Download ARVO 2012 Annual Meeting Abstracts 525 Contact Lens II (Basic

ARVO 2012 Annual Meeting Abstracts
525 Contact Lens II (Basic Research)
Thursday, May 10, 2012, 8:30 AM - 10:15 AM
Hall B/C Poster Session
Program #/Board # Range: 6076-6126/D897-D947
Organizing Section: Cornea
Program Number: 6076 Poster Board Number: D897
Presentation Time: 8:30 AM - 10:15 AM
Effect of Contact Lens Solutions on the Antimicrobial Efficacy of Human Tear
Proteins during Lens Disinfection
Bianca L. Price1A, Philip B. Morgan1B, Carole Maldonado-Codina1B, Curtis B.
Dobson1A. AFaculty of Life Sciences, BEurolens Research, Faculty of Life Sciences,
1
University of Manchester, Manchester, United Kingdom.
Purpose: Proteins in the tear film are deposited on and within soft contact lenses
during wear. We have previously shown that proteins recovered from lenses retain
their antimicrobial function, and that treatment of worn lenses with different care
solutions denatures tear proteins and reduces this activity. In the present study we
investigated whether the activity of ex vivo lens protein extracts is affected by the
solution in which the antimicrobial assays take place. Moreover, we tested whether
the potency of the tear protein antimicrobial activity is sufficient to enable it to be
detected during disinfection with standard contact lens care solutions, i.e. over and
above the antimicrobial activity of the biocides within those solutions.
Methods: Tear proteins were extracted from worn and unworn 1-day Acuvue
contact lenses with ACN/TFA. In order to assess the activity of extracted lens
proteins in the presence of contact lens cleaning solutions, suspensions of
Pseudomonas aeruginosa (ATCC 9027) and Staphylococcus aureus (ATCC 6538)
were challenged with or without tear protein extracts in the presence of various
MPS, stand-alone MPS solution components and PBS. The numbers of viable
bacteria after treatment were assessed by colony counting.
Results: Incubation of S. aureus and P. aeruginosa with tear proteins solubilised in
PBS resulted in decreased bacterial growth. However this effect was stronger in
partial MPS formulations lacking disinfectants, relative to that found in PBS. The
tear protein activity was also readily detectible in the presence of fully formulated
MPS, and the activity was once again stronger in full formulation MPS than that
found when assays were conducted with tear proteins in PBS alone.
Conclusions: These data show that tear proteins absorbed to soft contact lenses
possess potent antimicrobial activity which functions synergistically with MPS and
their ingredients, and which is demonstrable above and beyond the activity of fully
formulated MPS. These data suggest that tear protein antimicrobial activity is
important during lens disinfection and may be clinically significant.
Commercial Relationships: Bianca L. Price, Bausch + Lomb (F); Philip B.
Morgan, Abbott Medical Optics (R), Bausch + Lomb (F, R); Carole MaldonadoCodina, Bausch + Lomb (F, R); Curtis B. Dobson, Bausch + Lomb (F, R)
Support: N/A
Program Number: 6077 Poster Board Number: D898
Presentation Time: 8:30 AM - 10:15 AM
Effects Of Multi-purpose Solutions On The Viability And Encystment Of
Clinical Isolates Of Acanthamoeba Determined By Flow Cytometry
Masaki Imayasu1, Kissaou T. Tchedre1, H D. Cavanagh2. 1R&D Center, Menicon
Co Ltd, Kasugai, Japan; 2Ophthalmology, Univ Texas Southwestern Med Ctr,
Dallas, TX.
Purpose: The encystment process of Acanthamoeba spp is characterized by
trophozoite rounding. It was reported that the incidence of Acanthamoeba keratitis
(AK) in the United States was related to one specific multi-purpose solution (MPS),
COMPLETE Moisture PLUS (CMP), that induced the transformation of
Acanthamoeba trophozoites into resistant cyst. In this study, we simultaneously
evaluated the effects of MPS on the viability and encystment of clinically isolated
Acanthamoeba using flow cytometry.
Methods: Viability and encystment rate were evaluated using three clinical strains
of Acanthamoeba spp isolated from AK patients and Acanthamoeba castellanii
(ATCC50514) when treated with four PHMB-based MPSs including CMP.
Trophozoites (1.0×105) were exposed to each MPS for 24 hours. After dispensing
the cell suspension into two aliquots, one aliquot was stained with 0.004% Congo
Red (CR), a fluorescence dye to stain the inner cell wall of cyst, and the other
aliquot was stained with a mixture of Congo Red and 1% Sarkosyl (CRS), a
detergent to lyse the trophozoites and pseudo-cyst. Flow cytometric analysis of the
treated aliquots was carried out on EPICS ALTRA flow cytometer. The encystment
rate and disinfecting efficacies (percentage of rounded trophozoites, pseudo-cyst)
were calculated by the rates of CR-stained part, CR-non-stained part and CRSstained part. Ultra-structures of resistant (mature or immature) cyst and pseudo-cyst
were observed by scanning electron microscopy (SEM) and transmission electron
microscopy (TEM).
Results: Resistant cysts and rounded trophozoites (pseudo-cysts) were stained with
CR, whereas native (unrounded) trophozoites were not. Resistant cysts were also
stained with CRS unlike pseudo-cysts. No differences were found between the
viabilities of clinical isolates and that of ATCC strain; however, three clinical
isolates showed higher encystment rates (77.1%, 61.6%, 48.0%) than ATCC strain
(43.0%) when treated with CMP. Disinfecting efficacy of each MPS was not
directly related to each encystment rate. SEM and TEM observations showed basic
differences in the fine structure of pseudo-cysts produced by MPSs and resistant
cysts.
Conclusions: It was suggested that disinfection and encystment of Acanthamoeba
are independent phenomenon. Not only high encystment rate but also low
disinfecting efficacies of MPS are thought to be associated with the incidence of
AK.
Commercial Relationships: Masaki Imayasu, Menicon Co., Ltd. (E); Kissaou
T. Tchedre, Menicon Co., Ltd. (E); H. D. Cavanagh, Menicon Co., Ltd. (C)
Support: None
Program Number: 6078 Poster Board Number: D899
Presentation Time: 8:30 AM - 10:15 AM
Evaluation Of Commercially Available Novel Multipurpose Contact Lens
Care Solutions Effect On Membrane-associated Mucin Expression In The Rat
Cornea
Kissaou T. Tchedre1, Masaki Imayasu1, Yuichi Hori2, H D. Cavanagh3. 1R&D and
Innovation Center, Menicon LTD, Kasugai, Japan; 2Ophthalmology, Toho
University Sakura Medical Center, Sakura, Japan; 3Ophthalmology, Univ Texas
Southwestern Med Ctr, Dallas, TX.
Purpose: The purpose of this study is to determine whether commercially available
new multipurpose contact lens care solutions (MPSs) have any effect on
membrane-associated mucins (Muc1 & 16) expressions in the cornea using SV40
transformed Human corneal epithelial Cells (HCET) and Rat cornea. Membraneassociated mucins are one of the major components of the ocular surface that play a
vital role in the maintenance of the ocular surface integrity.
Methods: Human corneal epithelial cells were treated with different concentrations
of MPS-F (1ppm PHMB, no boric acid), MPS-G (1.3ppm PHMB, 1ppm PQ-1,
boric acid), MPS-H (1.6 ppm, Alexidine, 3ppm PQ-1, boric acid), MPS-I (1ppm
PHMB, boric acid), and MPS-J (5ppm ALDOX, 10ppm PQ-1, boric acid): 100%
treatment for 30 minutes and 10% treatment for 24 hours. Membrane-associated
mucins (Muc 1 and Muc 16) expressions were subsequently analyzed by Western
blot. Winstar Rats were also subjected to MPSs (1 drop in the right eye every 10
minutes for 1 hour). The left Eye was used as control (1 drop of PBS every 10 min
for 1 hour). Cornea lysates were subsequently prepared and used for western blot
analysis.
Results: Western blot results showed that MPSs containing boric acid downregulate membrane-associated mucins in the cornea while MPSs without boric acid
had no effect on membrane-associated mucins.
Conclusions: Boric acid used in commercially available multipurpose contact lens
care solutions as a buffer concentration should be chosen carefully to avoid MPSrelated ocular surface damage. Ocular surface damage simultaneously promotes
microbial pathogens and potentially increases clinical rates of infection.
Commercial Relationships: Kissaou T. Tchedre, Menicon (E); Masaki
Imayasu, Menicon (E); Yuichi Hori, None; H. D. Cavanagh, None
Support: None
Program Number: 6079 Poster Board Number: D900
Presentation Time: 8:30 AM - 10:15 AM
Comparison of Disinfection Efficacies of Four Contact Lens Care Regimens
Against Pseudomonas aeruginosa on Orthokeratology Lenses
Yoshie Itou1A, Nobuyuki Miyata1A, Tatsukata Kawagoe2, Mizuki Nobuhisa2, Eiichi
Okada1. AOkada Eye Clinic, 1Okada Eye Clinic, Yokohama, Japan; 2Department of
Ophthalmology and Visual Science, Yokohama City University, Yokohama, Japan.
Purpose: To compare four types of contact lens care (rigid gas permeable contact
lens cleaners, RGPC; hydrogen peroxide solution, H2O2; and two povidone iodine
solution, for soft lenses & rigid lenses, PVP-IS & PVP-IR) in the disinfection of
Pseudomonas aeruginosa from two orthokeratology lenses under experimental
conditions.
Methods: Emerald Lens (oprifocon A, fluorosilicone acrylate-based lens; Euclid
Systems Corporation, VA) or Alfa Ortho-K Lens (fluorosilicone methacrylatebased lens; Alpha Corporation, Japan) were incubated in Brain Heart Infusion
Broth (BHI; Eiken Chemical Corporation, Japan) containing 10 5 CFU/ml of
Pseudomonas aeruginosa (PAO1) for 15 hours at 36 degrees Celsius to allow
attachment to the lens. After incubation, lenses were either rinsed with saline
(control) or cleansed by lens care solutions (RGPC: Menicon O2 Care Milfa fresh,
Menicon Corporation, Japan; H2O2: AOSEPT CLEAR CARE, CIBA VISION
Corporation, Japan; PVP-IS: Bioclen First Care CT, Ophtecs Corporation, Japan;
PVP-IR: Bioclen O2 SEPT, Ophtecs Corporation, Japan) according to the
manufacturer‟s instructions. Also, RGPC was tested in two protocols, with rubbing
(following the instructions) and no rubbing. Then, lenses were soaked in BHI, and
bacteria were removed by sonication and vortex mixing. The bacterial fluid was
spread onto Trypto-soy agar plates (Eiken Chemical Corporation, Japan), incubated
for 15 hours at 36 degrees celcius, and colonies were counted. Statistical analysis
was performed by Steel-Dwass multiple comparison test.
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
Results: The number of Pseudomonas aeruginosa attachment was higher (p<0.01)
in fluorosilicone acrylate lenses (1.98 x 108 bacteria/lens) compared to
fluorosilicone methacrylate lenses (6.89 x 107 bacteria/lens). All regimens
significantly removed bacteria from both lenses compared to control (over 99.99%
removal, p<0.01). In fluorosilicone acrylate-based lens, the numbers of remaining
bacteria after care were RGPC (no rub) 2658 > RGPC (rub) 666 > PVP-IS 119 =
H2O2 47 = PVP-IR 11 (p<0.05). In fluorosilicone methacrylate-based lens, the
numbers of remaining bacteria after care were RGPC (no rub) 3316 > PVP-IS 42 =
RGPC (rub) 35 = PVP-IR 15 = H2O2 4 (p<0.05).
Conclusions: Multipurpose solution, hydrogen peroxide solution, and two types of
povidone iodine solution showed significant disinfection abilities against
Pseudomonas aeruginosa.
Commercial Relationships: Yoshie Itou, None; Nobuyuki Miyata,
None; Tatsukata Kawagoe, None; Mizuki Nobuhisa, None; Eiichi Okada, None
Support: None
Program Number: 6080 Poster Board Number: D901
Presentation Time: 8:30 AM - 10:15 AM
Evaluation of Acanthamoeba Encystment for a Novel One-Step Hydrogen
Peroxide Disinfecting Solution and Comparator Peroxide Disinfecting
Solutions
Shawn C. Lynch, Christopher J. Kovacs, Joseph G. Carr, Matthew A. Dehmler,
Kimberly A. Millard, Michael J. Schoene, Suzanne F. Groemminger, Timothy W.
Morris. Bausch & Lomb, Rochester, NY.
Purpose: Acanthamoeba Keratitis (AK) is a rare, sight-threatening contact lens
associated infection caused by Acanthamoeba protozoa. Withdrawal of a multipurpose lens disinfection solution in 2007 due to an association with AK has been
hypothesized to be related to an encystment promoting effect of the propylene
glycol demulcent. To assess the potential relevance of encystment measurements in
hydrogen peroxide systems, existing peroxide disinfection systems as well as a
novel demulcent-containing peroxide solution were evaluated for encystment
effects.
Methods: A. castellanii ATCC 50370 trophozoites were cultured in antibiotic-free
AC6 medium, treated with test solutions (novel peroxide, Clear Care, AOSEPT,
and Oxysept) in neutralizing lens cases for 20 - 24 hr, and evaluated for encystment
using bright field and fluorescent microscopy plus Calcofluor White staining.
Separately, A. castellanii trophozoites were also treated for 4, 6, or 24 hr in
neutralizing lens cases and the surviving trophozoites were enumerated by axenic
outgrowth plus Spearman-Karber most probable number computations to calculate
log reduction values.
Results: Encystment rates for all test solutions were ≤ 1.6% compared to the
positive control which caused ≥ 80% trophozoite encystment. When the novel
peroxide solution and the Clear Care comparator solution were tested for standalone biocidal activity against trophozoites, both solutions showed little or no
recovery of live amoeba (i.e. log reduction values ranged from 3.92 to 4.34 after 4,
6, or 24 hr treatments). Also, no encystment occurred when the novel peroxide
solution base formulation was tested in further dose-response experiments ranging
from 0 - 3 % hydrogen peroxide.
Conclusions: A novel one-step peroxide disinfecting solution and three one-step
comparator peroxide solutions showed no evidence for encystment effects,
suggesting that previously reported encystment effects for a MPS product are not
applicable to peroxide-based solutions, regardless of the presence or absence of an
ophthalmic demulcent in novel as well as in comparator peroxide solutions.
Commercial Relationships: Shawn C. Lynch, Bausch & Lomb, Inc. (E);
Christopher J. Kovacs, Bausch & Lomb, Inc. (E); Joseph G. Carr, Bausch &
Lomb, Inc. (E); Matthew A. Dehmler, Bausch & Lomb, Inc. (E); Kimberly A.
Millard, Bausch & Lomb, Inc. (E); Michael J. Schoene, Bausch & Lomb, Inc.
(E); Suzanne F. Groemminger, Bausch & Lomb, Inc. (E); Timothy W. Morris,
Bausch & Lomb, Inc. (E)
Support: None
Program Number: 6081 Poster Board Number: D902
Presentation Time: 8:30 AM - 10:15 AM
Antimicrobial Properties Of Selenium Covalently Incorporated Into The
Polymer Of Contact Lens Case Material
Ted W. Reid1A, Phat Tran1A, Courtney Jarvis1A, Josh Thomas1A, Khiem Tran1A,
Thomas Mosley2, Rob Hanes3, Abdul Hamood1B. AOphthal & Visual Science,
B
Microbiology, 1Texas Tech University Health Sciences Center, Lubbock, TX;
2
Selenium Ltd., Lubbock, TX; 3Selenium Ltd., Austin, TX.
Purpose: Biofilm formation on contact lens cases is a serious problem since it
allows bacteria to grow even in the presence of contact lens cleaning solution.
Recently, silver as an antimicrobial was incorporated into contact lens cases,
however, silver has several drawbacks. Any patient with silver or metal allergies
cannot use these cases and silver has minimal effects against Staphylococcus
aureus (S. aureus) and different fungi. In addition, silver is expensive and has to
leach out of the case to be active. Thus, silver has a limited active half-life. In
contrast, selenium does not have to leach out of the material to be active since it
kills by the catalytic formation of superoxide radicals and it is much less expensive.
Thus, this project was carried out to test the ability of selenium, covalently
incorporated into the polymer of contact lens case material, to inhibit biofilm
formation.
Methods: Selenium monomers were made that allowed for the incorporation of
selenium into the polymer of polypropylene. This material was then injection
molded. The resulting material was tested for its ability to inhibit biofilm
formation. S. aureus was tested since this bacteria was resistant to killing with
silver. The S. aureus was allowed to grow in the presence of the polypropylene
(with or without selenium) for 24 hours. The bacteria was then removed by
vortexing and assayed. In one assay the bacterial concentration was determined by
a colony forming unit assay (plating on agar). In another assay the bacteria was
imaged by confocal laser scanning spectroscopy and then the biofilm was
quantitated by COMSTAT analysis.
Results: The selenium containing polypropylene showed 7.9 logs (complete) of
inhibition against S. aureus and also was fully active after soaking in PBS for the
equivalent of 8 weeks.
Conclusions: The results showed that selenium covalently incorporated into a
polypropylene polymer could total inhibit a S. aureus biofilm formation. This
material could be injection molded and was still fully active after 2 months of
soaking.
