacement group and increased in the 1 and 3 month replacement groups over the 2-year period. Conclusions: Frequent replacement of soft lenses for daily wear as compared to non-replacement daily wear: 1) is less likely to cause contact lens induced complications; 2) reduces the number of unscheduled lens replacements; and 3) improves satisfaction with lens wear.

Pritchard,N., Jones,L., Dumbleton,K., Fonn,D. Epithelial inclusions in association with mucin ball development in high-oxygen permeability hydrogel lenses Optometry and Vision Science 2000;77(2):68-72 [ Show Abstract ]

Debris trapped behind contact lenses may be associated with adverse reactions in extended wear. Although streaks and clumps of cellular material have been reported after overnight wear of conventional materials, recent experience with several high-oxygen permeability (Dk), silicone-containing hydrogel lenses indicates that certain participants are prone to the development of a unique back surface debris. This debris forms as spherical, translucent entities and results in depressions within the ocular surface after lens removal. Little information is known about these spherical bodies, particularly with respect to their composition and development. In this report, we provide photographic evidence of this debris (sometimes termed 'mucin balls' or 'lipid plugs'), discuss its differential diagnosis and describe a case in which material seems to be embedded in the epithelium as a direct consequence of their presence.

Pritchard,N., Young,G., Coleman,S., Hunt,C. Subjective and objective measures of corneal staining related to multipurpose care systems Contact Lens and Anterior Eye 2002;363-9 [ Show Abstract ]

An objective, digital-imaging method of measuring corneal staining was evaluated in 24 subjects wearing soft contact lenses. The method was used to compare the clinical performance of common multipurpose care systems (MPS) for soft contact lens care. Subjects used three different MPS, one containing polyquaternium-1 (PQ) and two containing polyhexanide (PX1 and PX2), for 2 weeks in a randomised, single-masked (investigator) crossover study. Corneal staining induced with the three MPS was analysed using an image-processing program (ImageTool, UTHSCSA Version 2, University of Texas, USA). Conjunctival hyperaemia and papillae were also evaluated. The intraclass correlation coefficient was similar with image analysis to that of investigator grading (0.876, 0.879, respectively). Significant differences in staining response were detected using the objective method. There was significantly less staining area with polyquaternium-1 (PQ) than polyhexanide (PQ: 0.12 mm2, PX2:0.91 mm2). Inferior palpebral papillae were significantly greater with PX2 than with PQ (1.0, 0.7 (0-4), respectively). The technique was shown to be an effective method of evaluating different corneal staining responses. Bilateral corneal staining in three or more quadrants is useful in the diagnosis of MPS-related staining. © 2003 British Contact Lens Association. Published by Elsevier Science Ltd. All rights reserved.

Pucker,A. D., Jones-Jordan, L.A., Marx,S., Powell,D. R., Kwan,J. T., Srinivasan,S., Sickenberger,W., Jones,L., The role of soft contact lens wear on meibomian gland morphology and function Eye & Contact Lens 2019;45(4):276-277 [ Show Abstract ]

The impact of a contact lens on the eye has long been of interest to practitioners who prescribe contact lenses and to the patients who wear them. One particular area of concern within the past several years has been related to how a contact lens may impact the meibomian glands (MGs) because changes in MG structure and/or function have the potential to impact the overall integrity of the ocular surface and contact lens success. Ucakhan and Arslanturk-Eren's recent manuscript published in Eye & Contact Lens has attempted to expand our knowledge of this topic by studying a group of contact lens–wearing and non–contact lens–wearing subjects and seeking to understand how the use of silicone hydrogel contact lenses may impact MG health. Their study overall concluded that “soft CL wear causes significant morphological and functional changes in MG with thickening of MG presenting an early diagnostic finding of MG dysfunction on meibography.”

Pucker,A. D., Jones-Jordan, L.A., Marx,S., Powell,D. R., Kwan,J. T., Srinivasan,S., Sickenberger,W., Jones,L., Contact Lens Assessment of Symptomatic Subjects (CLASS) Study Group Clinical factors associated with contact lens dropout Cont Lens Anterior Eye 2019;42(3):318-324 [ Show Abstract ]

PURPOSE: Contact lens (CL) dropout is estimated to be approximately equal to the number of new wearers per year, resulting in virtually no growth in the global CL market. The purpose of this study was to determine ocular and CL factors associated with CL dropout.

METHODS: This five-site study recruited subjects 18-45 years of age who had ceased CL wear within the past 6-12 months due to discomfort. Dropout subjects were compared to age- and sex-matched currently successful CL wearers. Each subject was administered a symptoms survey and a study-specific survey that queried general CL history and compliance. Clinical testing included non-invasive tear break-up time, tear meniscus height, blepharitis assessment, meibum quality and expression, and meibography.

RESULTS: A total of 56 matched-pairs were recruited. Dry eye was found to significantly increase a subject's odds of dropping out of CLs. The odds of dropping out of CLs was also significantly increased with each worsening grade of upper or lower eyelid meibomian gland (MG) plugging, upper eyelid meibum quality, and upper eyelid MG tortuosity. No other factors analyzed increased a subject's odds of dropping out of CLs.

CONCLUSIONS: CL dropout may be precipitated by underlying dry eye symptoms, though most dry eye signs, with the exception of MG structure and function, had minimal predictive value for CL dropout. Nevertheless, evidence suggests that practitioners should screen for and educate CL patients about the importance of maintaining healthy MGs, which may potentially allow them to maintain comfortable CL use and increase their CL longevity.