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Richard J Braun - One of the best experts on this subject based on the ideXlab platform.
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Parameter Estimation for Evaporation-Driven Tear Film Thinning
Bulletin of Mathematical Biology, 2020Co-Authors: Rayanne A. Luke, Richard J Braun, Tobin A. Driscoll, Carolyn G. Begley, Deborah Awisi-gyauAbstract:Many parameters affect Tear Film thickness and fluorescent intensity distributions over time; exact values or ranges for some are not well known. We conduct parameter estimation by fitting to fluorescent intensity data recorded from normal subjects’ Tear Films. The fitting is done with thin Film fluid dynamics models that are nonlinear partial differential equation models for the thickness, osmolarity and fluorescein concentration of the Tear Film for circular (spot) or linear (streak) Tear Film breakup. The corresponding fluorescent intensity is computed from the Tear Film thickness and fluorescein concentration. The least squares error between computed and experimental fluorescent intensity determines the parameters. The results vary across subjects and trials. The optimal values for variables that cannot be measured in vivo within Tear Film breakup often fall within accepted experimental ranges for related Tear Film dynamics; however, some instances suggest that a wider range of parameter values may be acceptable.
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Mathematical Models of the Tear Film
Ocular Fluid Dynamics, 2019Co-Authors: Richard J Braun, Tobin A. Driscoll, Carolyn G. BegleyAbstract:The complex dynamics of the Tear Film are affected by its many processes and components. Mathematical models of the Tear Film allow the selective elimination or inclusion of various effects that are not otherwise possible in human subjects. Such models have been able to provide local estimates of osmolarity in Tear break up (TBU), for example, which to our knowledge cannot be measured directly. Models also suggest that different modes of TBU must be considered to make sense of in vivo data regarding response of the ocular epithelia and causes of dry eye. More complex models that include Tear Film formation via blinking are within our grasp, which will no doubt extend our knowledge of the Tear Film, its dynamics, and its role in ocular surface health.
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Duplex Tear Film Evaporation Analysis
Bulletin of Mathematical Biology, 2017Co-Authors: M. R. Stapf, Richard J Braun, P. E. King-smithAbstract:Tear Film thinning, hyperosmolarity, and breakup can cause irritation and damage to the human eye, and these form an area of active investigation for dry eye syndrome research. Recent research demonstrates that deficiencies in the lipid layer may cause locally increased evaporation, inducing conditions for breakup. In this paper, we explore the conditions for Tear Film breakup by considering a model for Tear Film dynamics with two mobile fluid layers, the aqueous and lipid layers. In addition, we include the effects of osmosis, evaporation as modified by the lipid, and the polar portion of the lipid layer. We solve the system numerically for reasonable parameter values and initial conditions and analyze how shifts in these cause changes to the system’s dynamics.
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On Tear Film breakup (TBU): dynamics and imaging.
Mathematical Medicine and Biology-a Journal of The Ima, 2017Co-Authors: Richard J Braun, Tobin A. Driscoll, Carolyn G. Begley, P. Ewen King-smith, Javed SiddiqueAbstract:We report the results of some recent experiments to visualize Tear Film dynamics. We then study a mathematical model for Tear Film thinning and Tear Film breakup (TBU), a term from the ocular surface literature. The thinning is driven by an imposed Tear Film thinning rate which is input from in vivo measurements. Solutes representing osmolarity and fluorescein are included in the model. Osmolarity causes osmosis from the model ocular surface, and the fluorescein is used to compute the intensity corresponding closely to in vivo observations. The imposed thinning can be either one-dimensional or axisymmetric, leading to streaks or spots of TBU, respectively. For a spatially-uniform (flat) Film, osmosis would cease thinning and balance mass lost due to evaporation; for these space-dependent evaporation profiles TBU does occur because osmolarity diffuses out of the TBU into the surrounding Tear Film, in agreement with previous results. The intensity pattern predicted based on the fluorescein concentration is compared with the computed thickness profiles; this comparison is important for interpreting in vivo observations. The non-dimensionalization introduced leads to insight about the relative importance of the competing processes; it leads to a classification of large vs small TBU regions in which different physical effects are dominant. Many regions of TBU may be considered small, revealing that the flow inside the Film has an appreciable influence on fluorescence imaging of the Tear Film.
