LipiFlow for the treatment of dry eye disease.

BACKGROUND: Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments. OBJECTIVES: To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials. There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) electronic databases. We also examined the reference lists of identified trials, review articles, and guidelines for information about relevant trials that may not have been identified by our search strategy. We contacted investigators regarding ongoing trials. The last database search was performed on 24 October 2022. SELECTION CRITERIA: We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included 13 trials that randomized a total of 1155 participants (28 to 236 participants randomized per study). Six trials were conducted in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were of single-center design, while four trials were of multicenter design; one trial did not report the number of participating centers. Study characteristics The study population of the included trials was 66% female (range 48% to 80%), with an age range of 19 to 86 years. LipiFlow, used as a stand-alone intervention, was compared with basic warm compresses in five studies, thermostatic device in five studies, oral intervention in one trial, and topical dry eye medications in one trial. LipiFlow was also evaluated together with eyelid hygiene product versus eyelid hygiene products alone in one trial. Findings Five trials compared LipiFlow with a basic warm compress applied for varying durations and frequencies during the trial period; only one of these trials combined a warm compress with eyelid massage. Analyzing symptom scores by different questionnaires (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED]) yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after four weeks. There was no evidence of a difference in meibomian gland expression, meibum quality, or tear breakup time when comparing LipiFlow with basic warm compresses. Another five trials compared LipiFlow with thermostatic devices. Analysis of symptom scores at four weeks showed that thermostatic devices had reduced OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I2 = 0, P = 0.007; 553 participants; very low certainty evidence) as compared with LipiFlow. When we compared LipiFlow plus eyelid hygiene with eyelid hygiene alone, there was no evidence of difference in signs or symptoms at any time point evaluated. Only one trial compared LipiFlow with a topical DED medication (lifitegrast 5%). The single-trial estimate suggested that 5% lifitegrast may increase meibomian gland expression scores compared with LipiFlow at day 42 (MD -1.21, 95% CI -2.37 to -0.05; 50 participants; low certainty evidence) by using a meibomian gland expression scale of 0 to 8. One trial compared LipiFlow with an oral intervention (doxycycline), finding that LipiFlow may result in significantly better SPEED scores than doxycycline at three months (MD -4.00, 95% CI -7.33 to -0.67; 24 participants; very low certainty evidence). No other significant differences in signs or symptoms were found between LipiFlow and doxycycline at three months. We did not find any other statistically significant differences in symptoms or signs for any other analysis performed in this review at the one- to four-week time point. Adverse events No trial reported any intervention-related, vision-threatening adverse events. AUTHORS' CONCLUSIONS: LipiFlow performs similarly to other commonly used DED treatments with regard to DED signs and symptoms. The best available evidence was deemed to have a high level of bias, leading to low or very low certainty evidence. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is therefore needed before any firm conclusions can be drawn regarding comparative benefits and harms.

In Silico and In Vitro Approach for Validating the Inhibition of Matrix Metalloproteinase-9 by Quercetin.

PURPOSE: To validate the mechanism and inhibitory activity of quercetin against matrix metalloproteinase-9 (MMP-9) using a hybrid in silico and in vitro approach. METHODS: The structure of MMP-9 was obtained from the Protein Data Bank, and the active site was identified using previous annotations from the Universal Protein Resource. The structure of quercetin was obtained from ZINC15. Molecular docking was performed to quantify the binding affinity of quercetin to the active site of MMP-9. The inhibitory effect of various concentrations of quercetin (0.0025, 0.025, 0.25, 1.0, and 1.5 mM) on MMP-9 was quantified using a commercially available fluorometric assay. The cytotoxicity of quercetin to immortalized human corneal epithelial cells (HCECs) was quantified by obtaining the metabolic activities of the cells exposed to various concentrations of quercetin for 24 hr. RESULTS: Quercetin interacts with MMP-9 by binding within the active site pocket and interacting with residues LEU 188, ALA 189, GLU 227, and MET 247. The binding affinity predicted by molecular docking was -9.9 kcal/mol. All concentrations of quercetin demonstrated significant inhibition of MMP-9 enzyme activity (all P <0.03). There was little to no reduction of HCEC metabolic activity after a 24-hr exposure to all concentrations of quercetin ( P >0.99). CONCLUSIONS: Quercetin inhibited MMP-9 in a dose-dependent manner and was well-tolerated by HCECs, suggesting a potential role in therapy for diseases with upregulated MMP-9 as part of its pathogenesis.

