Mohammadi,S., Jones,L., Gorbet,M. Extended latanoprost release from commercial contact lenses: In vitro studies using corneal models PLOS ONE 2014;9(9):e106653 [ Show Abstract ]

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6  of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitrocorneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

Mohseni,M., Shokrollahi,P., Barzin, J. Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release International Journal of Biological Macromolecules 2024;263, Part 1(April):Art No 130266 [ Show Abstract ]

Recently, a significantly greater clinical benefit has been reported with a combination of glucosamine sulfate and nonsteroidal anti-inflammatory drugs (NSAIDs) compared to either treatment alone for the growing osteoarthritis (OA) disease. So, this study introduces hydrogels using O-carboxymethyl chitosan (O-CMC, structurally akin glucosamine glycan), and Gelatin type A (GA) in a 1:2 ratio with β-glycerophosphate (βGPh) at varying percentages (5 %, 12.5 %, and 15 %). We show that hydrogel properties, adaptable for drug delivery or tissue engineering, can be fine-tuned based on OCMC:βGPh ratio. CMC/GA/βGPh-12.5 exhibited a swelling rate of 189 %, compressive stress of 164 kPa, and compressive modulus of 3.4 kPa. The self-healing hydrogel also exhibited excellent injectability through a 21-gauge needle, requiring only 5 N of force. Ibuprofen and Naproxen release from CMC/GA/βGPh-12.5 and CMC/GA/βGPh-15 of designed dimensions (bi-layer structures of different diameter and height) were measured, and drug release kinetics were estimated using mathematical equations (MATLAB and polyfit program). CMC/GA/βGPh-12.5 demonstrated significant antibacterial effects against E. coli and S. aureus, a high cell survival rate of 89 % against L929 fibroblasts, and strong cell adhesion, all indicating biocompatibility. These findings underscore potential of these hydrogels as promising candidates for treating inflammatory diseases such as osteoarthritis.

Morgan,P. B., Efron,N., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Twenty first century trends in silicone hydrogel contact lens fitting: An international perspective Contact Lens and Anterior Eye 2010;33(4):196-198

Morgan,P. B., Efron,N., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Demographics of international contact lens prescribing Contact Lens and Anterior Eye 2010;33(1):27-29

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

Morgan,P. B., Murphy,P. J., Gifford,K. L., Gifford,P., Golebiowski,B., Johnson,L., Makrynioti,D., Moezzi,A. M., Moody, K., Navascues-Cornago,M., Schweizer,H., Swiderska,K., Young,G., Willcox,M. CLEAR - Effect of contact lens materials and designs on the anatomy and physiology of the eye Contact Lens Anterior Eye 2021;44(2):192-219 [ Show Abstract ]

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia).

However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation.

In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.

Morgan,P., Efron,N., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in prescribing multifocal and monovision soft contact lenses to correct presbyopia (2000–2023): An update Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose: Numerous multifocal soft contact lenses have been introduced into clinical practice over the past half century. The purpose of this work is to update earlier surveys by describing international trends in multifocal and monovision soft lens fitting for presbyopia between 2000–2023, inclusive.

Method: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000–2023. Data relating to 52,580 soft daily wear lens fits to presbyopes (those ≥45 years of age) undertaken in 20 countries returning reliable longitudinal data were analysed in respect of multifocal and monovision soft daily wear lens fits.

Results: Overall, multifocal and monovision soft daily wear lens prescribing to presbyopes has more than doubled over the course of this survey, from 26.4 % of standard soft daily wear lens fits in 2000 to 61.1 % in 2023 (p < 0.0001). There were significant differences between countries in presbyopia soft daily wear lens prescribing (p < 0.0001). Of all soft daily wear fits to males, 45.1 % were multifocal and monovision soft lenses, compared with 52.7 % for females (p < 0.0001). When considered as the proportion of lenses fitted by age, multifocal soft lens fitting peaked between 50–65 years, followed by a precipitous drop until 85–90 years of age, and then an increase beyond 90 years of age. Analysis of 13,014 recent soft lens fits to presbyopes (2019–2023) revealed the following fitting proportions: multifocal lenses – 51 %; monovision – 10 %; and non-presbyopia fitting – 39 %.

