Peer-reviewed Articles

Please use the archived list on the right to look at past peer-reviewed articles.


Dalton,K., Sorbara,L. Fitting an MSD (Mini Scleral Design) rigid contact lens in advanced keratoconus with INTACS. Contact Lens and Anterior Eye 2011;34,6:274-281.

Dumbleton,K. A., Woods,C. A., Jones,L. W., Fonn,D. The relationship between compliance with lens replacement and contact lens-related problems in silicone hydrogel wearers. Contact Lens and Anterior Eye 2011;34,5:216-222. [ Show Abstract ]

To evaluate the relationship between compliance with replacement frequency (RF) and contact lens (CL)-related problems in silicone hydrogel (SiHy) wearers. Methods: 501 SiHy wearers from seven optometry offices completed surveys regarding their lens wear and any CL related problems which they may have experienced in the preceding 12 months. File review was subsequently conducted at their optometry offices to confirm the information provided. Results: 49% of respondents were wearing 2-week replacement (2WR) and 51% 1-month replacement (1MR) SiHy lenses. 67% wore their lenses for longer than the manufacturers' recommended RF (MRRF) and 60% for longer than their optometrist's recommended RF (ORRF). The mean RF was 2.6× the MRRF for 2WR and 1.5× for 1MR wearers (p< 0.001) with median values of 31 and 37 days, respectively. Twenty-three percent reported signs or symptoms consistent with potential complications relating to CL wear. This rate was significantly higher for wearers who were non-compliant with the ORRF than compliant wearers (26% versus 18%, p= 0.028). It was also higher for those multipurpose solution users who reported never/almost never rubbing and rinsing their lenses when compared with those who did this every night (29% versus 17%, p= 0.007). Conclusions: Two thirds of the SiHy wearers did not comply with the MRRF and 2WR wearers stretched the replacement interval of their lenses to a greater degree than 1MR wearers. Failing to replace lenses when recommended and failing to rub and rinse lenses were associated with a higher rate of patient-reported CL problems. © 2011 British Contact Lens Association.

Dumbleton,K. A., Woods,M., Woods,C. A., Jones,L. W., Fonn,D. Ability of patients to recall habitual contact lens products and enhancement of recall using photographic aids. Contact Lens and Anterior Eye 2011;34,5:236-240. [ Show Abstract ]

To determine the proportion of soft contact lens (CL) wearers who are able to recall their habitual products (lenses and care system) correctly from memory, and to evaluate the value of using photographic aids (PAs) to improve recall. Methods: 103 soft lens wearers attended 2 visits to investigate their habitual CL product use. At the first visit they were asked to recall which products they were using and then to identify their products from PAs. They returned for a second visit with their products for confirmation. Results: 51% correctly reported their lens brands from memory alone, which improved to 87% with the use of the PAs (p< 0.001). 41% correctly reported their habitual care system from memory alone, which improved to 80% with the use of PAs (p< 0.001). Females were better at recalling care system brand names than males (49% versus 27% correct, p= 0.040) and wearers with more than 1 year experience with their habitual CLs had better recall than those with up to 1 year experience (63% versus 27%, p= 0.014). Conclusion: Less than 50% of contact lens wearers were able to recall the names of their habitual lens and lens care products correctly from memory. PAs improved this recall significantly for both contact lenses and contact lens care systems. © 2011 British Contact Lens Association.

Efron,N., Morgan,P. B., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Soft toric contact lens prescribing in different countries. Contact Lens and Anterior Eye 2011;34,1:36-38.

