Soft toric contact lens wear improves digital performance and vision-A randomised clinical trial.

PURPOSE: To compare objective and subjective digital near visual performance and comfort in low to moderate astigmatic participants fitted with toric versus spherical equivalent silicone hydrogel daily disposable contact lenses. METHODS: This was a double-masked, randomised, crossover study. Participants aged 18 to 39 years with astigmatism of -0.75 to -1.50 D were recruited and fitted with toric and spherical contact lenses, in random order. Outcomes were measured at baseline and after 1 week of wear with each contact lens type after the follow-up visits. High- and low-contrast near logMAR visual acuity, automated visual acuity, zoom (%), contrast (%), reading distance (cm), critical print size (logMAR) and reading speed were assessed. Participants also completed the validated Near Activity Visual Questionnaire (NAVQ) and Contact Lens Dry Eye Questionnaire 8 (CLDEQ-8) for each correction type. RESULTS: Twenty-three participants completed the study (74% female, average age 24.4 ± 4.2 years). When participants wore toric contact lenses, near high- and low-contrast visual acuity and automated visual acuity improved by 3-4 letters (all p < 0.03) and participants were able to read faster on an iPad (p = 0.02). Participants were also able to read with 8% less contrast on the iPad with toric lenses (p = 0.01). Participants reported better subjective vision on the overall NAVQ (p = 0.001) and better comfort on the CLDEQ-8 (p = 0.02) with toric lenses. Fewer participants reported difficulty with maintaining focus at near, reading small print, reading labels/instructions, reading the computer display/keyboard and reading post/mail with toric correction. CONCLUSIONS: Toric contact lenses improve comfort, subjective and objective visual performance with digital devices and other near tasks compared with the spherical equivalent correction in participants with low to moderate astigmatism.

The structural and functional corneal reinnervation mechanism at different regions after LASIK-an in vivo confocal microscopy study.

PURPOSE: To determine the recovery of structural and functional corneal sensory nerves within the LASIK flap in order to provide insight to more proximal corneal reinnervation and symptoms post-LASIK. METHODS: Twenty participants underwent femtosecond LASIK with a superior flap hinge. Ocular Comfort Index in Chinese (OCI-C), Cochet-Bonnet esthesiometry, and in vivo confocal microscopy were conducted before surgery and 1 week, 1-, 3-, and 6-months post-LASIK to measure symptoms, corneal sensitivity, nerve fiber density, width, and the number of interconnections within the flap (central and mid-temporal regions), and next to the superior flap hinge. Linear mixed models were used to compare differences between corneal regions at each time point post-LASIK and changes over time post-LASIK. Spearman's correlation tests were used to examine the associations between variables post-LASIK. RESULTS: The least reduction in sensitivity (P < 0.03) and in nerve fiber density (P < 0.02) was found near the flap hinge compared to other regions, but no regional differences were found in nerve fiber width and interconnections. Nerve fiber density and the number of interconnections at all regions within the flap recovered over time (P < 0.02). The recovery of corneal sensitivity and nerve fiber width was only seen at the central and temporal regions (P < 0.04). No association was found between sensitivity and nerve parameters, but a higher OCI-C score was associated with a lower nerve fiber density near the hinge (r = - 0.43, P = 0.003) over time post-LASIK. CONCLUSION: Corneal sensitivity and density are preserved in the hinge, but this preservation of the corneal nerve damage does not affect the nerve morphology.

Alteration of the pattern of regenerative corneal subbasal nerves after laser in-situ keratomileusis surgery.