Conclusion: There has been a substantial increase in soft contact lens correction of presbyopia using multifocal and monovision corrections throughout the 24 years of this survey. A significant number of soft contact lens-wearing presbyopes are not receiving a presbyopia contact lens correction.

Morgan,P., Efron,N., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in daily disposable contact lens prescribing (2000–2023): An update Contact Lens Anterior Eye 2024;47(6):102259 [ Show Abstract ]

Purpose
Daily disposable contact lenses offer numerous benefits in terms of ocular health and wearer convenience. The purpose of this work is to update earlier surveys by describing global trends in daily disposable lens fitting between 2000 and 2023.

Method
An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 265,106 daily wear soft lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of daily disposable lens fitting.

Results
Overall, daily disposable lens prescribing increased over time, from 17.1 % of daily wear soft lens fits in 2000 to 46.7 % in 2023 (p < 0.0001). There were significant differences between countries in daily disposable lens prescribing (p < 0.0001), and between the percentage of males fitted with daily disposable lenses, as a proportion of all daily wear soft lenses (37.2 %), compared to females (35.2 %) (p < 0.0001). Daily disposable lens wearers are slightly younger at fitting than reusable soft lens wearers (31.0 vs 31.2 years, respectively) (p < 0.0001), although this difference is not clinically meaningful. Analysis of 50,240 daily wear soft lenses fitted recently (2019–2023) were found to be prescribed for the following replacement frequencies: daily – 47 %; monthly – 42 %; 1–2 weekly – 9 %; and ≥3 monthly – 2 %.

Conclusion
There has been a substantial increase in daily disposable lens fitting throughout the first 24 years of this century. The gradual nature of this increase is commensurate with the staged introduction of daily disposable lens designs and expanded parameter ranges over the survey period.

Morgan,P., Efron,N., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in prescribing extended wear soft contact lenses (2000–2023): An update Contact Lens Anterior Eye 2024;47(6):102285 [ Show Abstract ]

Purpose
Extended wear has long been considered as the ultimate contact lens modality in terms of user convenience. The purpose of this work is to update earlier surveys by describing international trends in extended wear soft lens fitting between 2000 and 2023, inclusive.

Method
An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 282,142 soft contact lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of extended wear soft lens fitting.

Results
Over the duration of the work there was a very small decrease in the prescribing of extended wear soft lenses (p < 0.0001). More detailed inspection shows that prescribing of these lenses steadily increased from 5.8 % of all soft lens fits in 2000 to 11.6 % in 2007, then steadily decreased to 5.2 % in 2023. Of all soft contact lenses prescribed to males, 9.2 % were fitted for extended wear, compared with 6.7 % for females (p < 0.0001). The mean age of extended wear soft lens wearers at fitting was 34.7 ± 14.7 years, compared to 31.1. ± 14.10 years for daily soft lens wearers (p < 0.0001). Analysis of 1,948 recent extended wear soft lens fits (2019–2023, inclusive), in terms of material type, revealed that, on average, 86 % and 14 % of extended wear soft lenses were fitted using silicone hydrogel and hydrogel materials, respectively.

Conclusion
A modest increase in extended wear soft lens prescribing from 2000 to 2007 corresponded with the introduction of high oxygen transmissibility silicone hydrogel lenses. However, prescribing of this lens type declined thereafter, probably due to ongoing concerns over their increased rate of microbial keratitis, resulting in a prescribing rate in 2023 (5.2%) that was little different to that observed in 2000 (5.8%).