Optimization of goblet cell density quantification methods.

The purpose of this study was to develop a standardized, accurate and efficient method for estimating conjunctival goblet cell density (GCD) via optimizing sample storage conditions and quantification methods. Conjunctival impression cytology (CIC) membranes were collected from both eyes of 32 participants and were randomized to two storage durations (2-3 weeks, 6-7 weeks) and two storage container types (microcentrifuge tube, flat histology cassette). The CIC membranes were stained and subdivided into 25 areas (5 mm × 5 mm) for imaging and the GCs were counted under 200X magnification using three different methods: (1) full CIC membrane GC count of the 25 images with cell-counting software ("full"; reference method), (2) partial membrane GC count of 9 images with cell-counting software ("partial"), and (3) manual counting of the 25 images ("manual"). In all cases, GCD was determined by dividing the GC count by the counting area. The average time required for quantification was recorded to gauge efficiency. Results showed no significant difference in GC count between the two storage durations (p = 0.745) or storage container types (p = 0.552). The median (interquartile range (IQR)) time required to quantify a CIC membrane for the full, partial, and manual methods of GC counting, was 14.8(17.6), 4.6(5.2) and 5.0 (5.0) minutes, respectively. The agreement of GCD values between the full and manual methods (bias: 0.4, 95% LOA: [-4.6, 5.5]) was stronger than that comparing the full and partial methods (bias: 0.5, 95% LOA: [-18, 17]). All together, through systematic examination of key procedural variables, an optimized method for GCD quantification within 7 weeks of sample collection was outlined. Adaption of procedures described in this paper to facilitate accurate and efficient GCD quantification may serve as a valuable step in clinical trials investigating DED pathophysiology and/or novel DED treatment strategies.

Quantifying the Effect of Spectacle Frame Dimensions on Wind-Induced Ocular Plane Evaporation Using an in Vitro Model.

PURPOSE: To quantify the effect of spectacle frame dimensions on wind-induced ocular plane evaporation. METHODS: A drop of 0.5 µL water was pipetted onto an eye of a mannequin head. The face was fitted with a spectacle frame. A fan positioned 10 cm away directed air (185 CFM) toward the face and the time required for the drop to evaporate was recorded. This procedure was repeated with 31 different frames to obtain evaporation times for various eye sizes, vertical heights, vertex distances, temperature, and humidity. This was also repeated 30 times without spectacle wear to obtain evaporation times for various temperature and humidity conditions. RESULTS: Spectacle wear increased evaporation times compared with nonspectacle wear, in both high (>35%) and low humidity (<30%) conditions (both P<0.01). Humidity was correlated with evaporation time, regardless of spectacle and nonspectacle wear (both P<0.01). Evaporation time did not correlate with spectacle eye size, vertical height, or vertex distance (all P≥0.21). CONCLUSION: This study showed that spectacle wear guarded against wind-induced evaporation at the ocular plane compared with nonspectacle wear. However, once spectacles were worn, eye size, vertical height, and vertex distance were not correlated with evaporation times. Humidity drove evaporation independent of spectacle wear.

Lysozyme Deposition on Contact Lenses in an In Vitro Blink-Simulation Eye Model Versus a Static Vial Deposition Model.