Gorbet,M. B., Tanti,N. C., Crockett,B., Mansour,L., Jones,L. Effect of contact lens material on cytotoxicity potential of multipurpose solutions using human corneal epithelial cells. Molecular Vision 2011;173458-3467. [ Show Abstract ]

Purpose: Multipurpose solutions (MPS) are used daily to clean and disinfect silicone hydrogel (SiHy) contact lenses. This in vitro study was undertaken to identify the potential for interaction between MPS, SiHy surface treatments, and lens materials, which may lead to changes in the response of human corneal epithelial cells (HCEC) to MPS-soaked lenses. Methods: The MPS tested were renu fresh (formerly known as ReNu MultiPlus; ReNu), OptiFree Express (OFX), OptiFree RepleniSH, SoloCare Aqua, and Complete Moisture Plus. The SiHy materials evaluated were lotrafilcon A, lotrafilcon B, comfilcon A, galyfilcon A, and balafilcon A (BA). MPS-soaked lenses were placed on top of adherent HCEC. The effect of MPS dilutions (0.1 to 10% final concentration in medium) was also characterized. Cell viability, adhesion phenotype and caspase activation were studied after 24-h cell exposure. OFX released from lenses was determined using UV absorbance. Results: A significant reduction in viability (between 30 to 50%) was observed with cells exposed to lenses soaked in ReNu and OFX. A significant downregulation of α3 and β1 integrins, with integrin expression ranging from 60% to 75% of control (cells with no lens), was also observed with OFX and ReNu-soaked lenses. With the exception of BA, all other lenses soaked in OFX resulted in significant caspase activation, whereby over 18% of cells stained positive for caspases. Minimal caspase activation was observed in cells exposed to ReNu and Solo soaked lenses. For both OFX and ReNu, exposing cells to at least a 5% dilution had a significant effect on viability and integrin expression. While Complete and Solo did not lead to reduction in viability, cells exposed to a 10% dilution showed reduced integrin expression down to less than 70% of control value. Comparing cell response to diluted MPS solutions and various MPS-soaked lenses showed that it is not possible to reliably use cell response to MPS dilution alone to assess MPS biocompatibility. Conclusions: Our results demonstrate that the reaction of HCEC to MPS are affected by the type of lenses the MPS is released from and may potentially be influenced by the surface treatment (or lack of it) of SiHy materials. © 2011 Molecular Vision.

Heynen,M., Lorentz,H., Srinivasan,S., Jones,L. Quantification of non-polar lipid deposits on senofilcon A contact lenses. Optometry and Vision Science 2011;88,10:1172-1179.

Kao,E. C. Y., McCanna,D. J., Jones,L. W. Utilization of in vitro methods to determine the biocompatibility of intraocular lens materials. Toxicology in Vitro 2011;25,8:1906-1911.

Keir,N. J., Simpson,T., Hutchings,N., Jones,L., Fonn,D. Outcomes of wavefront-guided laser in situ keratomileusis for hyperopia. Journal of cataract and refractive surgery 2011;37,5:886-893. [ Show Abstract ]

Purpose: To determine the impact of wavefront-guided laser in situ keratomileusis (LASIK) for hyperopia on corrected distance visual acuity (CDVA), contrast sensitivity, and higher-order aberrations (HOAs). Setting: Centre for Contact Lens Research, University of Waterloo, Waterloo, Ontario, Canada. Design: Case series. Methods: This study comprised patients who had LASIK for hyperopia. The HOAs up to the 4th order (5.0 mm pupil) in right eyes were analyzed. Results: The study enrolled 31 patients. The preoperative mean values were sphere, +2.60 diopters (D) ± 1.15 (SD) (range +1.00 to +5.00 D); astigmatism, -0.87 ± 0.74 D (range 0.00 to -3.75 D); and spherical equivalent (SE), +2.16 ± 1.00 D (range +0.63 to +4.50 D). The postoperative refractive SE was within ±0.50 D in 71.0% of eyes. The uncorrected distance visual acuity was 20/20 or better in 87.2% of eyes. There was no significant change in CDVA or contrast sensitivity (all P>.05). There was a significant change in Zernike coefficients Z(0,4), Z(-1,3), Z(-3,3), and Z(3,3) (range of mean absolute change ± SEM: 0.092 ± 0.013 μm to 0.208 ± 0.018 μm; all P<.001). Coefficients Z(-1,3) and Z(3,3) increased and Z(0,4) and Z(-3,3) decreased in magnitude; each had a reversal of sign. The only significant postoperative association was between low-contrast CDVA and Z(0,4) (r = 0.617, P<.001). Conclusions: Low-contrast CDVA after LASIK surgery for hyperopia was correlated with Z(0,4). There were no significant changes in CDVA or contrast sensitivity. The relative risk for losing low-contrast CDVA increased if more than 1 Zernike term had a sign change. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2011 ASCRS and ESCRS.

