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Background: Parkinson's disease symptoms mostly manifest after significant and irreversible neuropathology. Hence, there is a need to identify biomarkers that can provide indications of disease before significant neuronal degeneration occurs., Objective: To estimate the difference in the concentration of α-synuclein protein in tears between individuals with Parkinson's disease and healthy controls., Data Sources: PubMed, Scopus, and Web of Science. The last database search was on December 20, 2023., Study Eligibility Criteria: Primary prospective studies in humans measuring the level of α-synuclein in tears and clinical outcomes reported using mean or median., Participants and Interventions: Individuals with Parkinson's disease and healthy controls., Study Appraisal and Synthesis Methods: The risk of bias was assessed using the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity. The outcome measure was the difference in tear total and oligomeric α-synuclein. Mean difference (MD) was used to assess the outcome. The certainty of evidence was rated following the Grading of Recommendations Assessment and Development and Evaluation (GRADE) system., Results: Three hundred twenty-seven Parkinson's disease and 312 healthy control subjects from five studies and 177 Parkinson's disease and 166 healthy control subjects from two studies were included in total α-synuclein levels and oligomeric α-synuclein levels analysis, respectively. Total α-synuclein level was not different between Parkinson's disease and healthy controls (MD = 0.02 ng/mL [95% confidence interval {CI}: 0.00 to 0.05 ng/mL; I2 = 90%; Z = 1.79; p=0.07; number of studies = 5; GRADE rating = very low]). Stratifying the data based on disease duration, total α-synuclein was higher in subjects with Parkinson's disease duration ≥7 years compared with healthy controls (MD = 0.04 ng/mL [95% CI: 0.03 to 0.05 ng/mL; I2 = 0%; Z = 8.24, p<0.00001; number of studies = 2; GRADE rating = low]) but not different between the two groups (MD = -0.12 ng/mL (95% CI: -0.38 to 0.15 ng/mL; I2 = 93%; Z = 0.84, p=0.40; number of studies = 3; GRADE rating = very low]). Oligomeric α-synuclein level was higher in Parkinson's disease compared with controls (MD = 6.50 ng/mL [95% CI: 2.79 to 10.20 ng/mL; I2 = 94%; Z = 3.44; p=0.0006; number of studies = 2; GRADE rating = very low])., Limitations: High heterogeneity between studies. Potential sources of heterogeneity could not be explored due to the limited number of studies., Conclusions and Implications of Key Findings: Tear α-synuclein has the potential to be a noninvasive biomarker for Parkinson's disease. Studies are, however, needed to increase certainty in the biomarker and establish how the protein's changes in tears correlate with Parkinson's disease progression and severity., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2024 American Academy of Optometry.)

Significance: The dewetting process of contact lenses (CLs) is a result of material and solution properties as well as environmental factors. This article describes an investigational approach to observe and describe dewetting characteristics of different CL material and solution combinations., Purpose: This study aimed to determine the in vitro dewetting characteristics of various daily disposable CLs that were assessed using a noninvasive keratograph dewetting procedure (noninvasive keratograph dry-up time). In vitro dewetting data of the same CL materials soaked in saline solution and artificial tear solution (ATS) were measured to determine additional dewetting characteristics., Methods: Noninvasive keratograph dry-up time was measured for six different soft CL materials and three different test conditions, in their specific blister solution, after exposure to saline and an ATS. Twenty CLs of each solution/material combination were assessed after an 8-hour soaking, during a 180-second dewetting observation, and the results were expressed by area under the curve values., Results: Fastest dewetting occurred for all materials when measured out of saline, indicated by the highest averaged area under the curve value of 9243.3 ± 38.3 over all lens materials. Slower dewetting was detected for all materials when measured out of their specific blister solution (7755.9 ± 37.1) and out of ATS (7988.8 ± 40.0). Intragroup results were statistically significantly different for all solutions showing the smallest differences within the ATS group ( P < .001, Kruskal-Wallis test)., Conclusions: A pure saline thin film is not an ideal representation of a complex tear film layer of a healthy human because it lacks any evaporative protection by a lipid layer. The use of an ATS, which more likely mimics the natural tear film, allowed in this experimental in vitro project to decrease the gap to the in vivo field. In vitro dewetting information in connection with the blister solution allows only a theoretical conclusion about the initial lens wear after lens insertion., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

Significance: This analysis and review demonstrate that, although emerging data indicate that the prevalence of severe acute respiratory coronavirus 2 (SARS-CoV-2) on the ocular surface and coronavirus disease 2019 (COVID-19) conjunctivitis is rare, the ocular surface remains of interest as a potential inoculation and transmission site for SARS-CoV-2. Continued safety precautions should be taken as more data become available.COVID-19, caused by SARS-CoV-2, is a novel, global pandemic that has infected millions and, up to this point, caused more than two million fatalities worldwide. The ocular surface has become of interest as a possible vector for transmission by acting as a direct inoculation site, being a conduit for the virus into the respiratory system or as a method of transmission from potentially infected conjunctiva or tears. The components necessary for SARS-CoV-2 to theoretically infect ocular tissues are present: binding receptors (angiotensin-converting enzyme 2 and cluster of differentiation 147) and mechanisms for cell entry (transmembrane protease serine 2 and cathepsin L). This meta-analysis of COVID-19 prevalence data indicates that SARS-CoV-2 RNA has been infrequently found in conjunctival samples when tested with reverse transcriptase-polymerase chain reaction. This review estimates the prevalence of SARS-CoV-2 on the ocular surface and prevalence of conjunctivitis in patients with laboratory-confirmed COVID-19. There is much to be learned regarding ocular tropism of SARS-CoV-2., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Significance: Previous in vitro measurements of contact lenses commonly investigate the impact of nonpolar tear film lipids (i.e., sterols). Polar lipids, however, are equally important stabilizing components of the tear film. This research explores and presents further knowledge about various aspects of polar lipid uptake that may impact contact lens performance., Purpose: This study evaluated the impact of incubation time, lipid concentration, and replenishment of an artificial tear solution (ATS) on the uptake of phosphatidylcholine (PC) onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials., Methods: Four SHs and two CH lens materials (n = 4) were soaked in a complex ATS containing radioactive 14C-PC as a probe molecule. Phosphatidylcholine uptake was monitored at various incubation time points (1, 3, 7, 14, and 28 days), with different ATS lipid concentrations (0.5×, 1×, 2×) and with and without regular replenishment of the ATS. Phosphatidylcholine was extracted from the lenses, processed, and counted by a β counter, and accumulated PC (μg/lens) was extrapolated from standard lipid calibration curves., Results: All materials exhibited increasing PC deposition over time. Conventional hydrogel materials showed significantly lower PC uptake rates (P < .001) than any of the SH materials. Increasing lipid concentration in the ATS resulted in increased PC binding onto the contact lens materials (P < .001). Replenishing the ATS every other day, however, impacted the PC deposition differently, showing increased binding (P < .001) on CHs and reduced PC deposition for SH materials (P < .001)., Conclusions: Length of incubation, lipid concentration in the ATS, and renewal of the incubation solution all influenced the amount of PC that sorbed onto various lens materials and therefore need to be considered when conducting future in vitro deposition studies., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Significance: While evaluating the tear-film breakup time, a careful set of precise instructions should be given to the subjects regarding the blink type because it substantially impacts the assessment of tear-film surface quality., Purpose: The purpose of this study was to determine to what extent the type of blink affects the tear-film breakup time and its assessment using two types of videokeratoscopes and the fluorescein test., Methods: Thirty-three volunteers were assessed considering two different types of blinks: natural (short) and forced (unnaturally prolonged). Objective noninvasive breakup time estimation was performed using Oculus Keratograph 5M and Medmont E300, both equipped with tear-film analysis modules, followed by the fluorescein test. In addition, while overviewing videokeratoscopy recordings, noninvasive breakup time was assessed subjectively by one experienced observer marking the first noticeable distortion in the Placido-disk pattern. Statistical analyses included two-way ANOVA and paired-sample t test. The agreement between blinking and measuring modalities was assessed using Bland-Altman plots., Results: Forced blink significantly shortened the tear-film breakup time in all measuring modalities (two-way ANOVA, P = .003). The mean difference between breakup time after natural and forced blink was 3.2 (P = .002), 2.4 (P = .005), and 2.1 seconds (P = .002), for Keratograph 5M, E300, and fluorescein test, respectively. The group median of differences between objective and subjective noninvasive breakup time was less than 1 second with both videokeratoscopes. The objective noninvasive breakup time measured with Keratograph 5M was significantly longer than those with E300 and fluorescein test (both P < .001). No statistically significant difference was found between E300 objective assessment and fluorescein test (P = .19)., Conclusions: Forced blinks affect the assessment of tear-film stability. Hence, attention should be given in instructing the subjects before tear-film breakup time evaluation irrespectively to the method of measurement.

Significance: The tear film promotes ocular surface health and protection through its various constituents' functions. The application of methods for ocular surface examination is essential in the research of diseases that affect the tear film. Rabbits have been used as a model to study some human ocular diseases and to test ophthalmic products., Purpose: The aim of the present study was to determine the biochemical profile, osmolarity, and tear ferning patterns of rabbit tears., Methods: Ten rabbits (Oryctolagus cuniculus) were evaluated for tear osmolarity, tear ferning types and grades (using Rolando and Masmali scales), and biochemical analysis of total protein, urea, and electrolytes (chloride, phosphorus, iron, sodium, potassium, and calcium)., Results: Median ± semi-interquartile range for tear osmolarity was 283.5 ± 7.5 mOsm/L. Tear ferning test grades were type 1.0 ± 0.5 on the Rolando scale and 1.0 ± 0.5 on the Masmali scale. Type I and grade 1 were the most commonly observed ferning classifications (60 and 50%, respectively) for the rabbits' tears. Results for electrolytes and other biochemical compounds were as follows: total protein 4.40 g/dL, urea 130.60 mg/dL, chloride 196.51 mEq/L, phosphate 7.35 mg/dL, iron 95.76 μg/dL, sodium 202.04 mmol/L, potassium 12.74 mmol/L, and calcium 11.53 mg/dL., Conclusions: The results of the various tests described herein may serve as a basis for research using rabbits as an ophthalmic disease model and in the development of diagnostic and therapeutic agents used for ocular health.