Commercial Relationships: Ted W. Reid, Selenium Ltd. (P); Phat Tran,
None; Courtney Jarvis, None; Josh Thomas, None; Khiem Tran, None; Thomas
Mosley, Selenium Ltd. (E); Rob Hanes, Selenium Ltd. (E); Abdul Hamood, None
Support: None
Program Number: 6082 Poster Board Number: D903
Presentation Time: 8:30 AM - 10:15 AM
Comparison of Biocidal Efficacy of Hydrogen Peroxide Disinfecting Systems
and Total Peroxide Exposure Values
Jenilee Kilbury, Kimberly A. Millard, Suzanne F. Groemminger, Erning Xia.
Vision Care R&D, Bausch + Lomb Inc., Rochester, NY.
Purpose: Neutralization profiles of hydrogen peroxide contact lens disinfecting
solutions have been used in the past to imply antimicrobial effectiveness of
hydrogen peroxide systems. Many times, only the early time points of the
neutralization profile are displayed. Area Under Curve (AUC) values are
determined by integration of the neutralization profile, and this method can be used
to quantitate total peroxide exposure during the full recommended regimen cycle.
This study sought to compare the AUC to biocidal efficacy of four hydrogen
peroxide disinfecting systems. The solutions evaluated included high and low AUC
models, and control products utilizing either a catalytic disk or a catalase tablet for
neutralization.
Methods: Neutralization profiles were measured for each of the four solutions by
determining the change in hydrogen peroxide concentration over time. Peroxide
concentrations were measured at specified time points throughout a 6 hour
neutralization time using a standard redox titration method. The two model
formulations were neutralized using contact lens cases containing catalytic disks.
The two control products were neutralized according to the manufacturers
prescribed regimens. Biocidal efficacy was determined by ISO/FDA Stand Alone
Procedure for Disinfecting Products.
Results: The AUC values of the four formulations at the end of the test time period
varied from 6000-16000 ppm*hr. For the most difficult organisms to kill, yeast and
fungi, the total log kill directly correlated to the AUC for each of the systems. The
results of yeast and fungi reduction varied from <1 log for the lowest AUC model
to > 3 logs for the highest model. In terms of the bacteria, all systems demonstrated
99.99% kill after 6 hours, however the time required for this level of effectiveness
varied depending on the bacteria, from 15 minutes to 6 hours.
Conclusions: The Area Under Curve (AUC) value of a hydrogen peroxide contact
lens disinfecting system is a quantitative assessment of the total peroxide exposure
available to kill microorganisms. The AUC values can be used as an indicator of
biocidal efficacy of the solution, particularly against yeast and fungi. Higher AUC
values indicate a better overall kill against all organisms tested using this method.
Commercial Relationships: Jenilee Kilbury, Bausch + Lomb Inc. (E);
Kimberly A. Millard, Bausch + Lomb Inc. (E); Suzanne F. Groemminger,
Bausch + Lomb Inc. (E); Erning Xia, Bausch + Lomb Inc. (E)
Support: None
Program Number: 6083 Poster Board Number: D904
Presentation Time: 8:30 AM - 10:15 AM
Regimen Testing of a Novel One-Step Hydrogen Peroxide Disinfecting
Solution and Comparators with Soft Contact Lenses and Ocular Clinical
Isolates
Jessica M. Burger, Todd H. Bassage, Arthur J. Principe, Deborah McGrath,
Patricia A. Walsh, Timothy W. Morris. Microbiology, Bausch & Lomb, Inc.,
Rochester, NY.
Purpose: To evaluate a novel one-step hydrogen peroxide disinfecting solution and
one-step peroxide comparator solutions for performance in regimen testing
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
conducted with representative soft contact lenses and recent clinical ocular isolates
of pathogenic bacteria and fungi.
Methods: A novel one-step hydrogen peroxide disinfecting solution along with
Clear Care and Oxysept comparators were all tested in recommended companion
peroxide neutralizing lens cases for each solution. Regimen test methods were
based upon the ISO 14729 test standard for disinfecting products modified to
permit testing of both hospital-acquired (HA) and community-acquired (CA)
methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant
Pseudomonas aeruginosa (QRPA), Stenotrophomonas maltophilia, Candida
albicans, and Fusarium solani. SofLens 38 (polymacon), Acuvue 2 (etafilcon A),
or Acuvue Oasys (senofilcon A) lenses were inoculated with ~ 5 x 10 5 CFU of each
microbe suspended in 100% organic soil, transferred to lens cases, rinsed per
recommended instructions, and soaked for 4 and 6 hr. Inoculated lenses and soak
solutions were then filtered and plated by validated methods to recover surviving
microbes.
Results: All three peroxide solutions showed little or no recovery of surviving cells
for all four bacterial strains or the F. solani mold at either 4 or 6 hr time points,
with mean recoveries for all solution/lens/microbe combinations ranging from 0.0 6.8 CFU. For the C. albicans yeast clinical isolate, 0.0 - 3.3 mean CFU were
recovered from the novel peroxide and Clear Care treatments, while 3.0 - 13.8
mean CFU were recovered from Oxysept treatments.
Conclusions: The results indicate that all three one-step peroxide disinfection
systems substantially remove recent ocular clinical isolates of bacteria and fungi
from soft contact lenses in vitro, although Oxysept showed slightly less activity
than the novel peroxide and Clear Care systems against the C. albicans yeast
clinical isolate.
Commercial Relationships: Jessica M. Burger, Bausch & Lomb, Inc. (E); Todd
H. Bassage, Bausch & Lomb, Inc. (E); Arthur J. Principe, Bausch & Lomb, Inc.
(E); Deborah McGrath, Bausch & Lomb, Inc. (E); Patricia A. Walsh, Bausch &
Lomb, Inc. (E); Timothy W. Morris, Bausch & Lomb, Inc. (E)
Support: None
Program Number: 6084 Poster Board Number: D905
Presentation Time: 8:30 AM - 10:15 AM
Pharmacodynamic Analysis of Hydrogen Peroxide Solution Disinfection
Efficacy in One-Step Peroxide Neutralizing Lens Cases
Timothy W. Morris, Damien W. Cordero, Deborah McGrath, Suzanne F.
Groemminger, Kimberly A. Millard. Bausch & Lomb, Inc, Rochester, NY.
Purpose: Previous pharmacodynamic studies have demonstrated clear quantitative
relationships between total hydrogen peroxide exposures (expressed as ppm
peroxide x hr of exposure) and microbial killing (expressed as log reduction values)
for ISO/FDA specified bacteria, yeast, and mold tested at constant peroxide
concentrations in test tubes. Here, pharmacodynamic analysis was used to instead
evaluate efficacy of a model one-step peroxide lens disinfection system wherein
microbial killing and peroxide neutralization occur simultaneously in lens cases
containing platinum neutralizing disks.
Methods: A series of phosphate buffered solutions (pH 6.5, ~250 mOsm)
containing 1.0 - 5.0 % peroxide (10,000 - 50,000 ppm) were challenged with
Serratia marcescens (Sm) prepared in 10% organic soil in one-step neutralizing
lens cases per the ISO 14729 standard for disinfection efficacy testing. Inoculated
lens cases were sampled at 10, 20, 30, 60, and 120 min for parallel enumeration of
surviving bacteria (to determine log reduction values) plus colorimetric redox
titrations of residual peroxide concentrations (to determine total peroxide exposures
as ppm x hr).
Results: Sm log reduction values ranged from 0.0 for 10 min treatment with initial
1.0% peroxide to >4.8 for any treatment ≥ 10 min with initial 5.0% peroxide.
Corresponding total peroxide exposures ranged from 1,168 - 7,609 ppm x hr. For
all time points, complete killing (i.e. >4.8 log reduction) required ~5,000 ppm x hr,
intermediate killing (i.e. 3.4 log reduction) required ~3,700 - 4,300 ppm x hr, and
reduced killing (i.e. 1.6 - 1.8 log reduction) required ~2,400 - 2,800 ppm x hr
peroxide exposures. The R2 curve fit value for measured peroxide exposures versus
Sm log reductions in lens cases was 0.98.
Conclusions: Pharmacodynamic analysis of Sm killing conducted in one-step
peroxide neutralizing lens cases demonstrates that there remains a clear quantitative
relationship between total hydrogen peroxide exposures and microbial killing, even
when microbial killing and neutralization of active peroxide occur simultaneously.
For Sm in lens cases, short treatments with high peroxide concentrations are
quantitatively equivalent to longer treatments with lower peroxide concentrations.
Commercial Relationships: Timothy W. Morris, Bausch & Lomb Inc. (E);
Damien W. Cordero, Bausch & Lomb Inc. (E); Deborah McGrath, Bausch &
Lomb Inc. (E); Suzanne F. Groemminger, Bausch & Lomb Inc. (E); Kimberly A.
Millard, Bausch & Lomb Inc. (E)
Support: None
Program Number: 6085 Poster Board Number: D906
Presentation Time: 8:30 AM - 10:15 AM
Antimicrobial Efficacy of Melimine Covalently Bound to Contact Lenses
Debarun Dutta1,2, Nerida Cole1,2, Mark Willcox1,2. 1Brien Holden Vision Institute,
Sydney, Australia; 2School of Optometry and Vision Science, University of New
South Wales, Sydney, Australia.
Purpose: There remains a need to reduce microbial contamination of contact
lenses, and thus the rate of adverse events during wear. The purpose of the current
study was to evaluate antimicrobial efficacy
of melimine, a synthetic cationic peptide, against drug resistant and biofilm
producer strains of Pseudomonas aeruginosa and Staphylococcus aureus when
covalently bound to contact lenses.
Methods: Melimine was covalently incorporated into an Etafilcon A contact lens.
The amount of peptide present on the lens surface was quantified using dye
adsorption. Antimicrobial activity against the bacterial strains was evaluated by
measuring the amount of cell death compared to control lenses with no melimine.
High salt treatment (10% NaCl) was carried out to extract any adsorbed peptide to
ensure that the activity was only due to bound melamine. The stability of the bound
peptide to autoclaving at 120ºC for 15 minutes was measured.
Results: There was 7.4 ± 0.7 µg of melimine present on the lens surface. High salt
treatment significantly (p<0.05) reduced the amount of adsorbed melimine but
affect the antimicrobial activity by only 0.1
to 0.2 log. There remained good activity after salt treatment, with contact lenses
showing 3.1 log reduction against P. aeruginosa strain 6294 and 3.9 log inhibition
against S. aureus strain 31. There were negligible (0.2 to 0.3 log) reductions of
antimicrobial activity after heat sterilization. Covalently bound melimine was
active against multidrug resistant S. aureus strains 060 and 110, and P. aeruginosa
037, as well as against the strong biofilm producer P. aeruginosa 142, giving 2.4
log, 2.3 log, 4.1 log and 3.4 log reductions in bacterial counts respectively.
Conclusions: Melimine may offer excellent potential for development as a broad
spectrum antimicrobial coating for contact lenses, showing strong activity against
both gram negative and gram positive organisms which are resistant to antibiotics.
The coating is heat stable and thus has the potential to be developed further.
Commercial Relationships: Debarun Dutta, None; Nerida Cole, None; Mark
Willcox, None
Support: University International Postgraduate Award (UIPA), UNSW and by the
Brien Holden Vision Institute through a postgraduate grant to cover facilities
Program Number: 6086 Poster Board Number: D907
Presentation Time: 8:30 AM - 10:15 AM
Organo-Selenium Coated Contact Lenses: Effect Upon Bacterial Biofilm
Attachment
Phat Tran1A, Abdul Hamood1B, Courtney Jarvis1C, Josh Thomas1C, Blake Lackey1C,
Thomas Mosley2, Ted Reid1C. AOphthalmology and Visual Sciences,
B
Microbiology, COphthalmology, 1Texas Tech University Health Sciences Center,
Lubbock, TX; 2Selenium Ltd., Lubbock, TX.
Purpose: Bacterial biofilm on contact lenses has been cited as a possible cause of
corneal infection and acute red eye. A contact lens coating that blocks biofilm
formation might reduce the frequency of these clinically significant problems.
Selenium compounds can catalyze the formation of superoxide radicals in the tear
film, which are cytotoxic to bacteria. Thus, this study investigated the effectiveness
of a covalent organo-selenium coating on polyHEMA (Acuvue2) contact lenses.
Methods: The contact lenses were coated with organo-selenium compounds via
wet chemistry covalent bond formation. The inhibition of biofilm formation with
the organo-selenium coating was investigated by incubating organo-selenium
coated and uncoated contact lenses in a nutrient broth containing, either
Pseudomonas aeruginosa, Serratia marcescens or Staphylococcus aureus for 24
hours at 37oC. Biofilms were quantified by determining the CFU per lens. To
determine the CFU/lens, each lens was gently rinsed with sterile distilled H2O, and
placed into a microcentrifuge tube containing 1 ml phosphate buffered saline
(PBS), and then vigorously vortexed three times for 1 min vortex to detach the
cells. Suspended cells were serially diluted 10-fold in PBS and 10-μl aliquots of
each dilution were spotted on LB agar plates. The plates were incubated at 37oC
for 24 hours and the CFU were counted. For confocal laser scanning microscopy
(CLSM), we used the S. aureus strain AH1333 and the P. aeruginosa strain PAO1GFP strains. Both strains carry the gene that encodes the green fluorescent protein.
For scanning election microscopy (SEM), the lenses were fixed in 3%
glutaraldehyde and then imaged.
Results: Colony forming unit assays showed total inhibition, representing over 6
logs of bacterial killing on contact lenses coated with organo-selenium compounds.
Scanning election microscopy and confocal laser scanning microscopy confirmed
these results.
Conclusions: The organo-selenium coating successfully blocked the formation of a
bacterial biofilm on the polyHEMA (Acuvue2) contact lenses for Pseudomonas
aeruginosa, Serratia marcescens and Staphylococcus aureus in vitro.
Commercial Relationships: Phat Tran, None; Abdul Hamood, None; Courtney
Jarvis, None; Josh Thomas, None; Blake Lackey, None; Thomas Mosley,
Selenium Ltd. (E); Ted Reid, Selenium Ltd. (I, P)
Support: None
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
Program Number: 6087 Poster Board Number: D908
Presentation Time: 8:30 AM - 10:15 AM
Non-Cultivatable Bacterial Biofilm Communities in Used Contact Lens Cases
Judith L. Flanagan1, Martin Allgeier2, Mark D. Willcox3, Philip Hugenholtz4.
1
Brien Holden Vision Institute, Sydney, Australia; 2Joint Genome Institute, Walnut
Creek, CA; 3Brien Holden Vision Institute, Univ of New South Wales, Sydney,
Australia; 4Australian Centre for Ecogenomics, School of Chemistry and Molecular
Biosciences & Institute for Mol, University of Queensland, Queensland, Australia.
Purpose: Using phylogentic modeling, we sought to document the microbial
ecology of contaminating biofilms in used contact lens cases as the first step in an
effort to determine how these communities contribute to, or help to protect against,
adverse ocular events such as corneal infiltrative events (CIEs).
Methods: Lens cases from subjects (and control cases) were swabbed with PBS
(100 µl). DNA was extracted using Wizard Genomic DNA Isolation System
(Promega, CA, USA). SSU rRNA was amplified (35 cycles PCR) using primers
926F and 1392R with barcodes and 454 linker. Pyrosquencing was performed
using 454 titanium technology. Raw sequence reads were analysed using software
pyrotaggers followed by custom analysis.
Results: 6000 independent reads were generated from each lens case and indicated
a high microbial diversity including the presence of phyla previously implicated in
MK such as Propionibacterium, Staphylococcus, Streptococcus,
Gammaproteobacteria (including Stenotrophomonads, Pseudomonads), and
Tsukamurella. Shannon‟s diversity index (SDI) which typically ranges from 1.5
(low species richness and evenness) to 3.5 (high species evenness and richness)
indicated high diversity in the used contact lens cases (3.853 and 2.840), similar to
that found on human skin in which most sequences are assigned to 4 phyla:
Actinobacter, Firmicutes, Proteobacteria and Bacteroidetes. Most abundant phyla in
the lens cases were α- and γ-Proteobacteria, Firmicutes and Actinobacter. These
commensal profiles differ markedly from bacteria detected by culture from
asymptomatic subjects.
Conclusions: This pilot study provided evidence of very high microbial diversity
in used contact lens cases of healthy wearers. Whether these commensal bacteria
offer some protection against infection needs to be addressed through a larger
temporal study in which bacterial community dynamics can be monitored for both
healthy wearers and wearers who suffer a CIE.
Commercial Relationships: Judith L. Flanagan, None; Martin Allgeier,
None; Mark D. Willcox, None; Philip Hugenholtz, None
Support: None
Program Number: 6088 Poster Board Number: D909
Presentation Time: 8:30 AM - 10:15 AM
Evaluation of Antimicrobial Activity and Cytotoxicity of Diamidine as a
Disinfectant
Bandarage M. Bandara, Rani S. Bandara, Duojia Wu, Hua Zhu, Sylvie Franz,
Mark D. Willcox. Brien Holden Vision Institute, UNSW, Sydney, Australia.