Lorentz,H., Heynen,M., Kay,L. M. M., Dominici,C. Y., Khan,W., Ng,W. W. S., Jones,L. Contact lens physical properties and lipid deposition in a novel characterized artificial tear solution. Molecular Vision 2011;173392-3405. [ Show Abstract ]

Purpose: To characterize various properties of a physiologically-relevant artificial tear solution (ATS) containing a range of tear film components within a complex salt solution, and to measure contact lens parameters and lipid deposition of a variety of contact lens materials after incubation in this ATS. Methods: A complex ATS was developed that contains a range of salts, proteins, lipids, mucin, and other tear film constituents in tear-film relevant concentrations. This ATS was tested to confirm that its pH, osmolality, surface tension, and homogeneity are similar to human tears and remain so throughout the material incubation process, for up to 4 weeks. To confirm that silicone hydrogel and conventional hydrogel contact lens materials do not alter in physical characteristics beyond what is allowed by the International Organization for Standardization (ISO) 18369-2. The diameter, center thickness, and calculated base curve were measured for five different lens materials directly out of the blister pack, after a rinse in saline and then following a two week incubation in the modified ATS. To test the ATS and the effect of its composition on lipid deposition, two lens materials were incubated in the ATS and a modified version for several time points. Both ATS solutions contained trace amounts of carbon-14 cholesterol and phosphatidylcholine, such that deposition of these specific lipids could be quantified using standard methods. Results: This ATS is a complex mixture that remains stable at physiologically relevant pH (7.3-7.6), osmolality (304- 306 mmol/kg), surface tension (40-46 dynes/cm) and homogeneity over an incubation period of three weeks or more. The physical parameters of the lenses tested showed no changes beyond that allowed by the ISO guidelines. Incubations with the ATS found that balafilcon A lenses deposit significantly more cholesterol and phosphatidylcholine than omafilcon A lenses (p<0.05) and that removing lactoferrin and immunoglobulin G from the ATS can significantly decrease the mass of lipid deposited. Conclusions: This paper describes a novel complex artificial tear solution specially designed for in-vial incubation of contact lens materials. This solution was stable and did not adversely affect the physical parameters of the soft contact lenses incubated within it and showed that lipid deposition was responsive to changes in ATS composition. © 2011 Molecular Vision.

Maram,J., Sorbara,L., Simpson,T. Accuracy of Visante and Zeiss-Humphrey Optical Coherence Tomographers and their cross calibration with optical pachymetry and physical references. Journal of Optometry 2011;4,4:147-155.

Menzies,K. L., Jones,L. In vitro analysis of the physical properties of contact lens blister pack solutions. Optometry and Vision Science 2011;88,4:493-501. [ Show Abstract ]

Purpose. Since the initial development of silicone hydrogels, many modifications to the bulk and surface properties of the lenses have been undertaken to improve the wettability and comfort of the lenses. Recently, manufacturers have incorporated various "wetting agents" or surface-active agents into the blister packaging solutions (BPSs) of the lenses to improve initial comfort of the lens on eye. The purpose of this study was to measure and compare the pH, surface tension (ST), viscosity, and osmolality of BPSs for a variety of silicone hydrogel and polyHEMA-based hydrogel lenses. In addition, two saline solutions were tested for comparison purposes. Methods. The pH, osmolality, ST, and viscosity were measured for the BPSs for lotrafilcon B and lotrafilcon A and lotrafilcon B with a "modified BPS" (m-lotrafilcon A, m-lotrafilcon B) (CIBA Vision, Duluth, GA); balafilcon A (Bausch & Lomb, Rochester, NY); galyfilcon A, senofilcon A, and narafilcon A (Johnson & Johnson, Jacksonville, FL); and comfilcon A and enfilcon A (CooperVision, Pleasanton, CA) and BPSs from two conventional polyHEMA-based materials-etafilcon A (Johnson & Johnson) and omafilcon A (CooperVision). The two saline solutions tested were Unisol (Alcon, Fort Worth, TX) and Softwear Saline (CIBA Vision). Results. The pH results for the two saline solutions and all BPSs remained in the pH range of tears (6.6-7.8). The ST of the modified BPS was significantly lower (p 0.05) between BPSs made by the same manufacturer but were significantly different compared with BPSs made by different manufacturers (p < 0.05). Conclusions. The incorporation of wetting agents and surfactants into BPSs does alter the physical properties of the BPSs, which may have clinical implications regarding initial in-eye comfort. Copyright © 2011 American Academy of Optometry.