PURPOSE: To evaluate active lysozyme deposition on daily disposable (DD) contact lenses (CL) using a novel in vitro blink model. METHODS: Three conventional hydrogel DD CL materials (etafilcon A, omafilcon A, nelfilcon A) and three silicone hydrogel DD CL materials (delefilcon A, senofilcon A, somofilcon A) were tested. The device blink rate was set to 6 blinks/min with a tear flow rate of 1 µL/min using an artificial tear solution (ATS) containing lysozyme and other typical tear film components. After incubation at 2, 4, or 8 hr, lenses were removed, and lysozyme activity was measured. A separate experiment was conducted with lenses incubated in a static vial containing 480 µL of ATS. RESULTS: Etafilcon A deposited significantly higher amounts of active lysozyme (402±102 µg/lens) than other lens materials after 8 hr (P<0.0001). Etafilcon A had a higher amount of active lysozyme using the blink model compared with the static vial (P=0.0435), whereas somofilcon A (P=0.0076) and senofilcon A (P=0.0019) had a higher amount of lysozyme activity in the vial compared with the blink model. CONCLUSION: The blink model can be tuned to provide quantitative data that closely mimics ex vivo studies and can be used to model deposition of lysozyme on CL materials.

An imaging system integrating optical coherence tomography and interferometry for in vivo measurement of the thickness and dynamics of the tear film.

BACKGROUND: The outermost layer of the tear film consists of a thin lipid layer (LL). The lipid layer serves as a barrier against evaporation of the aqueous component of the tear film. The ability to simultaneously image both the lipid layer thickness and overall tear film thickness is novel, and will help further understandings of mechanisms of how the lipid layer assembles and interacts with the full tear film thickness. METHODS: We developed a system that combines simultaneous optical coherence tomography (OCT) and thickness dependent fringes (TDF) interferometry for in vivo imaging of the tear film. The OCT possesses an axial resolution of 1.38 µm in tear film, providing an accurate measurement of the thickness of the overall tear film. The TDF can detect a minimal change of approximately 15 nm in LL thickness. In addition, the spatial resolution of TDF images in x-y plane is 5 µm. RESULTS: The effect of instilling artificial tears on the PCTF and PLTF was examined. In both contact lens and non-contact lens wear, it could be observed from the OCT results that instillation of artificial tears increased the thickness of the overall tear film immediately, followed by a gradual reduction thereafter. These findings were consistent with other studies. However, unlike those previous reports, the thickness of the LL in this study was quantified simultaneously with the TDF subsystem. The results showed that bulking agents such as these artificial tears were not necessarily intended to increase the LL thickness. Immediately after instillation of artificial tears, the PCTF increased from 4.4 ± 0.97 to 20.3 ± 3.6 µm. The PCTF then decreased to 8.8 ± 2.1 µm at 4 min post-instillation. The thicknesses of the LL were 62.4 ± 14.5 nm, 48.7 ± 5.3 nm, and 55.2 ± 9.8 nm at pre-drop instillation, post-drop instillation, and 4-min post-drop instillation, respectively. CONCLUSIONS: In this work, we have described a novel imaging system that integrated OCT and TDF imaging techniques, which may facilitate the study of many physiological and clinical aspects of the tear film.

Short-Term Comfort Responses Associated With the Use of Eyelid Cleansing Products to Manage Demodex folliculorum.

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

A Comparison of Dry Eye Diagnostic Tests Between Symptomatic and Asymptomatic Age-Matched Females.

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

Dental Plaque Removal and Re-Accumulation: A Clinical Randomized Pilot Study Evaluating a Gel Dentifrice Containing 2.6% Edathamil.