Significance: Midday fogging of scleral contact lenses requires frequent lens removal and reapplication for a large portion of lens wearers. Using a lens filling solution that mimics the composition of tears is hypothesized to have an impact on the production of material trapped under a scleral lens., Purpose: The purposes of this open-label study were to assess the safety of a scleral lens filling solution, which closely approximates the ionic concentration and pH of human tears, and to assess signs and symptoms of midday fogging with this formulation and with subjects' habitual sodium chloride solutions., Methods: Existing scleral lens wearers with midday fogging (N = 22) were examined and completed surveys of symptoms. Subjects filled the concavity of their current lenses with test solution and were assessed immediately and approximately 4 hours later for safety monitoring. Test solution was dispensed and used for 5 to 9 days when subjects were reexamined and repeated the surveys. Biomicroscopy and anterior optical coherence tomography images were used to assess midday fogging objectively., Results: The median (interquartile range) Ocular Surface Disease Index score decreased from 27.1 (21.7) U when using habitual filling solution to 9.1 (20.1) U when using the test solution (P = .006). Current Symptoms Survey findings with the test solution compared with habitual solution resulted in statistically significant decreases in burning/stinging (P = .04), grittiness/foreign body sensation (P = .01), dryness (P = .002), blurry/fluctuating vision (P = .002), and overall pain/discomfort (P = .006). Objective assessment of corneal staining and fogging revealed decreases that were not statistically significant in this small sample size., Conclusions: This study establishes the safety and subject tolerance of a scleral lens filling solution that mimics the ionic composition of human tears. Significant improvements in subjective ratings, although likely biased in this unmasked trial, suggest that further studies of the effectiveness of this solution in reducing midday fogging are warranted.

Significance: Lotrafilcon B lenses packaged in and cared for with block copolymer-containing (polyoxyethylene-polyoxybutylene; EOBO) lens care solutions resulted in lower cholesterol extraction than each of the habitual silicone hydrogel lens/multipurpose solution (MPS) regimens tested., Purpose: This study aimed to compare the extracted cholesterol of lotrafilcon B lenses packaged in and cared for with EOBO-containing lens care solutions with the extracted cholesterol of habitual silicone hydrogel lenses cared for with MPS not containing EOBO., Methods: In this prospective, randomized, observer-masked parallel study, habitual wearers of senofilcon C, senofilcon A, comfilcon A, and samfilcon A contact lenses using a non-EOBO MPS were randomized 1:1 to lotrafilcon B lenses packaged in and cared for with EOBO-containing solutions or to their habitual lenses and MPS. Subjects randomized to lotrafilcon B were further randomized to one of two EOBO-containing lens care solutions, OPTI-FREE PUREMOIST or CLEAR CARE PLUS with HydraGlyde (Alcon Laboratories, Inc., Fort Worth, TX). A subset of right eye lenses was collected after wear, and total cholesterol was extracted and measured using a fluorometric enzymatic assay., Results: Of 143 lenses analyzed, 95 were from subjects randomized to their habitual lenses/MPS and 48 to lotrafilcon B + EOBO lenses plus CLEAR CARE PLUS with HydraGlyde or OPTI-FREE PUREMOIST. The mean amounts of cholesterol extracted from lotrafilcon B + EOBO lenses cared for with CLEAR CARE PLUS with HydraGlyde (0.28 ± 0.18 μg/lens) and OPTI-FREE PUREMOIST (0.28 ± 0.48 μg/lens) were significantly lower than those extracted from senofilcon C (4.18 ± 3.25 μg/lens), senofilcon A (2.19 ± 2.69 μg/lens), comfilcon A (2.17 ± 1.47 μg/lens), and samfilcon A (2.07 ± 1.48 μg/lens) lenses used with MPS (P < .0001 each)., Conclusions: Cholesterol sorption was significantly lower in wearers of lotrafilcon B lenses cared for with polyoxyethylene-polyoxybutylene-containing lens care solutions than in users of habitual silicone hydrogel lenses cared for with non-polyoxyethylene-polyoxybutylene MPS.

Significance: Tear osmolarity has been reported as one of the best diagnostic tests for dry eye disease and its management. Contact lens wear is thought to influence tear homeostasis. Understanding how regular wear of contact lenses and their type affect tear osmolarity is important., Purpose: The purpose of this study was to assess changes in tear osmolarity and ocular symptoms over a period of 12 months following refitting contact lens wearers with daily disposable contact lenses., Methods: Fifty subjects aged (mean ± SD) 26 ± 4 years were refitted with either silicone-hydrogel (delefilcon A, SiHy, n = 34) or hydrogel (omafilcon A, Hy, n = 16) daily disposable soft contact lenses. Study included seven visits: baseline measurements without contact lenses; two visits for contact lens fit and selection; follow-up measurements after 3, 6, and 12 months of contact lens wear; and a post-study visit without contact lenses. Lens type selection was based on a set of objective measurements. Subjects were instructed to follow strict wearing rules. Impedance-based osmometer was used to collect samples from the lower tear meniscuses. The Ocular Surface Disease Index (OSDI) and the eight-item Contact Lens Dry Eye Questionnaire were used to assess subject-reported ocular symptoms and contact lens discomfort, respectively., Results: Downward trend of tear osmolarity was noted over the time course of study. Statistically significant differences were noted in tear osmolarity (Friedman test, χ = 21.91 [P < .001], and χ = 13.89 [P = .003]) for the right and left eyes, respectively. A statistically significant decrease in tear osmolarity was apparent only for initially symptomatic subjects (for OSDI ≥13: χ = 26.25, P < .001; for OSDI <13: χ = 5.65, P = .13). Statistically significant differences were not noted in OSDI and the eight-item Contact Lens Dry Eye Questionnaire between the baseline and 12-month visit (χ = 5.92 [P = .12] and R = 0.015 [P = .87], respectively). There was a difference between baseline and post-study visits (P = .002) in OSDI, showing lower score at the latter visit., Conclusions: Refitting with daily disposable contact lenses was demonstrated to lower tear osmolarity.

Significance: Noninvasive high-speed videokeratoscopy equipped with specific software has shown potential for assessing the homeostasis of tear film, providing clinicians with a fast and consistent tool for supporting dry eye diagnosis and management., Purpose: The purpose of this study was to evaluate the efficacy of a recently proposed method for characterizing tear film dynamics using noninvasive high-speed videokeratoscopy in assessing the loss of homeostasis of tear film., Methods: Thirty subjects from a retrospective study, of which 11 were classified as dry eye and 19 as healthy, were included. High-speed videokeratoscopy measurements were performed using E300 videokeratoscope (Medmont Pty., Ltd., Melbourne, Australia). Raw data were analyzed using a recently proposed method to estimate the dynamics of the tear film based on a fractal dimension approach. This method provides three time-varying indicators related to the regularity of the reflected rings: tear film surface quality indicator, breaks feature indicator, and distortions feature indicator. From each indicator, five parameters were extracted and analyzed, including noninvasive breakup time, mean value of the indicator in the stability phase, mean value of the indicator in the whole interblink interval, mean value of the indicator in the leveling phase, and the general trend of the time series. Receiver operating characteristic curves were used to determine the sensitivity and specificity of each parameter in dry eye detection., Results: The best discrimination performance between dry eye and healthy subjects was achieved with the breaks feature indicator noninvasive breakup time parameter, with an area under the curve of 0.85. For a cutoff value of 10 seconds, the sensitivity was 100% and the specificity was 84%., Conclusions: The analyzed method improves the assessment of tear film homeostasis in comparison with previous high-speed videokeratoscopy methods showing higher potential in assisting dry eye diagnosis.

Significance: The proposed automated approach for estimating the quality of the tear film closes the gap between the manual and automated assessment, translating the high-speed videokeratoscopy technology from scientific laboratories to a clinical practice., Purpose: To develop and test a new method for characterizing Tear Film Surface Quality with high-speed videokeratoscopy utilizing a fractal dimension approach., Methods: The regularity of the reflected pattern in high-speed videokeratoscopy (E300; Medmont) depends on tear film stability. Thus, determining tear film stability can be addressed by estimating the fractal dimension of the reflected pattern. The method is tested on 39 normal subjects. The results of the fractal dimension approach are compared with those obtained using previously proposed automated method, based on a gray-level co-occurrence matrix approach, and with subjective results obtained by two operators that were assessing the video recordings in ideal conditions., Results: Fractal dimension method was less affected by eye movements and changes in the videokeratoscopic image background than gray-level co-occurrence matrix method. Median difference of the noninvasive break-up time between manual and automated methods was 0.03 s (IQR = 4.47 s) and 0.0 s (IQR = 2.22 s) for gray-level co-occurrence matrix and fractal dimension approaches, respectively. Correlation coefficient with manual noninvasive break-up time was r = 0.86 (P < 0.001) for gray-level co-occurrence matrix approach, and r = 0.82 (P < 0.001) for fractal dimension approach. Significant statistical difference was found between noninvasive break-up measurements of manual and gray-level co-occurrence matrix method (P = 0.008)., Conclusions: The proposed method has the potential to characterize tear film dynamics in more detail compared to previous methods based on high-speed videokeratoscopy. It showed good correlation with manual assessment of tear film.

