Peer-reviewed Articles

Please use the year list below to look at past peer-reviewed articles.

2018

Blackie,C. A., Coleman,C. A., Nichols,K. K., Jones,L., Chen,P. Q., Melton,R., Kading,D. L., O’Dell,L. E., Srinivasan,S. Asingle vectored thermal pulsation treatment for meibomian gland dysfunction increases mean comfortable contact lens wearing time by approximately 4 hours per day Clinical Ophthalmology 2018;12169-183 [ Show Abstract ]

Purpose: To evaluate the effect of a single vectored thermal pulsation (VTP) treatment in contact lens wearers with meibomian gland dysfunction (MGD) and dry eye symptoms. Methods: The prospective, nonsignificant risk, open-label, randomized, multi-center clinical trial included 55 soft contact lens (SCL) wearers with MGD and evaporative dry eye. Subjects were randomized to the single VTP treatment group or an untreated control. The controls received a crossover VTP treatment at 3 months (crossover treatment group). Primary effectiveness measures were meibomian gland secretion (MGS) score and Standard Patient Evaluation of Eye Dryness (SPEED) that were evaluated at baseline, at 1 and 3 months post-VTP treatment, and at 1 month post-VTP treatment in the crossover treatment group. Exploratory variables included fluorescein tear break-up time (TBUT), lid wiper epitheliopathy (LWE), lid parallel conjunctival folds (LIPCOF), ocular surface staining, frequency of over-the-counter (OTC) drop use, and hours of comfortable contact lens wear. Results: At 3 months, the treatment group showed significantly greater mean change from baseline in MGS (12.4±9.1 vs 1.4±6.4, p˂0.0001), SPEED (−8.4±4.7 vs −0.7±4.4, p˂0.0001) and significantly greater improvement in exploratory variables (TBUT, LWE, and frequency of OTC drop use) relative to the controls. Mean comfortable contact lens wearing time increased by 4.0±3.9 hours at 1 month. This was sustained for 3 months with no change in the control group. The crossover treatment group demonstrated similar results to the treatment group at 1 month post-VTP. Conclusion: In SCL wearers with MGD, a single VTP treatment significantly improved mean meibomian gland function and significantly reduced dry eye signs and symptoms compared to an untreated control. The treatment increased mean comfortable lens wearing time by 4 hours (approximately doubling the pretreatment findings). This was sustained for up to 3 months post-treatment on average. © 2018 Blackie et al.

Delaveris,A., Stahl,U., Madigan,M., Jalbert,I. Comparative performance of lissamine green stains Contact Lens and Anterior Eye 2018;41(1):23-27 [ Show Abstract ]

Purpose To investigate the performance of lissamine green strips from different manufacturers. Additionally, the repeatability, need for sequential dye instillation and impact of repeated lid evertion on lid wiper staining were assessed. Methods Study 1 was a prospective, randomised cross-over study where controlled volumes of lissamine green solution prepared from strips (Biotech, Lissaver, GreenGlo, OPGreen) were instilled (right eye: single; left eye: double instillation) on five different days, with OPGreen being tested twice. Lids were everted and digital photographs taken, which were later assessed by a masked observer. Study 2 was an investigator-masked, randomised, controlled study testing the impact of single versus repeated lid evertion. Lid wiper staining was graded (0 to 3 in 0.5 steps). Results Lid wiper staining differed significantly between lissamine green solutions, with GreenGlo showing the highest amount of staining, and Lissaver the least (all p > 0.009). There were no differences in lid wiper staining over two days, using the OPGreen solution (all p > 0.05). The number of drops instilled (single versus double) did not significantly affect lid wiper staining (all p > 0.05). Repeated lid evertion increased lid wiper staining (p = 0.007 when combined with double drop instillation). Light absorbance patterns and measured concentrations aligned with clinical findings. Conclusion There were significant differences in performance between lissamine green solutions. Lid wiper staining was impacted by repeated lid evertion but sequential instillation and use of the Korb grading scale provided little advantage over simpler methods Clinicians must consider this when investigating lid wipers, especially when interpreting a negative finding. © 2017 British Contact Lens Association

