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., Srinivasan,S., Houtman,D., Jones,L. The relief of dry eye signs and symptoms using a combination of lubricants, lid hygiene and ocular nutraceuticals Journal of Optometry 2017;10(1):26-33 [ Show Abstract ]

Purpose To determine the combined effect of TheraTears® Lubricant Eye Drops, TheraTears® SteriLid Eyelid Cleanser, and TheraTears® Nutrition on dry eye signs and symptoms. Methods This prospective study enrolled 28 dry eye participants. Participants were instructed to use the Lubricant Eye Drops at least 2–4× a day, SteriLid 1–2× a day, and Nutrition 3 gel caps once a day. Participants were followed up at baseline, 1 month and 3 months. Outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) questionnaire, non-invasive tear break-up time (NIBUT), osmolarity, number of meibomian glands blocked (#MG blocked), meibum quality, eyelid margin features, Schirmer's test, tear film lipid layer thickness (LLT), meniscus height, corneal and conjunctival staining. Results Twenty participants (mean age = 43, from 23 to 66, 17F, 3M) completed the study. Participants reported having used, on average, the Lubricant Eye Drop 2.4×/day, the SteriLid 1.1×/day, and the Nutrition 3 gel caps 1×/day. There was a significant change over time (p < 0.05) for OSDI (-21.2 points), SANDE (-32.4 points), NIBUT (+0.43 s), eyelid margin features (-1.1 grade), meibum quality (-1.0 grade), and #MG blocked (-4.0 glands). Conclusion By using a combination of TheraTears® Lubricant Eye Drop, SteriLid, and Nutrition, patients experience significant relief in both dry eye symptoms and signs. © 2016 Spanish General Council of Optometry

Ngo,W., Srinivasan,S., Jones, L., A comparison of dry eye diagnostic tests between symptomatic and asymptomatic age-matched females Eye and Contact Lens 2018;44(Suppl 1):S110-S114 [ Show Abstract ]

PURPOSE: To quantify the strength of association of dry eye (DE) symptoms to DE diagnostic tests in age-matched females.
METHODS: Twenty females with DE symptoms (Ocular Surface Disease Index, OSDI, ≥13) were age-matched with 20 females without DE symptoms (OSDI<13) in this cross-sectional study. Noninvasive tear breakup time (NIBUT), ocular staining, meibum quality, number of obstructed meibomian glands (MGs), lid wiper epitheliopathy, Marx line placement, eyelid margin score, Schirmer test, meibography, and visual acuity were assessed in both groups.
RESULTS: Twenty participant pairs completed the study. The age (median/interquartile range [IQR]) of the symptomatic group was 60/15 and the asymptomatic group was 62/15. The tests (median/IQR, P value) that were significantly different between the symptomatic group and the asymptomatic group were OSDI (35.4/35.4 vs. 3.1/6.7, P<0.01), NIBUT (2.1/0.7 sec vs. 3.0/3.0 sec, P=0.01), meibum quality (3.0/0.0 grade units vs. 2.0/1.0 grade units, P<0.01), number of obstructed MGs (7.0/2.0 glands vs. 5.0/4.8 glands, P<0.01), and ocular staining (5.5/3.8 grade units vs. 0.5/1.0 grade units, P<0.01). The tests (area under curve, [AUC], odds ratio [OR]) that were most strongly associated with DE symptoms were ocular staining (0.93, 5.0), number of obstructed MGs (0.79, 2.6), meibum quality (0.76, 2.4), and NIBUT (0.74, 3.2) (all P0.05), and similarly, no significant association to DE symptoms (all P>0.05).
CONCLUSION: The diagnostic tests most strongly associated with DE symptoms in older women were ocular staining, meibum quality, number of obstructed MGs, and tear film stability.

Ngo,W., Srinivasan,S., Jones,L. Historical overview of imaging the meibomian glands Journal of Optometry 2013;6(1):1-8 [ Show Abstract ]

Growing knowledge of the role of the meibomian glands in dry eye disease and contact lens discomfort has resulted in a surge of interest in visualizing these glands within the eyelids. This manuscript provides an overview of the many different visualization methods that have evolved over the past 30-40 years. Some of the visualization methods covered in this review include lid transillumination, video and non-contact meibography, and imaging methods employing confocal microscopy, optical coherence tomography and ultrasound. This review has also highlighted all the studies to date that have employed meibography as part of their methods. An overview of the available meibography dropout grading systems will also be provided. © 2012 Spanish General Council of Optometry.