Significance: A corneal heat-transfer model is presented to quantify simultaneous measurements of fluorescein tear-breakup area (TBA) and ocular-surface temperature (OST). By accounting for disruption of the tear-film lipid layer (TFLL), we report evaporation rates through lipid-covered tear. The modified heat-transfer model provides new insights into evaporative dry eye., Purpose: A quantitative analysis is presented to assess human aqueous tear evaporation rate (TER) through intact TFLLs from simultaneous in vivo measurement of time-dependent infrared OST and fluorescein TBA., Methods: We interpret simultaneous OST and TBA measurements using an extended heat-transfer model. We hypothesize that TBAs are ineffectively insulated by the TFLL and therefore exhibit higher TER than does that for a well-insulting TFLL-covered tear. As time proceeds, TBAs increase in number and size, thereby increasing the cornea area-averaged TER and decreasing OST. Tear-breakup areas were assessed from image analysis of fluorescein tear-film-breakup video recordings and are included in the heat-transfer description of OST., Results: Model-predicted OSTs agree well with clinical experiments. Percent reductions in TER of lipid-covered tear range from 50 to 95% of that for pure water, in good agreement with literature. The physical picture of noninsulating or ruptured TFLL spots followed by enhanced evaporation from underlying cooler tear-film ruptures is consistent with the evaporative-driven mechanism for local tear rupture., Conclusions: A quantitative analysis is presented of in vivo TER from simultaneous clinical measurement of transient OST and TBA. The new heat-transfer model accounts for increased TER through expanding TBAs. Tear evaporation rate varies strongly across the cornea because lipid is effectively missing over tear-rupture troughs. The result is local faster evaporation compared with nonruptured, thick lipid-covered tear. Evaporative-driven tear-film ruptures deepen to a thickness where fluorescein quenching commences and local salinity rises to uncomfortable levels. Mitigation of tear-film rupture may therefore reduce dry eye-related symptoms.

Significance: The concentration of selected proteins and inflammatory mediators in tears of symptomatic and asymptomatic contact lens wearers were quantified. The level of leukotriene B4 was higher in the symptomatic group. This may suggest that inflammation can be the cause of discomfort sensation at the end of day., Purpose: The present study aims to quantify the concentration of selected tear lipids and proteins in symptomatic and asymptomatic contact lens wearers., Methods: Unstimulated evening tears were collected using glass capillary tubes from 45 healthy, adapted contact lens wearers. Twenty-two had self-described symptoms of dryness and discomfort with contact lenses and 23 were asymptomatic. Tear proteins were assayed using selected reaction monitoring mass spectrometry. Enzyme immunoassay kits were used to measure prostaglandins, leukotriene B4, and cysteinyl leukotrienes. Ocular comfort was rated on a scale of 1 to 100 at the time of tear collection., Results: The average evening comfort level was above 70 for the asymptomatic (83.96 ± 9.51, mean ± SE) and equal or below 70 for the symptomatic group (57.28 ± 12.38) (P < .001). LTB4 was significantly higher in symptomatic than asymptomatic contact lens wearers (0.32 ± 0.06 ng/μL vs. 0.17 ± 0.04 ng/μL, respectively; P = .03). Lysozyme was slightly but not significantly lower in symptomatic subjects (symptomatic 0.58 ± 0.10 mg/mL vs. asymptomatic 1.73 ± 0.46 mg/mL; P = .10). The levels of lactoferrin, lipocalin 1, proline-rich 4, prolactin-induced protein, prostaglandins, and cysteinyl leukotrienes were unchanged (P > .1) between symptomatic and asymptomatic subjects., Conclusions: The LTB4 concentration was significantly higher in symptomatic contact lens wearers compared to the asymptomatic group, and this may partly mediate the discomfort response during lens wear in the symptomatic lens wearers. No other differences were found in the level of tear factors of interest between the two groups.

Purpose: To determine tear neuropeptide levels in contact lens wearers and non-wearers, and to examine relationships with indices of corneal innervation, tear function, and ocular discomfort., Methods: A cross-sectional, single-visit, investigator-masked pilot study. Assessments included Ocular Comfort Index (OCI), central and mid-peripheral corneal nerve density and morphology (HRT-Rostock), corneal sensitivity (Cochet-Bonnet aesthesiometer), tear Substance P and calcitonin gene-related peptide (CGRP) concentration (ELISA), in situ tear osmolarity (TearLab), tear secretion (Phenol Red Thread), and noninvasive tear break-up time (NITBUT; Keeler Tearscope). Groups were compared using independent t-test or Mann-Whitney U test, and regional differences assessed using paired t-tests. Associations were analyzed using Pearson or Spearman correlation. Significance was determined at P < .05., Results: Twenty contact lens wearers (7M:13F, 32 ± 5 years) and 20 non-wearers (7M:13F, 31 ± 5 years) completed the study. OCI score was numerically higher in lens wearers (32.27 ± 5.33) than non-wearers (27.66 ± 9.94). Tear osmolarity was higher [298.0 (IQR 291.0-309.8) vs. 288.5 (282.3-298.3) mOsmol/L; P = .01] whereas NITBUT was lower (9.8 ± 3.4 vs. 13.8 ± 5.6 s; P = .01) in lens wearers compared with non-wearers. Tear neuropeptide concentrations were not different between groups [Substance P 4.29 ng/ml (IQR 1.57-6.05), CGRP 14.89 ng/ml (5.08-59.26)], and there were no differences in nerve morphology or ocular surface sensitivity. Higher nerve density, interconnections, and tortuosity were observed in the central cornea than mid-peripherally (P < .05). OCI score was moderately associated with nerve tortuosity (r = 0.42, P = .01). CGRP was associated with central nerve density (ρ = 0.38, P = .02), as was tear secretion (r = -0.37, P = .02). Nerve interconnections were strongly associated with corneal sensitivity (ρ = 0.64, P < .001)., Conclusions: Relationships were demonstrated between nerve density, tear CGRP, and corneal sensitivity. Markers of corneal neurobiology and sensory function do not appear to be altered in contact lens wear despite worse tear function (osmolarity and stability) in lens wearers. This suggests that mechanisms other than overt changes in corneal innervation regulate tear function during lens wear. The relationship between nerve tortuosity and ocular discomfort requires elucidation.

Purpose: To determine the repeatability of the flush tear collection technique and the Schirmer strip for Substance P tear analysis., Methods: The tears of 10 healthy non-contact-lens wearers were collected via Schirmer strip and microcapillary following instillation of either 20 μL (F-20) or 60 μL (F-60) of saline. Each technique was conducted on two occasions and in a randomized order. Total protein content (TPC) and Substance P concentrations were determined. The overall protein separation profile of each type of tears was examined using one-dimensional gel electrophoresis (1DGE)., Results: Collection rates were significantly faster for the F-60 compared to F-20 (17.3 ± 6.9 μL/min and 11.9 ± 5.3 μL/min, respectively, P < .001), with an average Schirmer strip length of 1.5 ± 2.1 mm/min. The coefficient of repeatability between days and eyes was greatest for the Schirmer strip, with eyes and days being significantly different (P = .03 and P = .03, respectively) for Schirmer strip Substance P. TPC was 3.8 ± 2.6 mg/mL, 3.3 ± 1.8 mg/mL, and 3.6 ± 3.0 mg/mL for F-20, F-60, and Schirmer strip techniques, respectively, with no significant difference between techniques (P = .85). Substance P concentration was 13.1 ± 14.8 ng/mL, 9.1 ± 6.1 ng/mL, and 14.9 ± 10.6 ng/mL for F-20, F-60, and Schirmer strip tears, respectively, with no significant difference between techniques (P = .57). 1DGE profile showed similar electrophoresis patterns among F-20, F-60, and basal tears., Conclusions: The F-60 method allows faster collection than F-20, but the latter results in better repeatability than both the F-60 and Schirmer sampling techniques. All three techniques return the same concentrations of TPC and Substance P. This indicates that tear collection using the F-20 may be more appropriate when conducting comparative analysis, whereas the F-60 may be more appropriate when more volume is required.

Purpose: To evaluate the applicability of the fourth-generation OCULUS keratograph in measuring lower tear meniscus height., Methods: Seventy cases (140 eyes) with dry eye disease and 37 controls (74 eyes) were enrolled. Tear breakup time (TBUT), Schirmer test I, and corneal fluorescein staining were examined. The images of lower tear meniscus were obtained by OCULUS keratograph. The tear meniscus height was measured and its correlation with traditional tear film diagnostic tests were analyzed., Results: Using the hyper-reflective lines, the height of the tear meniscus was measured using the images of the OCULUS keratograph. For the inter-individual variation, the intraclass correlation coefficients and coefficient of variation values were 0.914 and 16.4%, respectively. For the intra-individual variation, the intraclass correlation coefficients and coefficient of variation values were 0.939 and 15.9%, respectively. The interobserver reproducibility and the intraobserver repeatability were for the control only. The average tear meniscus height value in dry eye disease group was 0.22 (0.19-0.24) mm, being significantly lower compared with 0.29 (0.26-0.34) mm in the control group (p<0.001). Tear meniscus height value had significantly correlation with TBUT and Schirmer test I (r=0.619 and 0.626, both p<0.001). The measurement of lower tear meniscus by OCULUS had lower individual variability and better repeatability., Conclusions: OCULUS keratograph is a quick, noninvasive, and reliable method to measure lower tear meniscus, whose value has a significant correlation with traditional dry eye disease diagnostic tests.

Purpose: To evaluate the efficacy of topical application of 3% diquafosol tetrasodium solution for the treatment of soft contact lens (SCL) wearers with dryness. In addition to clinical tests and subjective symptoms, we assessed the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) used as a marker of membrane-associated mucins and sialic acid concentration in tear fluids as a marker of secreted mucins., Methods: Twelve SCL wearers with dryness symptoms were treated with diquafosol for 4 weeks. Clinical tests included the tear film break-up time (BUT), corneal and conjunctival fluorescein staining scores, and Schirmer values. Subjective symptoms were evaluated by the Dry Eye-Related Quality-of-Life Score (DEQS). Fluorescence intensities in the central cornea were measured by fluorophotometry at 5 minutes after a 5% F-WGA solution was applied to the eye. The tears collected by the Schirmer test strips were analyzed by high-performance liquid chromatography (HPLC), and the concentrations of sialic acid; total protein; and the four major tear proteins secretory IgA, lactoferrin, lipocalin-1, and lysozyme proteins were measured., Results: Comparing the results before and after diquafosol treatment, BUT (p < 0.01), kerato-conjunctival staining score (p < 0.05), corneal staining score (p < 0.05), and DEQS score (p < 0.01) showed statistically significant improvements. The F-WGA fluorescence intensities (p < 0.0001) significantly increased after treatment, whereas the concentrations of sialic acid and tear proteins remained unchanged., Conclusions: Topical application of diquafosol solution to the SCL wearers with dryness improved biomarker of membrane-associated mucins, BUT, staining of cornea and conjunctiva, and subjective symptoms.