PURPOSE: Corneal nerves exhibit high plasticity, which allows successful reinnervation after nerve damage caused by laser in-situ keratomileusis (LASIK) surgery. This study aimed to examine corneal subbasal nerve orientation during regeneration after LASIK. METHODS: This study involved 20 healthy, myopic subjects who had undergone bilateral Femto-LASIK 12-16 months prior with a superior hinge position. The corneal subbasal nerve plexus at the central, mid-temporal and mid-superior cornea on the right eye were imaged using in vivo confocal microscopy. Global nerve fibre orientation (indicating the overall pattern) and variation of nerve fibre orientation (indicating the consistency of the orientation) was determined using customised MATLAB™ software (www.mathworks.com/products/matlab.html). Differences in nerve orientation variables between groups were examined using the Mann-Whitney U test. Linear mixed models with Bonferroni adjustment were conducted to examine differences between corneal regions, and over time, after LASIK. RESULTS: There were no differences between post-LASIK and control groups in global nerve orientation at any of the examined corneal regions. The post-LASIK subjects had a greater variation of nerve orientation at the central (p = 0.007) and temporal (p = 0.049) cornea than the controls. There was a difference in global nerve fibre orientation between corneal regions (p < 0.001) in the controls but not in the post-LASIK group. The variation of nerve fibre orientation was higher at the central, compared to the temporal and superior cornea after LASIK (p < 0.001), although there were no differences between corneal regions in controls. CONCLUSIONS: Our results demonstrate that there was an increased variability in the corneal subbasal innervation patterns following LASIK when compared to controls.

Topical Review: Effects of Contact Lens Wear on Corneal, Conjunctival, and Lid Margin Sensitivity.

SIGNIFICANCE: Contemporary soft contact lenses do not affect mechanical sensitivity of the cornea, whereas conjunctival sensitivity is increased compared with nonwearers. Orthokeratology lens wear, however, reduces corneal sensitivity. The effects of contact lenses on lid margin sensitivity are unclear, and the link between ocular surface sensitivity and discomfort requires further exploration.Although up to 50% of contact lens wearers experience discomfort with varying severity, impact, and frequency, the relationship between ocular surface sensitivity and ocular surface discomfort experienced during contact lens wear is unclear. The purpose of this review is to examine and summarize the current evidence for the impact of both historical and contemporary contact lens wear on ocular surface sensitivity, the etiology of changes in ocular surface sensitivity, contact lens wear-related factors associated with changes in ocular surface sensitivity, and the relationship between sensitivity and discomfort. Despite minimal effects on mechanical corneal sensitivity with contemporary soft contact lens wear, orthokeratology reduces corneal sensitivity through pressure-related effects. This review addresses the relevance of conjunctival and potentially lid margin sensitivity in tolerance and discomfort with contemporary lens wear and the impact of instrument and stimulus characteristics. Less invasive techniques particularly for lid margin sensitivity measurements are required. Given the potential interactions between a contact lens and the varied types of ocular surface nociceptors, instruments that allow for exploration of cold and chemical sensitivity particularly may better allow the effects of lens wear to be elucidated compared with those that explore high-threshold mechanical sensitivity alone. A better understanding of the relationships between lens wear and ocular surface sensitivity may result in improved management of contact lens discomfort.

Absorption and Extraction of Inflammatory Mediators From Contact Lens Materials.

OBJECTIVES: This report aimed to explore whether certain inflammatory mediators were absorbed, extracted, or bound by various contact lens materials. METHODS: Comfilcon A, balafilcon A, omafilcon A, and etafilcon A were soaked in 500 and 100 pg/mL of interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), or interleukin-1 receptor antagonist (IL-1Ra), and also in combined solutions of inflammatory mediators (500 pg/mL or 100 pg/mL) separately. Lenses were then extracted in 1:1 2% trifluoroacetic acid:acetonitrile. The extracted and residual concentrations of inflammatory mediators were determined using enzyme-linked immunosorbent assays. Absorbed (control-residual) and firmly bound (absorbed-extracted) concentrations were calculated for analysis. RESULTS: More MMP-9 was absorbed by omafilcon A (466±9 pg/mL) than balafilcon A (P=0.006; 437±11 pg/mL) or etafilcon A (P=0.001; 428±13 pg/mL) when soaked in 500 pg/mL, but no differences in 100 pg/mL. More MMP-9 remained firmly bound to omafilcon A (P=0.03; 174±3 pg/mL), comfilcon A (P=0.049; 168±34 pg/mL), and balafilcon A (P=0.01; 186±14 pg/mL) than etafilcon A (128±22 pg/mL). There were no differences in IL-8 absorption between lenses; however, more IL-8 remained firmly bound to omafilcon A (P=0.01; 336±25 pg/mL) than etafilcon A (106±133 pg/mL) when soaked in 500 pg/mL. No differences were found in concentrations of absorbed or firmly bound IL-1Ra between materials. When the mediators were combined, IL-8 was absorbed more in etafilcon A (P=0.03) than in other lens materials, but the absorbed IL-8 did not remain firmly bound. CONCLUSIONS: The uptake and extraction of inflammatory mediators from contact lenses was affected by competitive binding between the mediators.