Muntz,A., Subbaraman,L. N., Sorbara,L., Jones,L. Tear exchange and contact lenses: A review Journal of Optometry 2015;8(1):2-11 [ Show Abstract ]

Tear exchange beneath a contact lens facilitates ongoing fluid replenishment between the ocular surface and the lens. This exchange is considerably lower during the wear of soft lenses compared with rigid lenses. As a result, the accumulation of tear film debris and metabolic by-products between the cornea and a soft contact lens increases, potentially leading to complications. Lens design innovations have been proposed, but no substantial improvement in soft lens tear exchange has been reported. Researchers have determined post-lens tear exchange using several methods, notably fluorophotometry. However, due to technological limitations, little remains known about tear hydrodynamics around the lens and, to-date, true tear exchange with contact lenses has not been shown. Further knowledge regarding tear exchange could be vital in aiding better contact lens design, with the prospect of alleviating certain adverse ocular responses. This article reviews the literature to-date on the significance, implications and measurement of tear exchange with contact lenses.

Muntz,A., Subbaraman,L.N., Craig,J. P., Jones,L. Cytomorphological assessment of the lid margin in relation to symptoms, contact lens wear and lid wiper epitheliopathy Ocular Surface 2020;18(2):214-220 [ Show Abstract ]

Purpose: Lid wiper epitheliopathy (LWE) is insufficiently understood from a cytological perspective. This study explored the relationship between lid margin cytomorphology, LWE, contact lens wear, and lens-related symptoms. Methods: Habitual, symptomatic (n = 20) and asymptomatic (n = 20) soft, rigid gas permeable (n = 18) and non-contact lens wearers (n = 19) were enrolled. LWE was graded using lissamine green and the Korb scale. Subjective symptoms were assessed using the Ocular Surface Disease Index and the Contact Lens Dryness Evaluation Questionnaire. Impression cytology samples obtained from the central upper and lower lid margins of both eyes stained histologically to highlight keratinization and imaged using high-resolution microscopy. A masked investigator digitally delimited and measured the average sagittal width of the lid wiper conjunctiva and mucocutaneous junction using ImageJ. Results: The upper lid wiper conjunctiva measured 424 ± 171 μm, 404 ± 75, 667 ± 219 and 266 ± 64 in asymptomatic soft, symptomatic soft, rigid and non-contact lens wearers, respectively. The corresponding lower lid wiper conjunctivae measured 141 ± 57 μm, 232 ± 150, 519 ± 212 and 225 ± 102, which was significantly narrower than that of the upper eyelid in most cases (p < 0.05). Symptoms were not associated with lid margin changes; however, rigid lens wear and clinical LWE were associated with histologically enlarged lid wiper conjunctival areas and increased keratinization. Conclusion: A novel, exploratory account of histological measures of LWE and cytomorphological change associated with contact lens wear suggests mechanical or frictional cellular insult is occurring at the lid wiper conjunctiva.

Muntz,A., van Doorn,K., Subbaraman,L. N., Jones,L. W. Impression cytology of the lid wiper area Journal of Visualized Experiments 2016 (114): [ Show Abstract ]

Few reports on the cellular anatomy of the lid wiper (LW) area of the inner eyelid exist and only one report makes use of cytological methods. The optimization of a method of collecting, staining and imaging cells from the LW region using impression cytology (IC) is described in this study. Cells are collected from the inner surface of the upper eyelid of human subjects using hydrophilic polytetrafluoroethylene (PTFE) membranes, and stained with cytological dyes to reveal the presence of goblet cells, mucins, cell nuclei and various degrees of pre- and parakeratinization. Immunocytochemical dyes show cell esterase activity and compromised cell membranes by the use of a confocal scanning laser microscope. Up to 100 microscopic digital images are captured for each sample and stitched into a high-resolution, large scale image of the entire IC span. We demonstrate a higher sensitivity of IC than reported before, appropriate for identifying cellular morphologies and metabolic activity in the LW area. To our knowledge, this is the first time this selection of fluorescent dyes was used to image LW IC membranes. This protocol will be effective in future studies to reveal undocumented details of the LW area, such as assessing cellular particularities of contact lens wearers or patients with dry eye or lid wiper epitheliopathy. © 2016 Journal of Visualized Experiments.

Nagaarudkumaran,N., Mirzapur,P., McCanna,D. J., Ngo,W. Temporal Change in Pro-Inflammatory Cytokine Expression from Immortalized Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress Current Eye Research 2022;47(11):1488-1495 [ Show Abstract ]

Purpose
To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.