Purpose: Ocular discomfort is among the main causes of contact lens wear discontinuation. This study investigated the association between subjective ocular comfort ratings and diurnal changes in tear protein concentrations with and without contact lens wear., Methods: The study was a prospective, open-label, single-group two-staged investigation. Basal tears were collected from 30 experienced contact lens wearers twice a day (morning and evening) using a noninvasive method without lens wear (stage 1) and during wear of Etafilcon A contact lenses (stage 2) for 7 to 10 days. Subjects rated their ocular comfort on a scale of 1 to 100 (with 100 as extremely comfortable) at each time of tear collection. Tears were analyzed using liquid quadrupole mass spectrometry in conjunction with selected reaction monitoring (SRM) method., Results: End-of-day comfort was reduced when wearing lenses (87.8 ± 14.3 AM vs. 79.2 ± 16.6 PM) compared to no lens wear (88.3 ± 12.6 AM vs. 84.7 ± 13.3 PM) (AM vs. PM, p < 0.05). A greater reduction in comfort over the day was seen during lens wear (p < 0.01). The concentration of prolactin-induced protein increased from morning to evening in both stages (mean ± SD; 0.08 ± 0.04 mg/ml, AM vs. 0.09 ± 0.05 mg/ml, PM, p < 0.05). There was no change in the concentration of lactoferrin (1.20 ± 0.77 mg/ml), lysozyme (2.11 ± 1.50 mg/ml), lipocalin 1 (1.75 ± 0.99 mg/ml), or proline-rich protein 4 (0.80 ± 0.49 mg/ml). The prolactin-induced protein concentration was negatively associated with discomfort levels in tears (p < 0.05, r = -0.29)., Conclusions: Only the absolute concentration of prolactin-induced protein correlated with subjective comfort ratings. Taking into consideration that prolactin-induced protein can be associated with disruption in water transport in lacrimal glands, our findings may indicate that changes to aqueous secretion are associated with contact lens discomfort.

Purpose: To examine the possible role of corneal sensitivity and tear film quality in triggering a blink by investigating the relationship between blink rate, central corneal sensitivity threshold (CST), ocular surface temperature (OST), tear meniscus height (TMH), tear film quality (noninvasive tear break-up time [NIBUT]), and tear film lipid pattern under normal conditions., Methods: Forty-two volunteers (average age, 27.76 ± 5.36 years; 11 males) with good ocular health (Ocular Surface Disease Index, <15.0) were recruited for this cross-sectional cohort study. Blink rate, CST (noncontact corneal air gas aesthesiometry, NCCA), minimum and maximum OST in the central and inferior cornea between blinks (thermal infrared camera), TMH, NIBUT, and lipid pattern of the tear film (Keeler Tearscope Plus) were recorded on the right eye only., Results: Median blink rate was 11 blinks/min (interquartile range [IR], 6.95 to 17.05), CST was 0.35 mbars (IR, 0.30 to 0.40), minimum OST in the central cornea was 35.15°C (IR, 34.58 to 35.50), and NIBUT was 34.55 s (IR, 12.45 to 53.80). Moderate but statistically significant correlations were observed between CST and NIBUT (r = 0.535, p < 0.001), CST and blink rate (r = -0.398, p < 0.001), lipid pattern and OST (r = 0.556, p < 0.001), and between CST and OST (r = 0.371, p = 0.008). The correlations between blink rate and NIBUT (r = -0.696, p < 0.001) and between OST and NIBUT (r = 0.639, p < 0.001; Spearman test) achieved higher significance; this was highlighted by the linear regression model where NIBUT and minimum central and inferior OST were identified as significant predictor variables., Conclusions: There is strong evidence for significant interactions between corneal sensitivity, NIBUT, OST, and blink frequency, emphasizing that ocular surface conditions represent a possible important trigger for the initiation of a blink. However, the mechanisms involved in the initiation of a blink are complex, with local ocular sensory input as only one trigger, along with other external influences and internal factors under cortical control.

Purpose: To assess the interchangeability of tear osmolarity measurements between electrical impedance and freezing-point depression osmometers and to analyze inter-eye tear osmolarity variability measured with these osmometers in healthy subjects., Methods: Tear osmolarity was measured using the TearLab osmometer (OcuSense Inc., San Diego, CA) and the Fiske 210 microsample osmometer (Advanced Instruments Inc., Norwood, MA). We randomly selected one eye in 50 subjects (29 women, 21 men; mean age, 33.16 ± 6.11 years) to analyze whether osmolarity measurements by these osmometers were interchangeable. Both eyes of 25 patients (15 women, 10 men; mean age, 34.32 ± 6.37 years) were included to analyze inter-eye osmolarity variability., Results: The mean tear osmolarity values measured with the TearLab osmometer were higher (305.22 ± 16.06 mOsm/L) than those with the Fiske 210 osmometer (293.40 ± 12.22 mOsm/L), with the intraclass correlation coefficient being 0.23 (p = 0.051). A Bland-Altman plot showed that the systems were not interchangeable because there was a systematic difference, with the limits of agreement being -17.93 to 41.57 mOsm/L. There were no statistically significant differences (p = 0.5006 and p = 0.6533, respectively) between an individual's eyes measured with either osmometer., Conclusions: Because the TearLab tear osmolarity measurements were higher than those of the Fiske 210 measurements and the limits of agreement were too wide, the two osmolarity values cannot be used interchangeably. In healthy subjects, there is no difference in tear osmolarity between right and left eyes of the same individual measured with both instruments.

: The tear film is a complex multilayer film consisting of various proteins, enzymes, and lipids and can express a number of biomarkers in cases of disease. The development of a contact lens sensor presents a noninvasive alternative for the detection and management of various diseases. Recent work has resulted in the commercialization of a device to monitor intraocular pressure for up to 24 h, and there are extensive efforts underway to develop a contact lens sensor capable of continuous glucose tear film monitoring to manage diabetes. This clinical perspective will highlight the major developments within this field and list some of the major challenges that still need to be addressed.

Purpose: To evaluate the effect of moisture chamber spectacles (MCS) on tear functions in dry eye subjects., Methods: In this short-term study, 30 subjects with dry eye were recruited and randomly divided into two groups. Fifteen subjects (MCS group) were instructed to wear the appropriately sized MCS for a total of 90 min. Another 15 subjects (control group) received a drop of sterile nonpreserved 0.9% sodium chloride solution immediately after baseline measurement. Ocular comfort, tear meniscus height (TMH), noninvasive tear film break-up time (NIBUT), tear film lipid layer, and conjunctival hyperemia were evaluated in both groups at 15-min intervals for a period of 90 min (baseline and 15, 30, 45, 60, 75, and 90 min)., Results: There were significant improvements in ocular comfort, TMH, NIBUT, and lipid layer in the MCS group compared with those in the control group (p < 0.05). After wearing MCS, values of ocular comfort, TMH, NIBUT, and lipid layer continuously increased across time and reached the maximum at 60 min and then slowly decreased but still remained higher (p < 0.05) than baseline values. No significant differences were observed in conjunctival hyperemia in either group or between groups across time (p > 0.05)., Conclusions: Wearing MCS provided improvement in ocular comfort and tear film stability. Moisture chamber spectacles seem to be a safe and promising alternative treatment for dry eye, especially for patients who work in adverse environmental conditions.

Purpose: To evaluate the most important signs of dry eye, such as osmolarity, inflammation, and diadenosine tetraphosphate (Ap(4)A) concentration before and after wearing scleral lenses for 8 h in keratoconus patients., Methods: A pilot, experimental, short-term study involved 26 keratoconus patients (average age, 36.95 ± 8.95 years). They voluntarily enrolled in the study at the Optometry Clinic of the Faculty of Optics and Optometry in the University Complutense of Madrid. They were divided into two groups: patients with intrastromal corneal ring, the ICRS group, and patients without ICRS, the keratoconus (KC) group. Ocular Surface Disease Index questionnaire, the Schirmer test without anesthesia, tear break-up time, matrix metalloproteinase 9 (MMP-9) concentration, osmolarity, and Ap4A concentration were evaluated before and after wearing a scleral lens for 8 h., Results: The patients wore the scleral lenses from 6 to 9 h, with a mean of 7.59 ± 0.73 h. The mean scleral lens sag for all patients was 4310 ± 166.31 μm, ranging from 4200 μm to 4800 μm. No significant changes in the Schirmer test and tear break-up time were found for either group. Ocular Surface Disease Index scores were statistically lower after wearing scleral lenses for both groups (p < 0.05). A significantly lower osmolarity and a significant rise of MMP-9 concentration after wearing scleral lenses were found in both groups (p < 0.05). Diadenosine tetraphosphate concentration was lower after wearing the scleral lens in the KC group (p < 0.05) but no significant difference was found for the ICRS group (p > 0.05)., Conclusions: Short-term scleral lens wearing improves the symptomatology and some signs of dry eye, such as osmolarity and Ap4A concentration. The increase of MMP-9 concentration could be caused by tear film stagnation and use of preserved saline.

Dry eye disease (DED) is a common, multifactorial disease of the tears and anterior ocular surface. The clinical diagnosis of DED is complex, requiring the consideration of both patient symptoms and signs, which can be apparently contradictory. Misdiagnosis can lead to suboptimal clinical management. Studies of the practice behaviors of optometrists suggest that there is the potential to improve the translation of research evidence relating to the diagnosis of DED into primary ophthalmic care. This review describes an evidence-based, pragmatic approach to the contemporary clinical diagnosis of DED, as a means for guiding best practice for the care of dry eye patients.

