Director, UC Berkeley Clinical Research Center (CRC)
Chief, Ocular Surface Imaging Clinic
Co-Chief, Dry Eye Clinic
Ocular Surface Physiology
Effect of contact lenses and lens care solutions of human tear lipids
The interaction between tear proteins and lipids can affect the equilibrium surface tension of the lipid layers, suggesting that a similar mechanism could impact tear-film stability in vivo. However, human tear-film stability is likely dependent not only on the equilibrium surface tension, but also on the mechanical properties of film operating under dynamic conditions and high stresses exerted by the eyelids in a blinking cycle. In addition, currently available data stipulate that tear lipids spread on the eye as a film of thickness substantially (approximately 20 times) exceeding that of a monolayer. Recent clinical studies have shown that in vivo relaxation of tear lipid layers after a blink can be described as a visco-elastic process. Unfortunately, information regarding interfacial visco-elastic properties of lipid films is very scarce. Recently, we have published a novel technique [Svitova & Lin, OVS, 2010] to create thick tear lipid films at the air-aqueous interface and then to investigate the interfacial properties of these multilayered films under dynamic conditions that mimic human eye conditions more realistically. With this technique of reconstituting multilayered tear lipids, we have found that the delicate balance between interfacial visco-elastic properties of ex vivo human lipids and lysozyme existed for lipids collected from healthy subjects. The results obtained for ex vivo lipids collected from healthy Asian and non-Asian subjects indicated that there are substantial differences between visco-elastic properties for the lipids between the two ethnic groups. [Lin & Svitova, ARVO 2010] Using this technique, we also reported that visco-elastic properties of tear lipid can be adversely affected by lens care solutions and that the extent of this effect varies with different lens care solutions. [Svitova & Lin, OVS, 2010] We plan to employ this technique toward understanding mechanisms responsible for tear film instability.
Effects of ethnicity on contact lens wear
There are important fundamental differences in ocular anatomy and physiology between Asian and non-Asian eyes. Tear film thickness sandwiched between a soft contact lens and the cornea (post-lens tear film) is thinner for Asians than for non-Asians. [Lin et al., IOVS, 1999; Lin et al., Eye & CL, 2003] The combination of a thinner post-lens tear film and tighter upper lids may translate into higher shear force applied to the ocular surface, resulting in greater stress to the corneal epithelial cell layer. This hypothesis agrees with our recent finding that changes in corneal epithelial integrity following overnight wear of high-Dk/t lenses are significantly greater for Asian than non-Asian eye. [Lin et al., IOVS, 2002; Lin & Polse, Eye & CL, 2007] Therefore a lens of the same design and material may perform differently on eyes with diverse ocular characteristics. Further clinical investigations are warranted. Recently, we found that Asian lens wearers tend to report more frequent and severe dry-eye symptoms during contact lens wear, compared with non-Asians. [Lungrin et al, ARVO 2008] The pre-lens tear film is substantially more unstable for Asians than non-Asians. Using our recently published technique, we were able to show that ex vivo tear lipids collected from normal/asymptomatic Asian subjects have an interfacial viscosity 1.4 times higher and an interfacial elasticity 1.5 times lower than those of non-Asians (manuscript in preparation). [Lin & Svitova ARVO 2010] Differences in eyelid anatomy (e.g., palpebral aperture size, lid margin apposition against the ocular surface) between Asians and non-Asians may contribute to variability in tear-film thickness and related tear-film stability, which might be responsible for poor sensitivity and specificity of many diagnostic tools, as the diagnostic cut-off criteria do not take into account ethnic variability. These differences in physical properties of tear lipid could be, in part, responsible for our recent findings that the incidence of clinically significant corneal staining/surface disruption is significantly higher among Asians than non-Asians, given the same lenses and lens care solutions. [Lin, AAO, 2009] Additionally, the longer the history of contact wear is for Asians, the greater the increase in severities of discomfort experienced during lens wear. [Tran et al., AAO, 2009].