Methods
HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD).

Results
Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1β, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark.

Conclusion
Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line.

Navascues-Cornago,M., Guthrie,S., Morgan,P., Woods,J. Determination of the Minimal Clinically Important Difference (MCID) for Ocular Subjective Responses Transl Vis Sci Technol 2024;13(8):28 [ Show Abstract ]

Purpose: To determine the minimal clinically important difference (MCID) for contact lens (CL)-related subjective responses and explore whether MCID values differ between subjective responses and study designs.
Methods: This was a retrospective analysis of data from seven one-week bilateral crossover studies and 14 one-day contralateral CL studies. For comfort, dryness, vision, or ease of insertion, participants rated on a 0-100 visual analogue scale (VAS) and indicated lens preference on a five-point Likert scale featuring strong, slight, and no preferences. For each criterion, four MCID estimates were calculated and averaged: mean VAS score difference for "slight preference," lower limit of 95% confidence interval VAS score difference for "slight preference," difference in mean VAS score difference between "slight" and "no preference" and 0.5 standard deviation of VAS scores.
Results: The four calculation methods generated a small range of MCID values. For bilateral studies, the averaged MCID was 7.2 (range 5.4-8.8) for comfort, 8.1 (5.2-10.6) for dryness, 7.1 (5.5-9.3) for vision and 7.6 (6.0-10.5) for ease of insertion. For contralateral studies, the averaged MCID was 6.9 (6.1-7.6) for comfort at insertion and 7.5 (6.8-8.2) for end-of-day comfort.
Conclusions: This work demonstrated very similar MCID values across subjective responses and study designs, in a population of habitual soft CL wearers. In all cases, MCID values were on average seven units on a 0 to 100 VAS.
Translational relevance: This work provides MCID values which are important for interpreting ocular subjective responses and planning clinical studies.

Nelson,J. D., Craig,J. P., Akpek,E. K., Azar,D. T., Belmonte,C., Bron,A. J., Clayton,J. A., Dogru,M., Dua,H. S., Foulks,G. N., Gomes,J. A. P., Hammitt,K. M., Holopainen,J., Jones,L., Joo,C. -K, Liu,Z., Nichols,J. J., Nichols,K. K., Novack,G. D., Sangwan,V., Stapleton,F., Tomlinson,A., Tsubota,K., Willcox,M. D. P., Wolffsohn,J. S., Sullivan,D. A. TFOS DEWS II Introduction Ocular Surface 2017;15(3):269-275

Ng,A. Y., Keech,A., Jones,L. Tear osmolarity changes after use of hydroxypropyl-guar-based lubricating eye drops Clinical Ophthalmology 2018;12:695-700 [ 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 (p0.05). 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.

Ng,A. Y., Woods,J., Jahn,T., Jones,L., Ritter,J. Effect of a novel omega-3 and omega-6 fatty acid supplement on dry eye disease: a 3-month randomized controlled trial Optometry & Vision Science 2022;99(1):67-75 [ Show Abstract ]

SIGNIFICANCE
Supplementing diet with a novel combination of omega-3 and omega-6 fatty acids significantly improved symptoms in extremely symptomatic participants with dry eye disease (DED).

PURPOSE
This study aimed to determine the effect of daily intake of a novel combination of essential fatty acids on signs and symptoms of DED.

METHODS
Participants with moderate to severe DED were enrolled in a prospective, randomized, double-masked parallel group study. Participants ingested either the treatment supplement containing omega-3 and omega-6 fatty acids (1200 mg eicosapentaenoic acid, 300 mg docosahexaenoic acid, 150 mg γ-linoleic acid) or the placebo (coconut and olive oil) daily for 3 months. To determine compliance, Omega-3 Index blood tests were conducted. At baseline and at 1 and 3 months, the following assessments were conducted: Ocular Surface Disease Index (OSDI) questionnaire and Symptom Assessment Questionnaire in Dry Eye, noninvasive tear breakup time, tear meniscus height, tear osmolarity, ocular redness, surface staining, Schirmer test, and meibography.