Conjunctival MUC5AC+ goblet cell index: relationship with corneal nerves and dry eye.

PURPOSE: To evaluate the relative proportion of conjunctival MUC5AC+ and MUC5AC- goblet cells in a post-LASIK population and their association with dry eye indicators and corneal nerve morphology using a MUC5AC+ Goblet Cell Index. METHODS: Twenty subjects who had undergone LASIK > 12 months previously and 20 age-matched controls were recruited. Dry eye symptoms, tear breakup time, osmolarity, meniscus area and corneal nerve morphology were examined. Conjunctival impression cytology samples were collected from inferior-temporal bulbar conjunctiva using Millicell® inserts. Total goblet cell density was determined from positive cytokeratin-7 (CK7) immunolabelling; MUC5AC+ goblet cell density was determined from both CK7+- and MUC5AC+-immunolabelled cells. The ratio of MUC5AC+ to total density was defined as the "MUC5AC+ Goblet Cell Index". Differences in variables between groups and the associations between goblet cell variables and clinical assessments were examined. RESULTS: No significant differences in the total and MUC5AC+ goblet cell density and tear film parameters were found between groups, although greater ocular discomfort was reported in the post-LASIK group (P = 0.02). A higher MUC5AC+ Index was associated with worse/greater dry eye symptoms (ρ = 0.55, P = 0.01) and higher nerve tortuosity (ρ = 0.57, P = 0.01) in the post-LASIK group; lower nerve density and thickness was found in controls (ρ > -0.45, P < 0.05), but not associated with tear film parameters. CONCLUSIONS: The MUC5AC+ Goblet Cell Index provides an indicator of mucin secretion for assessing the goblet cell function in dry eye. In the post-LASIK participants, we found an increased MUC5AC+ Index associated with worse dry eye symptoms and adverse changes in corneal nerve morphology.

Tear Lactoferrin and Features of Ocular Allergy in Different Severities of Meibomian Gland Dysfunction.

SIGNIFICANCE: Meibomian gland dysfunction, but not atrophy, was associated with lower tear lactoferrin concentration, greater dry eye, and allergic symptoms, indicating greater inflammation and discomfort in patients with lower meibomian gland expressibility. PURPOSE: Meibomian gland dysfunction can potentially damage adjacent palpebral structures, which may induce inflammation in accessory lacrimal glands and affect lactoferrin secretion. This study aimed to examine the relationships between the severity of meibomian gland dysfunction with tear lactoferrin, conjunctival cell morphology, and clinical features of ocular allergy. METHODS: Forty subjects were divided into two groups based on the severity of meibomian gland plugging and expressibility and secondarily based on its atrophy. Dry eye and allergy questionnaires; slit-lamp examination, including lid telangiectasia; and meibography were performed. Tear lactoferrin concentration was measured using TearScan 270 MicroAssay. Impression cytology was performed on the upper palpebral conjunctiva, and goblet cell density and epithelial squamous metaplasia were quantified. RESULTS: Twenty-two subjects with meibomian gland dysfunction were categorized into severely obstructed group (case), whereas 19 subjects had minimal/no obstruction (comparison). Lower lactoferrin (1.3 ± 0.4 vs. 1.7 ± 0.4 mg/mL, P = .007), greater dry eye (7 [1 to 10] vs. 2 [0 to 5], P = .03), and allergy symptoms (9 [4 to 23] vs. 6 [0 to 9], P = .05) were found in the cases compared with the comparisons. There were no differences in conjunctival cell morphology between groups. The plugging score was correlated with lactoferrin concentration (ρ = -0.43, P = .006), dry eye (ρ = 0.36, P = .02), and allergic symptoms (ρ = 0.33, P = .04). Greater lid margin telangiectasia was associated with meibomian gland obstruction, but not atrophy. CONCLUSIONS: Meibomian gland activity/dysfunction, but not atrophy, may be associated with increased inflammation on the ocular surface. The inflammation may be sufficient to reduce tear lactoferrin production from damage to accessory lacrimal glands and/or meibomian gland and result in increased symptoms.