Genetic and environmental factors on non-contact-lens-induced dry eye
Dry eye is the primary reason for patient visits to eye care practitioners. In the United States, approximately 7–10 million Americans required artificial-tear topical ophthalmic medications, with consumers spending over $100 million per year. In recent years, researchers have, with increasing rapidity, recognized that different subtypes (e.g., evaporative vs. aqueous deficiency etiology), tear osmolarity, and inflammatory biomarkers play important roles in our understanding of dry eye. Yet despite the advancing knowledge in dry-eye and tear-film research, many issues remain unresolved. For example, information about whether laboratory and clinical parameters of human tears differ among various ethnic groups is scarce, and it is unknown how these ethnic differences affect current clinical practice in diagnosis and treatment of dry eye. Therefore, it is important to to investigate risk factors associated with tear-film instability and dry eye by first establishing a normal range of clinical parameters and biological markers in adults of different ages, ethnic groups, and life conditions, while epidemiologic analyses of clinical parameters and biomarkers in relation to the health of the ocular surface must include appropriate adjustments for such covariates. Given the current state of knowledge and our preliminary data, we hypothesize that tear films of different ethnic groups have particularized biophysical and biochemical characteristics, leading to inherent variations in clinical parameters. These differences lead to diverging risk factors in various ethnic groups and contribute to the variability of clinical parameters collected by common diagnostic tests; hence, the usefulness of these tests is limited by poor sensitivity and specificity, as ethnic differences have not been taken into account for standardizing appropriate cutoff criteria.
Factors affecting post-lens aqueous tear mixing under soft contact lenses
Previous work has shown that corneal epithelial barrier function is compromised by hypoxia during closed-eye contact lens wear. However, it is unclear whether the effect of hypoxia overrides the mechanical effect on corneal epithelial status induced by the physical presence of contact lenses during eye closure. To further refine this hypothesis, we designed a clinical trial using both rigid and silicone-hydrogel lenses with similar levels of oxygen transmissibility. The results strongly suggest that even with newly developed oxygen-transmissible contact lenses designed for overnight wear, the integrity of corneal epithelial barrier function can still be greatly compromised. [Lin et al., AAO, 2006] However, the status of corneal epithelium recovers much faster with rigid than with soft lenses. This observation indirectly suggests that the much greater efficiency of post-lens tear mixing upon awaking after overnight wear of rigid lenses may have a significant beneficial impact on the recovery of corneal epithelial barrier function. The results of this trial have led to another study, a longitudinal trial in which we have been examining whether irrigation with unpreserved saline solution upon awakening (enhanced post-lens tear mixing under a soft lens) can speed up the recovery process compared with the control group (no irrigation). The results from this trial may further our understanding of the relationship between corneal barrier function and other physiological responses to contact lens wear. Given the likely connection between insufficient or low tear exchange and adverse ocular response, it is possible that timely removal of debris and restoration of the normal fresh post-lens tear film is a requirement for safe extended wear. I am currently working on a project that employs anterior-segment optical coherence tomography (OCT) to enhance our understanding of the interaction between lens edge designs and tear mixing as well as between the lens edge and conjunctival tissues. We are the first research group to report the incidence rate of conjunctival epithelial flap induced by day-wear contact lenses [Lin, editorial, Silicone Hydrogel website, 2006] and the first to publish the incidence of this condition during continuous wear for both rigid and silicone hydrogel lenses [Graham, Truong, Lin OVS, 2009]. Conjunctival epithelial flap is an adverse event induced by a lens edge digging into the conjunctival epithelium, causing sheathing of the epithelial layers. Often, these lenses appear to have tight-fitting characteristics with minimum lens movement and tear exchange. The clinical implication of this condition is not well understood. With the advance in anterior segment OCT technology, we will be able to measure post-lens tear thickness in 3D rendering and to observe how the lens edge interacts with the ocular tissue in this high-resolution imaging system. We look forward to making significant progress in this research area.
Optometry 260A. Contact Lenses: Examination of the Contact Lens Patient
The physiological basis for fitting contact lenses; effects of a contact lens on the tears, lids, and cornea; examination procedures and instrumentation used in monitoring the ocular response to contact lenses; contact lens inspection, care, and handling.
Vision Science 206C. Anatomy and Physiology of the Eye and Visual System
Problem-based learning approach using clinical case examples (continuation of Vision Science 106A and 106B).