RESULTS
Fifty participants (mean ± standard deviation baseline OSDI score, 52.2 ± 16.5) completed the study: 24 randomized to treatment and 26 randomized to placebo. Although there was an improvement in OSDI score at 3 months for both groups (treatment: −13.4 points, P = .003; placebo: −7.8 points, P = .02), participants with baseline OSDI scores >52 demonstrated an even larger significant improvement in symptoms with the treatment at 3 months compared with baseline (n = 13, −20.8 points, P = .002). There were no significant changes in any of the ocular assessments at 1 or 3 months (all P > .05). After 3 months, Omega-3 Index increased by 34% in the treatment group (baseline, 5.3 ± 0.8; 3 months, 8.0 ± 2.1; P < .001) and did not change in the placebo group (baseline, 4.8 ± 0.8; 3 months, 4.8 ± 0.6; P = .95).

CONCLUSIONS
Supplementation with eicosapentaenoic acid, docosahexaenoic acid, and γ-linoleic acid resulted in a significant and clinically meaningful improvement of dry eye symptoms in extremely symptomatic participants with DED (OSDI ≥52).

Ng,A., Evans,K., North,R. V., Jones,L., Purslow,C. Impact of Eye Cosmetics on the Eye, Adnexa, and Ocular Surface Eye and Contact Lens 2016;42(4):211-220 [ Show Abstract ]

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film. © 2015 Contact Lens Association of Ophthalmologists.

Ng,A., Heynen,M., Luensmann,D., Jones,L. Impact of tear film components on lysozyme deposition to contact lenses Optometry and Vision Science 2012 [ Show Abstract ]

PURPOSE: To investigate the impact of lactoferrin and lipids on the kinetic deposition of lysozyme on silicone and conventional hydrogel lenses, using a complex artificial tear solution (ATS). METHODS: Two silicone hydrogel lenses (AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A) and two conventional hydrogel lenses (ACUVUE 2; etafilcon A and PROCLEAR; omafilcon A) were investigated. Lenses were incubated in four different solutions: a complex ATS consisting of various salts, lipids, proteins, and mucins, an ATS without lactoferrin (ATS w/o Lac), an ATS without lipids (ATS w/o Lip), and an ATS without lactoferrin and lipids (ATS w/o Lac & Lip), each containing 2% radiolabeled (125I) lysozyme (1.9 mg/ml). After each time point (4, 12 h and 1, 2, 3, 5, 7, 14, 21, 28 days), the amount of lysozyme per lens was quantified. RESULTS: After 28 days, lotrafilcon B lenses incubated in ATS deposited significantly less lysozyme (9.7 ± 1.4 μg) than when incubated in solutions not containing lactoferrin and lipids (more than 11.8 μg) (p < 0.001). Lysozyme uptake to senofilcon A lenses was higher in ATS w/o Lip (5.3 ± 0.1 μg) compared with other solutions (less than 3.9 μg) (p < 0.001). Etafilcon A lenses deposited the most lysozyme in all four solutions compared with the rest of the lens types (p < 0.001). For etafilcon A lenses, less lysozyme was deposited when incubated in ATS w/o Lip (588.6 ± 0.4 μg) compared with the other solutions (more than 642.6 μg) (p < 0.001). Omafilcon A lenses in ATS w/o Lac accumulated significantly less lysozyme (12.8 ± 1.0 μg) compared with the other solutions (more than 14.2 μg) (p < 0.001). CONCLUSIONS: An ATS containing lactoferrin and lipids impacts lysozyme deposition on both silicone and conventional hydrogel contact lenses. When performing in vitro experiments to study protein deposition on contact lenses, more complex models should be used to better mimic the human tear film.

