Lakshman Subbaraman

University of Waterloo | UWaterloo · School of Optometry & Vision Science

Purpose: The development of new contact lens materials and designs are necessary to minimise patient dropout. A lens material with water surface technology was recently developed to incorporate toric design. The on-eye stability of a toric contact lens is critical to a successful toric lens fitting. In an effort to establish if the new daily dispo...

Cytotoxicity testing is a regulatory requirement for safety testing of new ocular implants. In vitro toxicity tests determine whether toxic chemicals are present on a material surface or leach out of the material matrix. A method of evaluating the cytotoxicity of ocular implants was developed using fluorescent viability dyes. To assess the assay’s...

The purpose of this study was to develop a standardized, accurate and efficient method for estimating conjunctival goblet cell density (GCD) via optimizing sample storage conditions and quantification methods. Conjunctival impression cytology (CIC) membranes were collected from both eyes of 32 participants and were randomized to two storage duratio...

Purpose The amount of protein deposition on soft contact lenses and to what extent the proteins are denatured may have an impact on comfortable wearing times of contact lenses. The purpose of this study was to evaluate the effects of two lens care systems on total protein and the quantity and activity of lysozyme deposited on worn senofilcon A, sil...

Antimicrobial peptides are polypeptides composed of less than 100 amino acids and are a class of antibiotics with strong activity against some infectious bacteria. This study examined the safety of four chosen antimicrobial peptides using primary human corneal epithelial cells (HCEC) and explored their potential therapeutic use. The efficacy of the...

Purpose The deposition profile of cholesteryl ester on the surface and throughout the matrix of silicone hydrogel contact lens (CL) materials was determined under conditions that mimic a daily wear regimen. Methods In this in vitro study, four SiHy CL materials (senofilcon C, lotrafilcon B, comfilcon A and samfilcon A) were incubated in an artific...

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

Purpose Lipid deposition on contact lenses (CL) has traditionally been believed to reduce comfort during CL wear. The purpose of this study was to quantify lipid deposition on CL in a group of symptomatic and asymptomatic adapted CL wearers. Methods This was a single-masked, randomized clinical trial. Only confirmed symptomatic (comfortable lens w...

Purpose: This study investigated kinetic lipid uptake to four silicone hydrogel (SiHy) lenses over a period of four weeks, using an in-vitro radiolabel method. Methods: Four contemporary monthly replacement SiHy lenses (lotrafilcon B, senofilcon C, comfilcon A, samfilcon A) were incubated in three different solutions: 1) An artificial tear solution...

Corneal infection is a devastating sight-threatening complication that is associated with contact lens (CL) wear, commonly caused by Pseudomonas aeruginosa. Lately, Achromobacter xylosoxidans, Delftia acidovorans, and Stenotrophomonas maltophilia have been associated with corneal infection. This study investigated the adhesion of these emerging pat...

Purpose: Lid wiper epitheliopathy (LWE) is insufficiently understood from a cytological perspective. This study explored the relationship between lid margin cytomorphology, LWE, contact lens wear, and lens-related symptoms. Methods: Habitual, symptomatic (n = 20) and asymptomatic (n = 20) soft, rigid gas permeable (n = 18) and non-contact lens w...

The aim of this study was to determine the sorption location of full-length recombinant human proteoglycan 4 (rhPRG4) tagged with fluorescein isothiocyanate (FITC) to four silicone hydrogel contact lenses [balafilcon A (PureVision, Bausch + Lomb), senofilcon A (Acuvue Oasys, Johnson & Johnson), comfilcon A (Biofinity, CooperVision), lotrafilcon B (...

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...

Purpose: To develop an in vitro model to determine pre-lens non-invasive break-up time (NIBUT) and to subsequently use this method to compare the NIBUT over contemporary daily disposable (DD) contact lenses (CL). Methods: Three silicone hydrogel (SH) and two conventional hydrogel (CH) DD CLs were incubated in an artificial tear solution (ATS). A...

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 PV...

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 a...

Purpose: To determine the efficacy of multipurpose solutions (MPSs) on the removal of cholesterol deposits from silicone hydrogel (SH) contact lens materials using an in vitro model. Materials and methods: Five SH lens materials: senofilcon A, comfilcon A, balafilcon A, lotrafilcon A, and lotrafilcon B were removed from the blister pack (n=4 for...

Purpose: During contact lens wear, the amount of lysozyme deposited on contact lenses varies depending on the lens material. The binding of lysozyme to some contact lens materials may result in a conformational change that denatures the protein to an inactive form. This investigation evaluated the effect that denatured lysozyme has on human cornea...