Moezzi,A. M., Fonn,D., Varikooty,J., Richter,D. Distribution of overnight corneal swelling across subjects with 4 different silicone hydrogel lenses. Eye and Contact Lens 2011;37,2:61-65. [ Show Abstract ]

Purpose: To determine distribution of central corneal swelling (CCS) across subjects after 8 hr of sleep in eyes wearing silicone hydrogel lenses with various oxygen transmissibility (Dk/t) values and in eyes without lenses. Methods: Twenty-nine neophytes wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60), and senofilcon A (Dk, 103) lenses in powers -3.00, -10.00, and +6.00 diopters on separate nights, in random order, and on 1 eye only. The contralateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. Results: The average difference between the mean (7%) and the median (6.8%) CCS of all lenses was only 0.2%, suggesting a normal distribution. There was no correlation between the mean and the range of the CCS (r=0.058, P=0.766). Normal CCS distributions were also found with each lens-wearing eye and the control eye (P>0.20 for all). There was a significant correlation between lens-wearing eye and control eye (r=0.895, P<0.001) and between lotrafilcon A and each of the other 3 lenses for mean CCS across the study participants (P<0.001 for all). Conclusions: Distribution of corneal swelling in both lens-wearing eye and control eye followed a normal curve. An individual's corneal swelling response seems to be independent of lens type. © 2011 Lippincott Williams & Wilkins.

Morgan,P. B., Efron,N., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Global trends in prescribing contact lenses for extended wear. Contact Lens and Anterior Eye 2011;34,1:32-35.

Schulze,M. M., Hutchings,N., Simpson,T. L. Grading bulbar redness using cross-calibrated clinical grading scales. Investigative Ophthalmology and Visual Science 2011;52,8:5812-5817. [ Show Abstract ]

Purpose. To determine the between-scale agreement of grading estimates obtained with cross-calibrated McMonnies/Chapman- Davies (MC-D), Institute for Eye Research (IER), Efron, and Validated Bulbar Redness (VBR) grading scales. Methods. Modified reference images of each grading scale were positioned on a desk according to their perceived redness (within a 0 to 100 range) as determined in a previous psychophysical scaling experiment. Ten observers were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Only 0 and 100 were marked on the scale, but not the numerical position of the reference images. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. Results. Overall, perceived redness depended on the sample image and the reference scale used (repeated measures ANOVA; P = 0.0008); six sample images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability ranged from five units (IER vs. VBR) to eight units (IER vs. Efron) of the 0 to 100 range. Conclusions. The use of cross-calibrated reference grades for bulbar redness grading scales allows comparison of grading estimates obtained with different scales. Perceived redness is dependent on the dynamic range of the reference images of the scale, with redness estimates generally being found to be higher for scales with a shorter dynamic range. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Sorbara,L., Maram,J., Bizheva,K., Hutchings,N., Simpson,T. L. Case report: Chalazion and its features visualized by ultrahigh resolution optical coherence tomography. Contact Lens and Anterior Eye 2011;34,2:87-91.