Ngo,W., Srinivasan,S., Jones,L. An Eyelid Warming Device for the Management of Meibomian Gland Dysfunction J Optom 2019;12(2):120-130 [ Show Abstract ]

PURPOSE: To determine the effectiveness of the MGDRx EyeBag in managing meibomian gland dysfunction.

METHODS: This was a prospective, randomized, controlled, observer-masked, bilateral eye study that enrolled 29 participants. Participants were randomized into either the EyeBag group or the control group. The EyeBag group used the EyeBag 10minutes 2x/day, and the control group remained on their own dry eye treatment regimen (if applicable). All participants were observed at baseline, 2 weeks (2wk) and 4 weeks (4wk). At 4wk, participants in the EyeBag group were asked to stop using the EyeBag. All participants were seen again at 8 weeks (8wk). Primary outcomes were the Ocular Surface Disease Index (OSDI), Current Symptoms Questionnaire (CSQ), meibomian gland score (MG score), and non-invasive tear breakup time (NIBUT).

RESULTS: Twenty-five participants completed the study (mean age 38±15 years, 7 male). There was a significant change in OSDI over time for the EyeBag group (mean[lower 95% CI, upper 95% CI], baseline: 39.1[31.1,47.0], 2wk: 26.8[19.7,33.9], 4wk: 26.6[16.5,36.7], 8wk: 27.7[18.4,37.0]; p=0.01), but not in the control group (p=0.22), but no significant difference between groups at all time points (all p>0.27). Symptoms immediately improved after conducting the EyeBag based on at-home CSQ scores (Δ=-5.0 points, p<0.01), but not in the control group. For both groups, there was no significant change (p-value EyeBag,p-value control) in MG score (0.21,0.17) and NIBUT (0.49,0.06) over time.

CONCLUSIONS: The EyeBag may relieve symptoms of dry eye, but the effect on meibomian gland function and tear stability when used for only 4 weeks was undetectable.

Ngo,W., Srinivasan,S., Keech,A., Keir,N., Jones,L. Self versus examiner administration of the Ocular Surface Disease Index© Journal of Optometry 2017;10(1):34-42 [ Show Abstract ]

Purpose To compare the difference in Ocular Surface Disease Index© (OSDI) scores when participants were given the OSDI to complete on their own (self-guided, SG), versus under the guidance of the examiner (examiner-guided, EG). Methods 100 participants enrolled in this prospective two-visit study (fifty under-45 years old, 38F/12M; and fifty 45 years-and-older, 42F/8M). Participants who scored =1 on the Subjective Evaluation of Symptoms of Dryness (SESoD) were included in this study. Participants completed the OSDI SG during the first visit. Participants returned the next day and repeated the OSDI, but with EG (with standardized instructions). Participants were under deception and believed that they were comparing the OSDI to the SESoD. Results The mean OSDI score of the SG and EG administration was 32.0 ± 17.3 and 33.8 ± 19.6 respectively (p > 0.05) with 95% limits of agreement between -20.6 and +24.2. The correlation between SG and EG administration was Spearman's r = 0.81, p 0.05) for both the under-45 group, and 45-and-older group. The 95% limits of agreement for the under-45 group were smaller than the 45-and-older group (under-45: [-15.5, +13.1,], 45-and-older: [-23.3, +32.2]). A significant difference was found between 8 of the 12 questions items (all p = 0.01). However, the mean difference for each was <0.6 and was not considered to be clinically significant. Conclusion There was no clinically significant difference in OSDI score between SG and EG administration, however having instructions provided with EG administration affected variability of scores in the older group more than the younger group. © 2016 Spanish General Council of Optometry

Ngo,W., Srinivasan,S., Schulze,M., Jones,L. Repeatability of grading meibomian gland dropout using two infrared systems Optometry and Vision Science 2014;91(6):658-667 [ Show Abstract ]