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evaporation driven instability of the precorneal Tear Film
Advances in Colloid and Interface Science, 2014Co-Authors: Chengchun Peng, Richard J Braun, Colin Cerretani, C J RadkeAbstract:Abstract Tear-Film instability is widely believed to be a signature of eye health. When an interblink is prolonged, randomly distributed ruptures occur in the Tear Film. “Black spots” and/or “black streaks” appear in 15 to 40 s for normal individuals. For people who suffer from dry eye, Tear-Film breakup time (BUT) is typically less than a few seconds. To date, however, there is no satisfactory quantitative explanation for the origin of Tear rupture. Recently, it was proposed that Tear-Film breakup is related to locally high evaporative thinning. A spatial variation in the thickness of the Tear-Film lipid layer (TFLL) may lead to locally elevated evaporation and subsequent Tear-Film breakup. We examine the local-evaporation-driven Tear-Film-rupture hypothesis in a one-dimensional (1-D) model for the evolution of a thin aqueous Tear Film overriding the cornea subject to locally elevated evaporation at its anterior surface and osmotic water influx at its posterior surface. Evaporation rate depends on mass transfer both through the coating lipid layer and through ambient air. We establish that evaporation-driven Tear-Film breakup can occur under normal conditions but only for higher aqueous evaporation rates. Predicted roles of environmental conditions, such as wind speed and relative humidity, on Tear-Film stability agree with clinical observations. More importantly, locally elevated evaporation leads to hyperosmolar spots in the Tear Film and, hence, vulnerability to epithelial irritation. In addition to evaporation rate, Tear-Film instability depends on the strength of healing flow from the neighboring region outside the breakup region, which is determined by the surface tension at the Tear-Film surface and by the repulsive thin-Film disjoining pressure. This study provides a physically consistent and quantitative explanation for the formation of black streaks and spots in the human Tear Film during an interblink.
Rene M Werkmeister - One of the best experts on this subject based on the ideXlab platform.
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In vivo Tear Film thickness measurement and Tear Film dynamics visualization using spectral domain OCT and an efficient delay estimator
Proceedings of SPIE, 2016Co-Authors: Valentin Aranha Dos Santos, Leopold Schmetterer, Martin Groschl, Gerhard Garhofer, Rene M WerkmeisterAbstract:Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the Tear Film. Traditional methods used for the evaluation of Tear Film stability are invasive or show limited repeatability. Here we propose a new noninvasive approach to measure Tear Film thickness using an efficient delay estimator and ultrahigh resolution spectral domain OCT. Silicon wafer phantoms with layers of known thickness and group index were used to validate the estimator-based thickness measurement. A theoretical analysis of the fundamental limit of the precision of the estimator is presented and the analytical expression of the Cramer-Rao lower bound (CRLB), which is the minimum variance that may be achieved by any unbiased estimator, is derived. The performance of the estimator against noise was investigated using simulations. We found that the proposed estimator reaches the CRLB associated with the OCT amplitude signal. The technique was applied in vivo in healthy subjects and dry eye patients. Series of Tear Film thickness maps were generated, allowing for the visualization of Tear Film dynamics. Our results show that the central Tear Film thickness precisely measured in vivo with a coefficient of variation of about 0.65% and that repeatable Tear Film dynamics can be observed. The presented method has the potential of being an alternative to breakup time measurements (BUT) and could be used in clinical setting to study patients with dry eye disease and monitor their treatments.
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in vivo Tear Film thickness measurement and Tear Film dynamics visualization using spectral domain optical coherence tomography
Optics Express, 2015Co-Authors: Valentin Aranha Dos Santos, Leopold Schmetterer, Martin Groschl, Gerhard Garhofer, Doreen Schmidl, M Kucera, Angelika Unterhuber, Jeanpierre Hermand, Rene M WerkmeisterAbstract:Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the Tear Film. Traditional methods used for the evaluation of Tear Film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure Tear Film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator. Silicon wafer phantom were used to validate the thickness measurement. The technique was applied in vivo in healthy subjects. Series of Tear Film thickness maps were generated, allowing for the visualization of Tear Film dynamics. Our results show that the in vivo central Tear Film thickness measurements are precise and repeatable with a coefficient of variation of about 0.65% and that repeatable Tear Film dynamics can be observed. The presented approach could be used in clinical setting to study patients with dry eye disease and monitor their treatments.