OBJECTIVES: The goal of this clinical study was to determine the effects of a dental gel containing 2.6% edathamil on overnight plaque re-accumulation and plaque removal. METHODS: In this double-blind, randomized crossover study, 10 subjects first brushed for one week with a washout toothpaste. On the evening of Day 7, prior to tooth brushing, Plaque Index (PI) was recorded, then plaque stained and photographed. Subsequently subjects were randomized to either brush with the test dental gel or the control. After overnight plaque accumulation, PI was recorded. Plaque was stained and photographed before and after subjects brushed with the same toothpaste as the previous night. Subsequently, the process was repeated with the second toothpaste. Image J software was used to quantify plaque presence. RESULTS: Mean increase in PI overnight after brushing (1.78 versus 0.94) and final PI after tooth brushing the next morning (2.20 versus 1.31) were significantly (p < 0.05) better after use of the test gel. Tooth surface covered by plaque overnight was significantly higher after using the control gel (22.3%) than the test gel (11.8%; p < 0.05). After morning brushing, the residual area of plaque on the teeth was significantly higher for the control gel (9.2%) than for the test gel (3.6%; (p < 0.05). CONCLUSIONS: A test dental gel more effectively reduced overnight plaque re-accumulation and achieved better plaque removal than a control dentifrice.

Corneal Swelling with Cosmetic etafilcon A Lenses versus No Lens Wear.

PURPOSE: To determine if the use of pigments or adding polyvinyl pyrrolidone during the fabrication of 1-DAY ACUVUE DEFINE (AD) brand contact lenses impacts open-eye corneal swelling compared with no lens wear (NLW). METHODS: A partial double-masked, randomized, bilateral crossover study was conducted in 24 Asian subjects using AD, 1-DAY ACUVUE DEFINE with Lacreon (ADL), NLW, and a control lens with no tint (1-DAY ACUVUE MOIST [AM]). Central corneal thickness was measured before insertion and immediately after removal after 8 ± 1 h of open-eye wear using an optical pachymeter in one eye. Corneal thickness along a 10-mm cord was measured in the contralateral eye using the Visante optical coherence tomographer (OCT). Corneal swelling was tested for noninferiority using a 5% margin. The endothelial bleb response was measured at baseline and 20 min after lens insertion using specular microscopy. Subjective grading of corneal staining and limbal/bulbar hyperemia were also monitored. RESULTS: After 8 ± 1 h of open-eye wear, central corneal swelling across the study lenses with either optical pachymeter or OCT methods was negligible. Peripheral corneal swelling least-square mean differences with OCT were -0.03% (95% confidence interval [95% CI], -0.65 to 0.58%) and -0.26% (95% CI, -0.87 to 0.36%) between AD and ADL and the control lens (AM), respectively, and 1.67% (95% CI, 1.06 to 2.29%) and 1.45% (95% CI, 0.84 to 2.06%) between AD and ADL and NLW, respectively. No endothelial blebs were observed. No clinically significant differences were distinguished between the lenses and NLW for corneal staining and limbal/bulbar hyperemia. CONCLUSIONS: After 8 ± 1 h of open-eye wear, central and peripheral corneal swelling along the horizontal meridian with AD, ADL, AM, and NLW were equivalent. These results confirm that the addition of polyvinyl pyrrolidone or pigments to etafilcon A to obtain a limbal ring design have no impact on corneal swelling or limbal/bulbar hyperemia during normal open-eye wear.

Effect of Lid Debridement-Scaling in Sjögren Syndrome Dry Eye.

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

Paraplegia after aortic and superior mesenteric artery stenting for occlusive disease.

Paraplegia after endovascular therapy for aortic and visceral artery occlusive disease is an extremely uncommon occurrence. Two cases of paraplegia after placement of an aortic covered stent for infrarenal aortic stenosis and a superior mesenteric artery stent for chronic visceral ischemia are presented. In both patients, embolization of the arterial supply to the spinal cord was the presumed cause. One patient had a slight recovery after intense physical therapy and rehabilitation. The second patient did not have any recovery from her paraplegia.

Repeatability of grading meibomian gland dropout using two infrared systems.