Corneal Nerve Morphology, Sensitivity, and Tear Neuropeptides in Contact Lens Wear.

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.

Preinflammatory Signs in Established Reusable and Disposable Contact Lens Wearers.

SIGNIFICANCE: Established reusable contact lens (CL) wearers show higher tear inflammatory cytokine concentrations and greater conjunctival metaplasia in the region covered by standard soft CLs. The balance of proinflammatory to anti-inflammatory cytokines, but not individual tear cytokine concentrations, was associated with self-reported CL discomfort. PURPOSE: Daily disposable (DD) lenses are often used to improve CL discomfort, but the effect on ocular inflammatory responses has not been fully investigated. This study aimed to compare the concentrations of tear cytokines and conjunctival cell morphology in healthy habitual DD and reusable soft CL wearers. METHODS: Thirty-six established daily CL wearers, including 14 DD and 24 reusable wearers, were enrolled. Symptoms and ocular surface integrity were evaluated. The concentration of tear cytokines (interleukin 1ß [IL-1ß], IL-6, IL-10, IL-12(p70), IL-17A, and tumor necrosis factor α) were determined using Multiplex assays. The ratios of proinflammatory and anti-inflammatory cytokines were calculated. Impression cytology was performed on the conjunctiva, and goblet cell density and epithelial squamous metaplasia were quantified. Differences in variables by CL replacement schedules and the associations between variables were analyzed. RESULTS: Reusable CL wearers had higher concentrations (in pg/mL) of IL-1ß (26 ± 7 vs. 16 ± 11), IL-6 (42 ± 14 vs. 25 ± 20), IL-10 (83 ± 23 vs. 49 ± 36), IL-12(p70) (145 ± 44 vs. 91 ± 68), IL-17A (93 ± 26 vs. 54 ± 44), and tumor necrosis factor α (312 [171 to 468] vs. 189 [6 to 447]) (all P < .01) and greater conjunctival metaplasia in the region covered by CLs (0.7 [0.2 to 1.6] vs. 0.4 [0.04 to 1.2], P = .01) compared with DD wearers. There was a positive association between CL discomfort and ratios of IL-1ß to IL-10 and IL-12(p70) to IL-10 (ρ = 0.42 and ρ = 0.33, P < .05). CONCLUSIONS: Higher ocular inflammatory responses, as indicated by higher tear cytokine concentrations and higher conjunctival epithelial metaplasia, were found in reusable CL wearers than in DD CL wearers. The balance of proinflammatory and anti-inflammatory cytokines may be helpful to assess the inflammatory status of the eye.

Changes in Tear Cytokine Concentrations Following Discontinuation of Soft Contact Lenses-A Pilot Study.

PURPOSE: This study investigated changes in selected tear cytokine concentrations (IL-1ß, IL-1Ra, IL-6, IL-10, IL-12 (p70), and TNF-α) after a 1-week washout from soft contact lens wear (CLW), and the repeatability of cytokine measurements using custom multiplex assays. METHODS: A total of 10 subjects completed this 6-visit (immediately following contact lens removal, and after 1, 2, 3, 4, and 7 [±1] days without CLW) pilot study. Approximately 20 to 30 µL of pooled basal tears were collected from both eyes at each visit. Two custom multiplex assays were used by two operators to quantify the concentration of tear cytokines. Tear samples from subjects 1 to 6 were analyzed using the first kit by operator 1. Tear samples from subject 7 to 10 plus additional tear samples from subjects 1 to 5, which were used to determine the between-kit per operator repeatability, were analyzed using the second kit by operator 2. Linear mixed models were used to determine changes in tear cytokine concentrations over time. Between-kit per operator and within-kit per operator repeatabilities were assessed using the Bland and Altman analysis. RESULTS: There were no significant changes in tear cytokine concentrations over a 1-week washout of CLW. More than 99% of the tear samples had detectable levels of cytokines using custom multiplex assays. Within-kit per operator repeatability was good, but between-kit per operator repeatability was poor; likely due to protein degradation, differences in operator experience, and operating procedures. CONCLUSION: A washout period may not be necessary when evaluating changes in tear cytokines with new contact lenses or lens care products. A well-trained operator using standardized operating procedures can produce repeatable measurements using custom multiplex assays.

Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye.

PURPOSE: The most likely etiology of post-LASIK dry eye is corneal nerve damage; however, no direct relationship between post-LASIK dry eye symptoms and nerve damage has been established, and limited information is available about the relationship between dry eye signs and corneal reinnervation after LASIK. Tear neuropeptides (SP and CGRP) are important in the maintenance of corneal nerve health, but the impact of LASIK has not yet been studied. This study evaluated changes in nerve morphology, tear neuropeptide, and dry eye, so as to establish the relationship between reinnervation and dry eye and to assess the role of tear neuropeptides in reinnervation post-LASIK. METHODS: Twenty non-dry eye volunteers who had undergone bilateral myopic-LASIK completed this study. Corneal nerve morphology (density, width, interconnections, and tortuosity), SP and CGRP concentration, and dry eye were monitored over time prior to, 1 day, 1 week, 1, 3, and 6 months post-LASIK. RESULTS: Dry eye symptoms and tear function, except for osmolarity (P = 0.003), remained unchanged post-LASIK. Corneal nerve morphology decreased immediately, and did not return to preoperative levels by 6 months post-LASIK (P < 0.001). Increased tear SP concentration was observed 3 months post-LASIK (P < 0.001). Associations between reinnervation as measured by increased density and lower tear SP (P = 0.03), and between increased density and decreased dry eye symptoms (P = 0.01) were found post-LASIK. CONCLUSION: An inverse relationship between reinnervation post-LASIK and dry eye symptoms was found, confirming that post-LASIK dry eye is a neuropathic disease. This study is the first to demonstrate an association between tear SP and post-LASIK reinnervation, suggesting that strategies for manipulating neuropeptide concentration to improve reinnervation may improve ocular comfort post-LASIK.

Ocular surface sensitivity repeatability with Cochet-Bonnet esthesiometer.

PURPOSE: To determine the repeatability of ocular surface threshold measurements using the Cochet-Bonnet esthesiometer on the same day and 3 months apart. METHODS: Two separate studies were conducted to determine the repeatability of ocular surface threshold measurements made on the same day (n = 20 subjects) and 3 months apart (n = 29 subjects). The Cochet-Bonnet esthesiometer was used to measure corneal and inferior conjunctival thresholds using the ascending method of limits. The pressure exerted by the Cochet-Bonnet esthesiometer was determined using an analytical balance, for both the 0.08- and 0.12-mm-diameter filaments. This calibration was then used to convert filament length measurements to pressure. Repeatability was determined using a Bland and Altman analysis. RESULTS: The pressure exerted at each filament length differed between the two filament diameters. The measured pressure also differed from values provided by the manufacturer. Repeatability of threshold measurements at the central cornea was shown to be good, with better repeatability for same-day measurements (coefficient of repeatability [CoR] = ±0.23 g/mm²) than for those 3 months apart (CoR = ±0.52 g/mm²). Threshold measurements at the inferior conjunctiva, in contrast, were poorly repeatable (CoR = ±12.78 g/mm²). CONCLUSIONS: Cochet-Bonnet esthesiometry is repeatable when performed on the central cornea on the same day and 3 months apart, but this instrument is not recommended for conjunctival threshold measurements.

Changes in tear glucose and insulin concentrations following an oral glucose tolerance test.

CLINICAL RELEVANCE: Tear glucose and insulin are responsible for the health of the ocular surface; thus, it is important for clinicians to detect the tear glucose and insulin using point-of-care methods. AIM: To determine if changes in blood glucose and insulin levels following an oral glucose tolerance test are reflected in the tears and to test the association between gene expression and tear insulin and glucose. METHODS: Twenty healthy young adults were enrolled. Basal tears and peripheral blood samples were collected to assess glucose and insulin using a point-of-care glucometer and ELISA assays in fasted subjects, and 1.5 and 3 h after an oral glucose challenge. Conjunctival impression cytology was collected to determine gene expression of insulin receptor (INSR) and glucose transporters (GLUT1 and GLUT4). Changes were examined using non-parametric one-way ANOVA. Spearman tests were conducted to examine associations between variables. RESULTS: Glucose and insulin levels increased 1.5 h after oral glucose in both blood (P < 0.001) and tears (P < 0.049) and returned to near baseline values after 3 h. There was a positive correlation between glucose levels in the blood and tears (rho = 0.57, P < 0.001), but not between blood and tear insulin levels (P = 0.18). Glucose and insulin levels in tears were correlated (rho = 0.32, P = 0.048). Tear glucose concentration at 1.5 h after oral glucose was associated with INSR expression (rho = 0.49, P = 0.03), and there was a trend with GLUT1 (P = 0.06) but not GLUT4. CONCLUSION: Tear glucose reflected blood glucose levels but this correspondence was not observed for insulin. Further studies are required to determine the role of glucose and insulin on the ocular surface in both health and diabetes.

Tear proteomic analysis of young glasses, orthokeratology, and soft contact lens wearers.

Contact lens-related ocular surface complications occur more often in teenagers and young adults. The purpose of this study was to determine changes in tear proteome of young patients wearing glasses (GL), orthokeratology lenses (OK), and soft contact lenses (SCL). Twenty-two young subjects (10-26 years of age) who were established GL, OK, and SCL wearers were recruited. Proteomic data were collected using a data-independent acquisition-parallel accumulation serial fragmentation workflow. In total, 3406 protein groups were identified, the highest number of proteins identified in Schirmer strip tears to date. Eight protein groups showed higher abundance, and 11 protein groups showed lower abundance in the SCL group compared to the OK group. In addition, the abundance of 82 proteins significantly differed in children compared to young adult GL wearers, among which 67 proteins were higher, and 15 proteins were lower in children. These 82 proteins were involved in inflammation, immune, and glycoprotein metabolic biological processes. In summary, this work identified over 3000 proteins in Schirmer Strip tears. The results indicated that tear proteomes were altered by orthokeratology and soft contact wear and age, which warrants further larger-scale study on the ocular surface responses of teenagers and young adults separately to contact lens wear. SIGNIFICANCE: In this work, we examined the tear proteomes of young patients wearing glasses, orthokeratology lenses, and soft contact lenses using a data-independent acquisition-parallel accumulation serial fragmentation (diaPASEF) workflow and identified 3406 protein groups in Schirmer strip tears. Nineteen protein groups showed significant abundance changes between orthokeratology and soft contact lens wearers. Moreover, eighty-two protein groups significantly differed in abundance in children and young adult glasses wearers. As a pilot study, this work provides a deep coverage of tear proteome and suggests the need to investigate ocular responses to contact lens wear separately for children and young adults.

Corneal epithelial dendritic cells, tear neuropeptides and corneal nerves continue to be affected more than 12 months after LASIK.

PURPOSE: LASIK causes corneal nerve damage and may affect the neuro-immune crosstalk. This study examined the effects of LASIK on corneal epithelial dendritic cells (CEDC) density and morphology and explored their relationships with corneal nerves and tear neuropeptides. A grading system was developed to assess CEDC morphology. METHODS: Intra- and inter-observer repeatability of the CEDC morphology grading system was established using kappa (κ). In vivo confocal microscope images of the central cornea were captured from 20 participants who had undergone LASIK 12-16 months earlier and 20 controls (age 18-32 years, 55%F). CEDC density was counted manually, and CEDC morphology was assessed using a new grading system. CEDC sub-types (contacting nerves [CEDCc] and not contacting nerves [CEDCnc]) were also assessed. Differences in CEDC density and morphology were examined using mixed models and chi-squared test. Relationships between CEDC and corneal nerve parameters and tear substance P were explored using Spearman's correlation. RESULTS: Excellent intra- and inter-observer repeatability was demonstrated for the grading system (κ = 0.82-0.97). In post-LASIK participants, CEDC density was lower compared with controls (5 [0-34] vs. 21 [7-77] cells/mm2 ; p = 0.01), and the proportion of CEDC with thick dendrites was higher (55%-73% vs. 11%-21%, p < 0.003). Higher tear substance P levels were associated with higher CEDC density (rho = 0.48, p = 0.003). Fewer nerve interconnections were observed in participants in whom CEDC had dendrites (p = 0.03). CEDC sub-types followed a similar pattern to CEDC. CONCLUSIONS: The findings suggest that CEDC may remain altered more than 12 months post-LASIK. The association with substance P suggests a role for CEDC in corneal neurogenic inflammation.