Purpose: We evaluate the differences in lipid uptake and penetration in daily disposable (DD) contact lenses (CL) using a conventional "in-vial" method compared to a novel in vitro eye model. Methods: The penetration of fluorescently labelled 22-(N-(7-Nitrobenz-2-Oxa-1,3-Diazol-4-yl)Amino)-23,24-Bisnor-5-Cholen-3beta-Ol (NBD)-cholesterol on thre...

Purpose: To determine and compare the levels of surface versus bulk active lysozyme deposited on several commercially available hydrogel contact lens materials. Methods: Hydrogel contact lens materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon and etafilcon A with polyvinylpyrrolidone (PVP)] were incubated in an artificial te...

Purpose: To ascertain the effect that four contact lens (CL) multipurpose solutions (MPS) have on the viability and release of pro-inflammatory cytokines from human corneal epithelial cells (HCEC). Methods: HCEC were exposed to four different MPS at various concentrations for 18 hours. The cells were also exposed to phosphate buffer, borate buff...

Significance: Albumin deposition on contact lenses could be detrimental to contact lens (CL) wear because this may increase the risk of bacterial binding and reduce comfort. Lysozyme deposition on selected lens materials would reduce albumin deposition on lenses. Purpose: This study aims to determine if lysozyme deposition on CLs could act as a...

Contact lens friction significantly correlates with subjective comfort. Hyaluronan (HA) and proteoglycan 4 (PRG4) are natural boundary lubricants present in the body. The objective of this study was to assess the effect of crosslinked HA into the bulk of model contact lens materials pHEMA, pHEMA/TRIS, and DMAA/TRIS on surface wettability, protein s...

Significance: There remains only a small amount of data from human studies demonstrating the effect of contact lens/lens care solution combinations on the deposition of lipids. Therefore, information on the degree to which modern materials deposit lipids when used with contemporary care solutions would be valuable. Purpose: The present study aim...

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular sur...

Objective: To characterize the location of fluorescently labeled lysozyme on commercial contact lenses (CLs) using an in vitro eye model that simulates tear volume, tear flow, air exposure, and mechanical wear. Methods: One commercially available conventional hydrogel CL material (etafilcon A) and three silicone hydrogel CL materials (balafilcon...

The purpose of this study was to investigate the early and selective uptake of lysozyme and the location of deposited lysozyme on contemporary hydrogel contact lens (CL) materials after exposure to an artificial tear solution (ATS) for 16 hours. Seven different hydrogel CL materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon B, e...

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 silico...

Few reports on the cellular anatomy of the lid wiper (LW) area of the inner eyelid exist and only one report makes use of cytological methods. The optimization of a method of collecting, staining and imaging cells from the LW region using impression cytology (IC) is described in this study. Cells are collected from the inner surface of the upper ey...

Purpose: To evaluate the effect of four contemporary lens care solutions on total protein, total lysozyme, and active lysozyme extracted from three contact lens materials. Methods: Adapted contact lens wearers were recruited at three sites, and all subjects were randomly assigned to daily wear of either etafilcon A, galyfilcon A, or senofilcon A...

Purpose: To evaluate contact lens (CL) storage case contamination when used with four different CL care solutions during daily wear of three different CL materials. Methods: A parallel, prospective, bilateral, randomized clinical trial (n = 38) was conducted. Subjects were randomly assigned to use one of three CL materials (etafilcon A, senofilc...

Purpose: Current in vitro models to evaluate tear film (TF) deposition on various contact lenses (CLs) do not adequately simulate physiological ocular conditions. The aim of this study was to evaluate the differences in lipid uptake and penetration in daily disposable (DD) CLs using the conventional “in-vial” method compared to a novel in vitro eye...

Purpose: Current in vitro models to evaluate tear film (TF) deposition on various contact lenses (CLs) do not adequately simulate physiological ocular conditions. The aim of this study was to evaluate the differences in lipid uptake and penetration in daily disposable (DD) CLs using the conventional “in-vial” method compared to a novel in vitro eye...

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...

Purpose: The goal of this study was to analyze how various incubation times affect the uptake of cholesterol on silicone hydrogel (SH) and conventional hydrogel (CH) daily disposable (DD) contact lens materials using an in vitro radiochemical detection method. Methods: Three SH (somofilcon A, delefilcon A, and narafilcon A) and four CH (etafilco...

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. Method...

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...

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 (...