Purpose: Aromatic diamidines have been demonstrated to be active against
different pathogens, such as bacteria, fungi and protozoa. The purpose of this study
was to evaluate the antimicrobial activity and cytotoxicity of diamidine in
combination with polyhexamethylene biguanide (PHMB).
Methods: Antimicrobial activity of a solution containing diamidine and PHMB
was evaluated according to the stand-alone test for contact lens disinfection
products described by ISO 14729 (2001). ATCC strains of Serratia marcescens
13880, Staphylococcus aureus 6538, Pseudomonas aeruginosa 9027, F. solani
36031 and Candida albicans 10231 were used to challenge the test solutions.
Phosphate buffered saline was used as a control. After disinfection at 25°C for 6
hours, the numbers of viable microorganisms in the samples were determined and
the average log reductions in test samples for each strain were calculated. The
solutions were also challenged with trophozoites of Acanthamoeba polyphaga ROS
and Acanthamoeba castellani 044, and the number of survivors were determined
following 7 days of incubation at 32º C. Cytotoxicity of the solutions were
examined using agar overlay and acute ocular irritation assays according to ISO
10993-5 and 10993-10 standards respectively.
Results: Diamidine in combination with PHMB demonstrated complete kill of S.
marcescens, S. aureus, and P. aeruginosa (i.e. > 7 logs), and displayed 5.1 ± 0.5 or
2.4 ± 0.8 log reductions against C. albicans or F. solani respectively after 6 hours
of disinfection. Further, the combination of diamidine and PHMB also displayed
3.0 and 2.6 log reductions against trophozoites of A. polyphaga and A. castellanii
respectively after 6 hours of disinfection. Both agar overlay and acute ocular
irritation assays showed no toxic effect of the combination of diamidine and
PHMB.
Conclusions: The results have demonstrated that a combination of diamidine and
PHMB is effective against various microorganisms. The combination was not
toxic. This combination may be useful in development of safe and effective
disinfection solutions for soft contact lenses.
Commercial Relationships: Bandarage M. Bandara, None; Rani S. Bandara,
None; Duojia Wu, None; Hua Zhu, None; Sylvie Franz, None; Mark D.
Willcox, None
Support: None
Program Number: 6089 Poster Board Number: D910
Presentation Time: 8:30 AM - 10:15 AM
Membrane Permeability Of Staphylococcus Aureus Aggregates Exposed To
Contact Lens Care Solutions
David J. McCanna, Lyndon W. Jones. CCLR-School of Optometry, University of
Waterloo, Waterloo, ON, Canada.
Purpose: Microbial keratitis and corneal infiltrates have been associated with the
development of bacterial aggregates (biofilms) on the surface of contact lens cases.
Contact lens case contamination with biofilms occurs often due to the resistance of
the bacterial aggregates to the antimicrobials present in contact lens care solutions.
This study investigated the ability of contact lens care solutions to damage the cell
membranes of Staphylococcus aureus (SA) aggregates.
Methods: Staphylococcus aggregates were formed by growing the bacteria on
Mueller-Hinton Agar, harvesting with physiological saline and washing using
centrifugation (500 x g for 5 minutes). Commercial contact lens solutions evaluated
contained the antimicrobials polyquaternium-1 (PQ1) and polyhexamethylene
biguanide (PHMB), PHMB alone, PQ1 and alexidine (ALX), and PQ1 and
ALDOX. Each solution was challenged with 5 x 10(7)cfu/ml of SA (ATCC 6538)
for 4 hours. After exposure, the bacteria were stained with SYTO 9 and propidium
iodide (PI). Using a confocal microscope with a 488nm laser and the appropriate
emission filters for these two dyes, the number of cells with damaged cell
membranes was determined.
Results: The contact lens solution that caused the greatest damage to the SA cell
membranes was the formulation based on PQ1-ALX, with 81% of all cells being
permeable to PI. The other formulations caused some of the bacteria to lose
membrane integrity (13 - 30%), but did not cause as much damage to the bacteria
cell membranes (all p < 0.05) as the PQ1-ALX formulation.
Conclusions: One of the five lens care systems tested caused a substantial number
of SA bacteria to lose membrane integrity. Although membrane damage is only one
of the many mechanisms by which an antimicrobial can kill microorganisms,
understanding the ability of contact lens care solutions to damage bacteria cell
membranes in an aggregate formation could lead to improved formulations for
eradicating biofilms from contact lens cases.
Commercial Relationships: David J. McCanna, None; Lyndon W. Jones, None
Support: None
Program Number: 6090 Poster Board Number: D911
Presentation Time: 8:30 AM - 10:15 AM
Comparison Of Two Dual-disinfection Systems For Ocular Comfort, Corneal
Staining And Corneal Infiltrative Events
Daniel Tilia1, Percy Lazon De La Jara1,2, Nikki Peng1, Hua Zhu1, Mark D.
Willcox1,2, Brien A. Holden3,2. 1Brien Holden Vision Institute, Sydney, Australia;
2
School of Optometry and Vision Science, University of NSW, Sydney, Australia;
3
Brien Holden Vision Institute, Vision Cooperative Research Centre, Sydney,
Australia.
Purpose: To retrospectively compare ocular comfort ratings, corneal staining, and
the incidence of solution induced corneal staining (SICS) and corneal infiltrative
event (CIE) between two lens care products (LCPs) when used with a silicone
hydrogel contact lens
Methods: Ocular comfort ratings and corneal staining, SICS and CIE incidence
were extracted retrospectively from two prospective, unmasked studies involving
79 participants wearing balafilcon A (PureVision®, Bausch + Lomb, USA) and
using one of two LCPs; RevitaLens OcuTec® multipurpose disinfecting solution
(MPDS) (alexidine dihydrochloride and polyquaternium-1, Abbott Medical Optics,
Inc. USA) or Biotrue™ multipurpose solution (MPS) (PHMB and polyquaternium1, Bausch + Lomb, USA). Each study followed the same protocol Visits were at
baseline, two weeks, one month and three months. Comfort (1-10 scale) and
corneal staining (0-4 grade) were compared between LCPs using linear mixed
model. SICS and CIEs were reported as the first occurrence per 100 participantmonths for each LCP and compared using Fisher‟s exact test and mid-p test for
incidence rates
Results: There were no significant differences between RevitaLens OcuTec MPDS
and Biotrue MPS for comfort on insertion (7.6±1.6 v 8.0±1.5, p>0.05), comfort
during the day (8.1±1.4 v 7.8±1.5, p>0.05) or end of the day comfort (7.0±1.7 v
6.8±1.7, p>0.05). Corneal staining was significantly less with RevitaLens OcuTec
compared to Biotrue (0.7±0.6 v 1.8±0.8, p<0.001). SICS incidence was also
significantly lower with RevitaLens OcuTec compared to Biotrue (5.1% v 29.0%,
p<0.001), while there was no significant difference between LCPs for CIE
incidence (0 v 1.8%, p>0.05).
Conclusions: The PHMB/polyquat containing Biotrue MPS produced more SICS
than the alexidine/polyquat containing RevitaLens OcuTec MPDS. Similar ocular
comfort observed between the LCPs might be due to using the same contact lens
type and the low CIE incidence indicates both LCPs are effective in controlling
lens/case contamination.
Commercial Relationships: Daniel Tilia, Abbott Medical Optics, Inc. (F); Percy
Lazon De La Jara, Abbott Medical Optics, Inc. (F); Nikki Peng, Abbott Medical
Optics, Inc. (F); Hua Zhu, Abbott Medical Optics, Inc. (F); Mark D. Willcox,
Abbott Medical Optics, Inc. (F); Brien A. Holden, Abbott Medical Optics, Inc. (F)
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
Support: None
Clinical Trial: http://www.anzctr.org.au, ACTRN12610001068055
Program Number: 6091 Poster Board Number: D912
Presentation Time: 8:30 AM - 10:15 AM
Ocular Cytotoxic Potential Assessment Of Contact Lens Care Solutions And
Evidence For A Useful Rinse Step With Unpreserved Solution
Melody Dutot1A, Jacques VINCENT2, Isabelle FABRE2, Christine GRASMICK2,
Roxane Fagon1B, Patrice Rat3. AToxicology, BResearch&Development, 1YSLAB,
Paris, France; 2Direction des Laboratoires et des Contrôles, Agence Française de
Sécurité Sanitaire des Produits de Santé, Vendargues, France; 3Chimie-Toxicologie
Analytique et Cellulaire (EA 4463), Université Paris Descartes, Sorbonne Paris
Cité, Faculté de Pharmacie, Paris, France.
Purpose: Contact lens care solutions are known to have toxic effects for the ocular
surface. The evaluation of in vitro toxicity of contact lens care solutions is required
because of its predictive value for ocular irritation in humans. ISO 10993-5
standard assesses medical devices (such as contact lens care solutions)
biocompatibility through the evaluation of necrosis but needs some adjustments to
better discriminate multipurpose solutions. The aim of our study was double: first,
to run an interlaboratory study with French medical agency to propose adapted
tools to study contact lens care solutions cytotoxicity, and second to evaluate the
interest of adding a rinse step in contact lens cleaning procedure as a protection
against contact lens care solutions cytotoxicity.
Methods: In the first place, conjunctival cells (human WKD cell line) were
exposed for 30 minutes and 1 hour to neat contact lens care solutions (Optifree,
Alcon; Boston Simplus, Bausch-Lomb; Renu, Bausch-Lomb; and Menicare Plus,
Menicon). Cell viability was assessed using the neutral red and the alamar blue
tests, and benzalkonium chloride was used as a positive control. In the second
place, corneal cells (human HCE cell line) were exposed for 24 hours to contact
lenses (Acuvue Advance, Johnson&Johnson and Proclear, Cooper Vision)
previously soaked in 100mL contact lens care solutions (Optifree, Alcon; Biotrue,
Bausch-Lomb; and Renu, Bausch-Lomb) for 96 hours according to 1994 FDA
Premarket Notification 510(k) Guidance Document for Daily Wear Contact Lenses
and rinsed with a marine ionic solution (Lacrymer, Yslab, France).
Results: Optifree and Menicare Plus induced a loss of cell viability: 26% of living
cells according to neutral red assay and 49% of living cells according to alamar
blue assay for Optifree, 42% of living cells according to neutral red assay and 76%
of living cells according to alamar blue assay for Menicare Plus. Optifree, the most
cytotoxic multipurpose solution, was also adsorbed on both Acuvue Advance and
Proclear contact lenses and released on corneal cells. This release from Acuvue
Advance and Proclear induced a decrease in cell viability of 55% and 36%,
respectively. Optifree cytotoxicity was totally abolished when a rinse step with
Lacrymer was added to the cleaning procedure.
Conclusions: ISO 10993-5 standard could be improved for the evaluation of
contact lens care solutions: the cell line, the incubation time and the solutions
dilution have to be adapted to the ocular surface field to better discriminate contact
lens care solutions. Among the four contact lens care solutions tested, two were
highly cytotoxic. This cytotoxicity could be avoided by a rinse step with
unpreserved marine ionic solution.
Commercial Relationships: Melody Dutot, Yslab (E); Jacques Vincent,
None; Isabelle Fabre, None; Christine Grasmick, None; Roxane Fagon, Yslab
(E); Patrice Rat, None
Support: None
dispensed with silicone hydrogel lenses (lotrafilcon A, CIBA VISION, USA) on a
30-night overnight wear schedule. Clinic visits were conducted at 1 week, 1 month
and 3 months.
Results: Logistic regression analysis showed a reduced risk of mechanical events
(corneal erosion, superior epithelial arcuate lesion, contact lens papillary
conjunctivitis) with morning lens replacement (0.8%, p = 0.013 [1 month]) and
morning lens cleaning (1.0%, p = 0.031 [1 month] and p = 0.042 [3 months])
compared to nightly lens replacement (3.4%) and monthly lens replacement (5.2%).
These mechanical events were driven primarily by corneal erosions, the incidence
of which was 0.6% for morning lens replacement, 0.5% for morning lens cleaning,
3.4% for nightly lens replacement and 3.1% for monthly lens replacement.
Conclusions: Continuous contact lens wear related ocular mechanical adverse
events can be reduced by changes in cleaning or replacement modality and such
changes may be related to elimination of the overnight „debris accumulation‟ with a
morning replacement / cleaning modality.
Commercial Relationships: Jerome Ozkan, None; Mark D. Willcox,
None; Percy Lazon De La Jara, None; Varsha M. Rathi, None; Brien A.
Holden, None
Support: None
Clinical Trial: http://www.anzctr.org.au, ACTRN12610000336088
Program Number: 6093 Poster Board Number: D914
Presentation Time: 8:30 AM - 10:15 AM
Qualitative and Quantitative Lubricity of Experimental Contact Lenses
Robert C. Tucker, Brad Quinter, Dharmesh Patel, John Pruitt, Jared Nelson. R&D,
Alcon, Johns Creek, GA.
Purpose: Surface lubricity plays an important role in biomedical device comfort by
reducing stresses on tissue. A qualitative manual (finger) rubbing lubricity and a
quantitative inclined plane method have been developed to describe contact lens
lubricity and friction.
Methods: Experimental contact lenses with four different surface chemistries were
developed. Four lenses of each group were evaluated with qualitative manual
rubbing and quantitative inclined plane methods after overnight phosphate buffered
saline (PBS) soaking to remove any package saline additives.
To determine manual (finger) lubricity values, the lenses were rubbed between the
thumb and index finger for approximately 20 seconds. The lenses were ranked
according to their lubricity value from LV0 (best) to LV4 (worst). These values are
found to be inversely proportional to the crosslink density. The lubricity values
were repeatable in a blind test.
For the inclined plane, a clean glass plate is adjusted to the desired angle in a PBS
bath. The lens of interest is placed at the top of the glass plate, and a 0.8 g weight is
placed on the lens to initiate movement. A minimum critical angle is determined,
which just maintains lens movement over a distance of approximately 100 mm. The
tangent of the critical angle is the critical coefficient of kinetic friction (CCOF).
These values were compared with a lotrafilcon B control.
Results: Different experimental surface chemistries (on the same core lens
material) were able to be categorized repeatedly with distinct manual lubricity
values (LV, shown in figure 1). The kinetic coefficient of friction as measured by
the inclined plane method (CCOF) showed an increase in CCOF consistent with the
manual lubricity values. The experimental groups had a lower average CCOF than
the control lens (n=4, p<0.05), which has a different core and surface chemistry.
Conclusions: Two novel techniques (manual lubricity and inclined plane) have
been evaluated to rate and quantify the lubricity of contact lenses. This method
allows contact lens lubricity to be optimized by adjusting surface chemistry for
Program Number: 6092 Poster Board Number: D913
Presentation Time: 8:30 AM - 10:15 AM
Morning Cleaning or Replacement of Lenses Reduces Complications with
Extended Wear of Contact Lenses
Jerome Ozkan1A, Mark D. Willcox2, Percy Lazon De La Jara1, Varsha M. Rathi3,
Brien A. Holden4. AClinical Research & Trials Centre, 1Brien Holden Vision
Institute, Sydney, Australia; 2Brien Holden Vision Institute, Univ of New South
Wales, Sydney, Australia; 3Cornea, Contact lens, Refractive Surgery, LV Prasad
Eye Institute, Banjara Hills, Hyderabad, India; 4Brien Holden Vision Institute,
Vision Cooperative Research Centre, Sydney, Australia.
Purpose: A previous study has shown that the rate of microbial keratitis is
comparable to the rate corneal erosions coupled with gram negative contamination
of lenses. A retrospective analysis was conducted to determine if cleaning or
replacing lenses in the morning or evening, during continuous wear, influenced the
rate of corneal erosions.
Methods: Previously conducted continuous wear studies at the same site consisted
of: morning lens replacement study (n=87) and evening lens replacement study
(n=90) where subjects discarded worn lenses and replaced with a new lens each
morning or night, respectively; morning lens cleaning study (n=100) where subjects
removed and cleaned lenses with a commercial multipurpose solution
(COMPLETE® Easy Rub™, Abbott Medical Optics, USA) and immediately
reinserted the lenses. The historical control was monthly lens replacement (n = 95)
where lenses were worn for one month and then discarded. All subjects were
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
improved on-eye performance.
*Fagehi R, Tomlinson A, Manahilov V. ARVO 2011 E-abstract: 6524, 2011.
Commercial Relationships: Raied Fagehi, None; Alan Tomlinson,
None; Velitchko Manahilov, None
Support: None
Commercial Relationships: Robert C. Tucker, Alcon (E); Brad Quinter,
Alcon (E); Dharmesh Patel, Alcon (E); John Pruitt, Alcon (E); Jared Nelson,
Alcon (E)
Support: None
Program Number: 6094 Poster Board Number: D915
Presentation Time: 8:30 AM - 10:15 AM
Effect of Soft Contact Lens Storage Solutions on Lens Wettability In-Vitro
Raied Fagehi, Alan Tomlinson, Velitchko Manahilov. Vision Sciences, Glasgow
Caledonian University, Glasgow, United Kingdom.
Purpose: Developments in soft contact lens (SCL) polymers and multi-purpose
storage solutions (MPS) have improved biocompatibility of lens surfaces. This
study investigated in-vitro effects of MPS on SCLs wettability.