Patient and parent perceptions of myopia modalities.

PURPOSE: This study compared quality of life (QoL) of myopic adults and children who were established spectacle, soft contact lens (SCL), or orthokeratology (OK) wearers as well as parent/child responses using Pediatric Refractive Error Profile 2 (PREP2). METHODS: Forty-eight adults (aged 18-26 years), 49 children (aged 9-17 years), and the children's parent, completed PREP2, with 7 subscales (symptoms, vision, activities, appearance, peer perception, handling, and overall). Adults and children must have worn their correction for at least three years. Parents were asked to answer how they thought their child would answer. Scores were compared between age groups, among correction groups, and between children and their parents using non-parametric ANOVA, Mann-Whitney U and Wilcoxon Signed-Rank tests, as appropriate. Post-hoc pairwise comparisons among correction groups were conducted with Bonferroni adjustment. RESULTS: Average age of adults was 22 ± 2 and children was 14 ± 2 years, and duration of correction use was 8 ± 3 for adults and 5 ± 2 years for children (both p < 0.01). Adult OK wearers were more satisfied with vision (p = 0.04), activities (p < 0.001) and overall (p = 0.03) compared to spectacle wearers. Children OK wearers reported higher scores for activities than SCL (p = 0.048) and spectacle wearers (p < 0.001). Parents of contact lens wearers reported higher perceived QoL for activities (OK p < 0.001; SCL p = 0.02), handling (OK p = 0.02; SCL p < 0.001), appearance (SCL p = 0.001), and overall (OK p = 0.001; SCL p < 0.001) subscales than parents of child spectacle wearers. CONCLUSION: Activity-driven children and adults perceive significant benefits from OK over spectacles. Parents' perceptions did not align with their children's perceptions of their correction.

Epithelial Immune Cell Response to Initial Soft Contact Lens Wear in the Human Corneal and Conjunctival Epithelium.

Purpose: The purpose of this study was to assess the immediate ocular immune response to soft contact lens (CL) wear by examining presumed epithelial immune cell (EIC) density and morphology at the central, peripheral, limbal cornea, and conjunctiva. Methods: Fifty-four participants naïve to CL wear (mean age = 24.8 ± 9.8 years, 44% female participants), were examined using in vivo confocal microscopy at baseline and after 2 hours of CL wear (1-Day ACUVUE MOIST). Images were captured at the central, temporal far peripheral and limbal cornea, and bulbar conjunctiva. EIC density was counted manually and morphology was graded. Differences in EIC parameters pre- and post-CL wear were examined using a generalized estimating equation model with appropriate post hoc analyses. Results: After 2 hours of soft CL wear, there was a significant increase in EIC density in all regions other than the central cornea (all P < 0.001). Cell body size was significantly larger, and a higher proportion of participants exhibited EIC with long dendrites after lens wear at the central and peripheral cornea (both P < 0.001). There was a significant increase in the number of participants displaying EIC with thick dendrites at the peripheral (P = 0.04) and limbal cornea (P < 0.001) after lens wear. Conclusions: EICs were primarily recruited to the peripheral regions, whereas the central cornea shows no significant recruitment after short-term CL wear. Both central and peripheral corneas exhibited an enhanced antigen capture capacity, whereas migratory capacity was increased in the peripheral corneal regions suggesting EIC activation following a short period of CL wear.

Tear Proteomics of Children and Young Adult Soft Contact Lens, Orthokeratology and Spectacle Wearers - A Pilot Study.