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measurement of Tear Film thickness using ultrahigh resolution optical coherence tomography
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Rene M Werkmeister, Doreen Schmidl, Angelika Unterhuber, Aneesh Alex, Semira Kaya, Bernd Hofer, Jasmin Riedl, Michael Bronhagl, Martin Vietauer, Tilman SchmollAbstract:PURPOSE: To visualize the precorneal Tear Film with ultrahigh-resolution spectral domain optical coherence tomography, enabling quantification of Tear Film thickness in healthy subjects. METHODS: A custom-built spectral domain optical coherence tomography system comprising a broadband titanium:sapphire laser operating at 800 nm and a high-speed charge coupled device (CCD) camera with a read-out rate of 47 kHz was used for measurement of precorneal Tear Film thickness. The system provides a theoretical axial resolution of 1.2 μm in tissue. The signal-to-noise ratio close to the zero delay was measured with 94 dB. A total of 26 healthy subjects were included in this study. Measurement was started immediately after blinking and averaged over a period of 1 second. In a subset of eight healthy subjects, the reproducibility of the approach was studied by measuring the Tear Film thickness every 10 minutes over 1 hour. RESULTS: The average central Tear Film thickness of the measured population was 4.79 ± 0.88 μm. Reproducibility was very high, with an intraclass correlation coefficient of 0.97. A breakup of the Tear Film was observed in one subject after 14 seconds. CONCLUSIONS: Our data indicate that the human precorneal Tear Film can be measured with excellent reproducibility using ultrahigh-resolution optical coherence tomography. This technique may be a valuable tool in the management of dry eye syndrome.
Ewen P Kingsmith - One of the best experts on this subject based on the ideXlab platform.
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a model for Tear Film thinning with osmolarity and fluorescein
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Richard J Braun, Ewen P Kingsmith, Carolyn G. Begley, Nicholas Gewecke, Javed SiddiqueAbstract:PURPOSE: We developed a mathematical model predicting dynamic changes in fluorescent intensity during Tear Film thinning in either dilute or quenching regimes and we model concomitant changes in Tear Film osmolarity. METHODS: We solved a mathematical model for the thickness, osmolarity, fluorescein concentration, and fluorescent intensity as a function of time, assuming a flat and spatially uniform Tear Film. RESULTS: The Tear Film thins to a steady-state value that depends on the relative importance of the rates of evaporation and osmotic supply, and the resulting increase of osmolarity and fluorescein concentrations are calculated. Depending on the initial thickness, the rate of osmotic supply and the Tear Film thinning rate, the osmolarity increase may be modest or it may increase by as much as a factor of eight or more from isosmotic levels. Regarding fluorescent intensity, the quenching regime occurs for initial concentrations at or above the critical fluorescein concentration where efficiency dominates, while lower concentrations show little change in fluorescence with Tear Film thinning. CONCLUSIONS: Our model underscores the importance of using fluorescein concentrations at or near the critical concentration clinically so that quenching reflects Tear Film thinning and breakup. In addition, the model predicts that, depending on Tear Film and osmotic factors, the osmolarity within the corneal compartment of the Tear Film may increase markedly during Tear Film thinning, well above levels that cause marked discomfort.
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Tear Film breakup and structure studied by simultaneous video recording of fluorescence and Tear Film lipid layer images
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Ewen P Kingsmith, Richard J Braun, Kathleen Reuter, Jason J Nichols, Kelly K NicholsAbstract:PURPOSE: The 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. METHODS: An 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 μL2% 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. RESULTS: Areas 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. CONCLUSIONS: Areas 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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the thickness of the Tear Film
Current Eye Research, 2004Co-Authors: Ewen P Kingsmith, Barbara A Fink, Richard M Hill, Kurt W Koelling, John M TiffanyAbstract:Measurements of the thickness of the pre-corneal Tear Film, pre-lens Tear Film, post-lens Tear Film, and the lipid layer on the surface of the Tear Film are summarized. Spatial and temporal variations in Tear Film thickness are described. Theoretical predictions of Tear Film thickness are discussed. Mechanisms involved in the upward drift of the Tear Film after a blink, and in the formation of dry spots, are considered.