Subbaraman,L. N., Borazjani,R., Zhu,H., Zhao,Z., Jones,L., Willcox,M. D. P. Influence of protein deposition on bacterial adhesion to contact lenses. Optometry and Vision Science 2011;88,8:959-966. [ Show Abstract ]

Purpose. The aim of the study is to determine the adhesion of Gram positive and Gram negative bacteria onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials with and without lysozyme, lactoferrin, and albumin coating. Methods. Four lens types (three SH-balafilcon A, lotrafilcon B, and senofilcon A; one CH-etafilcon A) were coated with lysozyme, lactoferrin, or albumin (uncoated lenses acted as controls) and then incubated in Staphylococcus aureus (Saur 31) or either of two strains of Pseudomonas aeruginosa (Paer 6294 and 6206) for 24 h at 37°C. The total counts of the adhered bacteria were determined using the H-thymidine method and viable counts by counting the number of colony-forming units on agar media. Results. All three strains adhered significantly lower to uncoated etafilcon A lenses compared with uncoated SH lenses (p 0.05). Lactoferrin coating on lenses increased binding (total and viable counts) of Saur 31 (p < 0.05). Lactoferrin-coated lenses showed significantly higher total counts (p < 0.05) but significantly lower viable counts (p < 0.05) of adhered P. aeruginosa strains. There was a significant difference between the total and viable counts (p < 0.05) that were bound to lactoferrin-coated lenses. Albumin coating of lenses increased binding (total and viable counts) of all three strains (p < 0.05). Conclusions. Lysozyme deposited on contact lenses does not possess antibacterial activity against certain bacterial strains, whereas lactoferrin possess an antibacterial effect against strains of P. aeruginosa. © 2011 American Academy of Optometry.

Szczotka-Flynn,L., Benetz,B. A., Lass,J., Albright,M., Gillespie,B., Kuo,J., Fonn,D., Sethi,A., Rimm,A. The association between mucin balls and corneal infiltrative events during extended contact lens wear. Cornea 2011;30,5:535-542. [ Show Abstract ]

PURPOSE:: To determine the association between mucin ball formation and corneal infiltrative events (CIEs) during continuous wear with lotrafilcon A silicone hydrogel contact lenses. METHODS:: Subjects (n = 205) in the Longitudinal Analysis of Silicone Hydrogel Contact Lens Study wore lotrafilcon A contact lenses for 12 months of continuous wear. The primary outcome was a CIE. Kaplan-Meier methods were used to estimate the unadjusted cumulative incidence of remaining CIE free stratified by mucin ball presence. Cox proportional hazards regression was used to model the hazard of developing a CIE as a function of mucin ball formation and other covariates. RESULTS:: Over half (54.2%) of the subjects displayed some presence of mucin balls during at least 1 visit and about one third (32.8%) displayed repeated episodes. Mucin ball scores were correlated between the 2 eyes and weakly correlated with corneal curvature (P ≤ 0.005). Univariate analyses revealed that the relative hazard for a CIE was 0.35 [95% confidence interval (CI), 0.19-0.68] if a single episode of mucin balls was detected and 0.17 (95% CI, 0.06-0.43) if repeated episodes were detected. Upon multivariate analysis, repeated presence of mucin balls was associated with an 84% decreased hazard of experiencing a CIE (hazard ratio: 0.16; 95% CI, 0.06-0.44). CONCLUSIONS:: The presence of mucin balls is significantly associated with a decreased incidence of CIEs, and the effect is greatest when they are repeatedly present over time. We hypothesize that the mucin ball presence represents a more concentrated or viscous mucus layer, which prevents upregulation of the immune response against bacterial ligands. Copyright © 2011 by Lippincott Williams & Wilkins.

Tanti,N. C., Jones,L., Gorbet,M. B. Impact of multipurpose solutions released from contact lenses on corneal cells. Optometry and Vision Science 2011;88,4:483-492. [ Show Abstract ]