PURPOSE: To determine the interobserver and intraobserver repeatability in using the OCULUS Keratograph 4 (K4) and 5M (K5M) to grade meibomian gland (MG) dropout using meibography grading scales. METHODS: The inferior and superior eyelids of 40 participants (35 women, 5 men; mean age = 32 years) were imaged three times each on both instruments. The images were split into one training and two study sets; the latter were graded (four-point meibography scale) by two observers on two separate occasions (24 hours apart) to determine repeatability. Semiobjective quantification of percentage MG dropout was conducted using ImageJ on K4 and K5M images. A finer seven-point meibography scale was used to grade a separate set of K5M images. RESULTS: For the four-point scale, interobserver mean difference (MD) (±SD) was 0.08 (±0.55) on day 1 and 0.13 (±0.50) on day 2, and the concordance correlation coefficient (CCC) was 0.79 and 0.81 on days 1 and 2, respectively. Intraobserver MD (±SD) was 0.04 (±0.54), CCC = 0.79 for observer 1; intraobserver MD (±SD) was -0.09 (±0.60), CCC = 0.74 for observer 2. For the seven-point scale, interobserver MD (±SD) was 0.05 (±0.45), CCC = 0.89 on day 1, and interobserver MD (±SD) was 0.01 (±0.41), CCC = 0.91 on day 2. Intraobserver MD (±SD) was -0.10 (±0.35), CCC = 0.93 for observer 1, and intraobserver MD (±SD) was -0.06 (±0.30), CCC = 0.95 for observer 2. Percentage dropout measured between the K4 and K5M images showed lack of agreement, with 21.8% coefficient of repeatability. There was no significant correlation (r 0.05) between meibography score and clinical signs (corneal staining, gland expressibility, telangiectasia, vascularity, lash loss); however, there was a high correlation (r = 0.77; p < 0.05) between meibography score with percentage dropout. CONCLUSIONS: Observers graded from -1 to +1 grade units between and within themselves for a four-point scale, 95% of the time. Although the interobserver and intraobserver repeatability of the K4 and K5M were very similar, a high rate of disagreement in percentage dropout between K4 and K5M images suggests that the two instruments cannot be interchanged. Meibomian gland dropout scores did not correlate significantly with clinical signs. Using a finer scale may be beneficial for detecting change.

Nichols,J. J., Chalmers,R. L., Dumbleton,K., Jones,L., Lievens,C. W., Merchea,M. M., Szczotka-Flynn,L. The Case for Using Hydrogen Peroxide Contact Lens Care Solutions: A Review Eye & Contact Lens 2019;45(2):69-82 [ Show Abstract ]

Despite their established disinfection and safety benefits, the use of hydrogen peroxide (H2O2) lens care systems among today's wearers of reusable contact lenses remains low in comparison with multipurpose solution (MPS) use. Multipurpose solution systems, however, present several potential drawbacks that may impact patient outcomes, including the use of chemical preservatives for disinfection, biocompatibility issues, and challenges with respect to lens care compliance. Given their unique composition and mechanism of action, one-step H2O2 systems offer the opportunity to avoid many of the challenges associated with MPS use. This article reviews the evolution of H2O2 lens care systems and examines the current scientific and clinical evidence regarding the relative ease of use, lens and tissue compatibility, disinfection efficacy, and ocular surface safety of H2O2 systems. Evaluation of the available data indicates that in comparison with MPS, one-step H2O2 systems tend to promote more favorable compliance, efficacy, comfort, and ocular surface outcomes for a wide range of contact lens–wearing patients. Based on the current published evidence, the authors recommend that eye care practitioners consider making one-step H2O2 systems their first-line contact lens care recommendation for most wearers of reusable lenses.

Nichols,J. J., Jones,L., Daniel Nelson,J., Stapleton,F., Sullivan,D. A., Willcox,M. D. P. The TFOS International Workshop on Contact Lens Discomfort: Introduction Investigative Ophthalmology and Visual Science 2013;54(11):TFOS1-TFOS6

Nichols,J. J., Jones,L., Morgan,P. B., Efron,N. Bibliometric analysis of the meibomian gland literature Ocular Surface 2021;20(April):212-214 [ Show Abstract ]

There is a rich history of interest in the sebaceous glands located posterior to the tarsal plates in the eyelids, to which we refer today as the meibomian glands (MGs). Although there is acknowledgement of the MGs preceding the work of Johann Heinrich Meibom in the 1600's, he is credited with advancing our knowledge and study of these glands.