PURPOSE: To determine the interobserver and intraobserver repeatability in using the OCULUS Keratograph 4 (K4) and 5M (K5M) to grade meibomian gland (MG) dropout using meibography grading scales. METHODS: The inferior and superior eyelids of 40 participants (35 women, 5 men; mean age = 32 years) were imaged three times each on both instruments. The images were split into one training and two study sets; the latter were graded (four-point meibography scale) by two observers on two separate occasions (24 hours apart) to determine repeatability. Semiobjective quantification of percentage MG dropout was conducted using ImageJ on K4 and K5M images. A finer seven-point meibography scale was used to grade a separate set of K5M images. RESULTS: For the four-point scale, interobserver mean difference (MD) (±SD) was 0.08 (±0.55) on day 1 and 0.13 (±0.50) on day 2, and the concordance correlation coefficient (CCC) was 0.79 and 0.81 on days 1 and 2, respectively. Intraobserver MD (±SD) was 0.04 (±0.54), CCC = 0.79 for observer 1; intraobserver MD (±SD) was -0.09 (±0.60), CCC = 0.74 for observer 2. For the seven-point scale, interobserver MD (±SD) was 0.05 (±0.45), CCC = 0.89 on day 1, and interobserver MD (±SD) was 0.01 (±0.41), CCC = 0.91 on day 2. Intraobserver MD (±SD) was -0.10 (±0.35), CCC = 0.93 for observer 1, and intraobserver MD (±SD) was -0.06 (±0.30), CCC = 0.95 for observer 2. Percentage dropout measured between the K4 and K5M images showed lack of agreement, with 21.8% coefficient of repeatability. There was no significant correlation (r < 0.2; p > 0.05) between meibography score and clinical signs (corneal staining, gland expressibility, telangiectasia, vascularity, lash loss); however, there was a high correlation (r = 0.77; p < 0.05) between meibography score with percentage dropout. CONCLUSIONS: Observers graded from -1 to +1 grade units between and within themselves for a four-point scale, 95% of the time. Although the interobserver and intraobserver repeatability of the K4 and K5M were very similar, a high rate of disagreement in percentage dropout between K4 and K5M images suggests that the two instruments cannot be interchanged. Meibomian gland dropout scores did not correlate significantly with clinical signs. Using a finer scale may be beneficial for detecting change.

Ocular surface parameters repeatability and agreement -A comparison between Keratograph 5M and IDRA.

PURPOSE: To evaluate the repeatability and agreement in dry eye measurements using Oculus Keratograph 5M (K5M) and SBM Sistemi IDRA (IDRA). METHODS: A total of 108 participants were enrolled and 108 eyes were evaluated. Tear meniscus height (TMH) and first and average non-invasive break-up time (NIBUT) were measured using the K5M and IDRA (order randomly assigned). TMH was measured using the built-in caliper tool while NIBUT was computed by the automatic algorithm of the instruments. RESULTS: The Bland Altman plots analysis showed a good agreement between the two instruments for TMH (95 % Limits of Agreement (LoA), -0.17 to 0.16), but not the first NIBUT (95 % LoA, -8.13 to 14.79) and average NIBUT (95 % LoA, -7.89 to 10.32). The values of the first and average NIBUT measured using IDRA were significantly shorter than in K5M (difference = median (IQR) -2.75 (-6.48- -0.28)s, p < 0.001 and difference = median (IQR) -1.65 (-3.97-1.89)s, p = 0.008 respectively). The TMH (p = 0.037) and NIBUT average (p = 0.033) measured by K5M, as well as the TMH (p = 0.040) measured by IDRA, exhibited unstable measurements across the three measurement times. The remaining parameters exhibited stability with three repeated measurements. CONCLUSION: The NIBUT measurements are not interchangeable between IDRA and K5M, while the TMH was little difference between the two instruments. It is important to exercise caution when using different ocular surface analyzers to minimize errors in comparing multiple measurements.

A cross-sectional study of optometrists' attitudes towards dry eye disease management in Hong Kong: A web-based survey in Hong Kong.