Methods: A camera connected to a Doane interferometer captured images of prelens fluid films on 4 SCLs; ACUVUE ADVANCE and 1-DAY MOIST (Johnson &
Johnson); AIR OPTIX and DAILIES (CibaVision). Wettability was measured
direct from the pack, then after 8 and 48 hours storage in 5 MPS: OPTI-FREE
EverMoist and Express (Alcon), COMPLETE MPS (AMO), ReNu Multiplus
(Bausch & Lomb) and SOLO-care AQUA (CibaVision). Six recordings of
complete drying of each SCL were analysed by a MATLAB programme. Four
previously described parameters of wettability were assessed: onset latency (OL),
the time to first break-up; drying duration (DD), the duration of drying after first
break-up; the maximum speed of drying (MS); and the time to reach this maximum
speed (PL).*
Results: Effective parameters of wettability were DD, PL and MS; DD being the
primary (independent) measure. Univariate factor analysis revealed significant
main effects of lens polymer (for DD, F = 284.1, p<0.001), MPS (F = 216.4
p<0.001), and storage time (F = 203.3 p<0.001); a significant interaction was found
between these factors (F=22.3 p< 0.001).Blister pack solutions for most lenses
produced similar results; AIR OPTIX solution gave better initial wettability.
Storage in MPS produced benefit after 8 hours, but varied with MPS and SCL
(Figure 1). The effect was similar for SOLO-care and COMPLETE across all
lenses but significant wetting benefits were seen for EverMoist and ReNu with the
AIR OPTIX and DAILIES lenses and for Express with AIR OPTIX and 1-DAY
MOIST lenses.
Conclusions: Interactions effects on wettability between SCLs and the MPS
suggest that in prescribing some lenses, specific storage solutions should be
recommended.
Program Number: 6095 Poster Board Number: D916
Presentation Time: 8:30 AM - 10:15 AM
Robust Contact Lens Lubricity using Surface Gels
W. G. Sawyer1, Alison C. Dunn1, Juan M. Uruena1, Howard A. Ketelson2.
1
Mechanical and Aerospace Eng, University of Florida, Gainesville, FL; 2R & D,
Alcon Research Ltd, Fort Worth, TX.
Purpose: To determine the effects of a soft surface gel on the lubricity of contact
lenses. This study examines the friction response of the gel layer under varied
pressures and correlates the frictional behavior and frictional responses to the
mechanical properties of the gel layer.
Methods: Gradient gel surfaces (2-3 um thick) were formed on the surfaces of a
new type of silicone hydrogel daily disposable contact lens (DAILIES TOTAL1®).
These layers were minimally crosslinked and enveloped the entire lens. Friction
measurements were carried out on a precise micro-tribometer constructed
specifically to probe low contact pressure sliding in aqueous environments. This
apparatus can reliably perform experiments at contact pressures approaching 1 kPa,
and can go up to pressures in excess of those seen on the human eye during ocular
movements and blinking. Experimental soft contact lenses (20) were mounted into
a custom conformal holder, placed in a bath of borate-buffered saline (Unisol®),
and heated to physiological temperatures. Lubricity experiments were performed at
a range of contact pressures (1-10kPa) and sliding speeds (10um/s - 600um/s).
Results: This gel layer was designed to enhance lubricity and comfort of the
contact lenses by acting as a compliant foundation to spread contact, reduce
pressure, and promote boundary lubrication. Contact mechanics experiments and
indentation reveals that the gels have a low elastic modulus (<200KPa), and at
contact pressures below 18 kPa the friction coefficients are mu=0.03. The friction
coefficient is robust to pressure changes under the 18 KPa pressure threshold and
does not show any effect of sliding speed over the range examined.
Conclusions: Tribological probing of the surface gels indicates that they are
compliant but mechanically stable to pressures below 18 KPa. At pressures such as
those seen in the eye (3-5 kPa) the gel layers can support smooth sliding and
provide a lubricous surface with friction coefficients of mu=0.03 in the boundary
lubrication regime. These findings indicate that surface gels can be a route to
promote lubricity in contact lenses.
Commercial Relationships: W. G. Sawyer, None; Alison C. Dunn, None; Juan
M. Uruena, None; Howard A. Ketelson, Alcon (E)
Support: Alcon Research, Ltd.
Program Number: 6096 Poster Board Number: D917
Presentation Time: 8:30 AM - 10:15 AM
Improving The Wettability Of Silicone Hydrogel Contact Lenses
Alonzo Cook, Matthew Skinner, Jun Li, Christopher Loose, Karen Schultz, Zheng
Zhang. Semprus BioSciences, Cambridge, MA.
Purpose: We have developed stable, extremely hydrophilic polymers that reduce
fouling and improve surface wettability on medical devices. Recently, this
polybetaine chemistry was applied to a long-term vascular catheter and shown to
reduce the in vitro attachment of platelets and thrombus even after 60 days of blood
product exposure. The technology has now been adapted to silicone hydrogel
contact lenses to improve wettability. The hypothesis of this study is that by adding
polybetaine to the surface of contact lenses, the advancing contact angle will be
substantially decreased.
Methods: Silicone hydrogel contact lenses were surface modified using a one-step
controlled polymerization process. Contact lenses with biocompatible polybetainebased polymers were compared to unmodified (control) lenses. The surface
characteristics were analyzed with surface staining, SEM-EDS, XPS, dynamic
contact angle, and ATR-FTIR. The stability of the modification was evaluated
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
under oxidative conditions, after autoclaving, and after rubbing.
Results: Advancing contact angles were decreased by approximately 50 o.
Unmodified silicone hydrogel lenses (n=25) had an advancing contact angle of 80 o
+/- 3o and a receding angle of 29o +/- 2o. Semprus modified lenses (n=3) had an
advancing contact angle of 27o +/- 2o and a receding angle of 26o +/- 2o. The
surface modification had no effect on the bulk properties including clarity,
dimensions, and mechanical properties. The modification was stable to oxidative
solutions, sterilization and mechanical challenges.
Conclusions: The polybetaine surface modification provides a novel and viable
avenue for significantly improving the wettability of silicone hydrogel contact
lenses without affecting their bulk properties. The advancing contact angle was
substantially decreased while the receding contact angle was predictably
maintained at a low level. The one-step process method is adaptable to various
silicone hydrogel contact lenses with different formulations.
Commercial Relationships: Alonzo Cook, Semprus BioSciences (E); Matthew
Skinner, Semprus BioSciences (E); Jun Li, Semprus BioSciences (E);
Christopher Loose, Semprus BioSciences (E); Karen Schultz, Semprus
BioSciences (E); Zheng Zhang, Semprus BioSciences (E)
Support: None
Program Number: 6097 Poster Board Number: D918
Presentation Time: 8:30 AM - 10:15 AM
Proteoglycan 4 (lubricin) Enhances the Wettability Of Model Conventional
And Silicone Hydrogel Contact Lenses
Lakshman N. Subbaraman1, Tannin A. Schmidt2, Heather Sheardown1. 1Chemical
Engineering, McMaster University, Hamilton, ON, Canada; 2Biomedical
Engineering, University of Calgary, Calgary, AB, Canada.
Purpose: Proteoglycan 4 (PRG4), a mucin-like glycoprotein, is present in the
synovial joints and synovial fluid. PRG4 improves lubrication and contributes to
the overall maintenance and integrity of the knee joint. PRG4 has recently been
discovered at the ocular surface and as such may be useful in ocular applications as
a lubricant. The purpose of this study was to incorporate PRG4 into model
conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials and
to determine the effect of PRG4 on surface characteristics and protein-sorption
properties of these contact lenses.
Methods: One model CH (poly(2-hydroxyethyl methacrylate) [pHEMA]) and two
model SH (pHEMA,Methacryloxypropyltris(trimethylsiloxy)silane [pHEMA
TRIS] and N,N-Dimethylacrylamide, TRIS [DMAA TRIS]) lens materials were
prepared with and without hyaluronic acid (HA) of molecular weight 35 or 132
kDa. PRG4 was isolated and purified from articular cartilage disks harvested from
mature bovine stifle joints. PRG4 was incorporated into these materials at two
different concentrations (1% and 5% by weight). Advancing water contact angle
(CA), equilibrium water content, optical transparency (OT) and lysozyme sorption
on these lens materials were investigated.
Results: Presence of PRG4 significantly decreased the CAs of both the HA and
non-HA containing materials (p<0.05). Materials with higher concentration of
PRG4 (5% wt) showed lower CAs than those with lower concentration (1% wt)
(p<0.05). Incorporation of PRG4 did not have an effect on the OT when compared
to the control. While there was no significant difference between PRG4 containing
and non-PRG4 containing pHEMA-based materials (p>0.05), PRG4 containing SH
materials showed a significant reduction in lysozyme sorption when compared to
non-PRG containing SH materials (p<0.05). All the HA containing materials
showed significantly lower CAs and reduced lysozyme sorption than non-HA
containing materials (p<0.05).
Conclusions: Incorporation of PRG4 improves the hydrophilicity and reduces
protein sorption without affecting the OT in model SH contact lenses. SH materials
that contain PRG4 and HA have tremendous potential as hydrophilic, proteinresistant contact lens materials.
Commercial Relationships: Lakshman N. Subbaraman, None; Tannin A.
Schmidt, None; Heather Sheardown, None
Support: NSERC 20/20 Ophthalmic Network
Program Number: 6098 Poster Board Number: D919
Presentation Time: 8:30 AM - 10:15 AM
Estimating in-vivo Contact Lens Wettability Through Tear Film
Hydrodynamics
Jalaiah P. Varikooty1A, Nancy J. Keir1A, Trefford L. Simpson1B. ACCLR, School of
Optometry, BSchool of Optometry, 1University of Waterloo, Waterloo, ON,
Canada.
Purpose: The stability and ease of spread of the tear film over the lens surface may
be an indicator of contact lens wettability. The present in-vivo methods of
determining lens wettability are complex and do not predict the comfort of lens
wear. We introduce a novel and objective way of determining in-vivo lens
wettability.
Methods: 20 videos from 10 participants who had worn the same type of silicone
hydrogel lens for at least 8 hours were analysed. We imaged the spread of tear-film
over the lens surface after a blink, in the morning after lens insertion and also after
8 hours of lens wear. Using a customized, calibrated ImageJ macro the velocity of
reflective particles in the videos was determined. The results were analyzed using R
and ProFit.
Results: The upward particle velocity (UPV) was highest immediately after a blink
and declined with time. We were able to establish that the spread of the tear film
was different upon lens insertion than it was after 8 hours of lens wear by
measuring UPV (p=0.001). The exponential time constants were 11.5±1.7 for lens
insertion in the morning and 47.1 ± 28.0 after 8 hours of lens wear.
Conclusions: We have introduced a novel and non-invasive way to measure invivo wettability of the lens/tear-film interface. Additional studies are needed to
understand if this simple measure is associated with other aspects of lens
wettability or lens comfort.
Commercial Relationships: Jalaiah P. Varikooty, None; Nancy J. Keir,
None; Trefford L. Simpson, None
Support: None
Program Number: 6099 Poster Board Number: D920
Presentation Time: 8:30 AM - 10:15 AM
Hyaluronan Release from Contact Lenses in vitro and in vivo
Krista M. Fridman, Catherine A. Scheuer, Stephanie Su, Lening Zhang, Susan E.
Burke. Bausch + Lomb, Rochester, NY.
Purpose: Hyaluronan (HA), a natural ocular lubricant, provides hydration and
contributes to tear film stabilization. This study evaluates in vitro contact lens
adsorption and release of HA after soaking in multi-purpose solution containing
HA. Further, this study examined the concentration of HA in tear film of lens
wearers after use of MPS containing HA.
Methods: In vitro adsorption and release of HA from senofilcon A lenses (Acuvue
Oasys, Vistakon) were evaluated with fluorescence spectroscopy. Lenses were
soaked in MPS (Biotrue, Bausch+Lomb) prepared with fluorescent-tagged HA.
Release profiles were monitored over time with saline rinse of soaked lenses at the
rate of tear film secretions. In vivo release of HA from senofilcon A lenses soaked
in MPS containing HA (Biotrue, Bausch+Lomb) was evaluated with ELISA.
Twenty five subjects matched for age and sex (12 habitual lens wearers and 13 nonlens wearers) participated in this randomized, single-masked, contralateral study.
Tears were collected on Schirmer strips at baseline and after 2h of wearing MPS
soaked lenses or control lenses rinsed with Sensitive Eyes Saline. HA
concentrations were measured and adjusted for sample volumes. A repeated
measurement ANOVA model was used to evaluate differences in HA
concentrations.
Results: In vitro measurements showed adsorbed HA (19.72+/-2.03 µg HA/lens)
was released over time from senofilcon A. In vivo HA tear concentrations obtained
were in range with those previously reported (undetectable - 3018ng HA/ml tears).
No statistical differences were noted in this study population between lens wearers
and non-lens wearers, between baselines of treatment groups, or between saline
treatment group and baseline. An increase in HA concentration was observed in
tears collected from eyes that had worn lenses soaked in MPS containing HA
compared to baseline (p=0.009), and compared to those with saline rinsed control
contact lenses (p=0.033).
Conclusions: This study showed that senofilcon A lenses adsorbed HA when
soaked in MPS containing HA and that HA release was detected for 20h when
rinsed in vitro at the rate of tear film secretions. This study also showed that after
wearing senofilcon A lenses soaked in an HA containing MPS, the HA
concentration in tear film may be increased. The duration of in vivo HA increase
was not evaluated.
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
Commercial Relationships: Krista M. Fridman, Bausch + Lomb (E);
Catherine A. Scheuer, Bausch + Lomb (E); Stephanie Su, Bausch + Lomb (E);
Lening Zhang, Bausch + Lomb (E); Susan E. Burke, Bausch + Lomb (E)
Support: None
Clinical Trial: http://www.clinicaltrials.gov, 1317030
Program Number: 6100 Poster Board Number: D921
Presentation Time: 8:30 AM - 10:15 AM
Solute Release From Soft-contact-lens Hydrogels
Csaba Kotsmar, Teresa Nadolski, Nicole Taylor, Kevin Yeh, Clayton J. Radke.
Chemical & Biomolecular Eng, Univ of California at Berkeley, Berkeley, CA.
Purpose: Transport of solute molecules through soft-contact-lens (SCL) hydrogels,
such as salts, wetting agents, nutrients, and drugs, is important to on-eye behavior.
Typically, solutes are loaded into the gel and released over time. This work
measures the mesh size of contact-lens materials and demonstrates that solute
absorption and release times decrease with increasing mesh size. For solutes that
interact strongly with the gel matrix, release times are much slower than loading
times and can approach infinity for irreversible interactions.
Methods: Two-photon confocal microscopy detects the transient concentration
profiles of fluorescently tagged dextrans and proteins with different charges in
HEMA/MAA hydrogels during both loading and release (see Figure 1 for sodium
fluorescein). Diffusion theory gives the solute effective diffusion coefficient D.
Oscillatory shear rheometry gives the gel mesh size.
Results: For uncharged dextrans of molecular weight near 10 kDa, D increases
from 3.24±0.1 x 10-8 cm2/s to 4.02 ± 0.4 x 10-7 cm2/s both for absorption and
desorption as the mesh size increases from 3 to 9 nm. These solutes interact
reversibly with the gel. For protein oppositely charged to the gel network, the
diffusion coefficient in the loading direction greatly decreases to 5.2±0.3 x 10-9
cm2/s. Desorption of the anionic protein is extremely slow indicating strong
interaction with the gel strands.
Conclusions: Using rheometry and polymer physics, we successfully measure
mesh sizes of SCL materials. For reversibly interacting solutes, absorption and
release rates increase with gel mesh size and are identical in both loading and
release directions. For solutes that strongly interact with the gel, uptake rates are
diminished and release rates are extremely slow. It is not possible to predict solute
release rates from hydrogels using studies conducted in the loading direction only.
Commercial Relationships: Csaba Kotsmar, Alcon (F); Teresa Nadolski,
None; Nicole Taylor, None; Kevin Yeh, None; Clayton J. Radke, Alcon (F)
Support: Alcon
Program Number: 6101 Poster Board Number: D922
Presentation Time: 8:30 AM - 10:15 AM
Ocular Delivery Of Ketotifen Fumarate By Silicone Hydrogel And
Conventional Hydrogel Contact Lens Materials
Anthony Soluri, Alex Hui, Lyndon Jones. Centre for Contact Lens Research,
University of Waterloo, Waterloo, ON, Canada.
Purpose: To investigate the uptake and delivery of the anti-allergy drug ketotifen
fumarate (KF), by commercially available contact lenses.
Methods: A total of fourteen different commercially available contact lenses were
investigated, including five frequent replacement silicone hydrogels (balafilcon A,
comfilcon A, galyfilcon A, senofilcon A and lotrafilcon B), three conventional
hydrogels (alphafilcon A, etafilcon A, and polymacon) and six daily disposable
lenses (nelfilcon A, omafilcon A, etafilcon A + PVP, ocufilcon B, narafilcon A and
filcon II 3). Lenses were soaked in a 0.025% KF loading solution for 24 hours, and
the concentration of KF in solution over time was determined by UV absorbance at
297 nm. After the 24 hour loading period, lenses were placed into fresh vials
containing borate buffered saline (BBS), and the release of drug into solution at
34°C was monitored over 24 hours.