PURPOSE: Contact lens complications occur more often in older teenagers and young adults compared to children. This study explored differences in tear proteomics between children and young adults wearing soft contact lens (SCL), orthokeratology or spectacles for >3 years. METHODS: Twelve children and 12 sex- and correction-matched young adults were enrolled. Tears were collected via Schirmer strips for tear proteomic analysis using mass spectrometry. Proteome Discoverer was used for protein identification. Label-Free Quantitation was generated using Scaffold software; Fisher's Exact tests were used to compare proteins by age and correction groups. Generalized linear models were used to assess differences in overall protein levels by age and correction groups. A secondary analysis of proteins presented in >50% of samples of each group was conducted using the R/Bioconductor limma package. RESULTS: There were 385 proteins present only in young adults while 183 were unique in children. There were 528 unique proteins to SCL, 96 to orthokeratology and 149 to spectacle wearers. Based on Fisher's Exact analyses, 126 proteins were higher in young adults than children (all P < 0.048). Forty-seven protein levels were higher in SCL compared to orthokeratology (all P < 0.01), 33 protein levels were higher in SCL compared to spectacles (all P < 0.01), 15 protein levels were higher in orthokeratology compared to spectacle wearers (all P < 0.01). Based on generalized linear models, young adults had higher overall protein levels than children (P = 0.001), SCL had higher protein levels than spectacle wearers (P < 0.001) but no differences were found between orthokeratology and spectacle wearers (P = 0.79). Based on the secondary analysis, only Antileukoproteinase was higher in the young adult orthokeratology group compared to other groups (P < 0.01). CONCLUSIONS: Tear protein type and abundance differ by age and correction. Further research is needed to understand the effects of contact lens correction in children and young adults on the tear proteome.

Eye care providers' emerging roles in early detection of diabetes and management of diabetic changes to the ocular surface: a review.

US adults visit eye care providers more often than primary healthcare providers, placing these doctors in a prime position to help identify and manage patients with prediabetes and diabetes. Currently, diabetes is identified in eye clinics in an advanced stage, only after visible signs of diabetic retinopathy. Recent ophthalmic research has identified multiple subclinical and clinical changes that occur in the anterior segment of the eye with metabolic disease. The corneal epithelium exhibits increased defects and poor healing, including an increased risk of neurotrophic keratitis. Increased thickness and stiffness of the cornea artificially alters intraocular pressure. There is damage to the endothelial cells and changes to the bacterial species on the ocular surface, both of which can increase risk of complications with surgery. Decreased corneal sensitivity due to a loss of nerve density predispose patients with metabolic disease to further neurotrophic complications. Patients with diabetes have increased Meibomian gland dysfunction, blepharitis and reduced tear production, resulting in increased rates of dry eye disease and discomfort. Early detection of metabolic disease may allow eye care providers to be more proactive in recommending referral and intervention in order to reduce the risk of blindness and other diabetes-related morbidity. Continued research is needed to better understand the time course of changes to the anterior segment and what can be done to better detect and diagnose patients with prediabetes or undiagnosed diabetes and provide improved care for these patients.

Effect of age and contact lens wear on corneal epithelial dendritic cell distribution, density, and morphology.

PURPOSE: Contact lens wearers aged 15-25 years are at higher risk of corneal inflammation, yet little is known about corneal inflammatory state in this group. Previous investigations show density of corneal epithelial dendritic cells (CEDC) may increase with contact lens wear. However, it is not known how corneal distribution or morphology of CEDC alters with lens wear or whether these markers are affected by age. This study characterised CEDC in adolescent and young adult contact lens wearers to determine effects of contact lens wear and age on CEDC density, distribution and morphology. METHOD: Forty participants (20 contact lens wearers, 20 healthy non-wearers; age 16-36 years; 16M:24F) completed this pilot study. Corneal images were captured using in vivo confocal microscopy (HRTII, Rostock). CEDC were manually counted in a 1 mm2 area of the central and mid-peripheral cornea, and ratio of central to midperipheral density was calculated. CEDC morphology and dendrite length were graded. Differences between groups and between regions, and associations with age were examined. Significance was determined at P < 0.05. RESULTS: A lower ratio of central to mid-peripheral CEDC density was found with younger age (ρ = 0.42, P = 0.01). CEDC morphology was not associated with age or contact lens wear. CEDC density in the mid-peripheral cornea was higher in soft lens wearers than non-wearers (P = 0.04), but central density did not differ. CEDC density and morphology were not significantly different between centre (median density 11 cells/mm2, range 0-120) and mid-periphery (10 cells/mm2, 0-58). CONCLUSION: Density, distribution and morphology of CEDC do not differ in established contact lens wearers. A relatively lower density of CEDC in the central cornea of younger patients may allude to a more naive immune status in this group and warrants further study. Decreased central CEDC density identified in orthokeratology lens wear requires confirmation in a larger group.