A Mathematical Model for Ocular Tear and Solute Balance

Purpose: In this paper we develop a mathematical model that can predict the steady-state tear film thickness and the dynamic tear film thickness and the solute concentration after instillation of a solute-laden fluid in the eye. Methods: The mathematical model developed in this paper is based on a balance between the inflow and outflow of tears into the tear film. It incorporates a tear drainage model and a model that relates the tear film thickness to the meniscus radius of curvature. To predict the solute concentrations, the tear balance is coupled with the solute balance. The differential equations for the unsteady balances are solved numerically. Results: The model predicts that the tear film thickness depends on a number of physiological factors, such as rates of tear production and evaporation, geometry and modulus of the canaliculi, and surface tension and viscosity of tears, and varies from about 3 to 15 μ m. The model also predicts that the drainage time for an instilled volume of 15 μ l is 1283 s. Additionally, the time required for the tracer concentration to decay to 1% of the value immediately after instillation of a drug-laden 40 μ l drop is about 2480 s. Similarly, the time for intensity decay for a radioactive tracer after 25 μ l instillation is about 1566 s. Also, the model predicts that the fraction of the instilled drug that reaches the cornea is about 1.3% for topical application of timolol. Conclusions: The predicted results agree reasonably with the reported experimental results, at least qualitatively. The model developed here can serve as a useful tool to develop a more precise understanding of various issues related to tears and also evaluate the effect of various parameters on the tear volume.

[1]  J. Craig,et al.  Determination of relative contribution of the superior and inferior canaliculi to the lacrimal drainage system in health using the drop test , 2004, Clinical & experimental ophthalmology.

[2]  PD Dr. med. Friedrich Paulsen The Human Nasolacrimal Ducts , 2002, Advances in Anatomy Embryology and Cell Biology.

[3]  A. Chauhan,et al.  A Mathematical Model for Tear Drainage Through the Canaliculi , 2005, Current eye research.

[4]  A. Joshi,et al.  A novel method to evaluate residence time in humans using a nonpenetrating fluorescent tracer. , 2002, Investigative ophthalmology & visual science.

[5]  Ewen King-Smith,et al.  The thickness of the tear film , 2004, Current eye research.

[6]  J. Prydal,et al.  Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy , 1990, Eye.

[7]  P. J. Murphy,et al.  Changes in the tear film and ocular surface from dry eye syndrome , 2004, Progress in Retinal and Eye Research.

[8]  H F Edelhauser,et al.  Comparison of conjunctival and corneal surface areas in rabbit and human. , 1988, Current eye research.

[9]  O. Candia Electrolyte and fluid transport across corneal, conjunctival and lens epithelia. , 2004, Experimental eye research.

[10]  N. Eter,et al.  A new technique for tear film fluorophotometry , 2002, The British journal of ophthalmology.

[11]  F. Paulsen Introduction and Questions , 2003 .

[12]  S Kinoshita,et al.  The Height and Radius of the Tear Meniscus and Methods for Examining These Parameters , 2000, Cornea.

[13]  A. Bron,et al.  Retention of reversibly thermo-gelling timolol on the human ocular surface studied by video meniscometry , 2003, Current eye research.

[14]  A. Bron,et al.  Reflective meniscometry: a non-invasive method to measure tear meniscus curvature , 1999, The British journal of ophthalmology.

[15]  Norihiko Yokoi,et al.  [Tear dynamics and dry eye]. , 2004, Nippon Ganka Gakkai zasshi.

[16]  A. Bron,et al.  Physical properties of stimulated and unstimulated tears. , 1999, Experimental eye research.

[17]  S. Tseng,et al.  Paracellular permeability of corneal and conjunctival epithelia. , 1989, Investigative ophthalmology & visual science.

[18]  S. Thanos,et al.  Ultrasonic visualization of the effect of blinking on the lacrimal pump mechanism , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[19]  R M Hill,et al.  The thickness of the human precorneal tear film: evidence from reflection spectra. , 2000, Investigative ophthalmology & visual science.

[20]  Clive G. Wilson,et al.  Ocular contact time of a carbomer gel (GelTears) in humans , 1998, The British journal of ophthalmology.

[21]  Norihiko Yokoi,et al.  Non-invasive methods of assessing the tear film. , 2004, Experimental eye research.

[22]  M. Doane Blinking and the mechanics of the lacrimal drainage system. , 1981, Ophthalmology.

[23]  D. Maurice The dynamics and drainage of tears. , 1973, International ophthalmology clinics.

[24]  T. F. Patton Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume. , 1977, Journal of pharmaceutical sciences.

[25]  K. Tsubota,et al.  Important concepts for treating ocular surface and tear disorders. , 1997, American journal of ophthalmology.

[26]  L. T. Jones Anatomy of the tear system. , 1973, International ophthalmology clinics.

[27]  F. Miano,et al.  Residence Time of Netilmicin in Tears , 2002, Cornea.

[28]  C. Radke,et al.  Deposition and Thinning of the Human Tear Film , 1996, Journal of colloid and interface science.

[29]  K. Nagashima,et al.  Relative roles of upper and lower lacrimal canaliculi in normal tear drainage. , 1984, Japanese journal of ophthalmology.

[30]  K. M. Zinn,et al.  Transmission electron microscopy. , 1973, International ophthalmology clinics.

[31]  L. T. Jones Epiphora. II. Its relation to the anatomic structures and surgery of the medial canthal region. , 1957, American journal of ophthalmology.

[32]  M. Prausnitz,et al.  Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye. , 1998, Journal of pharmaceutical sciences.

[33]  F. Holly,et al.  Tear Film Physiology , 1980, International ophthalmology clinics.

[34]  J. Hardy,et al.  A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man , 1986, The Journal of pharmacy and pharmacology.

[35]  S. Klyce,et al.  Determination of tear volume and tear flow. , 1966, Investigative ophthalmology.

[36]  D. Maurice,et al.  The oily layer of the tear film and evaporation from the corneal surface. , 1961, Experimental eye research.

[37]  R. Hodges,et al.  Regulatory pathways in lacrimal gland epithelium. , 2003, International review of cytology.

[38]  J. Craig,et al.  Chapter 2 – Structure and function of the preocular tear film , 2002 .

[39]  Clive G. Wilson,et al.  Topical drug delivery in the eye. , 2004, Experimental eye research.

[40]  L. T. Do,et al.  In vivo tear-film thickness determination and implications for tear-film stability. , 1998, Current eye research.

[41]  Jianhua Wang,et al.  Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography. , 2003, Investigative ophthalmology & visual science.

[42]  R. Gurny,et al.  Gamma scintigraphic comparison of eyedrops containing pilocarpine in healthy volunteers. , 1996, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[43]  A. Urtti,et al.  Minimizing systemic absorption of topically administered ophthalmic drugs. , 1993, Survey of ophthalmology.

[44]  J. Robinson,et al.  The effect of polyethylene glycol molecular weight on corneal transport and the related influence of penetration enhancers , 1992 .

[45]  G. Wilson,et al.  The Lacrimal Drainage System: Pressure Changes in the Canaliculus* , 1976, American journal of optometry and physiological optics.