Results: All the lenses studied demonstrated significant uptake and release of KF
into the BBS (p<0.05 compared to initial time point). Lenses with charged surfaces
(balafilcon A, etafilcon A and etafilcon A + PVP) demonstrated the greatest uptake
and release of KF. Etafilcon A released 284.5 ± 29.8 µg/lens, while balafilcon A
released 227.6 ± 14.7 µg/lens, which was substantially more (p<0.05) than the
lowest releasing lenses (nelfilcon A; 40.4 ± 4.1 µg/lens and comfilcon A; 110.4 ±
8.9 µg/lens). The majority of lenses were able to match or exceed the total amount
of KF commonly administered to the eye using twice daily dosing of commercially
available (0.025%) eye drop formulations. Most of the lenses surveyed released to
a plateau concentration of KF relatively quickly, and no lens was able to release KF
for longer than four hours.
Conclusions: Commercially available lenses demonstrated the ability to release a
clinically relevant amount of KF compared to conventional eye drops. The use of
commercially available contact lenses as a KF delivery system in a daily disposable
wear scenario may be feasible.
Commercial Relationships: Anthony Soluri, None; Alex Hui, None; Lyndon
Jones, None
Support: NSERC, COETF, 20/20 Network for the Development of Advanced
Ophthalmic Materials, Ezell Fellowship, Vistakon Research Grant
Program Number: 6102 Poster Board Number: D923
Presentation Time: 8:30 AM - 10:15 AM
Development of a Drug released Soft Contact Lens that Releases Antibiotics in
a Sustained Manner
Shinichiro Kobayakawa1, Toru Matsunaga2, Kohji Kakisu1, Yoshiko Yamazaki2,
Takao Sato2, Tetsuo Tochikubo1. 11st Dept of Ophthalmology, Toho University,
Tokyo, Japan; 2SEED Co Ltd, Kounosu-shi, Japan.
Purpose: We developed a new soft contact lens (SCL) of a hydrogel material
capable of releasing antibiotics in a sustained manner. The purpose of this study
was to investigate the penetration of the antibiotics to the eye by the drug released
SCL (DR-SCL) in a rabbit model.
Methods: Gatifloxacin (GFLX) 0.3% and moxifloxacin (MFLX) 0.5% eye drops
were used. In twenty-seven rabbits, the antibiotics concentration of cornea, aqueous
humor and crystalline lens was measured with high-performance liquid
chromatography (HPLC). Those samples were collected at 10, 30, and 60 minutes
after three times topical administration at 15-min intervals by those eye drops (eye
drops group), and through the application with DR-SCL (DR-SCL group), also
collected at 24, 48, and 72 hours through the application with DR-SCL.
Results: The maximum GFLX concentration in cornea were 0.7μg/ml (@10 min),
and the MFLX concentration were 2.4μg/ml (@10 min) in eye drops group.
Whereas, those were 9.5μg/ml (@60 min) and 23μg/ml (@60 min) in DR-SCL
group, respectively. Those concentrations were significant differences between eye
drops group and DR-SCL groups at 10 min. The maximum GFLX concentrations
in aqueous humor were 1.1μg/ml (@60 min), and the MFLX concentration were
6.4μg/ml (@60 min) in eye drops group. Whereas, those were 13.4μg/ml (@60
min) and 60μg/ml (@60 min) in DR-SCL group, respectively. Those
concentrations were significant differences between eye drops group and DR-SCL
groups at 60 min. The maximum GFLX concentrations in crystalline lens were
0.02μg/ml (@60 min), and the MFLX concentration were 0.17μg/ml (@30 min) in
eye drops group. Whereas, those were 0.05μg/ml (@60 min) and 0.3μg/ml (@60
min) in DR-SCL group, respectively. Those concentrations in crystalline lens were
not significant differences between eye drops group and DR-SCL groups. Those
concentrations in cornea for GFLX in DR-SCL group decreased from 0.69μg/ml to
0.04μg/ml, and for MFLX decreased from 4.22μg/ml to 0.89μg/ml through 72
hours. Those concentrations in aqueous humor for GFLX decreased from 2.6μg/ml
to 0.08μg/ml, and for MFLX decreased from 7.9μg/ml to 3.2μg/ml. Those
concentrations in crystalline lens for GFLX decreased from 0.3μg/ml to 0.08μg/ml,
and for MFLX decreased from 0.6μg/ml to 0.3μg/ml.
Conclusions: Antibiotics concentrations of DR-SCL group either in aqueous
humor or in cornea were approximately ten times higher than those of eye drops
group. Those to crystalline lens in DR-SCL group were similar or higher than those
in eye drops group. Moreover, DR-SCL sustained release of antibiotics through 72
hours. DR-SCL may be an expectable drug delivery system into the interior of the
eye.
Commercial Relationships: Shinichiro Kobayakawa, None; Toru Matsunaga,
SEED Co Ltd (E); Kohji Kakisu, None; Yoshiko Yamazaki, SEED Co Ltd (E);
Takao Sato, SEED Co Ltd (E); Tetsuo Tochikubo, None
Support: None
Program Number: 6103 Poster Board Number: D924
Presentation Time: 8:30 AM - 10:15 AM
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
Surface versus Bulk Absorption of a Diblock Copolymer on/in Silicone
Hydrogels
Yuchen Huo1, Scott S. Perry1, Howard A. Ketelson2. 1Materials Science and
Engineering, University of Florida, Gainesville, FL; 2R & D, Alcon Research Ltd,
Fort Worth, TX.
Purpose: The interaction between ethylene oxide-block-butylene oxide (EOBO)
copolymer and the surfaces of four silicone hydrogel (SH) contact lenses
PureVision® (PV), O2OPTIX® (O2), ACUVUE® Oasys® (AO), and Biofinity®
(BF) was investigated using angle-resolved X-ray photoelectron spectroscopy (ARXPS) following treatment in test solutions containing various concentrations of
EOBO. The nature of this interaction was further understood by quantifying the
amount of eluted EOBO from each lens following the same treatment using ultra
performance liquid chromatography (UPLC).
Methods: Lenses were treated with solutions containing various concentrations of
EOBO. For a given lens type and a specific concentration level, identical paired
samples were prepared. The first sample was subjected to an elution study
involving UPLC. The second sample, analyzed using XPS, was prepared through a
vacuum drying procedure, in which the hydrogel is taken from a fully hydrated
state directly to an ultraclean, ultrahigh vacuum environment. Upon changing the
angle between the sample and the XPS analyzer, chemical compositions
corresponding to uppermost 10 nm of the surface were probed for each sample.
Results: The elution study revealed large disparity in the amount of EOBO uptake
by different samples following each solution treatment. For samples subjected to
the most concentrated solution treatment, the amount of EOBO recovered (in μg)
from the lenses was ranked as the following, from the highest to the lowest, PV
(151.77), BF (140.24), AO (77.96), and O2 (7.21). The XPS results, however,
suggested that the amount of EOBO retained on the surface of the lenses
demonstrated a largely different trend. For example, AO and BF displayed trivial
amount of signal at binding energy characteristic to the EO blocks, whereas O2 and
PV showed clear EO signature as a result of being present on the surface.
Conclusions: The disparity between the elution and XPS results highlights the
difference in the interaction mechanism of the EOBO copolymer with different
lenses. For lenses such as O2OPTIX®, this interaction is predominantly bound to
the surface; for ACUVUE® OASYS®, however, EOBO was preferentially
absorbed by the bulk.
Commercial Relationships: Yuchen Huo, Alcon Laboratories, Inc. (F); Scott S.
Perry, Alcon Laboratories, Inc. (F); Howard A. Ketelson, Alcon Laboratories,
Inc. (E)
Support: Alcon Laboratories, Inc.
Program Number: 6104 Poster Board Number: D925
Presentation Time: 8:30 AM - 10:15 AM
Understanding Lens Shape Dynamics During Off-Eye Dehydration of Contact
Lens Materials with Varying Water Content
Ian G. Cox, Rosa H. Lee. Vision Care, Bausch + Lomb, Rochester, NY.
Purpose: To understand the lens shape dynamics during off-eye dehydration for a
novel lens material and 3 commercially available daily disposable contact lenses.
Methods: Four -3.00D lenses of each lens (type, water content) (etafilcon A [AV
Moist], 43%; narafilcon B, 48%; nelfilcon A, 69%; investigational lens, 78%) were
tested. Each lens was taken out of the package and blotted to remove excess
packaging solution. All 16 lenses were allowed to dehydrate under the same
ambient conditions of approximately 72°F with a RH of 30%. A photo was taken
every 2 minutes over the 20min period. Four pairs of photos for each lens type
(time 0 and time 20mins) were presented to 12 random subjects who rated whether
the lens shape of image A compared to image B was similar or different, using a 10
point rating scale where 1 corresponded to “Extremely Similar” and 10
corresponded to “Extremely Different”.
Results: Shape changes occurred throughout the 20 minute period. All 3
commercially available contact lens materials showed significant edge “fluting” as
a result of lens dehydration at the end of the 20 minute test period, while the
investigational contact lens material did not. A one-way ANOVA showed a
statistically significant difference (p<0.0001) between the investigational lens (A)
compared to nelfilcon A (D), narafilcon B (C) and etafilcon A (B), where the mean
rating scores were 1.9, 8.8, 8.4, 6.8, respectively.
Conclusions: Traditional clinical literation and belief suggests that higher water
content lenses dehydrate more than lower water content lenses. In this study, the
novel lens material demonstrated a more consistent lens shape over the 20 minute
dehydration period compared to narafilcon B, 48%; nelficon A, 69%; and etafilcon
A, 43% lenses, suggesting that the investigational material has unique properties
relative to water retention. Further research is needed to understand the impact of
dehydration driven lens shape change on vision, comfort and fitting performance
in-vivo.
Commercial Relationships: Ian G. Cox, Bausch + Lomb (E); Rosa H. Lee,
Bausch + Lomb (E)
Support: None
Program Number: 6105 Poster Board Number: D926
Presentation Time: 8:30 AM - 10:15 AM
Oxygen Diffusion Behind Modern Scleral Rigid Gas Permeable Contact
Lenses
Sofia C. Peixoto-de-Matos1, Vicente Compañ2, Sergio Moya2, Jorge Jorge1, Jose
M. Gonzalez-Meijome1. 1Center of Physics, University of Minho, Braga, Portugal;
2
Applied Thermodynamics, Universidad Politécnica de Valencia, Valencia, Spain.
Purpose: Scleral lenses are used to compensate corneal irregularities creating a
vaulting effect over the cornea. The goal of this study is to develop a model to
define the theoretical oxygen tension behind modern scleral contact lenses made of
different rigid gas permeable (RGP) materials and thickness and assuming different
thickness of the tear layer behind the lens.
Methods: Simulations of the partial pressure of oxygen across the cornea behind
scleral contact lenses made of different materials (Dk=75 to 200 barrers) and
different thickness (Tav=100 to 300 microns) were performed. A post-lens tear film
thickness (Tpost-tear=100 to 350 microns) in the range of 150 to 350 microns was
considered.
Results: Combinations of thicker lenses with lower permeability fitted to create a
pos-lens tear film thicker than 150 microns reduce the partial pressure of oxygen at
the corneal front surface below 50 mmHg, similar to closed eye conditions without
lenses. The lower the oxygen permeability of the lens material, the more significant
the contribution of post-lens tear film layer to the depletion in oxygen availability
to the cornea. A 100 microns increase in lens thickness will reduce between 17 and
21% the partial pressure of oxygen at the corneal surface for a 75 barrers material
and about 6% for a 200 barrers material. The same increase in tear film thickness
will have an impact of 14 to 16% in the partial pressure of oxygen at the corneal
surface for a 75 barrers material and about 12 to 14% for a 200 barrers material.
Conclusions: Tear film layer behind scleral RGP CL can significantly limit the
diffusion of oxygen to the cornea. This effect is more significant for lower Dk
values considered even when they fall in the range of 75 to 125 barrers. Scleral
RGP CL must be manufactured with materials of at least 150 barrers of oxygen
permeability in order to avoid a significant hypoxic effect under open eye
conditions.
Commercial Relationships: Sofia C. Peixoto-de-Matos, None; Vicente
Compañ, None; Sergio Moya, None; Jorge Jorge, None; Jose M. GonzalezMeijome, PARAGON VISION SCIENCE (C)
Support: None
Program Number: 6106 Poster Board Number: D927
Presentation Time: 8:30 AM - 10:15 AM
Rapid Measurement of Tear Oxygen Tension underneath Soft Contact Lenses
by Frequency-Domain Phosphorimetry
Sangly P. Srinivas1, Giovanna Guidoboni2, Lucia Carichino2, Yiran Jiang1, Joseph
A. Bonanno1. 1Optometry, Indiana University, Bloomington, IN; 2Mathematics,
IUPUI, Indianapolis, IN.
Purpose: To measure the dynamics of tear oxygen tension (pO2) during soft
contact lens wear using a non-invasive approach following a brief closure of the
eyelids.
Methods: A slit-lamp fluorometer was modified for rapid measurement of the
oxygen-sensitive phosphorescence lifetime of Pd-meso-tetra (4-carboxyphenyl)
porphyrin (λex = 530 nm; λem > 630 nm). The dye, bound to albumin, was coated on
to the bottom surface of hydrogel lenses before use in healthy volunteers (Bonanno
et al., IOVS, 43(2), 2002). The output of a green LED (Nichia Inc), which was
modulated as a sine-wave at 1 KHz, was used as the excitation source.
Phosphorescence, collected by the emission optics, held parfocal to that of
excitation, was directed to the cathode of a photomultiplier tube (R928, Hamamatsu
Inc). Oxygen-sensitive phase delay and demodulation were detected using a lock-in
amplifier (SRS-830; 120 KHz bandwidth; Stanford Research Systems, Palo Alto,
CA) and sampled at 50 Hz. The dynamics of pO2, calculated from phase delay
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
using the Stern-Volmer equation, was compared to predictions from a 1-D transient
O2 transport model governing diffusion and consumption across the lens + cornea
matrix. The oxygen consumption across the cornea was assumed to follow Monod
kinetics (Chhabra et al., J Biomed Mater Res B Appl Biomater., 90(1), 2009).
Results: Rapid changes in the oxygen-sensitive phase delay and demodulations
were observed following brief closure of the eyelids. The time to recover to a
steady state increased with longer periods of eye closure (5 min). Thicker lenses (of
low Dk/L) produced slower return to steady state (taking up to 35 secs) compared
to that of the thin lens (< 5 secs). The corresponding dynamics of pO2 were similar
to those predicted by the mathematical model using parameters reported earlier
(Chhabra et al., 2009).
Conclusions: In contrast to the time-domain phosphorimetry (Bonanno et al.,
IOVS, 2002), the frequency-domain approach for phosphorescence lifetimes offers
much higher sampling frequencies (50 Hz compared to 1 Hz). This high sampling
rate will enable more accurate estimation of the oxygen consumption rate and other
parameters of interest in contact lens design.
Commercial Relationships: Sangly P. Srinivas, None; Giovanna Guidoboni,
None; Lucia Carichino, None; Yiran Jiang, None; Joseph A. Bonanno, None
Support: NSF-DMS 0811138 (GG) and IU Collaborative research grant (GG).
(Image Pro Analyser 7.0) was used to measure nerve length. One way independent
ANOVA and post hoc paired t-tests (with Bonferroni correction) were used to
compare groups.
Results: There was a significant difference in central NFD between the groups
(SCL: 24,870 ± 4,793 µm/mm2, OK: 18,466 ± 4,872 µm/mm2, NL: 24,931 ± 4,259
µm/mm2; ANOVA p<0.01). NFD was significantly less in OK than SCL (p<0.01)
and NL groups (p<0.01). SCL was not different from NL (p>0.05). There was no
difference in mid-peripheral NFD among all the groups (SCL: 23,544 ± 3,987
µm/mm2, OK: 22,677 ± 3,301 µm/mm2, NL: 22,435 ± 3,993 µm/mm2; ANOVA
p>0.05).
Conclusions: This study reveals an apparent decrease in central corneal nerve
density in the SBNP in OK lens wear. This suggests that the mechanism underlying
refractive change during OK treatment may also impact on the corneal nerve
morphology in lens wearers. The implications of this finding in relation to corneal
sensitivity require further study.
Commercial Relationships: Edward Lum, None; Blanka Golebiowski, None;
Helen A. Swarbrick, Bausch & Lomb Boston, BE Enterprises, Capricornia
Contact Lens. (F)
Support: Funded under the Australian Research Council Linkage Project
Program Number: 6107 Poster Board Number: D928
Presentation Time: 8:30 AM - 10:15 AM
Surface Characterization of a Water Gradient Silicone Hydrogel Contact Lens
(delefilcon A)
John Pruitt, Yongxing Qiu, Sibichen Thekveli, Rick Hart. Alcon, Johns Creek, GA.
Purpose: A water gradient silicone hydrogel contact lens recently introduced in
Europe provides substantially different properties at the lens surface compared to
the lens core. Multiple analytical techniques were utilized to characterize the core,
surface, and water gradient properties of DAILIES® TOTAL1® (delefilcon A)
contact lenses.
Methods: Lenses were cross-sectioned to measure the transition from the core of
the lens to the surface. The hydrated cross sections were placed on edge and
imaged using atomic force microscopy (AFM). The surface thickness and the local
compression modulus were measured along a line from the core to the outer
surface. Dried contact lens cross sections were also imaged by both SEM and AFM
to compare the dry vs. wet surface thickness to measure the surface water content.