McCanna,D. J., Oh,S., Seo,J., Coles-Brennan,C., Fadli,Z., Subbaraman,L. N., Jones,L. W. The effect of denatured lysozyme on human corneal epithelial cells Investigative Ophthalmology and Visual Science 2018;59(5):2006-2014 [ Show Abstract ]

PURPOSE. During contact lens wear, the amount of lysozyme deposited on contact lenses varies depending on the lens material. The binding of lysozyme to some contact lens materials may result in a conformational change that denatures the protein to an inactive form. This investigation evaluated the effect that denatured lysozyme has on human corneal epithelial cells (HCECs) by measuring cell viability and the release of inflammatory cytokines. METHODS. HCECs were exposed to lysozyme that was denatured to various activity levels. After 24-hour exposure to the lysozyme (1.9 mg/mL) in growth media, the cells were evaluated for cell viability using confocal microscopy. The metabolic activity of the cells was determined using an alamarBlue assay. Cell supernatants were analyzed for inflammatory cytokines. RESULTS. Using confocal microscopy, there was no detectable change in the viability of the HCECs after exposure to the denatured lysozyme. However, using alamarBlue, a decrease in the metabolic activity of the HCECs exposed to denatured lysozyme was detected. HCECs exposed to lysozyme that was 67%, 47%, and 22% active showed a reduction in metabolic activity when compared with native (100% active) lysozyme and the media controls (P < 0.05). Exposure to the denatured lysozyme also caused an increase in the release of inflammatory cytokines (P < 0.05) from the HCECs. CONCLUSIONS. The results of this study show that denatured lysozyme can have a detrimental effect on HCECs. Both a reduction in metabolic activity and an increase in the release of inflammatory cytokines occurred after HCEC exposure to denatured lysozyme. © 2018 The Authors.

Ng,A., Keech,A., Jones,L. Tear osmolarity changes after use of hydroxypropyl-guar-based lubricating eye drops Clinical Ophthalmology 2018;12695-700 [ Show Abstract ]

Purpose: To evaluate tear osmolarity after using a hydroxypropyl-guar (HP-guar)-based lubricating eye drop four times daily (QID) for 3 weeks. Methods: Thirty-one participants with dry eye disease (Ocular Surface Disease Index [OSDI] score ≥20 and tear osmolarity ≥300 mOsm/L in at least one eye) were enrolled in this prospective, dispensing, non-randomized study involving a baseline visit and 3‑week follow-up. Tear osmolarity, non-invasive tear break up time (NITBUT), conjunctival hyperemia, corneal and conjunctival staining were determined at baseline. Participants were instructed to instill one drop of a HP-guar-based drop QID in each eye for 3 weeks. At the follow-up visit, the symptoms and ocular surface parameters were reassessed. At this visit, one HP-guar drop was instilled into each eye and osmolarity was measured after 15 minutes, to examine short-term changes in osmolarity. Results: Twenty-eight participants completed the study (5M, 23F; median age 54 yrs, range 25-83 yrs). At baseline, mean OSDI score was 44.9±15.2 and mean osmolarities were 314.63±11.9/306.6±10.1 mOsm/L (worst eye [WE]/better eye [BE]). After 3 weeks, mean osmolarity reduced to 307.7±15.7/303.9±11.3 mOsm/L (WE/BE; p<0.05 and p=0.228, respectively) and mean OSDI scores reduced to 28.3±17.0 (p<0.01). A significant reduction in osmolarity was observed 15 minutes after instilling the lubricating drop (p<0.05 WE, p=0.09 BE). Significant improvements in central corneal staining (p<0.05 OU) and NITBUT (p<0.05 WE only) were observed. Reductions in conjunctival staining and hyperemia were observed, but were not significant (p>0.05). Conclusions: A significant reduction in tear osmolarity and improvements in dry eye symptoms, corneal staining, and NITBUT were observed after 3 weeks of QID use of a HP-guar-based lubricant drop. A decrease in osmolarity was also demonstrated 15 minutes after drop instillation.