The MGs produce a distinct lipid secretion (‘meibum’) made up of a variety of lipid classes, mostly composed of nonpolar wax and cholesterol esters, although other nonpolar and polar lipids are certainly known to exist in the meibum. The normal function of meibum is to make its way to the tear film lipid layer, ultimately forming a resistive barrier to evaporation of the aqueous component of the tear film. In disease, the MGs lose their ability to secrete a normal meibum composition and/or are impeded due to factors such as atrophy of the MGs, keratinization of the orifice of the gland from which the meibum is secreted onto the eyelid margin, or bacterial colonization of the eyelid, altering the secretion itself once expressed. These conditions today are known as blepharitis, including anterior and posterior blepharitis (which includes meibomian gland dysfunction).

Given the extensive study of MGs, a bibliometric analysis is warranted to acknowledge and celebrate those contributing to this important part of ophthalmic research.

Nichols,J. J., Jones,L., Morgan,P. B., Efron,N. Bibliometric analysis of the orthokeratology literature Contact Lens Anterior Eye 2021;44(4):101390 [ Show Abstract ]

The wearing of rigid lenses can result in changes to corneal curvature and the planned, temporary reduction of myopia by wearing flat-fitting rigid lenses (termed orthokeratology) was first reported in the 1960’s [1]. In the late 1970’s and early 1980’s, several studies evaluated this concept and concluded that the reduction in myopia was relatively short-lived, unpredictable, inconsistent and limited to only a low degree of myopia; as such, orthokeratology was largely ignored at this time [2, 3, 4].
A renewed interest in orthokeratology occurred in the late 1990’s and early 2000’s due to the simultaneous development of corneal topographers, highly oxygen permeable rigid lens materials and the development of sophisticated reverse geometry lenses that produced more predictable reductions in myopia [5, 6, 7, 8, 9]. This permitted contact lens fitters to adopt the concept of ‘overnight orthokeratology’, where patients wore the lenses during sleep and corneal shape changes occurred that reduced the degree of myopia to the point where the patient could remove the lens on waking and spend several days with no vision correction being required [10,11].
In 2005, Cho and colleagues reported that orthokeratology lenses used in children could slow the progression of myopia and this observation resulted in a resurgence in interest in orthokeratology [12]. Numerous publications since have shown that this myopia control effect is repeatable and many practitioners now adopt this modality on a routine basis to slow the progression of myopia, particularly in Asian countries [9,13, 14, 15, 16, 17].
The purpose of this paper is to report a bibliometric analysis of the literature on orthokeratology lenses so as to determine the most widely cited papers and most prolific authors, institutions, countries and journals related to this topic, and to recognise and celebrate the key stakeholders in this area of contact lens research.

Nichols,J. J., Morgan,P. B., Jones,L. W., Efron, N Bibliometric Analysis of Ophthalmic Journals JAMA Ophthalmology 2023;141(7):651-657 [ Show Abstract ]

KEY POINTS
Question: What articles, journals, authors, institutions, and countries in the ophthalmic literature are the most highly cited and prolific and have the highest h-index for ophthalmic journal articles?

Findings: In this qualitative study, the h-index for ophthalmic journal articles was determined to be 494, which appeared comparable with the journal literature of other medical disciplines.

Meaning: While these analyses excluded ophthalmology articles in general medical journals, they suggest a strong ophthalmic research base underpins eye care, with ophthalmology having the highest h-index across a range of ophthalmic and vision disciplines contributing to this literature.

ABSTRACT
Importance: The primary vehicle for reporting and testing advances in eye care is refereed ophthalmic journals, which can be characterized using targeted bibliometric analyses.

Objective: To identify all ophthalmic journals and evaluate citation metrics relating to articles, journals, authors, institutions, and countries published therein.

Design and Setting: A bibliometric analysis was undertaken of all ophthalmic journals included in the Scopus database (Elsevier). The search was restricted to all article types published in ophthalmic journals in English from inception through November 18, 2022. After excluding general medical journals, journals published in a language other than English, and spurious titles unrelated to the ophthalmic field, the Scopus database was found to list 335 ophthalmic journal titles that have published 471 184 articles, constituting the data set for this analysis. The 20 most highly cited articles were identified. Rank-order lists by article count were assembled for journals, authors, institutions, and countries.

Main Outcomes and Measures: An h-index for ophthalmic journal articles was derived from citations and article counts for each constituent of each category.