Gravimetric water content analysis was conducted on separately prepared samples
consisting of only the high water content surface hydrogel material or the core
silicone hydrogel material.
Results: A total surface thickness of 5.9 ± 0.8 microns was measured using AFM
of hydrated lens cross sections including a transition zone of 1-2 microns and an
outer surface layer of 4-5 microns. The surface layer was characterized by a lower
compression modulus than the core of the lens with a modulus gradient detectable
in the transition zone. Gravimetric analysis of a separately prepared sample of the
surface hydrogel material revealed a water content of 84.6% compared to a core
water content of 33 ± 2%. The surface thickness of a vacuum dried lens cross
section was measured at 1.2 microns, only 20% of the hydrated surface thickness
and consistent with an average water content in the surface layer of approximately
80%. SEM images of freeze-dried lens samples revealed a porous surface structure
as expected due to the high water content.
Conclusions: Delefilcon A contact lenses are composed of a core silicone hydrogel
material consisting of approximately 33% water which transitions to an outer
surface layer containing approximately 80% water. The surface is also
characterized by a lower compression modulus compared to the core of the lens.
This unique water gradient technology resulting in high oxygen transmission with a
lubricious surface represents the next generation of contact lenses.
Commercial Relationships: John Pruitt, Alcon (E); Yongxing Qiu, Alcon (E);
Sibichen Thekveli, Alcon (E); Rick Hart, Alcon (E)
Support: None
Program Number: 6109 Poster Board Number: D930
Presentation Time: 8:30 AM - 10:15 AM
Design and Development of an In Vitro Tear Replenishment System
Saman Mohammadi, Maud Gorbet. Systems Design Engineering, University of
Waterloo, Waterloo, ON, Canada.
Purpose: When testing contact lens biocompatibility, an important missing
element with in vitro models of the cornea is the constant hydration of the contact
lens and exchange of tear fluid that occurs in the eye. The purpose of this project
was to design a novel physiologically realistic microfluidic device to mimic tear
replenishment in the human eye through spraying, at physiological rates, artificial
tear fluid onto the surface of the contact lens on a curved in vitro cornea model.
Methods: The microfluidics system provides a pressurized artificial tear fluid
supply line controlled through a series of isolation valves and can deliver the
desired amount of artificial tear fluid on the surface of the in vitro model. A micropump was used to pump the artificial tear fluid through Teflon (TM) tubing. Sixwell inserts were curved using a stainless steel die designed to mimic the curvature
and dimension of the cornea. The curved inserts with or without human corneal
epithelial cells (HCEC) were transferred into the device in a sterilized environment.
The excess tear fluid was pumped out from each well into a waste container. The
entire device was placed in a cell incubator and tested for up to 12 hours.
Results: The experiments on contact lenses in the absence of cells showed the
device can keep the contact lens hydrated over any period of time while
maintaining lens exposure to air in between tear fluid delivery, mimicking in vitro
tear break-up over a contact lens. The device allowed enough air exchange within a
5% CO2 regulated incubator to maintain medium pH levels within physiological
range. MTT viability studies on a curved stratified culture of immortalized corneal
epithelial cells showed no significant change in cell viability with lotrafilcon A
lenses. Experiments using the tear replenishment system on the in vitro model
without a contact lens, showed slightly lower cell viability in the superficial layer
but no significant change in overall cell viability compared to controls where no
tear replenishment was applied.
Conclusions: Our results proved this physiologically realistic modeling of tear
replenishment system can provide artificial tear fluid to a lens on a curved surface
with or without a multilayer of HCEC, at flow rates and frequency similar to the
human eye. This device allows mimicking in vivo conditions more closely and will
contribute to a better understanding of corneal cell-lens interactions in vitro.
Commercial Relationships: Saman Mohammadi, None; Maud Gorbet, None
Support: NSERC, CIBA Vision
Program Number: 6108 Poster Board Number: D929
Presentation Time: 8:30 AM - 10:15 AM
Corneal Nerve Morphology In Soft And Orthokeratology Contact Lens Wear
Edward Lum, Blanka Golebiowski, Helen A. Swarbrick. Sch of Optometry/Vision
Sci, Univ of New South Wales, Sydney, Australia.
Purpose: To investigate the morphology of the corneal sub-basal nerve plexus
(SBNP) in soft and orthokeratology contact lens wearers using laser-scanning
confocal microscopy (LSCM).
Methods: Forty-three subjects (age range: 18 to 76 yrs) were recruited in a crosssectional study and grouped into three categories: daily wear soft (SCL, n=17,
median lens wear experience 10yrs), overnight orthokeratology (OK, n=8, median
lens wear experience 2yrs), and non-lens wearers (NL, n=18). Nerve morphology
was assessed by sampling a 1x1mm area of the SBNP using the Heidelberg Retina
Tomograph with Rostock Corneal Module at two locations: corneal apex and
temporal mid-periphery approximately 2.5mm from apex. Nerve fibre density
(NFD) was calculated by measuring the total length of all nerve fibres and branches
per square millimetre. A stylus and tracing tool in an image-processing program
Program Number: 6110 Poster Board Number: D931
Presentation Time: 8:30 AM - 10:15 AM
Evaluation of Contact Lens Image Stability and Predicted logMAR Image
Resolution as Lenses Dehydrate
Rosa H. Lee, Amanda C. Kingston, Gary Richardson. Product Design Group,
Bausch + Lomb, Rochester, NY.
Purpose: To use a novel optical bench technique to analyze the image stability and
predicted logMAR retinal image resolution of 1 investigational and 3 commercially
available daily disposable contact lenses as the lenses dehydrate.
Methods: Twenty -3.00D lenses of each product type (etafilcon A [AV Moist],
narafilcon B, nelfilcon A, test lens) were analyzed on an optical imaging bench.
The bench uses a model cornea that mimics the optics and physical dimensions of
an average human eye, and relays the retinal plane image of a target (US Air Force)
to a CCD camera. Multiple images were captured through each lens over time with
a target at optical infinity. Each lens was blotted to remove excess packaging
solution and conformed to a 7.8mm radius PMMA model cornea. Two drops of
rewetting solution were used to simulate the tear film. Images were acquired every
10s, as the lens is dehydrating, up to 180s following application of the rewetting
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
drops. A pattern-matching algorithm was used to calculate the predicted logMAR
score of the images from each lens following normalization against the initial time
zero image for each image series.
Results: A one-way ANOVA showed a statistically significant difference
(p<0.001) between the test lens compared to nelfilcon A, narafilcon B and etafilcon
A, where the overall predicted mean logMAR scores were -0.009, 0.116, 0.136 and
0.182. For the time 0 images, there was a statistically significant difference
between the test lens and nelfilcon A (p<0.03) with mean predicted logMAR scores
of -0.11 and -0.05, respectively. For the time 10s images (shorter than blink rates
associated with reading or computer use), there was a statistically significant
difference between the test lens compared to nelfilcon A and etafilcon A (p<0.001)
with mean predicted logMAR scores of -0.10, -0.02, -0.03, respectively.
Conclusions: This novel in-vitro method quantitates the predicted logMAR score
based on optical image quality as lenses dehydrate. The test lenses exhibited better
optical image quality than the 3 commercially available daily disposable lenses.
The test lens showed a more consistent and slower reduction in predicted retinal
image quality over time compared to narafilcon B and etafilcon A lenses. Within
10s, there was a predicted 4 letter difference between the test lens and nelfilcon A
and a 3.5 letter difference for etafilcon A. Further research is needed to understand
the clinical impact to visual stability.
Commercial Relationships: Rosa H. Lee, Bausch + Lomb (E); Amanda C.
Kingston, Bausch + Lomb (E); Gary Richardson, Bausch + Lomb (E)
Support: None
Program Number: 6111 Poster Board Number: D932
Presentation Time: 8:30 AM - 10:15 AM
Interfacial Interactions Of Cationic And Anionic Artificial Tears With Ionic
Hydrogel Contact Lens Surface
Muhammad Abdulrazik1, Simon Benita2. 1Ophthalmology/Innovative Interventions,
East Jerusalem Biomedical Institute, East Jerusalem, Palestine; 2Institute of Drug
Research, Hebrew University of Jerusalem, Jerusalem, Israel.
Purpose: Contact lens wear is a predisposing factor to dry eye. However, no
artificial tear product is approved for use while wearing contact lenses due to
biocompatibility concerns. Ionic and non-ionic hydrogel and silicon hydrogel soft
contact lenses are the most common in current clinical use. This study aims at
investigating interfacial interactions between cationic and anionic artificial tear
preparation and the surface of ionic hydrogel contact lenses.
Methods: The two studied ionic contact lenses were FDA category III and IV
hydrogel lenses (Hanita, pHEMA/MAA, 38% and 57% water content respectively).
The studied formulations with electrostatic charge were Refresh EnduraTM anionic
emulsion (Allergan) and Cationorm® cationic emulsion (Novagali Pharma). The
studied reference formulations were HyloComod® (Ursapharm), HypoTears®
(Novartis), GenTeal® (Novartis), Refresh® (Allergan) and Saline 0.9%. Contact lens
was mounted on freshly excised rabbit eye globe. Contact angles were measured by
FTA 125 system (First Ten Angstroms Inc.), formulation surface tension was
determined by multiwell plate tensiometer (Kibron Inc.) and spreading coefficients
were calculated from measured surface tensions and contact angles. Kruskal-Wallis
test was used for determination of significance (P less than 0.05).
Results: For each studied formulation, contact angles were significantly lower on
57% water content (WC) compared with 38% WC lens. Contact angle scores on
both contact lenses were lowest for the cationic emulsion (27.16±3.54 on 38% WC
surface and 8.98±2.32 on 57% WC surface), which significantly outperformed the
anionic emulsion (49.47±4.73 on 38% WC surface and 17.68±1.94 on 57% WC
surface). However, contact angle scores for the anionic emulsion were significantly
lower than the non-charged formulations on each contact lens (from 63.41±4.4
[REFRESH] to 80.76±2.43 [HYPOTEARS] on 38% WC surface, and from
45.25±0.68 [REFRESH] to 62.02±4.39 [HYPOTEARS] on 57% WC surface).
Conclusions: The effect of contact lens water content on contact angles was
steeper than the effect of formulation electrostatic charge. However, comparison
between formulation on each of the studied surfaces have shown the superiority of
the cationic emulsion that achieved approaching-zero spreading coefficients (-3.32
± -0.85 and -0.38 ± -0.19 mN/m, for 38% and 57% WC surface respectively)
(spreading coefficient = 0 represents a spontaneous and complete wetting),
suggesting that electrostatic attraction have a strong impact on interfacial
interaction between instilled eye drop and contact lens surface. The results support
the utilization of cationic-charge approach in the design of tear substitutes for
contact lens wearers.
Commercial Relationships: Muhammad Abdulrazik, None; Simon Benita,
inventor (P)
Support: None
Program Number: 6112 Poster Board Number: D933
Presentation Time: 8:30 AM - 10:15 AM
Contact Lens/Contact Lens solution Combinations Determine the
Inflammatory Changes on the Ocular Surface: A Laser In Vivo Confocal
Microscopy Study
Bernardo M. Cavalcanti1, Andrea Cruzat2, Yureeda Qazi3A, Neda Baniasadi4,
Monique Trinidad3B, Amy Watts3C, Douglas Critser5A, Charles Leahy3C, Christine
W. Sindt5B, Pedram Hamrah1. 1Cornea/Ophthalmology, Harvard Medical
School/MEEI, Boston, MA; 2Cornea / Ophthalmology, Harvard Medical
Sch/MEEI, Boston, MA; AOphthalmology, BCornea Research, CContact Lens,
3
Massachusetts Eye and Ear Infirmary, Boston, MA; 4Cornea/Ophthalmology, MA
Eye & Ear Infirm/Harvard Med Sch, Boston, MA; AContact Lens,
B
Ophthalmology, 5University of Iowa, Iowa City, IA.
Purpose: To assess the subclinical immune responses to various contact lenses
(CL) and CL solutions in naive CL wearers.
Methods: Multicenter, randomized, double-blinded, clinical trial. Sixty-five naïve
CL wearers (130 eyes), fitted with silicone hydrogel CL (PureVision® [PV];
Oasys® [OA]; Biofinity® [BF]), were enrolled into one of 3 CL solution groups
(OPTI-FREE RepleniSH® (OF, n=21); Clear Care® (CC, n=21); ReNu
MultiPlus® (RM, n=23). Corneal, limbal, and conjunctival staining, ocular
injection, as well as laser in vivo confocal microscopy (IVCM; HRT3/RCM) of the
central and peripheral corneal quadrants were performed at baseline and weeks 1
and 6 post-CL wear. Three masked observers analyzed the images for dendritic cell
(DC) and non-dendritic inflammatory cell (IC) density.
Results: Increased ocular surface staining, but minimal ocular injection was
observed in all groups. Conjunctival staining correlated to peripheral DC density
(r>0.40 for all quadrants). RM demonstrated significantly increased staining for all
conjunctival, limbal and cornea areas, correlating with highest increase in DC
density in central cornea (58%), nasal (26%) and temporal (24%) quadrants at 6
weeks, as compared to OF and CC (p<0.05 between groups). Comparison of CL
types showed significantly increased limbal and corneal staining for OA (p<0.05)
and corneal staining with PV (p<0.04), but minimal staining with BF, with OA
demonstrating highest increase in total DC (27%) as compared to PV (13%) and BF
(12%) (p<0.05 between groups). Surprisingly, each CL and CL solution
demonstrated combinations with minimal surface staining and no significant
increase in DC as well as combinations with significant increase staining, with
increase in peripheral DC.
Conclusions: IVCM revealed increased immune cell infiltration in all groups after
CL wear as early as 1 week, while corneal and conjunctival staining were detected
later at 6 weeks. While our data demonstrates that increased ocular surface staining
and immune cell density are both due to CL and CL solutions, proper combination
will both prevent or worsen staining and subclinical increase in immune cells.
Commercial Relationships: Bernardo M. Cavalcanti, None; Andrea Cruzat,
None; Yureeda Qazi, None; Neda Baniasadi, None; Monique Trinidad, None;
Amy Watts, Alcon (F); Douglas Critser, None; Charles Leahy, Alcon (F);
Christine W. Sindt, Alcon (F); Pedram Hamrah, Alcon (F)
Support: Support: NIH K08-EY020575, New England Corneal Transplant
Research Fund, Falk Medical Research Trust, Alcon Research LTD.
Clinical Trial: http://www.clinicaltrials.gov, NCT01250925
Program Number: 6113 Poster Board Number: D934
Presentation Time: 8:30 AM - 10:15 AM
Stress Induced Frictional Transitions in Cross-Linked Surface Gels
Thomas E. Angelini1, Alison C. Dunn1, Juan M. Uruena1, Howard A. Ketelson2, W
G. Sawyer1A. AMechanical and Aerospace Eng, 1University of Florida, Gainesville,
FL; 2R & D, Alcon Research Ltd, Fort Worth, TX.
Purpose: To determine the contact pressure limits on lubricity for a lightly
crosslinked gel surface layer as a function of cross-link density. This study
examines the friction response of the gel layer under varied loads and sliding
speeds and correlates the changes in lubricity to contact pressure and the mechanics
of the gel surface.
Methods: A series of experimental and minimally-crosslinked 2-3 um thick
gradient gel layers (5) were created on silicone hydrogel contact lens surfaces
(DAILIES TOTAL1®). Friction measurements were carried out on a custom
micro-tribometer under low sliding speeds of v=20 um/s and very low pressures
down to single kPa. Instrumented indentation experiments were performed using a
micro-indentation platform, and the elastic constants of the gels were determined
from these experiments.
Results: The majority of samples showed a clear transition between dynamic stickslip friction (mu~0.25 with fluctuations of ~0.25) to extremely smooth and low
friction (mu~0.03 with no measurable fluctuations) at forces ranging 230-490 mN.
Based on the contact mechanics experiments performed on these lenses this
corresponds to contact pressures between 9-13 kPa. There was a clear and
monotonic trend indicating that gel stiffness and the transition pressure increase
with increasing crosslinked density. All gels transitioned at surface deformations on
the order of their thicknesses, thus it is hypothesized that the mechanisms of these
frictional transitions is due a collapse of the fluid retaining network.
Conclusions: The crosslinked density and resulting elasticity define the critical
transition pressure between stick-slip and smooth friction. This transition
deformation is comparable to gel thickness. At pressures greater than the threshold,
the surface gel layer collapses locally, causing undesirable stick-slip friction. The
conditions under which a soft surface gel layer on a bulk soft contact lens provides
smooth sliding have been identified.
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
Commercial Relationships: Thomas E. Angelini, None; Alison C. Dunn,
None; Juan M. Uruena, None; Howard A. Ketelson, Alcon (E); W. G. Sawyer,
None
Support: Alcon Research, Ltd.
Program Number: 6114 Poster Board Number: D935
Presentation Time: 8:30 AM - 10:15 AM
Surface Mechanical and Tribological Properties of Silicone Hydrogels
Measured by Atomic Force Microscopy
Alexander Rudy1, Yuchen Huo1, Scott S. Perry1, Howard A. Ketelson2. 1Materials
Science and Engineering, University of Florida, Gainesville, FL; 2R & D, Alcon
Research Ltd, Fort Worth, TX.