Ng,A., Heynen,M., Luensmann,D., Subbaraman,L. N., Jones,L. Impact of tear film components on the conformational state of lysozyme deposited on contact lenses Journal of Biomedical Materials Research - Part B Applied Biomaterials 2013;101(7):1172-1181 [ Show Abstract ]

Purpose To investigate the impact of lactoferrin and lipids on the kinetic denaturation of lysozyme deposited on silicone and conventional hydrogel lenses, using a complex artificial tear solution (ATS). Methods Two silicone hydrogel lenses (AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A) and two conventional hydrogel lenses (ACUVUE 2; etafilcon A and PROCLEAR; omafilcon A) were incubated in four solutions: an ATS, ATS without lactoferrin, ATS without lipids, and ATS without lactoferrin and lipids. At various time points over a 28-day period, the percentage of active lysozyme per lens was determined using a fluorescence activity assay and an ELISA. Results After 28 days, the percentage of active lysozyme extracted from etafilcon A lenses in all solutions was significantly higher than all other lens materials (p 0.05). The inclusion of lipids in the ATS significantly increased the lysozyme denaturation on both silicone hydrogel materials (p 0.05). The inclusion of lipids in the ATS significantly increased the lysozyme denaturation on both silicone hydrogel materials (p 0.05). Conclusions Lactoferrin and lipids have an impact on the denaturation of lysozyme deposited onto silicone hydrogel contact lenses, while conventional hydrogel lenses were unaffected. Future in vitro studies should consider the impact of tear film components when investigating protein deposition and denaturation on contact lenses. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 1172-1181, 2013. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Ng,A., Heynen,M., Luensmann,D., Subbaraman,L. N., Jones,L. Optimization of a fluorescence-based lysozyme activity assay for contact lens studies Current eye research 2013;38(2):252-259 [ Show Abstract ]

Purpose: To optimize a fluorescence-based lysozyme activity assay to investigate the conformational state of lysozyme in solution and to determine the impact of extraction and evaporation procedures and the possible interference of contact lens materials on lysozyme activity. Methods: The fluorescence-based lysozyme activity assay, Enzchek (Molecular Probes Inc, Eugene, OR) which utilizes fluorescently quenched Micrococcus lysodeikticus, was compared to the gold standard, classical lysozyme turbidity assay, using four differently concentrated lysozyme samples (20, 10, 5.0 and 2.0 ng/µL). Furthermore, six differently concentrated lysozyme samples (2.0, 1.0, 0.5, 0.25, 0.125 and 0.01 µg/µL) were quantified using the fluorescence-based assay in the presence of extraction solvents consisting of 0.2% and 0.02% trifluroacetic acid/acetonitrile and following evaporation procedures. Results: A standard curve was generated by the fluorescence-based assay ranging from 2 to 150 ng. The total active lysozyme quantified in the four lysozyme samples was not significantly different between the two assays (p > 0.05) and the concordance correlation coefficient was determined to be 0.995. However an average discrepancy between the two assays was found to be 0.474 ng, with the turbidity assay typically reporting higher active lysozyme measurements. The sensitivity of the fluorescence-based assay was higher than the classical turbidity assay when quantifying 20 ng or less active lysozyme. Following the extraction and evaporation procedures and the addition of lens extracts, the total active lysozyme recovered was 95% or greater. Conclusions: In comparison to the classical turbidity assay, the fluorescence-based assay is a very sensitive method, making it a favorable technique, particularly when studying contact lens materials that deposit relatively low levels of lysozyme. © Informa Healthcare USA, Inc.

Ngo,W., Caffery,B., Srinivasan,S., Jones,L. W. Effect of lid debridement-scaling in sjögren syndrome dry eye Optometry and Vision Science 2015;92(9):e316-e320 [ Show Abstract ]