Contact lens friction was recently shown to correlate with in vivo comfort, with lower friction lenses providing improved comfort. Proteoglycan 4 (PRG4) is a recently discovered ocular surface boundary lubricant. The objectives of this study were to measure the friction of commercially available silicone hydrogel (SiHy) contact lenses against human...

Purpose: Bacterial biofilm formation in contact lens cases is a risk factor in the development of both microbial and infiltrative keratitis. This investigation evaluated three emerging pathogens: Stenotrophomonas maltophilia, Elizabethkingia meningoseptica, and Delftia acidovorans for biofilm formation and metabolic activity in lens cases. Also, g...

Within a few minutes of wear, contact lenses become rapidly coated with a variety of tear film components, including proteins, lipids, and mucins. Tears have a rich and complex composition, allowing a wide range of interactions and competitive processes, with the first event observed at the interface between a contact lens and tear fluid being prot...

Purpose: To develop a novel, in vitro model to determine pre-lens non-invasive tear breakup time (NIBUT) and to compare the NIBUT values of different daily disposable (DD) contact lenses (CLs) using this model. Methods: Three silicone hydrogel (SH) (delefilcon A, somofilcon A, narafilcon B) and two conventional hydrogel (CH) (etafilcon A, nesofilc...

Achromobacter xylosoxidans and Pseudomonas aeruginosa biofilms can develop in ophthalmic products and accessories such as contact lens cases, leading to the development of ocular infections. This study evaluated the efficacy of the antimicrobials polyaminopropyl biguanide (PAPB) and benzalkonium chloride (BAK) against A. xylosoxidans and P. aerugin...

To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and an in vitro eye model. Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, naraf...

Tear exchange beneath a contact lens facilitates ongoing fluid replenishment between the ocular surface and the lens. This exchange is considerably lower during the wear of soft lenses compared with rigid lenses. As a result, the accumulation of tear film debris and metabolic by-products between the cornea and a soft contact lens increases, potenti...

Purpose: The antifungal agent natamycin can effectively form inclusion complexes with beta-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-βCD) 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 functiona...

Purpose: To compare two techniques for measuring the activity of lysozyme deposited onto hydrogel contact lens and to image the binding of Micrococcus lysodeikticus to contact lenses. Methods: Using a previously described protein extraction technique and a recently developed in situ technique, we measured the time-dependent activity of adsorbed...

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 dr...

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 commercia...

PurposeTo investigate the impact of lactoferrin and lipids on the kinetic denaturation of lysozyme deposited on silicone and conventional hydrogel lenses, using a complex artificial tear solution (ATS). Methods Two silicone hydrogel lenses (AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A) and two conventional hydrogel lenses (ACUVUE 2;...

Jones, L., Brennan, N. A., Gonzalez-Meijome, J., Lally, J., Maldonado-Codina, C., Schmidt, T. A., … Nichols, J. J. (2013). The TFOS International Workshop on Contact Lens Discomfort: Report of the Contact Lens Materials, Design, and Care Subcommittee. Investigative Opthalmology & Visual Science, 54(11), TFOS37. https://doi.org/10.1167/iovs.13-13215

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 (TRI...

: This study was designed to assess the duration of hyaluronic acid (HA) release from model contact lens materials when HA was physically incorporated into the hydrogel during synthesis and to assess the effects of the HA release on lysozyme sorption. : Model conventional and silicone hydrogel contact lens materials containing HA of various molecul...

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,...

Purpose: To optimize a fluorescence-based lysozyme activity assay to investigate the conformational state of lysozyme in solution and to determine the impact of extraction and evaporation procedures and the possible interference of contact lens materials on lysozyme activity. Methods: The fluorescence-based lysozyme activity assay, Enzchek (Mole...

Purpose: To determine the relationship between clinical signs and symptoms and protein deposition over 8 h of wear of etafilcon A lenses in symptomatic and asymptomatic contact lens wearers. Methods: Thirty adapted soft contact lens wearers (16 symptomatic and 14 asymptomatic) were fitted with etafilcon A lenses. In vivo wettability, non-invasiv...

Materials such as hydrogels have a long history of use in the eye. The need for ophthalmic coatings arises because desired surface properties, such as low fouling and lack of bacterial adhesion, are often inconsistent with the properties necessary in the bulk materials. Commercially, a host of different modifications are used to generate the desire...

The aim of the study is to determine the adhesion of Gram positive and Gram negative bacteria onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials with and without lysozyme, lactoferrin, and albumin coating. Four lens types (three SH-balafilcon A, lotrafilcon B, and senofilcon A; one CH-etafilcon A) were coated with lys...