Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View.
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ABSTRACT:
SUBMITTER: Eftimov P
PROVIDER: S-EPMC7764870 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View.
Eftimov Petar P Olżyńska Agnieszka A Melcrová Adéla A Georgiev Georgi As GA Daull Philippe P Garrigue Jean-Sebastien JS Cwiklik Lukasz L
International journal of molecular sciences 20201214 24
The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film ...[more]
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Project description:PurposeThe thinning of the precorneal tear film between blinks and tear film breakup can be logically analyzed into contributions from three components: evaporation, flow into the cornea, and tangential flow along the corneal surface. Whereas divergent tangential flow contributes to certain types of breakup, it has been argued that evaporation is the main cause of tear thinning and breakup. Because evaporation is controlled by the tear film lipid layer (TFLL) it should therefore be expected that patterns of breakup should match patterns in the TFLL, and this hypothesis is tested in this study.MethodsAn optical system is described for simultaneous video imaging of fluorescein tear film breakup and the TFLL. Recordings were made from 85 subjects, including both with healthy and dry eyes. After instillation of 5 ?L2% fluorescein, subjects were asked to blink 1 second after the start of the recording and try to maintain their eyes open for the recording length of 30 or 60 seconds.ResultsAreas of tear film thinning and breakup usually matched corresponding features in the TFLL. Whereas thinning and breakup were often matched to thin lipid, surprisingly, the corresponding lipid region was not always thinner than the surrounding lipid. Occasionally, a thin lipid region caused a corresponding region of greater fluorescence (thicker aqueous layer), due to convergent tangential flow.ConclusionsAreas of tear thinning and breakup can generally be matched to corresponding regions of the TFLL as would be expected if breakup is largely due to evaporation. Surprisingly, in some examples, the corresponding lipid area was not thinner and possibly thicker than the surrounding lipid. This indicates that the lipid was a poor barrier to evaporation, perhaps because of deficiency in composition and/or structure. For example, bacterial lipases may have broken down esters into component acids and alcohols, causing a defective TFLL structure with increased evaporation.
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Project description:BackgroundDry eye syndrome is one of the most common ocular diseases, and meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye syndrome. When the tear film lipid layer becomes thin due to obstructive or hyposecretory meibomian gland dysfunction, the excessive evaporation of the aqueous layer can occur, and this causes evaporative dry eye syndrome. Thus, measuring the lipid layer thickness (LLT) is essential for accurate diagnosis and proper treatment of evaporative dry eye syndrome.MethodsWe used a white LED panel with a slit lamp microscope to obtain videos of the lipid layer interference patterns on the cornea. To quantitatively analyze the LLT from interference colors, we developed a novel algorithm that can automatically perform the following processes on an image frame: determining the radius of the iris, locating the center of the pupil, defining region of interest (ROI), tracking the ROI, compensating for the color of iris and illumination, and producing comprehensive analysis output. A group of dry eye syndrome patients with hyposecretory MGD, dry eye syndrome without MGD, hypersecretory MGD, and healthy volunteers were recruited. Their LLTs were analyzed and statistical information-mean and standard deviation, the relative frequency of LLT at each time point, and graphical LLT visualization-were produced.ResultsUsing our algorithm, we processed the lipid layer interference pattern and automatically analyzed the LLT distribution of images from patients. The LLT of hyposecretory MGD was thinner (45.2 ± 11.6 nm) than that of dry eye syndrome without MGD (69.0 ± 9.4 nm) and healthy volunteers (68.3 ± 13.7 nm) while the LLT of hypersecretory MGD was thicker (93.5 ± 12.6 nm) than that of dry eye syndrome without MGD. Patients' LLTs were statistically analyzed over time, visualized with 3D surface plots, and displayed using 3D scatter plots of image pixel data for comprehensive assessment.ConclusionsWe developed an image-based algorithm for quantitative measurement as well as statistical analysis of the LLT despite fluctuation and eye movement. This pilot study demonstrates that the quantitative LLT analysis of patients is consistent with the functions of meibomian glands clinically evaluated by an ophthalmologist. This approach is a significant step forward in developing a fully automated instrument for evaluating dry eye syndrome and for providing proper guidance of treatment.