Purpose: To assess the surface tear breakup time and clinical performance of three daily disposable silicone hydrogel contact lenses over 16 hours of wear., Methods: Thirty-nine patients (mean [± SD] age, 22.1 [± 3.5] years) bilaterally wore (narafilcon A, filcon II-3, and delefilcon A) contact lenses in a prospective, randomized, masked, 1-week crossover clinical trial. Tear film was assessed by the tear meniscus height (TMH), ocular/contact lens surface temperature dynamics, and lens surface noninvasive breakup time at 8, 12, and 16 hours of wear. Clinical performance and ocular physiology were assessed by subjective questionnaire, by high-/low-contrast logMAR (logarithm of the minimum angle of resolution) acuity, and through bulbar and limbal hyperemia grading. Corneal and conjunctival staining were assessed after lens removal., Results: Delefilcon A demonstrated a longer noninvasive breakup time (13.4 [± 4.4] seconds) than filcon II-3 (11.6 [± 3.7] seconds; p < 0.001) and narafilcon A (12.3 [± 3.7] seconds; p < 0.001). A greater TMH (0.35 [± 0.11] mm) was shown by delefilcon A than filcon II-3 (0.32 [± 0.10] seconds; p = 0.016). Delefilcon A showed less corneal staining after 16 hours of lens wear (0.7 [± 0.6] Efron grade) than filcon II-3 (1.1 [± 0.7]; p < 0.001) and narafilcon A (0.9 [± 0.7]; p = 0.031). Time was not a significant factor for prelens tear film stability (F = 0.594, p = 0.555) or TMH (F = 0.632, p = 0.534). Lens brand did not affect temperature (F = 1.220, p = 0.308), but it decreased toward the end of the day (F = 19.497, p < 0.001). Comfort, quality of vision, visual acuity and contrast acuity, and limbal grading were similar between the lens brands but decreased with time during the day (p < 0.05)., Conclusions: The tear breakup time over the contact lens surface differed between lens types and may have a role in protecting the ocular surface.

Purpose: To investigate the relationship between ocular surface temperature (OST) and tear film thinning and breakup., Methods: Simultaneous imaging of OST and fluorescein tear thinning and breakup (FTBU) was performed on 20 subjects. Subjects were asked to open their eyes and refrain from blinking for as long as they could during testing. Ocular surface temperature was measured using an infrared thermographic camera (FLIR A655sc) and rates of ocular surface cooling (OSC) were analyzed using commercially available software. A method was developed to quantify the rate of FTBU formation using image-processing software., Results: Areas of FTBU and regions of OSC were observed to be colocalized, with localized cooling preceding the formation of FTBU. The rates of OSC and FTBU formation were positively correlated (r = 0.74). A second-order polynomial model accurately describes the physiological relationship between the area of FTBU and OST (p < 0.001). A linear approximation provides a more clinically interpretable rate of FTBU formation with decreasing OST (p < 0.001), while still retaining high R., Conclusions: The results suggest a direct relationship between FTBU formation and OSC. That cooling of the ocular surface precedes FTBU formation implies a process of evaporation contributing to tear film thinning and breakup. Our study suggests that measuring the OSC rate could be an indirect assessment of tear evaporation and could contribute to the management of evaporative dry eye.

Purpose: Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye., Methods: We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye., Results: Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1., Conclusions: Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.

Purpose: The purpose of this study was to examine the precision and accuracy of the Fiske 110 Osmolarity System under different protocols to determine the possible applications of this device in tear film research and clinical practice., Methods: Three separate studies were performed. In the first, Fiske 110 measurements were made on undiluted and diluted (1:1, 1:4, and 1:9 dilutions) standard samples of different osmolarity values: 50, 290, and 850 mOsm/kg and 297 and 338 mOsm/L. In the second study, measurements were made on different types of contact lens care solutions. Finally, in an agreement study, measurements were made in two sets of 60 subjects to compare TearLab versus Fiske 110 (using both 2- and 4-μL tear sample)., Results: Although osmolarity measurements for undiluted solutions differed statistically from reference standard values, all biases were in the tolerance range proposed by the manufacturer except for the 850-mOsm/kg solution. No significant differences from reference osmolarity values were observed for the 1:1 and 1:4 diluted 297- and 338-mOsm/L H2O solutions, respectively, although all diluted solutions showed a possible bias out of the range provided. Osmolarities for the soft contact lens solutions fell within the range 293 to 309 mOsm/kg with the exception of Opti-Free Express (225 mOsm/kg). In the agreement study, significant differences were observed between measurements obtained using the TearLab and both Fiske 110 procedures, although the Fiske 110 (4 μL) procedure was closer to the TearLab than the Fiske (2 μL) procedure., Conclusions: For undiluted solutions, the Fiske 110 shows good performance, making it a useful device for osmolarity measurements in lens care solutions or eye drops. A worse performance was observed for more diluted standard solution samples. When testing diluted samples, performance was acceptable for osmolarity values close to tear values.

Purpose: To assess the changes in intraocular scattering before and after instillation of diquafosol ophthalmic solution in patients with short tear breakup time (TBUT) dry eye., Methods: We prospectively examined 20 eyes of 20 short TBUT dry eye patients (study group) and age-matched 20 eyes of 20 healthy subjects (control group). Intraocular scattering was measured as the objective scattering index (OSI) at 0.5-second intervals over 10 seconds without blinking. Patients were instructed to start topical administration of 3% diquafosol ophthalmic solution six times daily for 4 weeks., Results: The OSI significantly deteriorated after 7.0 seconds compared with the initial value of OSI after the blinking in the study group. The OSI was also significantly higher in the study group than in the control group at 4.5 to 10.0 seconds after the blinking (p < 0.05). We found significant improvements 2 weeks after treatment not only in TBUT (p < 0.001) but also in the mean OSI, the OSI change rate, and the slope of the linear regression line of the OSI within 10 seconds (p < 0.001, p = 0.003, and p = 0.002, respectively). We also found significant improvements 4 weeks after treatment in these variables., Conclusions: Intraocular scattering deteriorates significantly with time in patients with short TBUT dry eye. Diquafosol ophthalmic solution exhibits an improvement not only in TBUT but also in intraocular scattering, indicating that diquafosol is also effective for improving the optical quality of the eye.

Purpose: To examine the relationships among tear osmolarity, tear film stability, and several measures of dry eye (DE) symptoms in a multivariable analysis., Methods: A cross-sectional study was conducted with 137 subjects (68 non-contact lens [CL] wearers and 69 soft CL wearers) recruited from a university campus. Tear breakup time (TBUT) was measured noninvasively (NITBUT) and with fluorescein (FTBUT). Tear osmolarity was measured by an osmometer. Dry eye symptoms were assessed using the Dry Eye Flow Chart and several different questionnaires., Results: Subjects ranged in age from 18 to 67 years, with a mean of 28 years. Subjects had a mean (SD) osmolarity of 293 (10) mOsm/L, NITBUT of 14.1 (10.9) seconds, and FTBUT of 14.8 (12.6) seconds. Shorter NITBUT and FTBUT were significantly associated with female sex (p = 0.001 and p = 0.027, respectively) and Asian ethnicity (p = 0.030 and p = 0.004, respectively). There were no clinically significant relationships between tear osmolarity and FTBUT, NITBUT, or DE symptoms. Higher Dry Eye Flow Chart score (i.e., worse symptoms) was associated with older age (p < 0.001), female sex (p = 0.014), CL wear (p < 0.001), shorter NITBUT (p < 0.001), and shorter FTBUT (p = 0.028). The sensitivities and specificities for using clinical measurements to diagnose moderate to severe DE were as follows: osmolarity, 0.67 and 0.46, respectively; NITBUT, 0.72 and 0.52, respectively; and FTBUT, 0.68 and 0.57, respectively., Conclusions: In a population of asymptomatic, mild and moderate DE patients, increased tear osmolarity was not significantly associated with reported symptom severity and frequency. Tear osmolarity, NITBUT, and FTBUT exhibited similar sensitivities and specificities when used to diagnose moderate to severe DE.

Purpose: To determine the repeatability and agreement between the noninvasive Keratograph tear break-up time (NIK-BUT) as measured by the Oculus Keratograph 4 and fluorescein tear break-up time (FBUT)., Methods: Sixty subjects were recruited for two study visits separated by 7 (± 2) days. At each visit, three NIK-BUT measures and FBUT measures were obtained. Each NIK-BUT measure from the Keratograph included a first and an average NIK-BUT. The means of the measures obtained, first NIK-BUT, and average NIK-BUT and FBUT were calculated for each visit. Between- and within-visit agreement was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) analyses of log-transformed data., Results: Between-visit ICCs were 0.53 [95% confidence interval (CI), 0.32 to 0.69] for first NIK-BUT, 0.59 (95% CI, 0.40 to 0.73) for average NIK-BUT, and 0.66 (95% CI, 0.49 to 0.78) for FBUT, whereas 95% LoA were -0.65 to 0.67, -0.44 to 0.48, and -1.14 to 1.10 [back transformed: (visit 1 + 0.01)/(visit 2 + 0.01) = 0.22 to 4.68, 0.36 to 3.02, and 0.07 to 12.59] for the aforementioned methods, respectively. The visit 1 within-visit ICC between first NIK-BUT and FBUT was 0.44 (95% CI, 0.21 to 0.62), whereas the 95% LoA was -0.84 to 1.18 [back transformed: (first NIK-BUT + 0.01)/(FBUT + 0.01) = 0.14 to 15.14]. Likewise, the visit 1 within-visit ICC between average NIK-BUT and FBUT was 0.41 (95% CI, 0.18 to 0.60), whereas the 95% LoA was -0.58 to 1.44 [back transformed: (average NIK-BUT + 0.01)/(FBUT + 0.01) = 0.26 to 27.54]., Conclusions: The 95% LoA suggest that the average NIK-BUT has better between-visit agreement compared with the first NIK-BUT or FBUT. The first NIK-BUT showed better within-visit agreement with the FBUT than the average NIK-BUT. In addition, there is better between- and within-visit agreement for all measures at lower values.