Purpose: The surfaces of four types of silicone hydrogel (SH) contact
lenses(PureVision®, ACUVUE® Oasys®, ACUVUE® TruEye®, DAILIES®
TOTAL1®) and the pHEMA-based ACUVUE® 2 were analyzed using atomic
force microscopy (AFM) in aqueous environment. The elastic modulus, frictional,
and adhesive properties of each lens were evaluated using calibrated
instrumentations, providing a basis for comparing the distinctive surface properties
of these lenses at the top 1 μm of the surface.
Methods: All samples were prepared by soaking in buffered saline (Unisol® 4) for
24 hours to exchange out the blister pack solutions. Cantilevers modified with 5μm (diameter) silica colloidal probes were employed in the following experiments.
Elastic modulus was measured by indenting the probe into the surface of the
hydrogel in a controlled manner (i.e. approach speed and maximum applied force),
such that the maximum indentation depth was restricted to sub-micron levels. A
modulus value was obtained by fitting the characteristic force versus indentation
behavior to a mathematical model. The frictional force was measured for the
sliding contact of the probe and the surface at the length scale of 500 nm and with
applied loads up 20 nN. The friction coefficient was realized by evaluating the
linear dependence of friction force on applied normal load.
Results: The lenses examined exhibited an order of magnitude difference_from the
softest to the stiffest sample_in modulus value, generally reflective of the distinct
surface treatments they received during manufacturing. For example, the pHEMAbased ACUVUE® 2 was shown to have a modulus between 100 and 130 kPa,
whereas PureVision®‟s was an order of magnitude higher in value. The frictional
properties followed a similar trend with plasma surface treated lenses, such as
PureVision®, exhibiting coefficients of friction five times those of a non plasma
treated lens, such as DAILIES® TOTAL1®.
Conclusions: The elastic modulus and frictional properties of different lenses have
been evaluated on a nanoscopic level by AFM, depicting a strong correlation
between the surface treatments and the apparent mechanical behaviors of the
lenses.
Commercial Relationships: Alexander Rudy, Alcon Laboratories, Inc. (F);
Yuchen Huo, Alcon Laboratories, Inc. (F); Scott S. Perry, Alcon Laboratories,
Inc. (F); Howard A. Ketelson, Alcon Laboratories, Inc. (E)
Support: Alcon Laboratories, Inc.
Program Number: 6115 Poster Board Number: D936
Presentation Time: 8:30 AM - 10:15 AM
Surface Segregation of Chemical Moieties in Silicone Hydrogels
Scott S. Perry1, Clay Argenbright1, Yuchen Huo1, Howard A. Ketelson2. 1Materials
Science and Engineering, University of Florida, Gainesville, FL; 2R & D, Alcon
Research Ltd, Fort Worth, TX.
Purpose: This objective of this study was to determine the extent to which
compositional variation occurs within the near-surface region of silicone hydrogels
as a function of chemical environment. As few analytical techniques are available
for in-vivo lens characterization, it is necessary to understand the influence of
measurement environment on surface properties, as similar effects may impact the
in-eye performance of these hydrogel lenses.
Methods: X-ray photoelectron spectroscopy (XPS), a vacuum-based surface
analytical technique was used to measure the chemical composition of the nearsurface region (~10 nm) of three silicone hydrogel (SH) contact lenses (
DAILIES® TOTAL1®, ACUVUE® TruEye®, and PureVision®). Lenses were
introduced into a vacuum load lock in a fully hydrated state and then cryogenically
cooled to 100K under a 1 atm nitrogen environment. The frozen lens was then
transferred to an UHV environment while maintaining the lens temperature below
140K so as to avoid the complete desorption of the covering ice layer. The lens was
then annealed to specific temperatures to sequentially remove water from the
interface. The core level spectra of the lens elemental constituents were recorded as
a function of temperature and used to calculate relative compositions as a function
of lens dehydration.
Results: The temperature-dependent surface compositions, correlated with lens
dehydration, depict the mobility of chemical moieties within the hydrogel structure
and the migration of species to the interface as dehydration occurs. For example, a
5 atomic % increase in N was observed upon dehydration of the DALIES®
TOTAL1® lens. For the entire series, it is noted that only single digit changes are
observed over the entire range of temperatures. Variations in the extent of
compositional changes are consistent with known surface treatments of the
different lens types.
Conclusions: XPS represents a powerful probe of silicone hydrogel surface
composition. While performed in a vacuum environment, temperature-programmed
dehydration of the lens surface demonstrates that only minor changes in
composition are observed in moving from a fully hydrated to fully dehydrated state.
Commercial Relationships: Scott S. Perry, Alcon Laboratories (F); Clay
Argenbright, Alcon Laboratories (F); Yuchen Huo, Alcon Laboratories (F);
Howard A. Ketelson, Alcon Laboratories (E)
Support: Alcon Laboratories
Program Number: 6116 Poster Board Number: D937
Presentation Time: 8:30 AM - 10:15 AM
Surface Characterization of Dailies Contact Lens Material
James W. Davis, Howard A. Ketelson. R & D, Alcon Research Ltd, Fort Worth,
TX.
Purpose: This study describes the wetting and lipophilic properties of two silicone
hydrogel daily disposable contact lenses, DAILIES TOTAL1® (DT1) and
ACUVUE® TruEye® (ATE), under various experimental conditions from out of
pack, 24 hour saline soak and air/saline rinses.
Methods: Two contact angle methods were used to measure the advancing contact
angles (ACA) of the lenses. The sessile drop (SD) was used to measure the static
angle, while Captive Bubble (CB) was used to measure the static and dynamics of
re-wetting. The bulk and lens surface properties were characterized using a
lipophilic dye, Sudan IV, soak with the lenses. This was then extracted and UVVIS absorbance was measured at the maxima.
Results: SD demonstrated low ACA for both DT1 and ATE, from OOP, 3.3° ± 2°
and 2.3° ± 2° respectively. SD demonstrated low ACA for both DT1 and ATE,
from a 24hour saline soak, 3.8° ± 2° and 4.8° ± 2° respectively. SD demonstrated
significant differences in ACA for both DT1 and ATE, from 10 cycle rinse with
saline/90sec air, 32.2° ± 4° and 89.6° ± 5° respectively (p<0.05). For CB, both
lenses demonstrated low ACA for OOP and 24 hour saline soak. CB demonstrated
differences in ACA at 160sec for both DT1 and ATE from 10 cycle rinse with
saline/90sec air, 21.9° ± 3° and 30.3° ± 5° respectively (p<0.05). The lipophilic dye
amount from 16 hour exposure demonstrated a lower amount for DT1, 920ppm ±
60ppm, vs ATE, 2900ppm ± 130ppm (p<0.05).
Conclusions: We demonstrate that the new DAILIES® TOTAL1® provides
superior wetting and hydrophilic properties under various experimental and
environmental conditions. The new DAILIES® TOTAL1® material has superior
hydrophilic surface and bulk properties that can impact in-eye daily lens
performance.
Commercial Relationships: James W. Davis, Alcon Laboratories, Inc. (E);
Howard A. Ketelson, Alcon Laboratories, Inc. (F)
Support: None
Program Number: 6117 Poster Board Number: D938
Presentation Time: 8:30 AM - 10:15 AM
Evaluation of In Vitro Cytotoxicity Assays for Contact Lens Multi-Purpose
Solutions
Mercedes Salvador-Silva1A, Ling C. Huang1A, Charles H. Powell1B, Lisa Hoong1B,
Rosanne M. Yetemian1A. AR&D - Biological Sciences, BCorneal R&D, 1Abbott
Medical Optics (AMO), Santa Ana, CA.
Purpose: Previous methods assessing in vitro cytotoxicity of Contact Lens MultiPurpose Solutions (MPS) show a lack of correlation in relative responses. This
study evaluates correlations among MPS effects on cell cytotoxicity, metabolic
activity, membrane integrity, and biocompatibility.
Methods: Six MPS were used: - MPS-1: polyquaternium (PQ-1) + alexidine
(ALX), MPS-2: PQ-1 + 5 ppm myristamidopropyl dimethylamine (MAPD) +
nonanoyl-EDTA, MPS-3: PQ-1 + 5 ppm MAPD, MPS-4: PQ-1 + 6 ppm MAPD,
MPS-5: PQ-1 + polyhexamethylene biguanide (PHMB), and MPS-6: PHMB +
poloxamer 237 (PLX). Five soft contact lens types (CLs) were used in this study:
balafilcon A, senofilcon A, galyfilcon A, lotrafilcon B, and comfilcon A. In vitro
biocompatibility was assessed according to ISO 10993. MPS-treated CLs (100mL,
4 days, n=3) were placed onto confluent HCEC SV40 cells for 24hrs. Cells were
scored for reactivity according to USP Direct Contact Test criteria and quantitative
analysis. MPS were evaluated at 100%, 50%, and 25% as diluted in cultured
medium. Cytotoxicity and metabolic activity were determined using alamarBlue®
dye. Corneal epithelial barrier function was assessed by ZO-1 IHC and lens
preservative uptake-release by HPLC.
Results: Results indicate that effects of MPS on HCEC are dependent on
concentration, time of exposure, and the specific assay used. Lens preservative
uptake-release data support the observed correlation between relative in vitro
cytotoxicity of MPS and previously published clinical results. MPS-1, MPS-5, and
MPS-6 demonstrated better ocular biocompatibility than MPS-2, 3 and 4 as
measured by direct contact cytotoxicity score (0-2 vs. 2-4, respectively) and percent
cell viability (>80% vs.< 45%, respectively, n=3). MPS did not alter integrity of
corneal epithelial tight junctions under simulating in-use conditions when diluted at
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
50% with 5 minutes exposure.
Conclusions: MPS effects on in vitro cell cytotoxicity are best demonstrated by
correlation through multiple assays: cell metabolic activity, membrane integrity,
and biocompatibility. These in vitro results showed that MPS-1 (PQ-1 + ALX) is
highly compatible with all soft hydrogel lenses examined and provided evidence of
similar performance to MPS-5 (PQ-1 + PHMB) or MPS-6 (PHMB + PLX), and
better than MPS 2-4 (PQ-1 + MAPD combinations).
Commercial Relationships: Mercedes Salvador-Silva, Abbott Medical Optics
(E); Ling C. Huang, Abbott Medical Optics (E); Charles H. Powell, Abbott
Medical Optics (E); Lisa Hoong, Abbott Medical Optics (E); Rosanne M.
Yetemian, Abbott Medical Optics (E)
Support: None
Program Number: 6118 Poster Board Number: D939
Presentation Time: 8:30 AM - 10:15 AM
Cytotoxic and Inflammatory Effects of Contact Lens Multipurpose Solutions
on Human Corneal Epithelial Cells
Nir Erdinest1A, Yoni Grosman1A, Rina Harari1A, Haim Ovadia1B, Abraham
Solomon1B. AOphthalmology, BNeurology, 1Hadassah Hebrew University Medical
Center, Jerusalem, Israel.
Purpose: Clinical data show that contact lens (CL) multipurpose solutions (MPS)
may cause damage to the ocular surface. This study examined the cytotoxic and
inflammatory effects of eight commercially available CL MPS and hydrogen
peroxide lens disinfection system on cultured human corneal epithelial (HCE) cells.
Methods: HCE cells were exposed to eight different commercially available MPS
products (MPS A, ReNu MultiPlus®; MPS B, Opti Free® EverMoist; MPS C,
Solo-care Aqua®; MPS-D, Complete®; MPS-E, Unica Sensitive®; MPS-F,
Options Multi®; MPS-G, Biotrue®; MPS-H, COMPLETE® RevitaLens) at
concentrations of 30% v/v to 50% v/v for 4 to 18 hours. Cytotoxic effects were
examined with FITC-Annexin V/ PI and MTT assay. The protein contents of the
pro-inflammatory cytokines interleukin (IL)-6, IL-8, IL-1β and tumor necrosis
factor-α (TNF-α) were examined by multiplex fluorescent bead immunoassay, and
the mRNA expression of these cytokines was examined by Real time PCR.
Lipopolysaccharide (LPS) complex (LPS combined with CD14 and LPS binding
protein) and non-neutralized hydrogen peroxide lens disinfection system served as
positive controls, and phosphate-buffered saline (PBS) was added as a negative
control.
Results: Incubation of the various MPS with HCE cells showed that all of the CL
MPS examined induced higher levels of pro-inflammatory cytokines compared to
the negative control. Multiplex fluorescent bead immunoassay results demonstrated
that all five MPS, A, B, E, F and H stimulated the highest levels of proinflammatory cytokines in HCE cells. MPS H induced the highest concentrations of
pro-inflammatory cytokines production (up to 5-fold higher levels of IL-6, up to
2.5-fold higher levels of IL-8, up to 39-fold higher levels of IL-1β and up to 14-fold
higher levels of TNF-α) compared to the negative control (p<0.05). MPS E, B, A
and F elicited up to 28-fold, 25.7-fold, 25.3-fold and 22.5-fold higher levels of IL1β, respectively. Similar responses were recorded in the expression profiles of the
remaining cytokines. In contrast, no significant differences were noted in the
cytotoxic and inflammatory effects between the hydrogen peroxide lens
disinfection system and the negative control.
Conclusions: MPS induced significant cytotoxic and inflammatory effects on
cultured HCE cells compared to the negative control. In contrast, hydrogen
peroxide lens disinfection system was the least cytotoxic and did not induce any
inflammatory effect on human corneal epithelial cells. Taken together, these data
suggests that hydrogen peroxide lens disinfection system is preferable as
disinfecting and sterilizing system for CL compared to most of the commercially
available MPS.
Commercial Relationships: Nir Erdinest, None; Yoni Grosman, None; Rina
Harari, None; Haim Ovadia, None; Abraham Solomon, None
Support: This study was supported by grant no. 7803 from the Chief Scientist
Office of the Ministry of Health, Israel. Nir Erdinest is grateful to the Azrieli
Foundation for the award of an Azrieli Fellowship.
Program Number: 6119 Poster Board Number: D940
Presentation Time: 8:30 AM - 10:15 AM
The Impact of Intermittent Air Exposure on the Deposition of Lipids on
Silicone Hydrogel and Conventional Hydrogel Contact Lens Materials
Holly I. Lorentz, Miriam Heynen, Warda Khan, Diana Trieu, Lyndon Jones. Centre
for Contact Lens Research, University of Waterloo, Waterloo, ON, Canada.
Purpose: To evaluate the influence of air exposure during in vitro deposition of
two model lipids on silicone hydrogel (SH) and conventional hydrogel (CH)
contact lens materials, via a custom-designed model blink cell (MBC).
Methods: Four SH (balafilcon A “BAL”; lotrafilcon B “LOB”; comfilcon A
“COM”; senofilcon A “SEN”) and two CH (etafilcon A “ETA” and omafilcon A
“OMA”) contact lens materials were mounted on six pistons and placed in a
controlled atmosphere chamber at 35°C with a relative humidity of 18%. The
pistons were connected to a motor that cycled the contact lenses in and out of an
artificial tear solution (ATS). Lenses were cycled for 10 hours; 2 seconds in the
ATS then exposed to air for 5 seconds, which allowed the tear film to break over
the surface of the contact lens. Control lenses were kept submerged for 10 hours.
The ATS used contained lipids, proteins, mucin, salts and a trace amount of one of
the radioactive lipids; 14C-cholesterol (C) or 14C-phosphatidylcholine (PC).
Following incubation, each lens was extracted twice, evaporated under nitrogen, resuspended in chloroform and then scintillation cocktail. Extracts were counted in a
beta counter and raw data were translated into absolute amounts (ng/lens) via
extrapolation from standard curves.
Results: For the two model lipids tested, SH lens materials deposited statistically
more lipid than the CH lens materials, with BAL depositing the most lipid. Air
exposure significantly increased the amount of C that deposited on BAL, OMA,
COM, and SEN (p≤0.03). No change in deposition was seen for LOB and ETA
(p>0.05). All lenses exposed to air resulted in increased amounts of PC deposited.
These levels were statistically significantly higher (p<0.04) for LOB, SEN, COM
and OMA, but not statistically significant (p>0.05) for BAL or ETA.
Conclusions: This model has demonstrated that lipid deposition kinetics can be
impacted by air exposure and that lipid deposition profiles are contact lens
dependent. In vitro models must begin to use more physiologically relevant
incubation solutions and conditions that mimic contact lens wear within the natural
tear film if in vitro data is to be extrapolated to the in vivo situation.
Commercial Relationships: Holly I. Lorentz, Alcon (F); Miriam Heynen,
Alcon (F); Warda Khan, None; Diana Trieu, None; Lyndon Jones, Alcon (F)
Support: NSERC Canada.
Program Number: 6120 Poster Board Number: D941
Presentation Time: 8:30 AM - 10:15 AM
Clinical Performance and “ex-vivo” Dehydration of Silicone Hydrogel Contact
Lenses with Two New Multipurpose Solutions
Jose Manuel Gonzalez-Meijome, Ana Carla da Silva, Daniela Lopes-Ferreira,
Helena Neves, Antonio Queiros Pereira. Center of Physics-Optometry, University
of Minho, Braga, Portugal.