Oh,S., McCanna,D., Subbaraman,L.N., Jones,L. Cytotoxic and inflammatory effects of contact lens solutions on human corneal epithelial cells in vitro Contact Lens and Anterior Eye 2018;41(3):282-289 [ Show Abstract ]

Purpose: To ascertain the effect that four contact lens (CL) multipurpose solutions (MPS) have on the viability and release of pro-inflammatory cytokines from human corneal epithelial cells (HCEC). Methods: HCEC were exposed to four different MPS at various concentrations for 18 hours. The cells were also exposed to phosphate buffer, borate buffer, and PHMB. The cell viability was evaluated using the alamarBlue assay. The release of pro-inflammatory cytokines was measured using a Multiplex electrochemiluminescent assay. Results: MPS-A, MPS-B and MPS-C all reduced cell metabolic activity p < 0.05 from control with MPS-A showing the greatest cytotoxic effect (maximum reduction, 90.6%). In contrast, MPS-D showed no significant reductions in cytotoxicity except at the highest concentration tested (19% reduction at 20% MPS concentration). Of the four cytokines evaluated MPS-C showed a substantial increase in the release of IL-1β, IL-6, IL-8, and TNF-α at higher concentrations when compared to control p < 0.05. At the 20% concentration of MPS-A and MPS-B the release of IL-1 β increased p < 0.05 but the release of IL-6, IL-8, and TNF-α decreased. MPS-D did not cause a change in the release of cytokines IL-1β, IL-6, IL-8 and TNF-α p > 0.05. Exposing the cells to borate buffer and PHMB caused an increase in the release of TNF-α p < 0.05. Conclusions: This investigation demonstrates that at different concentration levels, several of the MPS tested showed a decrease in viability and an increase in the release of inflammatory cytokines from HCEC. The borate buffer component as well as PHMB appears to contribute to this pro-inflammatory reaction.

Omali,N.B., Subbaraman,L.N., Heynen,M., Ng,A., Coles-Brennan,C., Fadli,Z., Jones,L. Surface versus bulk activity of lysozyme deposited on hydrogel contact lens materials in vitro Contact Lens and Anterior Eye 2018;41(4):329-334 [ Show Abstract ]

Purpose: To determine and compare the levels of surface versus bulk active lysozyme deposited on several commercially available hydrogel contact lens materials. Methods: Hydrogel contact lens materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon and etafilcon A with polyvinylpyrrolidone (PVP)] were incubated in an artificial tear solution for 16 h. Total activity was determined using a standard turbidity assay. The surface activity of the deposited lysozyme was determined using a modified turbidity assay. The amount of active lysozyme present within the bulk of the lens material was calculated by determining the difference between the total and surface active lysozyme. Results: The etafilcon A materials showed the highest amount of total lysozyme activity (519 ± 8 μg/lens, average of Moist and Define), followed by the ocufilcon material (200 ± 5 μg/lens) and these two were significantly different from each other (p < 0.05). The amount of surface active lysozyme on etafilcon and ocufilcon lens materials was significantly higher than that found on all other lenses (p < 0.05). There was no active lysozyme quantified in the bulk of the nelfilcon material, as all of the active lysozyme was found on the surface (1.7 ± 0.3 μg/lens). In contrast, no active lysozyme was quantified on the surface of polymacon, with all of the active lysozyme found in the bulk of the lens material (0.6 ± 0.6 μg/lens). Conclusions: The surface and bulk activity of lysozyme deposited on contact lenses is material dependent. Lysozyme deposited on ionic, high water content lens materials such as etafilcon A show significantly higher surface and bulk activity than many other hydrogel lens materials.

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

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

Stahl,U., Jalbert,I. Exploring the links between contact lens comfort, osmolarity and lid wiper staining Contact Lens and Anterior Eye 2018;41(1):110-116 [ Show Abstract ]