The clinical perspective that dry eye is, at best, an incomplete diagnosis and the benefit of an etiology-based approach to dry eye are presented. To provide context for this perspective, the historical and current definition of dry eye is reviewed. The paradigm shift introduced by the Meibomian Gland Dysfunction (MGD) Workshop, that MGD is likely the leading cause of dry eye, is discussed in combination with the advancements in the diagnosis and treatment of MGD. To facilitate discussion on the benefit of an etiology-based approach, a retrospective observational analysis was performed on deidentified data from eligible, fully consented, refractory dry eye patients, where conventional sequelae-based dry eye treatment had failed. In this refractory population, the diagnosis of MGD, which directed treatment to evacuating gland obstructions and rehabilitating gland function, was successful. The clinical perspective that "dry eye" is the wrong diagnosis for millions is provocative. However, the MGD-first approach has the potential to revolutionize the timing of diagnosis and the choice of frontline therapy in most patients with dry eye. Additionally, the ability to screen for MGD in its earliest stages, during routine care, expands the scope of clinical practice to include early intervention. For most patients, we are no longer constrained to delay diagnosis until the tear film has decompensated and the cascade of inflammation has ensued. We do not have to wait for our patients to tell us there is a problem.

Purpose: To analyze dry eye disease (DED) tests and their consistency in similar nonsymptomatic population samples living in two geographic locations with different climates (Continental vs. Atlantic)., Methods: This is a pilot study including 14 nonsymptomatic residents from Valladolid (Continental climate, Spain) and 14 sex-matched and similarly aged residents from Braga (Atlantic climate, Portugal); they were assessed during the same season (spring) of two consecutive years. Phenol red thread test, conjunctival hyperemia, fluorescein tear breakup time, corneal and conjunctival staining, and Schirmer test were evaluated on three different consecutive visits. Reliability was assessed using the intraclass correlation coefficient and weighted kappa (κ) coefficient for quantitative and ordinal variables, respectively., Results: Fourteen subjects were recruited in each city with a mean (± SD) age of 63.0 (± 1.7) and 59.1 (± 0.9) years (p = 0.08) in Valladolid and Braga, respectively. Intraclass correlation coefficient and κ values of the tests performed were below 0.69 and 0.61, respectively, for both samples, thus showing moderate to poor reliability. Subsequently, comparisons were made between the results corresponding to the middle and higher outdoor relative humidity (RH) visit in each location as there were no differences in mean temperature (p ≥ 0.75) despite RH values significantly differing (p ≤ 0.005). Significant (p ≤ 0.05) differences were observed between Valladolid and Braga samples on tear breakup time (middle RH visit, 2.76 ± 0.60 vs. 5.26 ± 0.64 seconds; higher RH visit, 2.61 ± 0.32 vs. 5.78 ± 0.88 seconds) and corneal (middle RH, 0.64 ± 0.17 vs. 0.14 ± 0.10; higher RH, 0.60 ± 0.22 vs. 0.0 ± 0.0) and conjunctival staining (middle RH, 0.61 ± 0.17 vs. 0.14 ± 0.08; higher RH, 0.57 ± 0.15 vs. 0.18 ± 0.09)., Conclusions: This pilot study provides initial evidence to support that DED test outcomes assessing the ocular surface integrity and tear stability are climate dependent. Future large-sample studies should support these outcomes also in DED patients. This knowledge is fundamental for multicenter clinical trials. Lack of consistency in diagnostic clinical tests for DED was also corroborated.

Purpose: The aim of this study was to determine if Demodex infestation is more frequent in contact lens wearers than in nonwearers. Secondary aims were to evaluate the effects of Demodex on the ocular surface (symptoms and signs) and to evaluate the ability of confocal laser scanning microscopy to detect and quantify the Demodex infestation compared with the conventional light microscopic technique., Methods: Forty Asian female participants (20 nonwearers, 20 lens wearers) with a mean (± SD) age of 27 (± 9) years were recruited. Ocular comfort scores (Ocular Surface Disease Index, Ocular Comfort Index, and Dry Eye Questionnaire), vital staining (corneal, conjunctival, and lid wiper), tear osmolarity, tear breakup time, and meibomian gland evaluation were evaluated. Demodex was detected using in vivo confocal microscopy and conventional light microscopy., Results: The number of Demodex was higher in lens wearers than in nonwearers (7.6 [± 5.8] vs. 5.0 [± 3.1]; p = 0.02). Demodex was observed in a large majority (90%) of lens wearers and in 65% of nonwearers using confocal microscopy (p = 0.06). The detection rate was lower in both groups using conventional light microscopy (p = 0.003) where Demodex could only be confirmed in 70% and 60% of lens wearers and nonwearers, respectively. The number of Demodex tended to increase with age (ρ = 0.28, p = 0.08), but Demodex did not appear to affect ocular comfort or any clinical signs (p > 0.05)., Conclusions: Contact lens wearers harbor Demodex as frequently as nonwearers and in higher numbers, which is best detected using in vivo confocal microscopy. The significance of these findings is uncertain because no associations were found with any symptoms and signs of dry eye disease.

Purpose: To determine the clinical performance of DAILIES TOTAL1 (DT1), Clariti 1Day (C1D), and 1-DAY ACUVUE TruEye (AVTE) silicone hydrogel daily disposable contact lenses (SiHy DDCLs)., Methods: Eligible participants, subdivided into asymptomatic and symptomatic groups, wore each SiHy DDCLs for three consecutive days. Each participant attended three visits (on day 1 at 0 hours; on days 1 and 3 after 8 hours of wear) per lens type. The order of lens wear was randomized, with at least 1 day washout between lenses. Lens-related performance was evaluated by assessing lens surface deposits, wettability, pre-lens noninvasive tear breakup time, lens movement, and centration; ocular response assessments included conjunctival redness, corneal staining, and conjunctival staining and indentation., Results: Fifty-one asymptomatic and 53 symptomatic participants completed the study. For all visits, the mean noninvasive tear breakup time was about 1 second longer with DT1 than with C1D and AVTE (p < 0.01). Overall, the wettability of all three lenses was good; however, DT1 was graded marginally better than the other lenses (both p < 0.01). On day 3, eyes wearing AVTE had significantly more dehydration-induced corneal staining compared with DT1 (AVTE, 24%; DT1, 11%; p < 0.01). After 8 hours, conjunctival staining was different between lenses (greatest with C1D and least with DT1; all p < 0.01). Conjunctival indentation was more prevalent with the C1D lenses (n = 70) compared with DT1 (n = 1; p < 0.01) and AVTE (n = 11; p < 0.01). There were no differences between asymptomatic and symptomatic lens wearers for any of the clinical parameters (all p > 0.05)., Conclusions: Each of the three SiHy DDCLs performed well. Noninvasive tear breakup time was longest and wettability was greater with DT1. C1D had the most conjunctival staining conjunctival indentation. There was no difference between asymptomatic and symptomatic wearers with regard to ocular response and contact lens-related parameters. These results suggest that SiHy DDCLs may be an excellent contact lens modality for the symptomatic patient.

Purpose: To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients., Methods: In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum - maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated., Results: The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017)., Conclusions: Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.

Purpose: To examine the relationship between tear meniscus height (TMH) and subjective meniscus grading (subjective tear meniscus [TM]) with tear osmolarity., Methods: Tear osmolarity measurements (using TearLab) and digital images of the TM were obtained in 177 consecutive patients undergoing an eye examination at our optometry clinic (Universidad de Santiago de Compostela, Spain) who fulfilled the study's inclusion criteria. Participants were also administered the McMonnies and Ocular Surface Disease Index questionnaires for the detection of dry eye disease. The lower TM was videotaped by a digital camera attached to a slit lamp in its central portion without fluorescein instillation. After the study, a masked observer extracted an image from each video and measured the TMH using open source software (NIH ImageJ). Subsequently, the masked observer subjectively graded the appearance of each meniscus. For statistical analysis, subjects were stratified by age and by dry eye symptoms as indicated by their scores in the two questionnaires., Results: In the whole study population, a significant relationship was observed between osmolarity and TMH (r = -0.41, p < 0.001) and osmolarity and subjective TM (r = 0.35, p < 0.001). A cluster analysis revealed similar correlations when subjects were stratified by age or dry eye symptoms, these correlations being more pronounced in older and more symptomatic subjects. Objective TMH measurements and subjective meniscus quality were also correlated (r = -0.75, p < 0.001)., Conclusions: Osmolarity and both objective TMH measurements and subjective interpretation of the meniscus showed high correlation, especially in older symptomatic subjects.

Purpose: To compare the effects of different volumes of fluorescein on tear breakup time (FTBUT) and to investigate if and to what extent the tear breakup time determined by an automated noninvasive instrument (NITBUT) differs from FTBUT., Methods: Twenty-four healthy volunteers were recruited to the study. Fluorescent tear breakup time was measured with different volumes of fluorescein solution delivered by either glass rod or objective directly by fluorescein strip. Noninvasive tear breakup time was measured with a noninvasive instrument (Oculus Keratograph 5M, Germany; K5). The average levels of the tear breakup times (TBUTs) and the variability of the successive recordings for each measurement were compared., Results: Increasing the volume of fluorescein delivered from 1 to 7 μl lengthened FTBUT by a mean ratio of 1.26-fold (p = 0.019) for the glass rod technique. No significant difference was detected in the FTBUT measured by the fluorescein strip technique when the delivered volume was increased from 4.5 to 7 μl. The variability of successive recordings was stable across the tested volumes for both techniques. Noninvasive tear breakup time determined by K5 was significantly longer than FTBUTs (mean difference: 3.90 seconds, p = 0.003 and 4.12 seconds, p = 0.002, respectively). Although no significant difference was detected in the average SD for successive recordings among K5 and the other two invasive techniques (p = 0.325), the variability of NITBUT was found significantly dependent on the observed TBUT (r = 0.532, p = 0.007)., Conclusions: The Oculus Keratograph 5M usually produced substantially longer TBUT compared with invasive techniques tested. The variability of readings by this novel method increased with the values of NITBUT. Given the small sample size in the current experiment, however, these findings need to be confirmed in a larger study.