Results: The h-index for ophthalmic journal articles was determined to be 494. The journal with the highest h-index was Ophthalmology (h-index, 297). The journal with the greatest number of articles was American Journal of Ophthalmology (38 441 articles). The most highly cited article was by Quigley and Broman, 2006 (5147 citations), concerning the epidemiology of glaucoma. The author with the highest h-index for ophthalmic journal articles was Ronald Klein, MD (h-index, 126), and the most prolific was Carol L. Shields, MD (1400 articles). Johns Hopkins University (h-index, 215) was the institution with the highest h-index for ophthalmic journal articles, and Harvard University was the most prolific (10 071 articles). The United States was the nation with the highest h-index for ophthalmic journal articles (h-index, 444) and was the most prolific (180 017 articles).

Conclusions and Relevance: In this study, the most highly cited articles published in ophthalmic journals were revealed, as well as the leading journals, authors, institutions, and countries. While excluding ophthalmology articles in general medical journals, this investigation affords a means of identifying highly cited authors, institutions, and countries which individuals or institutions can use as a guide regarding contributions to the field.

Nichols,J. J., Morgan,P. B., Jones,L. W., Efron, N The history of optometry journals from a bibliometric perspective Hindsight 2023;54(2):36-43 [ Show Abstract ]

The rich history of optometric journal publications has been well documented, but the scientific impact of all optometry journals over all time has not been published. This work aims to determine the most impactful papers, authors, institutions and countries publishing in optometry journals. A h-index for “optometry journal publications” (the “hOJP-index”) was derived for each constituent of each category to serve as a measure of impact. The hOJP-index for the 34,565 papers published in all optometry journals is 136; these papers have been cited 294,239 times. Optometry and Vision Science is the most impactful and prolific journal (hOJP=118; n=13,095 papers). The most highly cited paper, by Richard Armstrong, is entitled “When to use the Bonferroni correction” (1,172 citations). Australian optometrist Nathan Efron is the most impactful and prolific author (hOJP=41; n=273). UNSW Sydney and the University of California, Berkeley are the most impactful institutions (both hOJP=58), and UNSW Sydney is the most prolific (n=963). The most impactful and prolific nation is the United States (hOJP=109; n=12,050). This quantitative bibliometric analysis demonstrates an impactful optometric research base enshrined in optometry journals.

Nichols,J. J., Morgan,P. M., Efron,N, Jones,L. W. Global optometrist research ranking derived from a science-wide author database of standardised citation indicators Clinical and Experimental Optometry 2022;105(1):20-25 [ Show Abstract ]

Clinical relevance
Publications in refereed scientific journals provide a rigorous research base that underpins clinical optometric practice. Leading optometrists who generate this literature can be identified and ranked using standardised citation indicators.

Background
This work seeks to identify and rank all optometrists included in a Science-Wide author database of standardised citation indicators (S-W) and to compare this ranking with the Global Optometrist Top 200 Research Ranking (T200).

Methods
A search was conducted for the names of all optometrists in the T200 who were included in the S-W, which is a world-wide listing of the top 2% of scientists in each of 174 subfield disciplines, ranked according to a composite citation indicator (cns) that excludes self-citations and corrects for multiple authorships and author order.

Results
The names of 66 optometrists are found in the S-W. Of these, 58 are designated as working in the primary sub-field ‘Ophthalmology & Optometry’; this listing, in rank-order of cns, is referred to as the ‘S-W-derived Optometrist Research Ranking’ (S-WORR). Australian optometrist Nathan Efron is ranked #1 in the S-WORR. The number (%) of optometrists in the S-WORR from each country is: the United States – 26 (45%), Australia – 12 (21%), the United Kingdom – 11 (19%), Canada – 5 (9%), Spain – 2 (3%), Hong Kong – 1 (2%) and South Africa – 1 (2%). The universities housing the equal highest number of optometrists in the S-WORR (five each) are the University of California, Berkeley, USA; the University of New South Wales, Australia; and Queensland University of Technology, Australia. There is a moderately strong correlation between T200 and S-WORR rankings (ρ = 0.6017, N = 58, p < 0.0001).

Conclusions
The S-WORR represents an elite cohort of optometrists who ought to be celebrated for their outstanding, leading and impactful contributions to optometric research.