Kazuo Tsubota - One of the best experts on this subject based on the ideXlab platform.
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interferometry in the evaluation of precorneal Tear Film thickness in dry eye
American Journal of Ophthalmology, 2011Co-Authors: Eri Hosaka, Takushi Kawamorita, Yuko Ogasawara, Nanami Nakayama, Hiroshi Uozato, Kimiya Shimizu, Murat Dogru, Kazuo Tsubota, Eiki GotoAbstract:PURPOSE: To compare Tear Film thickness between normal subjects and aqueous Tear deficiency dry eye patients by Tear interferometry. DESIGN: Prospective case-control study. METHODS: Central precorneal Tear Film thickness was measured noninvasively using an interference thin-Film thickness measurement device (Quore MSPA1100; Mamiya-OP). Tear Film thickness of 14 eyes from 14 normal subjects and of 28 eyes from 28 aqueous Tear deficiency dry eye patients were compared along with noninvasively measured Tear meniscus height, DR-1 (Kowa) dry eye severity grading, fluorescein and rose bengal staining scores, Tear Film break-up time, and Schirmer test results. Among dry eye patients, 13 eyes underwent punctal occlusion, and Tear Film thickness was compared before and after the surgery. RESULTS: Tear Film was significantly thinner in dry eye patients (2.0 ± 1.5 μm) than normal subjects (6.0 ± 2.4 μm; P < .0001). Tear Film thickness showed good correlation with other dry eye examinations. After punctal occlusion, Tear Film thickness increased significantly from 1.7 ± 1.5 μm to 4.9 ± 2.8 μm (P = .001) with the improvement of Tear meniscus height, fluorescein and rose bengal staining scores, Tear Film break-up time, and Schirmer test values. CONCLUSIONS: Interferometric Tear Film thickness measurement revealed impaired precorneal Tear Film formation in aqueous Tear deficiency dry eyes and was useful for showing the reconstruction of Tear Film after punctal occlusion surgery. Interferometry of precorneal Tear Film may be helpful for the evaluation of aqueous Tear deficiency in conjunction with other dry eye examinations.
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Tear Film lipid layer alterations in allergic conjunctivitis
Cornea, 2006Co-Authors: Shintaro Suzuki, Murat Dogru, Eiki Goto, Naoko Asanokato, Yukihiro Matsumoto, Yutaka Hara, Hiroshi Fujishima, Kazuo TsubotaAbstract:Purpose: To assess the alterations of the Tear Film lipid layer and Tear functions in patients with seasonal allergic conjunctivitis (SAC) and to compare the results with healthy control subjects. Methods: Seventy-eight eyes of 39 consecutive patients diagnosed as SAC (mean age 32.6 years; 11 male, 28 female) as well as 20 eyes of 10 healthy control subjects (mean age 32.5 years; 6 male, 4 female) underwent slit-lamp examinations, Tear Film breakup time measurements (BUT), comeal fluorescein stain scoring, Schirmer test, and Tear Film lipid layer interferometry. The 2 groups were then compared for the examined parameters. RAST and serum IgE level evaluations were also carried out in the patients to confirm the diagnosis of allergy. Results: The mean BUT was 3.4 ± 1.5 seconds in patients with SAC compared with the mean value of 12.4 ± 2.4 seconds in the controls (P < 0.05). There were no significant differences in relation to Schirmer test values between the 2 groups; 78% of the patients with SAC had grade 3 or above dry eye change in Tear Film lipid layer interferometry, whereas none of the controls had an interferometry grade greater than 3 (grade 1-2 normal; grade 3-4 dry eye; grade 5 severe dry eye). Eyes with SAC had significantly higher Tear Film lipid layer thickness ranges compared with the control eyes (P < 0.05). Conclusion: SAC was associated with advanced Tear instability and thickening of the Tear Film lipid layer. Evaluation of the Tear Film lipid layer thickness might be useful in the assessment of the extent of dry eye disease and the treatment outcomes in patients with allergy.