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Project description:BackgroundTo evaluate the correlations between lipid layer thickness (LLT) and morphology and function of the meibomian glands in patients who were diagnosed as meibomian gland dysfunction (MGD) in different age groups.MethodsPatients who have diagnosed as obstructive MGD were included in this prospective, cross-sectional study. Patients were divided into three groups: young (ages 20-39 years), middle-aged (ages 40-59 years), and older (aged ≥60 years). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and were evaluated for LLT, tear meniscus height (TMH), noninvasive tear film break-up time (NI-BUT) measurement, invasive TBUT (ITBUT), corneal fluoresceinstaining (CFS) score, eyelid margin abnormalities, Schirmer I test, and MG function and morphology, by using the Keratograph 5 and LipiView interferometer.ResultsTwo hundred and nine patients (209 eyes) were included. The median LLT of all patient was 57 nm (IQR, 36.5 nm), and the LLT values were significantly different among the young group (median, 51 nm; IQR, 23.5 nm), middle-aged group (median, 59.5 nm; IQR 46.5 nm) and older group (median, 62 nm; IQR, 42.5 nm) (P = 0.033, Kruskal-Wallis test). In regression analyses controlling for confounder factors sex and MG loss, the LLT was positively correlated with age (β = 5.539, P = 0.001). There was a negative correlation between LLT and MG dropout in the all (r = - 0.527, P < 0.001), young (r = - 0.536, P < 0.001), middle-aged (r = - 0.576, P < 0.001), and older (r = - 0.501, P < 0.001) groups. LLT was positively correlated with the MG expressibility in the all (r = 0.202, P = 0.003), middle-aged (r = 0.280, P = 0.044) and older (r = 0.452, p < 0.001) groups, but it was no statistical significance in the young group (r = 0.007, P = 0.949).ConclusionsThe thickness of LLT was increased with age and significantly correlated with both MG secretion and morphology in middle-aged and older patients with obstructive MGD. LLT measurement is a useful screening tool for detecting obstructive MGD and age as an influential factor should be accounted for when interpreting the meaning of the LLT value.Trial registrationNCT02481167 ; Registered 25 June, 2015.
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Project description:In this work, we describe the development of a tunable, acellular in vitro model of the mucin layer of the human tear film. First, supported lipid bilayers (SLBs) comprised of the phospholipid DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) and biotinyl cap PE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(cap biotinyl)) are created on the surface of a glass dome with radius of curvature comparable to the human eye. Next, biotinylated bovine submaxillary mucins (BSM) are tethered onto the SLB using streptavidin protein. The mucin presentation can be tuned by altering the concentration of biotinylated BSM, which we confirm using fluorescence microscopy. Due to the optically smooth surface that results, this model is compatible with interferometry for monitoring film thickness. Below a certain level of mucin coverage, we observe short model tear film breakup times, mimicking a deficiency in membrane-associated mucins. In contrast, the breakup time is significantly delayed for SLBs with high mucin coverage. Because no differences in mobility or wettability were observed, we hypothesize that higher mucin coverage provides a thicker hydrated layer that can protect against external disturbances to thin film stability. This advance paves the way for a more physiological, interferometry-based in vitro model for investigating tear film breakup.
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Project description:PURPOSE:Artificial tears are the first line of therapy for dry eye disease (DED) and are also the most frequently used treatment approach for this common condition. Despite this, there are few published studies that directly compare the effectiveness of different drop preparations, especially those formulated specifically for dry eye. In this study, we tested a new artificial tear product, Rohto® Dry-Aid™, for its ability to relieve the signs and symptoms of DED. The study used a second drop, Systane® Ultra, as a positive comparator. MATERIALS AND METHODS:This was a prospective, single-center, open-label, parallel-group study comparing the effects of the two products when used continuously over ~30 days (Clinical Trials registration number NCT03183089). Subjects were randomly assigned to one of the two test groups and were monitored 2 and 4 weeks after enrollment. Efficacy endpoints included ocular staining, visual function, and ocular discomfort. RESULTS:Treatment groups had similar ocular staining and ocular comfort scores, and both showed statistically significant ocular discomfort score improvement. Subjects in the Rohto group reported significant improvements in visual tasking activities such as watching television and driving at night. There was also a tendency for diary symptom scores to worsen from morning to evening in the Systane group, but not in the Rohto group; this trend was not significant, but warrants further study. CONCLUSION:The two products, Rohto Dry-Aid and Systane Ultra, elicited comparable effects on the signs and symptoms of DED. While both products are designed to provide long-lasting relief, subjects in the Rohto group experienced a superior relief from discomfort associated with visual tasking activities and daily diaries, indicating that the Rohto drops may provide a longer duration of symptomatic relief over the course of the day.
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