Purpose: To determine whether tear collection by flushing the ocular surface with saline (flush tears) or collection by stimulation (reflex tears) can be used as an alternative to basal tear collection for the identification and quantification of lipids in the tear film., Methods: Tear samples were collected from 10 participants with no history of ocular surface disease or contact lens wear. Up to 10 μl of basal, reflex, and flush tear samples were collected from each eye using a microcapillary tube on three occasions with the order of methods randomized and allowing at least 24 hours between each collection method. Lipids were quantified from each tear sample using nano-electrospray ionization tandem mass spectrometry., Results: Total lipids significantly differed in their concentration (pmol/μl) and mole % with each collection technique. Cholesterol esters [mean % (SE)] formed the major component of the total lipidome in basal [54.8% (3.1)], reflex [35.7% (6.4)], and flush [33.0% (3.1)] tear samples. However, the mole % of each lipid class substantially varied with each tear collection method. Nonpolar lipids, including cholesterol, wax esters, and triacylglycerols, dominated the tear lipidome in basal [92.8% (1.9)], reflex [71.8% (7.9)], and flush [83.6% (3.8)] tear samples. However, the mole % of phospholipids in reflex [27.5% (8.1)] and flush [15.8% (3.8)] tear samples was higher (p = 0.005) than that in basal tears [5.4% (2.0)]., Conclusions: Flush or reflex tears did not have similar lipid profiles in either concentration or in mole % to basal tears. It is recommended that basal tears are used for tear lipid analysis as the reflex or flush tears contain very low levels of most lipid components.

Purpose: Alterations in tear film lipids may be important in modulating discomfort during contact lens wear. This study investigates associations between clinical and biological components of the lipid layer and seeks to determine the effect of lipid supplementation on contact lens wear comfort., Methods: Participants were grouped into symptomatic (n = 10) and asymptomatic (n = 10) contact lens wearers according to the Contact Lens Dry Eye Questionnaire. After 6 hours of lens wear, noninvasive surface drying time (NISDT) and the lipid layer grade were assessed using a Tearscope. Basal tears were collected using a microcapillary tube and assayed for concentration and activity of the secretory phospholipase A2 enzyme and concentration of the lipid aldehyde malondialdehyde. Mass spectrometry was used to characterize the tear lipidome. In the second phase, a liposomal spray (Tears Again, BioRevive) or a saline spray was sprayed over the upper eyelids of each subject during their down gaze and during lens wear. Noninvasive surface drying time and ocular comfort were obtained soon after spraying and again at 2 and 6 hours after the initial spray. Statistical tests included the Student t test, repeated-measures analysis of variance, and the Pearson correlation test where appropriate., Results: Noninvasive surface drying time was lower (p = 0.01) in symptomatic (4.5 ± 0.6 seconds) than in asymptomatic (9.9 ± 3.1 seconds) contact lens wearers. The mole percentage of wax esters in the total lipidome increased with NISDT (R = 0.70, p = 0.01). Secretory phospholipase A2 enzyme activity in tears was associated with higher levels of malondialdehyde (R = 0.65, p = 0.01) and shorter NISDT (R = 0.84, p = 0.001). Noninvasive surface drying time reduced over the time course for the saline spray (p = 0.01) but did not reduce until the 6-hour time point with the liposomal spray. With liposomal spray, NISDT was higher (p = 0.03) immediately after instillation compared with 6 hours later (9.5 ± 1.9 vs. 5.2 ± 2.1 seconds). A longer NISDT was associated with improved ocular comfort for those using the liposomal spray (R = 0.25, p = 0.005) but not with saline., Conclusions: Degraded lipids and a lower mole percentage of wax esters in the tear film may be associated with a lower NISDT. Lipid supplements may improve ocular comfort during lens wear by increasing NISDT.

Purpose: To investigate the capability of a new portable digital meniscometer (PDM) to measure tear meniscus radius (TMR) and tear meniscus height (TMH) at different locations along the lower lid and to evaluate relationships between tear meniscus regularity and the degree of lid-parallel conjunctival folds (LIPCOFs)., Methods: Using the PDM, the TMR and TMH of 42 subjects were measured at three locations along the lower lid of one eye: central, perpendicularly below the pupil center (TMR-C, TMH-C), and temporal (TMR-T, TMH-T) and nasal (TMR-N, TMH-N), perpendicularly below the limbus. Nasal and temporal LIPCOF grades were recorded. Correlations between the measurements were analyzed using the Pearson coefficient (or Spearman rank in nonparametric data), and the differences were evaluated by paired t tests or analysis of variance and post hoc Fisher least significant difference test., Results: Temporal TMR was 0.041 mm flatter (p = 0.002) and TMH-T was 0.063 mm higher (p < 0.001), whereas TMR-N was 0.026 mm flatter (p = 0.038) and TMH-N was 0.046 mm higher (p < 0.001) than TMR-C and TMH-C. Temporal LIPCOF grades were significantly correlated to temporal alterations in TMH (r = 0.590; p < 0.001) and TMR (r = 0.530; p < 0.001), and nasal LIPCOF grades were significantly correlated to nasal alterations in TMH (r = 0.492; p = 0.001) and TMR (r = 0.350; p = 0.023)., Conclusions: The PDM is able to noninvasively detect significant differences in TMR and TMH along the lower lid. The flatter TMR and higher TMH at the nasal and temporal locations are associated with increased LIPCOF. Because increased LIPCOF scores may affect tear film disruption along the lower lid, measuring TMR and TMH at the central position below the pupil may provide the best intersubject reliability.

Purpose: To assess the correlation between tear osmolarity readings and symptoms of dry eye in a nonclinical convenience sample and to determine how well symptoms and osmolarity correlate with the self-assessment of dry eye., Methods: Two hundred forty-nine attendees in the exhibit hall at an optometric educational meeting agreed to participate in a dry eye study. Contact lens wearers were excluded. Volunteers supplied demographic information and completed a 5-item Dry Eye Questionnaire (DEQ-5) and answered the question "Do you think you have dry eye" with a yes or no response. Osmolarity testing was done using the TearLab instrument on the right eye, then on the left eye. Pearson correlation analyses were performed to determine the relationship between variables., Results: There was no correlation between DEQ-5 scores and average tear osmolarity (correlation coefficient, 0.02) and highest osmolarity (correlation coefficient, 0.03). The mean DEQ-5 score was significantly higher among subjects who self-reported dry eye (mean, 11.3; p < 0.0001) compared with those who did not (mean, 5.4; p < 0.0001). No differences were observed between the yes and no self-reported dry eye groups and average osmolarity (p = 0.23) and highest osmolarity (p = 0.14)., Conclusions: In this nonclinical population, there was no significant correlation between tear osmolarity and ocular symptoms as reported or between tear osmolarity and the self-assessment of dry eye.

Purpose: The aims of this study were (i) to develop a new portable slit-lamp mounted digital meniscometer (PDM) and (ii) to test its accuracy and repeatability compared to the existing Yokoi et al. videomeniscometer (VM)., Methods: We developed a novel application for an iPod or iPhone, which created an illuminated target of parallel black and white bands. This was used as a portable device with which to perform reflective meniscometry. The medians of three consecutive measurements on five glass capillaries (internal radii, 0.100 to 0.505 mm) were compared between VM and PDM at two different sessions. Also, the central lower tear meniscus radius (TMR) in 20 normal subjects (10 males and 10 females; mean [SD] age, 32.3 [9.3] years) was measured using both techniques. Correlations between the instruments were analyzed using the Pearson coefficient. Differences between sessions and instruments were analyzed using Bland-Altman plots, coefficient of repeatability, and paired t-tests., Results: The PDM and VM were accurate in vitro (95% confidence interval [CI] of difference: PDM -0.0134 to +0.0074 mm, p = 0.468; VM -0.0282 to + 0.0226 mm; p = 0.775) and reproducible between sessions (95% coefficient of repeatability, 0.019 and 0.018, respectively). The mean difference between the PDM and VM in vitro was 0.0002 mm (95% CI, -0.0252 to + 0.0256; p = 0.984). In human subjects, mean (SD) TMR measured with the PDM (0.34 [0.10] mm) and VM (0.36 [0.11] mm) was significantly correlated (r = 0.940; p < 0.001), and there was no statistically significant difference between the measured TMR of the instruments (p = 0.124)., Conclusions: This new slit-lamp mounted digital meniscometer produces accurate and reliable measurements and provides similar values for tear meniscus radius, in human studies, to the existing VM. The instrument is suitable for use in both research and clinical practice.

Purpose: To explore interfacial behaviors and effects of temperature and dilatation on dynamic properties of multilayered human tear lipids extracted from silicone hydrogel (SiH) lenses worn by asymptomatic Asian and white subjects., Methods: Interfacial properties of lipids extracted from Focus N&D lenses worn by 14 subjects continuously for 1 month were studied. The lipids were deposited on an air bubble immersed in a model tear electrolyte (MTE) solution to form 100 ± 20-nm-thick films. Surface pressure was recorded during slow expansion/contraction cycles to evaluate compressibility and hysteresis of lipid films. Films were also subjected to fast step-strain dilatations at temperatures of 22 to 45°C for their viscoelastic property assessment., Results: Isocycles for Asian and white lipids were similar at low surface pressures but had distinctly different compressibility and hysteresis at dynamic pressures exceeding 30 mN/m. Rheological parameters of reconstituted lipids were also dissimilar between Asian and white. The elastic modulus E∞ for white lipids was 1.5 times higher than that for Asian lipids, whereas relaxation time (t) was on average 1.3 times higher for Asian. No significant changes were observed in rheological properties of both Asian and white lipids when temperature increased from 22.0 to 36.5°C. However, for white lipids, E∞ reduced considerably at temperatures higher than 42.0°C, whereas t remained unchanged. For Asian lipids, both E∞ and t started to decline as temperature increased to 38°C and higher., Conclusions: Higher elastic modulus of white lipids and elasticity threshold at certain deformations indicate stronger structure and intermolecular interactions as compared with more viscous Asian lipids. The differences in interfacial behaviors between Asian and white lipids may be associated with the differences in their chemical compositions.