C J Radke - One of the best experts on this subject based on the ideXlab platform.
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evaporation driven instability of the precorneal Tear Film
Advances in Colloid and Interface Science, 2014Co-Authors: Chengchun Peng, Richard J Braun, Colin Cerretani, C J RadkeAbstract:Abstract Tear-Film instability is widely believed to be a signature of eye health. When an interblink is prolonged, randomly distributed ruptures occur in the Tear Film. “Black spots” and/or “black streaks” appear in 15 to 40 s for normal individuals. For people who suffer from dry eye, Tear-Film breakup time (BUT) is typically less than a few seconds. To date, however, there is no satisfactory quantitative explanation for the origin of Tear rupture. Recently, it was proposed that Tear-Film breakup is related to locally high evaporative thinning. A spatial variation in the thickness of the Tear-Film lipid layer (TFLL) may lead to locally elevated evaporation and subsequent Tear-Film breakup. We examine the local-evaporation-driven Tear-Film-rupture hypothesis in a one-dimensional (1-D) model for the evolution of a thin aqueous Tear Film overriding the cornea subject to locally elevated evaporation at its anterior surface and osmotic water influx at its posterior surface. Evaporation rate depends on mass transfer both through the coating lipid layer and through ambient air. We establish that evaporation-driven Tear-Film breakup can occur under normal conditions but only for higher aqueous evaporation rates. Predicted roles of environmental conditions, such as wind speed and relative humidity, on Tear-Film stability agree with clinical observations. More importantly, locally elevated evaporation leads to hyperosmolar spots in the Tear Film and, hence, vulnerability to epithelial irritation. In addition to evaporation rate, Tear-Film instability depends on the strength of healing flow from the neighboring region outside the breakup region, which is determined by the surface tension at the Tear-Film surface and by the repulsive thin-Film disjoining pressure. This study provides a physically consistent and quantitative explanation for the formation of black streaks and spots in the human Tear Film during an interblink.
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in vivo Tear Film thickness determination and implications for Tear Film stability
Current Eye Research, 1998Co-Authors: J L Creech, Long Trang Do, Irving Fatt, C J RadkeAbstract:PURPOSE. Previous measurements of Tear-Film thickness in vivo are limited and cannot be easily applied in a clinical setting. A novel technique to measure Tear-Film thickness indirectly is introduced here, requiring only a slit lamp, video camera, and computer. A recent fluid mechanical theory relates Tear-Film thickness h, to the Tear meniscus radius R, Tear surface tension s, Tear viscosity µ, and upper lid velocity U. This theory yields the result that h/R = 2.12 (µU/s) 2/3. All parameters except h/R are taken as known physical constants, and R was measured for each subject, allowing the above equation to establish h. Tear-Film breakup was also evaluated and correlated with Tear-Film thickness. METHODS. A clinical study was performed in which aqueous Tear-Film thickness was determined for 45 subjects, including 24 non-lens subjects, 15 hydrogel contact lens wearers, and 6 RGP lens wearers. R was measured by instilling fluorescein dye in the form of an eyedrop and videotaping the Tear meniscus in profil...
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deposition and thinning of the human Tear Film
Joint International Conference on Information Sciences, 1996Co-Authors: Harris Wong, Irving Fatt, C J RadkeAbstract:Abstract The exposed part of the eyeball is covered by a Tear Film, which is vital for the proper function of the eye. The Film thickness has been measured to be roughly 10 μm; however, how a Tear Film of this thickness is generated has not been clearly explained. It is proposed that the Tear Film is deposited analogous to a coating process by the rising meniscus of the upper lid during a blink. A coating model is formulated that not only predicts correctly the Film thickness, but also captures the postblink lipid spreading commonly observed in experiments. A deposited Tear Film thins rapidly near the Tear meniscus surrounding the Film. Numerical simulation of this thinning reveals that the minimum Film height obeys a power law. When the minimum height reaches the effective range of dewetting intermolecular forces, the Film ruptures. The thinning time therefore defines a breakup time, and the thinning law shows explicitly how this breakup time is related to Tear viscosity, surface tension, meniscus radius, and initial and final Film thicknesses. The calculated breakup time agrees with those observed experimentally.