Purpose To evaluate the effect of lid debridement-scaling (LDS) on dry eye signs and symptoms in subjects with Sjögren syndrome (SS). Methods This prospective randomized controlled study enrolled 14 female subjects with SS. Seven subjects were randomized into the treatment group where they were selected to receive LDS; the remainder did not receive LDS and served as control subjects. Lid debridement-scaling was conducted using a stainless steel golf club spud (Hilco Wilson Ophthalmics, Plainville, MA) on both the upper and lower eyelids of both eyes. Outcome variables were assessed before LDS and again 1 month later. The outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) visual analog scores, ocular staining (SICCA OSS [Sjögren's International Collaborative Clinical Alliance Ocular Staining Score]), fluorescein tear breakup time (FLBUT), meibomian gland score (MGS), meibomian gland yielding liquid secretions (MGYLS) score, and line of Marx's (LOM) position. Results Thirteen subjects completed the study. Data from only the right eye were analyzed. For the control group (n = 6; mean [±SD] age, 62.3 [±11.6] years), the pre-LDS, post-LDS, and significance level (pre-LDS mean [±SD] vs. post-LDS mean [±SD]; p value) were as follows: OSDI (58.3 [±22.1] vs. 48.3 [±29.0]; p = 0.051), SANDE (77.4 [±22.1] vs. 89.6 [±32.6]; p = 0.20), SICCA OSS (7.0 [±4.5] vs. 8.2 [±3.5]; p = 0.25), MGS (1.3 [±1.5] vs. 1.0 [±0.9]; p = 0.75), MGYLS (0.3 [±0.5] vs. 0.0 [±0.0]; p = 0.50), FLBUT (2.99 [±1.54] vs. 2.85 [±1.79]; p = 0.63), and LOM (2.0 [±0.0] vs. 2.0 [±0.0]; p = n/a). For the treatment group (n = 7; mean [±SD] age, 58.0 [±8.1] years), the pre-LDS, post-LDS, and significance level were as follows: OSDI (63.2 [±13.3] vs. 46.9 [±19.4]; p = 0.04), SANDE (72.6 [±17.1] vs. 77.0 [±28.0]; p = 0.54), SICCA OSS (6.6 [±2.9] vs. 5.0 [±3.9]; p = 0.02), MGS (1.0 [±1.2] vs. 3.1 [±1.7]; p = 0.01), MGYLS (0.0 [±0.0] vs. 0.6 [±1.0]; p = 0.50), FLBUT (3.13 [±0.81] vs. 3.45 [±1.03]; p = 0.53), and LOM (0.9 [±0.9] vs. 1.0 [±1.0]; p = 1.00). Conclusions This pilot study showed that LDS improved symptoms, ocular staining, and meibomian gland function for the group that received LDS. This indicates that LDS can aid in the management of SS dry eye. © 2015 American Academy of Optometry.

Ngo,W., Heynen,M., Joyce,E., Jones,L. Impact of protein and lipid on neutralization times of hydrogen peroxide care regimens Eye and Contact Lens 2009;35(6):282-286 [ Show Abstract ]

Purpose: To investigate the effect of protein, lipid, and lens material on the neutralization kinetics of one-step hydrogen peroxide disinfection systems. Methods: A UV-based assay was used to determine the rate of neutralization of three one-step hydrogen peroxide systems (CIBA Vision Clear Care; CIBA Vision AOSEPT; Abbott Medical Optics UltraCare). Protein (bovine serum albumin and lysozyme) and various lipids were added to the lens cases during the neutralization phase to determine whether they influenced the rate of neutralization. Finally, rates were determined when the cases contained a silicone hydrogel lens material (lotrafilcon A) or Food and Drug Administration group IV (etafilcon A) lenses. Results: Neutralization for all three systems was complete within 90 minutes. The rate of neutralization for Clear Care and AOSEPT were not significantly different from each other (P=NS). UltraCare exhibited statistically higher levels of peroxide up to the 20-minute time point (P<0.001) Protein, lipid, or lens material did not significantly affect the rate of neutralization for any regimen (P=NS). Conclusions: Tablet-based one-step disinfection systems neutralize at a slower rate than disc-based peroxide systems, but this difference is only significant during the first 20 minutes after the onset of neutralization. Neither lens deposition nor lens material plays a role in the speed of neutralization of peroxide-based systems. © 2009 Lippincott Williams & Wilkins.