Purpose: The aims of this study were to investigate the clinical practices of Australian optometrists as related to the diagnosis, quantification, and management of dry eye and to assess whether these are consistent with research evidence and current guidelines., Methods: An online survey was distributed to registered optometrists (n = 654). Respondents provided information regarding their preferred diagnostic procedures and management strategies for dry eye, practice modality, year of commencing practice, and whether they possessed an interest in dry eye., Results: Respondents (n = 144) used multiple procedures for diagnosis. Recording patient symptoms ranked as the most important, most valuable, and most commonly used technique. The main objective tests were fluorescein-assisted tear breakup time, corneal fluorescein staining, and meibomian gland evaluation. Optometrists with an interest in dry eye more frequently used lissamine green, phenol red test, interference fringes, and tear osmolarity than nonspecialist practitioners. Dry eye treatment varied with severity. The mainstay of therapy was nonpreserved lubricants and eyelid hygiene; more practitioners recommended topical corticosteroids, systemic omega-3 fatty acid supplementation and increased dietary intake of omega-3 fatty acids for moderate and severe disease, respectively. The primary sources of information used to guide practitioners' management were derived from continuing education conferences., Conclusions: This study indicates that although Australian optometrists use subjective and objective diagnostic tests and stratify treatment based on dry eye severity, there is a lack of uniformity regarding diagnostic testing, infrequent use of standardized grading scales, and significant variability in clinical care. These findings highlight the potential to improve the translation of dry eye research evidence and evidence-based guidelines into Australian optometric practice.

Purpose: To compare effects of small-incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (F-LASIK) on corneal sensation and dry eye parameters., Methods: In this prospective, randomized, contralateral-eye study, 28 patients with myopia or myopic astigmatism in both eyes were enrolled. One eye of each patient was treated by SMILE, and the fellow eye was treated by F-LASIK. Mean outcome measures Cochet-Bonnet esthesiometry, Schirmer test with anesthesia, tear breakup time, and tear film osmolarity were evaluated preoperatively as well as 1 week, 1 month, 3 months, and 6 months after surgery., Results: Corneal sensation was reduced after both SMILE and F-LASIK surgeries 1 week, 1 month, and 3 months after surgery (p < 0.05 in both groups). Corneal sensation was significantly lower after F-LASIK than after SMILE at postoperative 1 week, 1 month, and 3 months (p < 0.01 for all points). Dry eye parameters such as tear breakup time, Schirmer test, and tear film osmolarity did not change significantly in any of the procedures and were not significantly different between the procedures at any follow-up visits., Conclusions: The findings of the study revealed that, although both F-LASIK and SMILE procedures changed the corneal sensation 1 week, 1 month, and 3 months after surgery, they did not affect the dry eye parameters at any point.

Purpose: Dry eye is the most common complication after LASIK procedure and is associated with corneal denervation. We conducted the study to compare dry eye parameters and corneal sensitivity (CS) after laser in situ keratomileusis (LASIK) with a femtosecond laser (FS) or microkeratome (MK)., Methods: In this prospective, nonrandomized, comparative study, 87 consecutive patients with myopia were assigned to receive either LASIK surgery with an FS (n = 44) or MK-assisted LASIK surgery (n = 43). The groups were age and sex matched. Corneal sensitivity, Schirmer testing, tear breakup time (TBUT), conjunctival and corneal stainings, and a subjective questionnaire (Ocular Surface Disease Index [OSDI]) were evaluated preoperatively, at 1 week, and at 1, 3, and 6 months postoperatively., Results: Preoperative spherical equivalent and sphere, calculated ablation depth, and suction time differed significantly between the two groups (p < 0.01, all comparisons). Postoperatively, CS decreased in both groups and gradually recovered. Schirmer test values were not significantly different throughout the postoperative time points between the groups. Laser in situ keratomileusis-induced corneal epitheliopathy was also increased after operation in both groups. However, there was no significant difference between the groups in corneal and conjunctival staining scores. The OSDI scores were increased postoperatively in both groups. After adjustment for the calculated ablation depth, TBUT was the only parameter that was statistically higher in the FS group than in the MK group (p = 0.03)., Conclusions: Both FS- and MK-assisted LASIK reduced CS and TBUT and increased corneal staining and OSDI scores. However, TBUT was significantly higher in the FS group than in the MK group after operation.

Purpose: The purpose of this study was to evaluate the repeatability of tear evaporimetry based on infrared thermography in a clinical room setting and to test the effect of changing environmental humidity on ocular surface temperature (OST) and tear evaporation rates (TERs) in a controlled adverse environmental (CAE) chamber., Methods: Twenty-six healthy participants were enrolled, of whom 16 underwent repeatability measurements in a clinical room and 10 were exposed to a constant temperature of 30°C with a humidity of 45 and 65% in a CAE. Participants were acclimatized to each condition for at least 20 minutes before OSTs were taken. Tear film breakup time was assessed in the CAE only. Number of blinks and OSTs were continuously measured for 20 seconds for the cornea, conjunctiva, and overall ocular surface with an infrared camera; corresponding TERs were calculated., Results: The OSTs and TERs showed acceptable strength of agreement between the first and second measurements. The coefficients of repeatability were 0.4°C for OST and 6.0 W m for TER. An increase in chamber humidity (from 45 to 65%) increased OST (p < 0.05). The TER was not changed significantly (p > 0.05). The tear film breakup time and number of blinks were not significantly affected by different humidity conditions., Conclusions: This technique has acceptable repeatability and has potential to document individual tear evaporation changes with time where humidity may differ by less than 20%.

Purpose: To compare tear film osmolarity measurements between in situ and vapor pressure osmometers. Repeatability of in situ measurements and the effect of sample collection techniques on tear film osmolarity were also evaluated., Methods: Osmolarity was measured in one randomly determined eye of 52 healthy participants using the in situ (TearLab Corporation, San Diego, CA) and the vapor pressure (Vapro 5520; Wescor, Inc., Logan, UT) osmometers. In a subset of 20 participants, tear osmolarity was measured twice on-eye with the in situ osmometer and was additionally determined on a sample of nonstimulated collected tears (3 μL) with both instruments., Results: Mean (SD) tear film osmolarity with the in situ osmometer was 299.2 (10.3) mOsmol/L compared with 298.4 (10) mmol/kg with the vapor pressure osmometer, which correlated moderately (r = 0.5, P < 0.05). Limits of agreement between the two instruments were -19.7 to +20.5 mOsmol/L. Using collected tears, measurements with the vapor pressure osmometer were marginally higher (mean [SD], 303.0 [11.0] vs 299.3 [8.0] mOsmol/L; P > 0.05) but correlated well with those using the in situ osmometer (r = 0.9, P < 0.05). The mean (SD) osmolarity of on-eye tears was 5.0 (6.6) mOsmol/L higher than that of collected tears, when both measurements were conducted with the in situ osmometer. This was a consistent effect because the measurements correlated well (r = 0.65, P < 0.05).The in situ osmometer showed good repeatability with a coefficient of repeatability of 9.4 mOsmol/L (r = 0.8, P < 0.05)., Conclusions: Correlation between the two instruments was better when compared on collected tear samples. Tear film osmolarity measurement is influenced by the sample collection technique with the osmolarity of on-eye tears being higher than that of collected tears. This highlights the importance of measuring tear film osmolarity directly on-eye. The in situ osmometer has good repeatability for conducting this measurement.

Purpose: To analyze tear osmolarity over time after instillation of two commercially available eyedrops., Methods: This prospective, nonrandomized, simultaneous, comparative, open-label, unmasked study included 40 eyes of 20 consecutive subjects (mean age, 34.8 ± 11.8 years) with a diagnosis of moderate dry eye. Subjects were instructed to administer contralaterally controlled lubricants to the right ([RE] Blink Intensive Tears, Abbott Medical Optics, Santa Ana, CA) and left ([LE] Optive Eye Drops, Allergan Inc., Irvine, CA) eyes three times daily for 21 days. The impact of hypoosmotic (RE) and osmoprotective (LE) drops on tear osmolarity (TearLab Osmolarity System, TearLab Corporation, San Diego, CA) was measured before and 30, 60, 90, 120, and 180 minutes after instillation of the first set of drops. Follow-up measurements were performed 22 days later, 1 day after the subjects stopped using the drops., Results: In RE, compared with baseline, tear osmolarity values were significantly reduced at all time points after instillation, including at 180 minutes (p < 0.01). In LE, osmolarity was significantly reduced from baseline at all time points through 120 minutes (p < 0.01) but returned toward baseline at 180 minutes (p < 0.11). The minimal value reached at 90 minutes after instillation or the average reduction from baseline osmolarity was 27.6 ± 9.5 mOsm/L for RE as compared with 22.1 ± 12.3 mOsm/L for LE. Both groups showed significantly lower tear osmolarity at 21 days compared with that at baseline (hypoosmotic, 307.8 ± 11.9 mOsm/L vs. 329.4 ± 8.4 mOsm/L, p < 0.001; osmoprotective, 316.1 ± 12.5 mOsm/L vs. 327.6 ± 8.4 mOsm/L, p < 0.002)., Conclusions: Our results showed that both eyedrops reduced tear osmolarity within a short time frame after drop instillation (i.e., up to 120 minutes) and after a longer time frame (i.e., 21 days of application). However, hypoosmotic drops with sodium hyaluronate reduce tear osmolarity at a greater and more sustained rate than glycerin and carboxymethylcellulose-based osmoprotectants.