Purpose. To assess, in vitro, the effect of the release of contact lens multipurpose solutions (MPS) from two silicone hydrogel lenses on human corneal epithelial cells. Methods. A monolayer of immortalized human corneal epithelial cells was seeded in a 24-well plate in keratinocyte serum-free medium. Lotrafilcon A (LA) and balafilcon A (BA) lenses were placed on top of the adherent cells for 8 and 24 h, after being soaked in MPS, borate-buffered (Unisol) or phosphate-buffered saline overnight. Cells were assayed for viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay or for α3, β1, and β4 integrin expression and caspase activation by flow cytometry. Results. After 8 h, LA lenses soaked in Unisol, Opti-Free Express (OFX), and ReNu MultiPlus (ReNu) showed decrease in cell viability. LA and BA soaked in Complete Moisture Plus (Complete) had similar viability at around 85% of control. After 24 h, a further decrease in viability was observed with all MPS-soaked lenses; LA soaked in OFX significantly reduced viability compared with Unisol-soaked lenses. In addition, reduced levels of integrin expression for lenses soaked in OFX and ReNu, and for BA soaked in Complete were observed. At 24 h, only LA soaked in OFX led to an increase in caspase activation. Conclusions. Our results indicate an increase in cytotoxicity with borate-based MPS solutions in vitro when compared with both phosphate-buffered saline and borate-exposed lenses, suggesting that biocides and/or additives play a role in the observed cell reaction. Moreover, the mechanism of in vitro solution-induced toxicity appeared to be mediated by lens type, suggesting differences in the preferential adsorption/release profile of certain compounds. Copyright © 2011 American Academy of Optometry.

Weeks,A., Luensmann,D.,Boone,A, Jones,L., Sheardown,H. Hyaluronic acid as an internal wetting agent in model DMAA/TRIS contact lenses. 2011001-10. [ Show Abstract ]

Model silicone hydrogel contact lenses, comprised of N,N-dimethylacrylamide and methacryloxypropyltris (trimethylsiloxy) silane, were fabricated and hyaluronic acid (HA) was incorporated as an internal wetting agent using a dendrimer-based method. HA and dendrimers were loaded into the silicone hydrogels and cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. The presence and location of HA in the hydrogels was confirmed using X-ray photoelectron spectroscopy and confocal laser scanning microscopy, respectively. The effects of the presence of HA on the silicone hydrogels on hydrophilicity, swelling behavior, transparency, and lysozyme sorption and denaturation were evaluated. The results showed that HA increased the hydrophilicity and the equilibrium water content of the hydrogels without affecting transparency. HA also significantly decreased the amount of lysozyme sorption (p < 0.002). HA had no effect on lysozyme denaturation in hydrogels containing 0% and 1.7% methacrylic acid (MAA) (by weight) but when the amount of MAA was increased to 5%, the level of lysozyme denaturation was significantly lower compared to control materials. These results suggest that HA has great potential to be used as a wetting agent in silicone hydrogel contact lenses to improve wettability and to decrease lysozyme sorption and denaturation.

Woods,C. A., Dumbleton,K., Jones,L., Fonn,D. Patient use of smartphones to communicate subjective data in clinical trials. Optometry and Vision Science 2011;88,2:290-294. [ Show Abstract ]

Purpose. Various methods have been used in clinical trials to collect time-sensitive subjective responses, including study diaries, telephone interviews, and use of text messaging. However, all of these methods are limited by the uncertainty of when the participants enrolled in the study actually record their responses. This technical note reports on the utility of the BlackBerry smartphone to collect such data and why such a system provides advantages over other methods to report subjective ratings in clinical studies. Methods. The Centre for Contact Lens Research developed an on-line web-enabled system that permits participants to record and immediately transmit subjective rating scores in numerical form directly into a web-enabled database. This, combined with the utility of BlackBerrys, enabled time-specific e-mail requests to be sent to the study participants and then for that data to be simultaneously transmitted to the web-enabled database. This system has been used in several clinical trials conducted at the Centre for Contact Lens Research, in which data were collected at various times and in several specific locations or environments. Results. In the clinical trials conducted using this system, participants provided responses on 97.5% of occasions to the requests for data generated by the automated system. When the request was for data on a set date, this method resulted in responses of 84.1% of the time. Conclusions.The series of clinical trials reported here show the benefits of the utilization of the BlackBerry to collect time- or environment-sensitive data via a web-enabled system. Copyright © 2011 American Academy of Optometry.

Youn,H. -Y, McCanna,D. J., Sivak,J. G., Jones,L. W. In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells. Molecular Vision 2011;17237-246.