Ngo,W., Jones, L., Bitton, E. Short-Term Comfort Responses Associated With the Use of Eyelid Cleansing Products to Manage Demodex folliculorum Eye and Contact Lens 2018;44(Suppl 2):S87-S92 [ Show Abstract ]

PURPOSE: To quantify the discomfort over time of various eyelid cleansers against Demodex.
METHODS: This was a prospective, randomized, controlled, crossover, open-label study that enrolled 26 participants. The cleansers used in this study were Biotissue Cliradex (CD), OCuSOFT Lid Scrubs Plus (OP), OCuSOFT OUST Demodex Swabstix (ODS), TheraTears Theralid (TT), NovaBay Avenova (NA). Bausch+Lomb Sensitive Eyes Plus saline was used as a control. Participants were asked to close their eyes as the product was gently rubbed (10 cycles of gentle lateral motion) into the eyelashes. Participants verbally rated their discomfort (0 = no discomfort, 10 = maximum tolerable discomfort) every 15 sec for the first 5 min, and every 30 sec for 5 min after, for a total of 10 min. The order of products used was randomized, and washout period between cleansing was 48 hr.
RESULTS: Twenty-five participants completed the study (mean age=26±6). There was no significant difference in discomfort scores at pre-application. The discomfort levels of saline, OP, and NA over the 10-min period were not significantly different than their pre-application discomfort at all time points (all P≥0.99). The discomfort of CD was significantly higher than pre-application levels between t=15 sec and t=180 sec (all P≤0.01), with maximum median (interquartile range [IQR]) discomfort of 3.0 (5.0) occurring at t=45 sec. The discomfort of TT was significantly higher than pre-application levels between t=45 and t=90 (all P<0.02), with maximum median (IQR) discomfort of 1.0 (1.5) occurring at t=75 sec. The discomfort of ODS was significantly higher than pre-application levels starting from t=60 sec and onward, with maximum median (IQR) discomfort of 6.0 (5.0) occurring at t=300 sec.
CONCLUSION: Of the cleansers used in this study, the ones that induced significant discomfort were CD, TT, and ODS. The results from this study may help clinicians educate patients about what to expect when approaching the topic of eyelid Demodex treatment.

Ngo,W., Nagaarudkumaran,N., Huynh,C. B. Refrigeration reduces instillation discomfort of a 0.09% cyclosporine A solution Optometry and Vision Science 2025;102(1):14-19 [ Show Abstract ]

Significance: Topical cyclosporine A (CsA) for the treatment of dry eye disease is often associated with instillation discomfort, which may negatively influence patient adherence to therapy. This study found that refrigerating topical CsA reduced instillation discomfort compared with instillation of warm CsA. Thus, refrigerating CsA prior to instillation may improve patient experience when using CsA to manage dry eye disease.

Purpose: This study aimed to quantify instillation discomfort associated with cold or warm instillation of a 0.09% CsA.

Methods: Forty participants with symptomatic aqueous deficient dry eye were enrolled. A drop of cold (4°C) CsA was instilled in one eye, and a drop of warm (23°C) CsA was instilled in the other eye. The order and eye receiving the cold drop were randomized. Participants rated the discomfort of each eye (0, no discomfort; 10, maximal discomfort) prior to drop instillation, immediately post-instillation, and at each subsequent minute for 10 minutes. Area under the curve was used to quantify cumulative discomfort.

Results: Forty participants (39.6 ± 18.9 years old, 82% female) completed the study. A majority of participants (n = 24, 60%) experienced reduced cumulative discomfort with cold CsA, whereas the remainder experienced minimal difference (n = 10, 25%) or increased cumulative discomfort (n = 6, 15%). For those with reduced discomfort (n = 24), cumulative discomfort associated with cold instillation (median, 11.5 [2.2, 20.0]) was significantly lower (p<0.01) than cumulative discomfort associated with warm instillation (median, 17.5 [11.2, 32.2]). Cold instillation was associated with a median reduction of 1 discomfort point immediately post-instillation and at all subsequent time points (all p≤0.04, but not significant at t = 10), compared with warm instillation.

Conclusions: Up to 60% of participants found that cold instillation of CsA solution induced less discomfort than warm instillation, lasting up to 9 minutes post-instillation. In contrast, although 15% of participants found reduced discomfort with warm instillation, the magnitude of discomfort associated with warm instillation was not significantly different than cold instillation.