Purpose: To evaluate the potential benefits of two novel multipurpose solutions
(MPS) Complete RevitaLens® and Biotrue in preventing silicone hydrogel contact
lens dehydration and the potential impact of lower dehydration in higher subjective
comfort rates and better optical quality.
Methods: This was a prospective, double-blind, bilateral and randomized study.
Twenty-five neophytes wore Air Optix Aqua (Ciba Vision, Duluth, GA) for 1
month. They used one MPS solutions in one eye and the other MPS in the fellow
eye in a random and double-masked way. After dispensing patients were evaluated
after 2 and 10 hours of lens wear in the first day and after 2 and 10 hours of lens
wear after 30 days. Tear film analysis with Tearscope Plus (Keeler, UK) and whole
eye aberrations.
Results: Lenses dehydrated to a similar extent regardless of the solution being
used. There were no significant changes in the optical quality of the eye during the
month of duration of the study compared to baseline or between eyes using either
MPS. NIBUT data showed a drop in tear stability from baseline at the end of day 1
and day 30 with both solutions. Burning sensation at insertion was significantly
higher at 1 month visit compared to day 1 visit for Biotrue (p<0.05) while end-ofday dryness worsen similarly with both solutions after one month. However,
overall satisfaction did not change significantly over the month of lens wear despite
a drop below 8 out of 10 rating for Biotrue.
Conclusions: Both MPS solutions evaluated showed a good performance regarding
objective measures of dehydration, tear stability and subjective performance when
combined with a silicone hydrogel contact lens.
Commercial Relationships: Jose Manuel Gonzalez-Meijome, PARAGON
VISION SCIENCES (C); Ana Carla da Silva, None; Daniela Lopes-Ferreira,
None; Helena Neves, None; Antonio Queiros Pereira, None
Support: None
Program Number: 6121 Poster Board Number: D942
Presentation Time: 8:30 AM - 10:15 AM
In Vitro Dehydration of Daily Disposable and Silicone Hydrogel Contact Lens
Materials
Hendrik Walther, Lakshman Subbaraman, Lyndon W. Jones. CCLR, University of
Waterloo, ON, Canada.
Purpose: To investigate the in vitro bulk dehydration of various daily disposable
(DD) and silicone hydrogel (SiHy) contact lens materials.
Methods: Four conventional hydrogel (CH) DD (hilafilcon B, nelfilcon A,
omafilcon A, etafilcon A), four SiHy DD (delefilcon A, narafilcon A, narafilcon B,
filcon II 3) and seven SH frequent replacement (FR) (balafilcon A, lotrafilcon A,
lotrafilcon B, comfilcon A, enfilcon A, senofilcon A, galyfilcon A) contact lenses
(n=3) were removed from their blister packs and dehydration analysis was
performed gravimetrically (Sartorius MA 100H). Wet weights were measured
immediately after removing the lenses from the blister pack and dry weights were
determined after lenses were dried for 2 min, using a 600W microwave. In
addition, lens materials were continuously assessed for water loss over a 20 min
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
time period at 22°C and 34°C.
Results: There was a significant reduction in the water content (WC) over time for
all the tested lens materials (p<0.01). Overall, SiHy lenses exhibited slower rates of
dehydration than CH lenses. Among the DD lenses, delefilcon A (the DD lens with
the lowest WC) displayed the lowest dehydration (31.9±1.7% at 22°C and
29.4±0.8% at 34°C). The higher WC materials showed the highest amount and
fastest rate of dehydration (p<0.01). Among the SiHy FR materials, lotrafilcon A
showed the least amount (23.3±2.9% at 22°C) and slowest rate of dehydration,
although it was not statistically significant (p>0.05) compared with lotrafilcon B
and senofilcon A. Comfilcon A (FR SiHy with highest WC) exhibited the highest
amount (41.3±0.9% at 22°C) and fastest rate of dehydration (p>0.05). There was a
good correlation between measured and manufacturer quoted values for WC
(R2=0.99).
Conclusions: Bulk dehydration rates of contact lenses are closely related to the
initial WC of the material. Lens materials with a higher WC dehydrate more and
faster than low WC materials. Increasing the ambient temperature leads to a
reduction in the rate of dehydration for some lens materials. Further work is
required to relate these in vitro dehydration rates to dehydration rates in eye.
Commercial Relationships: Hendrik Walther, CIBA VISION Corporation (F);
Lakshman Subbaraman, CIBA VISION Corporation (F); Lyndon W. Jones,
CiBA VISION Corporation (F)
Support: CIBA VISION Corporation
Program Number: 6122 Poster Board Number: D943
Presentation Time: 8:30 AM - 10:15 AM
Differential Surface Friction Analysis of Silicone Hydrogel Contact Lenses
Treated with Block Co-Polymer Multi-Purpose Solutions
Peter Maziarz, III1, X. Michael Liu2, Charles P. Lusignan2, Mohinder M. Merchea3.
1
Research & Development, Bausch + Lomb, Brockport, NY; 2Research &
Development, Bausch + Lomb, Rochester, NY; 3Bausch & Lomb, Rochester, NY.
Purpose: To understand whether the immersion of silicone hydrogel (SiHy)
contact lenses in multipurpose solutions (MPS) using different block co-polymer
surfactants impacts lubricity, expressed as the kinetic coefficient of friction (CoF).
CoF is a system property that may be an important factor related to in-vivo
comfort. It may be influenced by the MPS used, as well as, the lens properties (e.g.
surface roughness, surface energetics, and rheology).
Methods: Two commercially available multipurpose solutions, MPS A (renu
fresh™) or MPS B (PureMoist™) and two SiHy lenses, lotrafilcon B (AirOptix
Aqua), and senofilcon A (Acuvue Oasys) were studied. SiHy contact lenses were
removed from the blisters, rinsed, and soaked in a large excess of stirred Borate
Buffered Saline (BBS) overnight to remove the packaging solution. Subsequently,
lenses were equilibrated in MPS A or MPS B for 24 hrs. CoF was characterized
with a CSM Nanoscratch Tribometer equipped with a custom-built lens holder. The
samples were oriented apex-down in 0.75ml of MPS spread over a Kapton®
substrate. CoF was measured under a 30 mN normal load at a speed of 5 mm/min.
Multiple data points (n=5), using samples of each lens, were analyzed to determine
a mean value and standard deviation.
Results: CoF was calculated as the ratio of the lateral force (pull) to the normal
force (weight) applied to move the lens relative to the Kapton® at a constant speed.
Kinetic friction (motion at constant speed) is different than static friction (incipient
motion) and we report only kinetic friction values. The mean (± 1SD) CoF of
lotratfilcon A with MPS A and MPS B respectively were 0.06 ± 0.01 and 0.05 ±
0.02. The mean (± 1SD) CoF of senofilcon A with MPS A and MPS B respectively
were 0.04 ± 0.03 and 0.03 ± 0.02. There was no statistically significant difference
in CoF between MPS A and MPS B for either lotrafilcon A (t-test, p≥0.15) or
senofilcon A (t-test, p≥0.57).
Conclusions: Although the MPS are formulated with different block copolymer
surfactants for improved wettability and lubricity, this study demonstrated that no
statistically significant difference (P>0.15) was observed in lubricity between SiHy
lenses treated in MPS A or MPS B, under the applied experimental conditions.
Further study is warranted to understand the impact of specific surfactants in MPS
formulations on in-vivo SiHy lens comfort.
Commercial Relationships: Peter Maziarz, III, Bausch + Lomb (E); X.
Michael Liu, Bausch + Lomb (E); Charles P. Lusignan, Bausch + Lomb (E);
Mohinder M. Merchea, Bausch + Lomb (E)
Support: None
Program Number: 6123 Poster Board Number: D944
Presentation Time: 8:30 AM - 10:15 AM
Differential Contact Angle and Protein/Lipid Deposition Profiles On a Novel
Daily Disposable Contact Lens Material
Mohinder M. Merchea, Patricia S. Harmon, E. P. Maziarz, X. M. Liu. Bausch +
Lomb, Rochester, NY.
Purpose: To assess the surface wettability and deposition characteristics of a novel
CL material compared to commercially available daily disposable contact lenses
using sessile drop contact angle and chromatographic techniques.
Methods: The sessile drop contact angle was measured by dispensing a 0.6µL
droplet of water onto a blotted anterior lens surface of a novel lens material,
narafilcon B (AV TruEye) and etafilcon A (AV Moist). The contact angle was
measured at two different points on each lens, resulting in four to six data points for
each type of lens in each experiment. Lenses were analyzed both directly out of the
packaging solution without rinsing, as well as after being soaked for 18 hours in an
artificial tear fluid (ATF) containing common lipids and proteins to simulate lens
wear. Quantification of lipid and protein deposits on the lenses soaked in the ATF
was performed using GC and HPLC methods.
Results: The test lens material demonstrated a more wettable surface based on a
statistically significantly lower sessile drop water contact angle than both
narafilcon B (p = 9.60 x 10-5) and etafilcon A (p = 5.88 x 10-6) directly out of the
blister. After soaking in ATF, the test lens material had a statistically significantly
lower contact angle than narafilcon B (p = 2.34 x 10-3) and etafilcon A (p = 6.25 x
10-6). The test lens material also demonstrated the lowest overall deposition level
after overnight exposure to an ATF. GC and HPLC demonstrated 13 µg/lens
combined lipids and proteins were deposited on the test lens material, which is
statistically significantly lower than the 90 µg/lens (p = 7.39 x10 -6) deposited on
narafilcon B and 33 µg/lens (p = 2.81 x10-5) deposited on etafilcon A.
Conclusions: Based on sessile drop contact angle analysis, the test lens was
statistically significantly more surface wettable than either narafilcon B or etafilcon
A. The test lens also had statistically significantly fewer combined lipid and protein
deposits after being soaked in an artificial tear fluid for 18 hours than either the
narafilcon B and etafilcon A. Lower total deposition on lenses may contribute to
lower contact angles and enhanced wettability and comfort at end of day.
Commercial Relationships: Mohinder M. Merchea, Bausch + Lomb (E);
Patricia S. Harmon, Bausch + Lomb (E); E. P. Maziarz, Bausch + Lomb (E); X.
M. Liu, Bausch + Lomb (E)
Support: None
Program Number: 6124 Poster Board Number: D945
Presentation Time: 8:30 AM - 10:15 AM
Study Of Novel Chitosan-coated Contact Lens As An Equivalent Substrate
For The Therapeutic Delivery Of Rabbit Limbal Epithelium
Xiao-Wei Tan, Donald Tan, Roger W. Beuerman, Jodhbir S. Mehta. Singaopore
Eye Research Institute, Singapore Eye Research Institute, Singapore, Singapore.
Purpose: To determine the efficiency of chitosan (CS) coated etafilcon A contact
lens, as a substrate and carrier for rabbit limbal epithelial allograft.
Methods: Chitosan was coated on contact lens surface via polydopamine
crosslinking. HCET cells were seeded on the surface of contact lens to study the
cell attachment rate. Rabbit limbal epithelial tissue explants were co-cultured with
3T3 feeder cells on the CS-coated contact lens. The cell attachment and cytokeratin
expression profile of rabbit epithelium was determined by light microscope and
immunostaining. Tissue equivalents were tracked by DII and delivered to the
surgically injured host rabbit to reconstruct the ocular surface. Cornea epithelium
recovery, grafted cell proliferation, migration and differentiation were determined
by slit-lamp examination and immunohistological analysis.
Results: CS-coated contact lens supported HCET cell attachment. Rabbit limbal
epithelial cell proliferate and differentiate on the CS-coated contact lens in a coculture system. Epithelial cells are able to form multilayer on the CS coated lens
with strong immunoreactivity to CK3, CK12 and connexin 43. Moreover, CScoated contact lens support the rapid delivery of epithelium layers onto the rabbit
cornea. Grafted cells are proliferating (P63+ Ki67+) and differentiated (CK12+
Connexin43 +).
Conclusions: We modified the biocompatible CS-coated bandage contact lens to
support the attachment, proliferation, delivery, and differentiation of rabbit limbal
epithelial cells. This technique may be useful for the efficient delivery of the human
corneal tissue equivalent to treat the patients with severe ocular surface diseases.
Commercial Relationships: Xiao-Wei Tan, None; Donald Tan, None; Roger
W. Beuerman, None; Jodhbir S. Mehta, None
Support: SHSC R834
Program Number: 6125 Poster Board Number: D946
Presentation Time: 8:30 AM - 10:15 AM
Measuring The Kinetics and Activity of Adsorbed Proteins: In Vitro
Lysozyme Deposited Onto Contact Lenses Over Short Time Periods
Brad Hall1A, Lyndon Jones1A, James A. Forrest1B. ASchool of Optometry,
B
Department of Physics ＆ Astronomy, 1University of Waterloo, Waterloo, ON,
Canada.
Purpose: To develop a process to measure the biological activity of an intact layer
of adsorbed lysozyme at the surface of hydrogel contact lens materials.
Methods: We use this technique to measure the time dependent amount and
activity of adsorbed lysozyme on a number of commercial contact lens biomaterials
during the first 2 hours of protein interaction with the material surface. The
quantity of adsorbed lysozyme is measured using standard radiolabeled protein.
The activity of the surface adsorbed protein is measured using a standard
micrococcal activity assay, with extra steps to distinguish between protein on the
surface and protein in solution. We use the measured quantities in our experiment
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2012 Annual Meeting Abstracts
to estimate a total layer activity.
Results: The amount of active protein is essentially independent of the total
protein, and is similar to what one would expect from monolayer coverage. We
calculate the amount for a theoretical monolayer of lysozyme on a contact lens to
be 692-1035ng, depending on the orientation of lysozyme, and thus can calculate a
percentage of active lysozyme in a surface layer for each lens type. The percent of
active lysozyme for senofilcon A, lotrafilcon B, and comfilcon A were 3-4, 4-5,
and 2-3 percent respectively. Balafilcon A had the highest percent activity in a
surface layer for all the silicone hydrogels tested at 30-45 percent. Etafilcon A was
the only conventional hydrogel tested and showed 78-117 percent activity in a
surface layer of lysozyme, which was the highest of all lens materials tested.
Conclusions: This study has established an effective technique to evaluate the
activity of an intact lysozyme coating on a biomaterial. Our results show that
protein can rapidly deposit and can rapidly lose its biological function on
biomaterials in as little as 10 seconds of protein-surface interaction. Despite the
simplicity of the technique, to the best of our knowledge this is the first report
quantifying the biological activity of an intact layer of surface-adsorbed protein on
hydrogel materials.
transparency, strength and potential for drug delivery.
Commercial Relationships: Marcia W. Patchan, Cellulose-Based Hydrogels
and Methods of Making Thereof (P); Jenna Graham, Cellulose-Based Hydrogels
and Methods of Making Thereof (P); Zhiyong Xia, None; Jeffrey Maranchi,
Cellulose-Based Hydrogels and Methods of Making Thereof (P); Jennifer
Elisseeff, Cellulose-Based Hydrogels and Methods of Making Thereof (P); Oliver
D. Schein, None; Morgana Trexler, Cellulose-Based Hydrogels and Methods of
Making Thereof (P)
Support: USAMRMC Grant W81XWH-09-2-0173
Commercial Relationships: Brad Hall, None; Lyndon Jones, None; James A.
Forrest, None
Support: Natural Sciences and Engineering Research Council (NSERC) of Canada
Program Number: 6126 Poster Board Number: D947
Presentation Time: 8:30 AM - 10:15 AM
Regenerated Cellulose Hydrogels with High Optical Transparency and
Mechanical Strength for Corneal Applications
Marcia W. Patchan1, Jenna Graham1,2, Zhiyong Xia1, Jeffrey Maranchi1, Jennifer
Elisseeff2,3, Oliver D. Schein3, Morgana Trexler1. 1Milton Eisenhower Research
Center, Johns Hopkins University Applied Physics Lab, Laurel, MD; 2Biomedical
Engineering, Johns Hopkins University, Baltimore, MD; 3Ophthalmology, Johns
Hopkins Wilmer Eye Inst, Baltimore, MD.
Purpose: To optimize the mechanical and optical properties of regenerated
cellulose hydrogels for corneal applications.
Methods: Cellulose hydrogels were prepared by activating two grams of cellulose
powder in 100mL N,N-dimethylacetamide (DMAc) with stirring for 24 hours, after
which 8g of LiCl was added with continued stirring and gentle heating until the
solution became clear. The resulting solution was poured into silicone molds of the
appropriate dimensions for mechanical testing or onto glass plates to obtain thin
sheets. The gelled samples were gently washed in water to remove excess
LiCl/DMAc and stored in water prior to characterization. The gels were
characterized for tensile strength, tear strength, crosslinking density, crystal
structure, optical transparency, and biocompatibility.
Results: Cellulose hydrogels were prepared from different types of cellulose
(cotton, plant, and bacteria derived). After initial characterization, the cellulose
types with the highest tensile strength and optical transparency (Figure 1) were
further characterized based on synthesis parameters (cellulose concentration,
gelation humidity, and stir time).
Conclusions: Cellulose hydrogels with optimized material properties can be
synthesized by controlling the gelation humidity and cellulose concentration. These
materials show promise for corneal applications due to their biocompatibility,
Copyright 2012 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected].