Pattern visual evoked potential and foveal sensitivity in amblyopia.

PURPOSE: Amblyopic eyes show impaired visual functions such as poor visual acuity and reduced foveal sensitivity. The purpose of this study was to determine the association between foveal threshold and visual evoked potentials (VEP) in strabismic and anisometropic amblyopia. METHODS: Forty-five subjects (age range: 7-28 years, 43.3% female) including 15 strabismic and 15 anisometropic amblyopes, and 15 age-similar control subjects participated in this study. Each subject had pattern visual evoked potentials and foveal threshold recorded in each eye using RetiScan (Roland Consult, Germany) and Humphrey Visual Field Analyzer II (HFA II; Carl Zeiss Meditec Inc., Dublin, CA), respectively. These outcomes were compared among the amblyopic eyes, their fellow eyes, and the control eyes. RESULTS: Compared to the amblyopic eyes (Mean ± SD: 33.4 ± 3.48 dB), the foveal threshold was higher in fellow eyes (37.0 ± 2.04 dB, p = 0.0002) and in control eyes (38.7 ± 0.96 dB, p < 0.0001). Strabismic amblyopes had a lower foveal threshold than anisometropic amblyopes (31.8 ± 3.86 vs. 35.0 ± 2.17 dB, p = 0.005). Relative to the P100 peak time in fellow eyes (1° checks:116.1 ± 9.00 ms; 0.25° checks:118.8 ± 5.67 ms), amblyopic eyes had delayed P100 peak times for both 1° (122.7 ± 11.4 ms, p < 0.0001) and 0.25° (130.4 ± 11.2 ms, p < 0.0001) check sizes. There were also significant differences in P100 peak time between amblyopic and control eyes (1°:122.7 ± 11.4 vs.112.4 ± 5.01 ms, p = 0.15; 0.25°:130.4 ± 11.2 vs.113.9 ± 5.71 ms, p < 0.0001) and between fellow and control eyes (0.25°:118.8 ± 5.67 vs.113.9 ± 5.71 ms, p = 0.009). Amblyopic eyes exhibited lower N75-P100 amplitudes than fellow eyes (1°:12.6 ± 7.96 vs.15.9 ± 8.82 µV, p = 0.01; 0.25°:10.6 ± 6.11 vs. 15.8 ± 10.6 µV, p = 0.001) and control eyes (0.25°: p = 0.0008). Foveal threshold correlated negatively with P100 peak time (1°: r = -0.45, p = 0.002 and 0.25°: r = -0.58, p < 0.0001) and positively with N75-P100 amplitude responses (1°: r = 0.42, p = 0.004 and 0.25°: r = 0.52, p = 0.002). CONCLUSIONS: Amblyopic eyes showed reduced pattern VEP amplitudes and delayed peak times with significant associations with the foveal sensitivity. However, the VEP measures overlapped extensively between amblyopic and control eyes with no apparent criterion value for optimal discrimination, suggesting that foveal sensitivity might be a better discriminator of amblyopia than pattern VEP.

Topical Review: Optometry in Nepal-Clinical Practice, Research Advances, and Challenges.

SIGNIFICANCE: This article reviews educational standard, clinical practice, research advances, and challenges associated with optometry in Nepal and provides critical considerations for contemporary and new optometry programs in countries with similar socioeconomic status and health care systems.Optometry education started in Nepal in 1998 with the primary objective of addressing the unmet needs of eye health and vision care in the country. Over the last two decades, this program has made significant contributions to facilitating and improving the delivery of quality eye care and establishing the nation's eye health system as an exemplary model in South Asia. Despite the positive impact in a short time, optometry education and the profession continue to face several challenges, including a shortage of training resources and facilities, poor quality control and regulation of practice standards, lack of professional recognition, limited pathways for entry to governmental jobs via the national public service commission, and limited clinical and academic opportunities in existing eye care programs. This article reviews current education and clinical practice standards, highlights research advances, and discusses present and future challenges in sustaining and improving the quality of education and advancing the scope of practice of optometry in Nepal. Given the limited access to primary eye care services in Nepal, appropriate professional recognition and integration into the national health system, and initiatives targeted at improving the delivery of optometry education in alignment with successful international models may provide a long-sought solution to making eye care services accessible to all and lowering the burden of visual impairment in the country.

Repeated Low-level Red-light Therapy: The Next Wave in Myopia Management?

SIGNIFICANCE: Exposure to long-wavelength light has been proposed as a potential intervention to slow myopia progression in children. This article provides an evidence-based review of the safety and myopia control efficacy of red light and discusses the potential mechanisms by which red light may work to slow childhood myopia progression.The spectral composition of the ambient light in the visual environment has powerful effects on eye growth and refractive development. Studies in mammalian and primate animal models (macaque monkeys and tree shrews) have shown that daily exposure to long-wavelength (red or amber) light promotes slower eye growth and hyperopia development and inhibits myopia induced by form deprivation or minus lens wear. Consistent with these results, several recent randomized controlled clinical trials in Chinese children have demonstrated that exposure to red light for 3 minutes twice a day significantly reduces myopia progression and axial elongation. These findings have collectively provided strong evidence for the potential of using red light as a myopia control intervention in clinical practice. However, several questions remain unanswered. In this article, we review the current evidence on the safety and efficacy of red light as a myopia control intervention, describe potential mechanisms, and discuss some key unresolved issues that require consideration before red light can be broadly translated into myopia control in children.

Tree shrews do not maintain emmetropia in initially-focused narrow-band cyan light.

We asked if emmetropia, achieved in broadband colony lighting, is maintained in narrow-band cyan light that is well focused in the emmetropic eye, but does not allow for guidance from longitudinal chromatic aberrations (LCA) and offers minimal perceptual color cues. In addition, we examined the response to a -5 D lens in this lighting. Seven tree shrews from different litters were initially housed in broad-spectrum colony lighting. At 24 ± 1 days after eye opening (Days of Visual Experience, DVE) they were housed for 11 days in ambient narrow-band cyan light (peak wavelength 505 ± 17 nm) selected because it is in focus in an emmetropic eye. Perceptually, monochromatic light at 505 nm cannot be distinguished from white by tree shrews. While in cyan light, each animal wore a monocular -5 D lens (Cyan -5 D eyes). The fellow eye was the Cyan no-lens eye. Daily awake non-cycloplegic measures were taken with an autorefractor (refractive state) and with optical low-coherence optical interferometry (axial component dimensions). These measures were compared with the values of animals raised in standard colony fluorescent lighting: an untreated group (n = 7), groups with monocular form deprivation (n = 7) or monocular -5 D lens treatment (n = 5), or that experienced 10 days in total darkness (n = 5). Refractive state at the onset of cyan light treatment was low hyperopia, (mean ± SEM) 1.4 ± 0.4 diopters. During treatment, the Cyan no-lens eyes became myopic (-2.9 ± 0.3 D) whereas colony lighting animals remained slightly hyperopic (1.0 ± 0.2 D). Initially, refractions of the Cyan -5 D eyes paralleled the Cyan no-lens eyes. After six days, they gradually became more myopic than the Cyan no-lens eyes; at the end of treatment, the refractions were -5.4 ± 0.3 D, a difference of -2.5 D from the Cyan no-lens eyes. When returned to colony lighting at 35 ± 1 DVE, the no-lens eye refractions rapidly recovered towards emmetropia but, as expected, the refraction of the -5 D eyes remained near -5 D. Vitreous chamber depth in both eyes was consistent with the refractive changes. In narrow-band cyan lighting the emmetropization mechanism did not maintain emmetropia even though the light initially was well focused. We suggest that, as the eyes diverged from emmetropia, there were insufficient LCA cues for the emmetropization mechanism to utilize the developing myopic refractive error in order to guide the eyes back to emmetropia. However, the increased myopia in the Cyan -5 D eyes in the narrow-band light indicates that the emmetropization mechanism nonetheless detected the presence of the lens-induced refractive error and responded with increased axial elongation that partly compensated for the negative-power lens. These data support the conclusion that the emmetropization mechanism cannot maintain emmetropia in narrow-band lighting. The additional myopia produced in eyes with the -5 D lens shows that the emmetropization mechanism responds to multiple defocus-related cues, even under conditions where it is unable to use them to maintain emmetropia.

The acute effect of atropine eye drops on the human full-field electroretinogram.

PURPOSE: Atropine eye drops are a common and effective treatment for slowing myopia progression, but the site and mode of action of atropine in controlling myopia are unclear. We investigated the early retinal sites of action of atropine by examining its effects on the human full-field electroretinogram (ffERG). METHOD: Baseline ffERGs were recorded in both eyes of 24 healthy subjects (mean ± SD: 21.0 ± 2.3 years; spherical equivalent refraction, range: + 1.63 to - 0.75 D) using 6 standard ISCEV protocols, 30 min after bilateral pupil dilation with 1% Tropicamide. Atropine (1 drop, 0.1%) was then instilled into the non-dominant eye. 24 h later, ffERGs were again recorded in both eyes. Ratios (post-atropine: pre-atropine) of dark-adapted (DA) and light-adapted (LA) ffERGs were compared between atropine-treated and control eyes using multivariate repeated measures general linear models. RESULTS: Atropine-treated eyes responded with 14% lower DA3.0 OP (oscillatory potential) amplitude (p = 0.003) and 4% delay in the DA10.0 a-wave peak time (p = 0.00099) compared with control eyes. Amplitudes and peak times were not different between atropine-treated and control eyes for DA0.01, LA3.0, and LA3.0 flicker ERGs. While atropine caused a small (1.26 mm2, p = 0.03) extra increase in pupil area in the treated eye, atropine-induced changes in ffERG responses bore no relationship with changes in pupil area (R2 = 2-5%, p > 0.05). CONCLUSIONS: The observed changes in oscillatory potentials corroborate previous findings that atropine affects neural activity in the inner retina. However, observed changes to the a-wave suggest that atropine also affects activity in photoreceptors.

Amber light treatment produces hyperopia in tree shrews.

PURPOSE: Exposure to narrow-band red light, which stimulates only the long-wavelength sensitive (LWS) cones, slows axial eye growth and produces hyperopia in tree shrews and macaque monkeys. We asked whether exposure to amber light, which also stimulates only the LWS cones but with a greater effective illuminance than red light, has a similar hyperopia-inducing effect in tree shrews. METHODS: Starting at 24 ± 1 days of visual experience, 15 tree shrews (dichromatic mammals closely related to primates) received light treatment through amber filters (BPI 500/550 dyed acrylic) either atop the cage (Filter group, n = 8, 300-400 human lux) or fitted into goggles in front of both eyes (Goggle group, n = 7). Non-cycloplegic refractive error and axial ocular dimensions were measured daily. Treatment groups were compared with age-matched animals (Colony group, n = 7) raised in standard colony fluorescent lighting (100-300 lux). RESULTS: At the start of treatment, mean refractive errors were well-matched across the three groups (p = 0.35). During treatment, the Filter group became progressively more hyperopic with age (p < 0.001). By contrast, the Goggle and Colony groups showed continued normal emmetropization. When the treatment ended, the Filter group exhibited significantly greater hyperopia (mean [SE] = 3.5 [0.6] D) compared with the Goggle (0.2 [0.8] D, p = 0.01) and Colony groups (1.0 [0.2] D, p = 0.01). However, the refractive error in the Goggle group was not different from that in the Colony group (p = 0.35). Changes in the vitreous chamber were consistent with the refractive error changes. CONCLUSIONS: Exposure to ambient amber light produced substantial hyperopia in the Filter group but had no effect on refractive error in the Goggle group. The lack of effect in the Goggle group could be due to the simultaneous activation of the short-wavelength sensitive (SWS) and LWS cones caused by the scattering of the broad-band light from the periphery of the goggles.

Flash VEP in clinically stable pre-term and full-term infants.

PURPOSE: Pre-term infants are at risk of abnormal visual development that can range from subtle to severe. The aim of this study was to compare flash VEPs in clinically stable pre-term and full-term infants at 6 months of age. METHODS: Twenty-five pre-term and 25 full-term infants underwent flash VEP testing at the age of 6 months. Monocular VEPs were recorded using flash goggles on a RETIscan system under normal sleeping conditions. Amplitude and peak time responses of the P2 component in the two eyes were averaged and compared between the two groups. Multiple regression analyses were performed to assess the relationship of the P2 responses with birth weight (BW) and gestational age (GA). RESULTS: At 6 months corrected age, pre-term infants had significantly delayed P2 peak times than full-term infants (mean difference: 10.88 [95% CI 4.00-17.76] ms, p = 0.005). Pre-term infants also showed significantly reduced P2 amplitudes as compared to full-term infants (mean difference: 2.36 [0.83-3.89] µV, p = 0.003). Although the regression model with GA and BW as fixed factors explained 20% of the variance in the P2 peak time (F2,47 = 5.98, p = .0045), only GA showed a significant negative relationship (ß = -2.66, p = .003). Neither GA (ß = 0.21, p = .28) nor BW (ß = 0.001, p = .32) showed any relationship with P2 amplitude. CONCLUSIONS: Our results demonstrate that, compared with full-term infants, clinically stable pre-term infants exhibit abnormal flash VEPs, with a delay in P2 peak time and a reduction in P2 amplitude. These findings support a potential dysfunction of the visual pathway in clinically stable pre-term infants as compared to full-term infants.

Repeatability of Arterial Spin Labeling MRI in Measuring Blood Perfusion in the Human Eye.

BACKGROUND: Quantifying blood perfusion in ocular tissues is challenging, partly because the majority of the blood is carried by the choroid, which is difficult to visualize because it is located between the retina and sclera. PURPOSE/HYPOTHESIS: To evaluate the intra- and interday repeatability of MRI measures of chorio-retinal blood perfusion. STUDY TYPE: Prospective, cross-sectional, observational study. POPULATION: Twenty young healthy adults (six male, age: 25 ± 5 years) scanned twice within a single session repeated at the same time of day on 2 days. FIELD STRENGTH/SEQUENCE: Arterial spin labeling (ASL) MRI at 3.0T using pseudocontinuous ASL (PCASL) labeling scheme and a 3D turbo-gradient-spin-echo (TGSE) acquisition, including axial T2 -weighted structural images using a 2D turbo-spin-echo (TSE) sequence. ASSESSMENTS: Region-of-interest analysis for assessment of chorio-retinal blood perfusion. STATISTICAL TESTS: Intra- and interday repeatability of measures analyzed using intraclass correlation coefficients (ICC), Pearson's correlation analysis, paired t-tests, and Bland-Altman plots. RESULTS: The mean chorio-retinal perfusion was 77.86 (standard deviation [SD] = 29.80) ml/100ml/min. Perfusion measurements correlated strongly within a single session (r = 0.95, 95% confidence interval [CI] [0.880-0.980], P < 0.001) and between the two sessions based on a single run (r = 0.80 [0.582-0.913], P < 0.001), and two runs (r = 0.80 [0.479-0.918], P < 0.001). There were mean differences of 2.69 [16.85 to -22.23] ml/100ml/min for intraday measures, -7.44 [27.45 to -42.32] ml/100ml/min for single-run interday measures, and 5.73 [28.71 to -40.17] ml/100ml/min for two-run interday measures, but none were significant (all P > 0.05). DATA CONCLUSION: Quantitative ASL-MRI measurements of chorio-retinal blood perfusion showed high intra- and interday repeatability. The ASL-MRI technique provides reliable measures of chorio-retinal perfusion in vivo. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:966-974.

Refractive Status in Nepalese Pre-Term and Full-Term Infants Early in Life.

SIGNIFICANCE: This study suggests that pre-term infants, even without retinopathy of prematurity, are at risk for abnormal refractive development and informs the need for close monitoring of refractive error in such infants, regardless of their retinopathy of prematurity status. PURPOSE: The present study aims to investigate the refractive error trend in Nepalese pre-term infants without retinopathy of prematurity (ROP) in the first 6 months of life and explore the association of refractive error with birth weight (BW) and gestational age (GA). METHODS: Thirty-six pre-term infants without ROP and 40 full-term infants underwent cycloplegic retinoscopy at birth, term (for pre-term only), 3 months, and 6 months chronologically. Refractive status was classified into emmetropia (mean spherical equivalent refraction [SER] 0 to +3.00D), myopia (SER < 0.00D), and significant hyperopia (SER > +3.00D). Refractive parameters at various age points were compared between the pre-term and full-term infants using general linear model repeated measures ANOVA. RESULTS: At birth, the SER in the pre-term infants was +0.84 ± 1.72D; however, there was a shift toward myopia at 6 months of age (SER = -0.33 ± 1.95D). There was a significant difference in SER, astigmatism, and anisometropia between pre-term and full-term infants by 6 months of age (P < .01). Astigmatism and anisometropia showed an increasing trend with age in pre-term infants (P < .05 at 6 months) in contrast to a decreasing trend in full-term infants (P < 0.05 at 3 and 6 months). In pre-term infants, there was a statistically significant positive relationship between GA and SER (ß = 0.32, R = 17.6%, P < .05) but a negative relationship between BW and astigmatism (ß = -1.25, R = 20.6%, P < .01). CONCLUSIONS: Pre-term infants who do not develop ROP show a trend toward increasing myopia and demonstrate greater astigmatism and anisometropia than full-term infants in their first 6 months of life.

Response of the human choroid to short-term changes in eyelid and periocular temperature.

CLINICAL RELEVANCE: Choroidal thickness measurement is gaining popularity in clinical practice and research as an early indicator of myopia progression. Understanding the influence of temperature on choroidal thickness changes will improve the reliability of the measures. BACKGROUND: It has been suggested that environmental temperature may affect choroidal thickness and blood flow, with potential implications for ocular disease and refractive development. This study investigates the effect of changes in eyelid/ocular adnexa temperature on choroidal thickness. METHODS: In a paired-eye study, 20 young, healthy subjects received a warm stimulus (heat pack) over one closed eye and simultaneously a cold stimulus (ice pack) over the other for 10 min. Eyelid temperatures were monitored with thermal probes, and optical coherence tomography scans of the retina and choroid were taken before and after heating and cooling, and then every 5 min during a 15-min recovery period. Retinal and choroidal thicknesses were measured across the macular region (6 mm), including the subfoveal (1 mm), parafoveal (1-3 mm), and perifoveal (3-5 mm) regions, and compared between the cooled and warmed eyes. RESULTS: When the thermal stimuli were applied, eyelid surface temperatures changed predictably and remained significantly different (by approximately 10-15°C) between the eyes after 2 min (p < .001). Relative to the warmed eye, macular choroidal thickness in the cooled eye increased significantly after 10 min of treatment (p = .004). This choroidal thickening response occurred in the subfoveal, parafoveal, and perifoveal regions (all p < .05). Upon removal of the thermal stimuli, choroidal thickness rapidly returned to the baseline and was no longer different between the cooled and warmed eye (p = .641). CONCLUSION: Cooling the anterior eye by application of a cold stimulus directly onto the closed eyelid caused a small but significant increase in choroidal thickness relative to warming the anterior eye, demonstrating that the choroid can modulate its thickness rapidly and transiently in response to local temperature changes.

BCLA CLEAR presbyopia: Mechanism and optics.

With over a billion adults worldwide currently affected, presbyopia remains a ubiquitous, global problem. Despite over a century of study, the precise mechanism of ocular accommodation and presbyopia progression remains a topic of debate. Accordingly, this narrative review outlines the lenticular and extralenticular components of accommodation together with the impact of age on the accommodative apparatus, neural control of accommodation, models of accommodation, the impact of presbyopia on retinal image quality, and both historic and contemporary theories of presbyopia.

Limited bandwidth short-wavelength light produces slowly-developing myopia in tree shrews similar to human juvenile-onset myopia.

During postnatal development, an emmetropization feedback mechanism uses visual cues to modulate the axial growth of eyes so that, with maturation, images of distant objects are in focus on the retina. If the visual cues indicate that the eye has become too long, it generates STOP signals that slow eye elongation. Myopia is a failure of this process where the eye becomes too long. The existing animal models of myopia have been essential in understanding the mechanics of emmetropization but use visual cues that lead to rapidly progressing myopia and don't match the stimuli that lead to human myopia. Form deprivation removes esssentially all spatial contrast. Minus lens wear accurately guides axial elongation to restore sharp focus: technically it is not a model of myopia! In contrast, childhood myopia involves a slow drift into myopia, even with the presence of clear images. We hypothesize that, in the modern visual environment, STOP signals are present but often are not quite strong enough to prevent myopic progression. Using tree shrews, small diurnal mammals closely related to primates, we have developed an animal model that we propose better represents this situation. We used limited bandwidth light to provide limited chromatic cues for emmetropization that are not quite enough to produce fully effective STOP signaling, resulting in a slow drift into myopia as seen in children. We hypothesize that this animal model of myopia may prove useful in evaluating anti-myopia therapies where form deprivation and minus lens wear would be too powerful.

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.

Optometry in Nepal: a historical perspective.

Optometry education in Nepal began in 1998 in collaboration with the University of Auckland, New Zealand, with the primary objective of addressing the unmet needs of eye health and vision care. Over the last two decades, the development of optometry education has seen significant progress, including a shift from a three-year to a four-year curriculum, an increase in the uptake of students, and recent launches of two additional bachelor's degree and a master's degree programmes. Complementary to the educational progress, several professional advances have occurred in the intervening years. These include the formation of the Nepalese Association of Optometrists that oversees the professional development and the rights, welfare, security, and protection of Optometrists, memberships into the World Council of optometry and the Asia Pacific Council of optometry, integration of the profession into the governmental regulatory body Nepal Health Professional Council, and formulation of the code of ethics and minimum requirements for a Bachelor's level University degree in optometry. This article briefly presents the historical events leading to the establishment of optometry in Nepal and the evolution of the program in the intervening years.

Inflammatory proteins associated with contact lens-related dry eye.

PURPOSE: To evaluate the levels and regulation of tear film inflammatory proteins in contact lens-related dry eye (CLDE). METHODS: One hundred healthy, daily wear (non-overnight), experienced soft contact lens wearers were classified into normal (n = 50) and CLDE (n = 50) groups based on Contact Lens and Dry Eye Questionnaire scores, tear break-up times, and comfort (a two-hour difference between total and comfortable daily lens wear hours). Tear samples (up to 5 µL) were collected by capillary extraction from the inferior meniscus of each eye, and pooled tear samples (10 per group) were tested using a customized Quantibody array. Mann Whitney tests with the Benjamini-Hochberg procedure with a 5% false discovery rate were used to compare the normal and CLDE groups. RESULTS: Relative to the normal group, the CLDE group showed a significantly increased tear concentration of several inflammatory mediators, including interleukin (IL)-7 (p = 0.001), IL-8 (p = 0.001), IL-13 (p = 0.001), IL-15 (p = 0.001), IL-12 p70 (p = 0.002), growth-related oncogene-alpha/ chemokine (CXC motif) ligand 1 (p = 0.003), granulocyte-colony stimulating factor (p = 0.005), IL-11 (p = 0.008), epidermal growth factor receptor (p = 0.01), IL-1 receptor antagonist (RA) (p = 0.013), macrophage colony-stimulating factor (p = 0.013), Eotaxin/CC motif chemokine ligand 11 (CCL11) (p = 0.016), and IL-2 (p = 0.016). The following cytokines were increased three-fold or more in the CLDE group: IL-13 (p = 0.001), Eotaxin/CCL11 (p = 0.016), and IL-1RA (p = 0.013). CONCLUSIONS: Several inflammatory markers, including interleukins, were increased in tears of subjects with CLDE. These results support a growing body of evidence that suggests a potential role of inflammation in CLDE.

Human meibum and tear film derived cholesteryl and wax esters in meibomian gland dysfunction and tear film structure.

PURPOSE: This study evaluated the presence and roles of cholesteryl esters (CEs) and wax esters (WEs) from human tear film and meibum in meibomian gland dysfunction (MGD). METHODS: Out of 195 enrolled subjects, 164 and 179 subjects provided tear and meibum samples, respectively. Subjects were classified into normal, asymptomatic MGD, MGD, and mixed (MGD & aqueous deficient). The precorneal tear film (PCTF) thinning rate (evaporation) was measured using optical coherence tomography. Lipids extracted from tear and meibum samples were infused into a SCIEX 5600 TripleTOF mass spectrometer. CE and WE intensities quantified with Analyst 1.7 TF and LipidView 1.3 were compared across disease groups in MetaboAnalyst 5.0 and correlated with PCTF thinning rates. RESULTS: The numbers of unique CEs and WEs identified in the samples were 125 and 86, respectively. Unsupervised Principal Component (PC) analysis and supervised Partial Least Square Discriminant analysis exhibited little separation among groups for both CEs and WEs in tears and meibum. Spearman's correlation analyses showed no association between either the first or second PC scores with PCTF thinning rates. CONCLUSION: The abundances of human PCTF and meibum-derived CEs and WEs were independent of MGD disease status and PCTF thinning (evaporation). CEs and WEs alterations do not contribute to alterations in tear film dynamics in MGD, such as has been demonstrated by the (O-acyl) ω-hydroxy fatty acids (OAHFAs).

The effect of cellphone position on driving and gaze behaviour.

Legislation frequently restricts the use of cellphones while driving. Despite this, many people continue to interact with cellphones covertly while driving, typically by concealing their device in their lap. This strategy leads to frequent diversion of the drivers' gaze from the road ahead, potentially reducing their driving performance. To evaluate the influence of cellphone use on driving, 30 participants took part in three randomly ordered 7-min virtual reality driving simulations. In each condition, drivers were presented with either (a) no cellphone, (b) a cellphone fixed to the windscreen, or (c) a cellphone positioned at lap level. Their task was to maintain road position and observe speed limits while answering maths problems (delivered intermittently via 'text message') and searching for external target objects. Outcome measures included speed, lane position standard deviation (LPSD), and fixation behaviour, which were compared between trials. In trials where a cellphone was present, participants shifted fixation more frequently, drove approximately 6 km/h faster, exhibited a lower LPSD and spent more time in the correct lane on the road (compared to the no-cellphone condition; all p < 0.001). Cellphone position influenced eye gaze behaviour, with drivers looking at the cellphone less frequently, and the speedometer more frequently. when the cellphone was in their lap compared to when the cellphone was positioned on the windscreen. Our results are consistent with participants driving more cautiously-checking speed and lane position more frequently-when they have a cellphone in the lap. Real-world driving data would be useful to determine whether this change in driving behaviour we observed is sufficient to offset the increased risk introduced by spending less time looking at the road ahead.

Human precorneal tear film and lipid layer dynamics in meibomian gland dysfunction.

PURPOSE: To evaluate the precorneal tear film (PCTF) and lipid layer (TFLL) thicknesses and thinning rates in meibomian gland dysfunction (MGD) using a combined ultra-high-resolution optical coherence tomography (OCT) and thickness dependent fringe (TDF) interferometry system. METHODS: Based on the Tear Film and Ocular Surface Society (TFOS) International Workshop on Meibomian Gland Dysfunction diagnostic algorithm, the Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify subjects into four groups: Normal (OSDI<13 and MGS<10), MGD (OSDI≥13 and MGS≥10), Asymptomatic MGD (OSDI<13 and MGS≥10), and Mixed (OSDI≥13 and MGS<10). The OCT/TDF system was used to capture PCTF and TFLL thicknesses and thinning rates. Kruskal-Wallis was used to compare median PCTF and TFLL thicknesses and thinning rates. RESULTS: There were 190 subjects categorized into four groups: Normal (n = 63), MGD (n = 51), Asymptomatic MGD (n = 29), and Mixed (n = 47). The PCTF was significantly thinner in the Mixed group (3.3 [1.2]) than in the Normal (p < 0.001), MGD (p < 0.001) and Asymptomatic MGD (p = 0.009) groups. Relative to the Normal (4.5 [4.5] µm/min) and Mixed (5.0 [2.0] µm/min) groups, the rate of PCTF thinning was faster in the MGD (8.1 [3.0] µm/min, both p < 0.001) and Asymptomatic MGD (6.9 [3.1] µm/min, p = 0.009 and p = 0.04, respectively) groups. The correlation between PCTF thinning rate and TFLL thickness was ρ = -0.46, p < 0.001. CONCLUSIONS: Symptomatic and asymptomatic MGD shows rapid PCTF thinning rates (evaporation), while the PCTF thickness was reduced in mixed disease. Thicker lipid layers were associated with slower PCTF thinning.

Human meibum and tear film derived (O-acyl)-omega-hydroxy fatty acids in meibomian gland dysfunction.

PURPOSE: The molecular basis of the tear film and lipid layer alterations in meibomian gland dysfunction (MGD) is unknown. This study aimed to identify and compare (O-acyl)-omega-hydroxy fatty acids (OAHFAs) derived from human meibum and tears in MGD. METHODS: Of 195 eligible subjects (18-84 years, 62.6% female), 183 and 174 provided samples for tears and meibum, respectively. Subjects were classified into four groups: Normal, Asymptomatic MGD, MGD, and Mixed. Samples from the right eye of each subject were infused into the SCIEX 5600 TripleTOF mass spectrometer in negative ion mode. Lipid intensities identified with Analyst1.7 TF and SCIEX LipidView1.3 were normalized by an internal standard and total ion current, then statistically compared in MetaboAnalyst 4.0. RESULTS: In meibum and tears, 76 and 78 unique OAHFAs were identified, respectively. The five most frequent and abundant OAHFAs were 18:2/16:2, 18:1/32:1, 18:1/30:1, 18:2/32:1, and 18:1/34:1. Two OAHFAs, 18:2/20:2 and 18:2/20:1, were identified only in tears. Initial univariate analysis revealed three differently regulated OAHFAs in meibum and eight in tears. Partial Least Square Discriminant Analysis showed 18:1/32:1, 18:2/16:2, 18:1/34:1 and 18:0/32:1 in tears, and 18:2/16:2, 18:1/32:1 and 18:2/32:2 in meibum, had variable importance in projection scores >1.5 and contributed the most to the separation of groups. In both meibum and tears, all OAHFAS except 18:2/16:2 were reduced in MGD compared to the normal group. CONCLUSION: MGD is accompanied by differential expression of specific OAHFAs in meibum and tears. These results suggest OAHFAs play a role in the altered biochemical profile of the tear film lipid layer in humans with MGD.