Purpose: This study aimed to explore the practices of optometrists in Hong Kong towards diagnosing and managing dry eye disease (DED). Methods: From September 2021 to March 2022, an online questionnaire was distributed to optometrists in Hong Kong through several professional associations. The questionnaire included questions about the importance and usefulness of various diagnostic tests, as well as inquiries about management strategies and recommended follow-up schedules for DED. Responses were compared between optometrists who were more or less proactive in continuing education to identify potential differences. Results: The analysis included 68 valid responses. Sixty-one of them were Part 1 optometrists that represents 5.5 % of registered Part 1 optometrists back in 2022. Assessment of clinical symptoms was the most commonly performed investigation (93 %) and considered the most important (75 %) procedure in DED assessments, followed by corneal staining and fluorescein tear break-up time. Traditional diagnostic tests were preferred over newer methods, such as osmolarity, which were not yet commonly used. Unpreserved lubricants (90 %) and lid hygiene (63 %) were the primary treatments recommended for mild DED. Optometrists who had more experience and frequent participation in continuing education were more confident in diagnosing and managing DED, and more likely to recommend omega-3 supplements for moderate DED. Conclusion: The diagnostic and management strategies of optometrists in Hong Kong were generally consistent with the recommendations of the Dry Eye Workshop II report. However, standardized DED questionnaires and newer diagnostic tools were not commonly used. Evidence-based optometric care for dry eye management should be encouraged in Hong Kong optometric practice.

Evaluating the in vitro wettability and coefficient of friction of a novel and contemporary reusable silicone hydrogel contact lens materials using an in vitro blink model.

PURPOSE: To evaluate the in vitro wettability and coefficient of friction of a novel amphiphilic polymeric surfactant (APS), poly(oxyethylene)-co-poly(oxybutylene) (PEO-PBO) releasing silicone hydrogel (SiHy) contact lens material (serafilcon A), compared to other reusable SiHy lens materials. METHODS: The release of fluorescently-labelled nitrobenzoxadiazole (NBD)-PEO-PBO was evaluated from serafilcon A over 7 days in a vial. The wettability and coefficient of friction of serafilcon A and three contemporary SiHy contact lens materials (senofilcon A; samfilcon A; comfilcon A) were evaluated using an in vitro blink model over their recommended wearing period; t = 0, 1, 7, 14 days for all lens types and t = 30 days for samfilcon A and comfilcon A (n = 4). Sessile drop contact angles were determined and in vitro non-invasive keratographic break-up time (NIKBUT) measurements were assessed on a blink model via the OCULUS Keratograph 5 M. The coefficient of friction was measured using a nano tribometer. RESULTS: The relative fluorescence of NBD-PEO-PBO decreased in serafilcon A by approximately 18 % after 7 days. The amount of NBD-PEO-PBO released on day 7 was 50 % less than the amount released on day 1 (6.5±1.0 vs 3.4±0.5 µg/lens). The reduction in PEO-PBO in the lens also coincided with an increase in contact angles for serafilcon A after 7 days (p < 0.05), although there were no changes in NIKBUT or coefficient of friction (p > 0.05). The other contact lens materials had stable contact angles and NIKBUT over their recommended wearing period (p > 0.05), with the exception of samfilcon A, which had an increase in contact angle after 14 days as compared to t = 0 (p < 0.05). Senofilcon A and samfilcon A also showed an increase in coefficient of friction at 14 and 30 days, respectively, compared to their blister pack values (p < 0.05). CONCLUSION: The results indicate that serafilcon A gradually depletes its reserve of PEO-PBO over 1 week, but this decrease did not significantly change the lens performance in vitro during this time frame.

TFOS Lifestyle Report: Impact of environmental conditions on the ocular surface.

Environmental risk factors that have an impact on the ocular surface were reviewed and associations with age and sex, race/ethnicity, geographical area, seasonality, prevalence and possible interactions between risk factors are reviewed. Environmental factors can be (a) climate-related: temperature, humidity, wind speed, altitude, dew point, ultraviolet light, and allergen or (b) outdoor and indoor pollution: gases, particulate matter, and other sources of airborne pollutants. Temperature affects ocular surface homeostasis directly and indirectly, precipitating ocular surface diseases and/or symptoms, including trachoma. Humidity is negatively associated with dry eye disease. There is little data on wind speed and dewpoint. High altitude and ultraviolet light exposure are associated with pterygium, ocular surface degenerations and neoplastic disease. Pollution is associated with dry eye disease and conjunctivitis. Primary Sjögren syndrome is associated with exposure to chemical solvents. Living within a potential zone of active volcanic eruption is associated with eye irritation. Indoor pollution, "sick" building or house can also be associated with eye irritation. Most ocular surface conditions are multifactorial, and several environmental factors may contribute to specific diseases. A systematic review was conducted to answer the following research question: "What are the associations between outdoor environment pollution and signs or symptoms of dry eye disease in humans?" Dry eye disease is associated with air pollution (from NO2) and soil pollution (from chromium), but not from air pollution from CO or PM10. Future research should adequately account for confounders, follow up over time, and report results separately for ocular surface findings, including signs and symptoms.

Eyelid Warming Devices: Safety, Efficacy, and Place in Therapy.

Meibomian gland dysfunction (MGD) is characterized by the obstruction and/or inflammation of the meibomian glands that result in decreased and altered meibum secretion. This results in deficiencies in the tear film lipid layer which contributes to increased evaporation and destabilization of the tear film. One of the mainstay therapies for MGD is medical devices that apply heat and/or pressure to the eyelids and promote the liquification and outflow of meibum into the tear film. Over the past two decades, there have been a surge of interest in diagnosing and managing MGD. As a result, numerous medical devices have been developed and each have their own unique approach to treating MGD. This narrative review was conducted to summarize the current state of knowledge on eyelid warming devices, specifically warm eye coverings, devices that direct heat and/or pressure to the eyelids, moisture chamber goggles, and light-based therapy. This review summarized 58 human clinical studies and found that most eyelid warming devices were efficacious in improving signs and symptoms in a wide range of MGD severities and were generally safe to use.

Characterization of the thickness of the Tear Film Lipid Layer in Meibomian Gland Dysfunction using high resolution optical microscopy.

PURPOSE: To evaluate the thickness of the tear film lipid layer (TFLL) in meibomian gland dysfunction (MGD) using a high-resolution optical microscope. METHODS: The Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify 190 subjects into four groups: normal (OSDI<13 and MGS<10), mixed (OSDI≥13 and MGS<10), asymptomatic MGD (OSDI<13 and MGS≥10), and MGD (OSDI≥13 and MGS≥10). The high-resolution optical microscope was used to capture TFLL images in vivo. The histograms of TFLL thickness were analyzed and curve-fitted using probability density functions (PDFs). RESULTS: There were three obvious peaks in the distributions of TFLL across the groups. From the curve-fitting process, the main outcomes are displayed according to each Gaussian function with the position of peak (µ) and the summed percentage within the range of standard deviation (σ). The normal group had distribution as follows: 33.3 ± 0.005 nm, 26%; 53.9 ± 0.019 nm, 40%; 79.4 ± 0.064 nm, 12%. The mixed group had a distribution as follows: 33.8 ± 0.004 nm, 32%; 53.1 ± 0.115 nm, 21%; 71.7 ± 0.232 nm, 27%. The asymptomatic MGD group had a distribution as follows: 33.5 ± 0.004 nm, 20%; 49.2 ± 0.041 nm, 25%; 62.9 ± 0.063 nm, 47%. The MGD group had a distribution as follows: 34.3 ± 0.004 nm, 34%; 53.7 ± 0.022 nm, 28%; 74.9 ± 0.060 nm, 16%. CONCLUSIONS: The MGD and mixed groups had the largest percentages of TFLL thicknesses fall within the thinnest modes (peak 34.3 and 33.8 nm, respectively). These data show that measures of central tendency (e.g., averages, medians) do not fully appreciate the variable distributions of TFLL across disease spectra.

Temporal Change in Pro-Inflammatory Cytokine Expression from Immortalized Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress.

PURPOSE: To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. METHODS: HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD). RESULTS: Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1ß, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark. CONCLUSION: Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1ß, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line.