Purpose Contact lens discomfort remains poorly understood, not least due to lack of associations between clinical signs and symptoms. This study aimed to explore the relationships between osmolarity, comfort and lid wiper epitheliopathy in contact lens wear. Methods Twenty subjects participated in a randomized, cross-over study where comfilcon A and lotrafilcon A lenses were each worn for 10 days separated by a 7 days washout period. Tear and contact lens osmolarity, ocular symptoms including comfort, tear stability and production, and lid wiper epitheliopathy were measured. Results Comfort and tear stability decreased and upper lid wiper staining and foreign body sensation increased with lens wear. These were not affected by lens type. A reduction in tear production was seen after 10 days of comfilcon A lens wear. High proportions of lid wiper epitheliopathy were observed at the upper (range 65%–85%) and lower (range 90%–100%) lid margins. Tear and contact lens osmolarity were unaffected by lens wear or type. Contact lens osmolarity was associated with comfort (r = 0.45, p = 0.009). Tear osmolarity moderately correlated with tear stability (r = -0.53, p = 0.014) and tear production (r = -0.44, p = 0.012) but not with lid wiper staining. Conclusions A relationship between comfort and contact lens osmolarity and between tear osmolarity and tear stability and production were found, however, this study was unable to demonstrate an association between comfort and tear osmolarity or lid wiper epitheliopathy. Further studies using contact lenses with a wider range of comfort responses are warranted to investigate these associations further. © 2017 British Contact Lens Association

Wallerstein,A., Jackson,W.B., Chambers,J., Moezzi,A., Lin,H., Simmons,P.A Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose Clinical Ophthalmology 2018;12839-848 [ Show Abstract ]

Purpose: To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK).
Methods: This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer’s test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled.
Results: A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer’s test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated.
Conclusion: CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK.

Wong,S., Murphy,P.J., Jones,L. Tear evaporation rates: What does the literature tell us? Contact Lens and Anterior Eye 2018;41(3):297-306 [ Show Abstract ]

Purpose: A previous literature review reported tear evaporation rates (TERs) from studies conducted on rabbits and humans between 1941 and 2003. Closer examination of the presented data revealed inaccuracies in the reporting of some values. This paper presents updated tables of TERs using values from the original papers cited in the review, in addition to incorporating new studies published between 2003 and 2016. Methods: A copy of each paper cited in the literature review was obtained and checked against the evaporation rate reported in the review. If the expected value could not be found in the cited paper, other papers by the same author were consulted to see if the value had been reported elsewhere. A PubMed and Scopus database search was conducted to find papers published on tear evaporimetry since 2003. Results: Two new tables of TERs were created, based on the values reported by the original author. To aid in interpretation, the majority of results are expressed in units of x 10−7 g/cm2/sec. Where it was not possible to convert these values, some values are expressed as x 10−7 g/sec, x 10−7 g/sec/eye or W/min. Conclusions: Two new tables of TERs have been compiled to provide an accurate representation of the values reported in the original papers. These tables can be used as a point of reference for other researchers to compare their results.

Yang,M., Luensmann,D., Fonn,D., Woods,J., Jones,D., Gordon,K., Jones,L. Myopia prevalence in Canadian school children: A pilot study Eye 2018;32(6):1042-1047 [ Show Abstract ]

Purpose: A pilot study to determine the prevalence of myopia, proportion of uncorrected myopia and pertinent environmental factors among children in a suburban region in Canada. Methods: Refraction with cycloplegia and ocular biometry were measured in children of two age groups. Myopia was considered at a spherical equivalent refraction (SER) ≤-0.50 D in at least one eye. Parents completed a questionnaire that captured the child's daily activities. Results: A total of 166 children completed the study (83 aged 6-8 and 83 aged 11-13). Myopia prevalence was 17.5% among the overall group, 6.0% among ages 6-8 and 28.9% among ages 11-13. Mean subjective SER in myopic children was -1.10 D (95% confidence interval (CI), -0.34 to -1.86 D) at ages 6-8 and -2.44 D (95% CI, -1.71 to -3.18 D) at ages 11-13. In this study, 34.5% of the myopic children were uncorrected, which represented 6.0% of the entire group of children. Mean axial length (AL) increased by 1.03 mm from ages 6-8 (mean 22.62 mm; 95% CI, 22.45 to 22.79 mm) to ages 11-13 (mean 23.65 mm; 95% CI, 23.45 to 23.84 mm; p < 0.01). The correlation coefficient between AL and SER was -0.618 (p < 0.01). Binary logistic regression between outdoor time and the prevalence of myopia showed that one additional hour of outdoor time per week lowered the odds of a child having myopia by 14.3% (p = 0.007). Conclusion: Myopia prevalence increased from 6% at ages 6-8 to 29% at ages 11-13. Thirty-five per cent of the myopes in this study were uncorrected. More time outdoors may be beneficial to protect against myopia onset.