Peer-reviewed Journal Articles
Li W, Graham AD, Selvin S, Lin MC. Ocular Surface Cooling Corresponds to Tear Film Thinning and Breakup. Optom Vis Sci. 2015 Jul 22. (PDF)
Satjawatcharaphong P, Ge S, Lin MC. Clinical Outcomes Associated with Thermal Pulsation System Treatment. Optom Vis Sci. 2015 Jul 17. (PDF)
Lin MC, Polse KA. Improving Care for Patients with Dry Eye Symptoms: See What the Experts Say. Optom Vis Sci. 2015 Jul 13. (PDF)
Yeh TN, Graham AD, Lin MC. Relationships among Tear Film Stability, Osmolarity, and Dryness Symptoms. Optom Vis Sci. 2015 Jul 3. (PDF)
Moy A, McNamara NA, Lin MC. Effects of Isotretinoin on Meibomian Glands. Optom Vis Sci. 2015 Jul 3.(PDF)
Pucker AD, Jones-Jordan LA, Li W, Kwan JT, Lin MC, Sickenberger W, Marx S, Srinivasan S, Jones LW. Associations with Meibomian Gland Atrophy in Daily Contact Lens Wearers. Optom Vis Sci. 2015 Jul 3. (PDF)
Leung T, Zhou Y, French H, Lin MC. Factors Affecting Corneal Epithelial Permeability. Invest Ophthalmol Vis Sci. 2014 Aug. 12. (PDF)
Svitova TF, Lin MC: Dynamic interfacial properties of lens care solution induced alterations in human tear-lipid films. Contact Lens & Anterior Eye. 2014. Jul 14. (PDF)
Tan B, Graham AD, Zhou Y, Tsechpenakis G, Lin MC. A Novel Analytical Method to Quantitatively Describe the Corneoscleral Junction Using Optical Coherence Tomography (OCT). Optom Vis Sci. 2014 Jun;91(6):650-7. (PDF)
Lin MC, French, HM, Graham AD, Sanders TL. Effects of Daily Irrigation on Corneal Epithelial Permeability and Adverse Events With Silicone Hydrogel Contact Lens Continuous Wear. Invest Ophthalmol Vis Sci. 2014;55:776–783. DOI:10.1167/iovs. 13-13508 (PDF)
Svitova TF & Lin MC: Racial Variations in Interfacial Behavior of Lipids Extracted from Worn Silicone-Hydrogel Lenses. Optom Vis Sci. 2013, 90(12):1361-1369. (PDF)
Truong TN, Graham AD, Lin MC: Factors in Contact Lens Symptomatology: Evidence from a Multi-Study Database. Optom Vis Sci 2013, 91(22):133-141. (PDF)
Niimi J, Tan B, Chang J, Zhou Y, Ghanekar A, Wong M, Lee A, Lin MC: Diurnal pattern of tear osmolarity and its relationship to corneal thickness and de-swelling. Cornea 2013, 32(10):1305–1310. (PDF)
Lin MC, Yuen J, Graham AD. Ethnic Disparity in Ocular Response to Contact Lens Care Solutions. ECL. 2014 May 30.
Tan B, Zhou Y, Svitova TF, Lin MC: Objective quantification of fluorescence intensity on the corneal surface using a modified slit lamp technique. Eye Contact Lens. 2013; 39(3): 239-246. (PDF)
Tran N, Graham AD, Lin MC. Ethnic Differences in Dry Eye Symptoms: Effects of Corneal Staining and Length of Contact Lens Wear. Contact Lens & Anterior Eye 2013. (PDF)
Yeh TN, Green HM, Zhou Y, Pitts J, Kitamata-Wong B, Lee S, Wang SL, Lin MC. Short-Term Effects of Overnight Orthokeratology on Corneal Epithelial Permeability and Biomechanical Properties. Invest Ophthalmol Vis Sci. 2013 May 7. pii: iovs.13-11874v1. doi: 10.1167/iovs.13-11874. [Epub ahead of print] (PDF)
Li WY, Hsiao C, Graham AD, Lin MC. Corneal Epithelial Permeability: Ethnic Differences between Asians and non-Asians. Contact Lens & Anterior Eye 2013. Accepted for Publication. (PDF)
Lin MC & Yeh TN. Mechanical Complications Induced by Silicone Hydrogel Contact Lenses. Eye & Contact Lens 2013 Jan;39(1):115-24. (PDF)
Vedamurthy I, Lin MC, Tong J, Yeh T, Graham AD, Green H, Wang SL, Schor CM. Does Ethnicity Influence the Short-Term Adaptation to First Reading Correction? Optom Vis Sci. April 2012. 89(4):A4- A7. (PDF)
Svitova TF & Lin MC. Wettability Conundrum: Discrepancies of Soft Contact Lens Performance in vitro and in vivo. European Physical Journal – Special issue: Wetting and Spreading Phenomena. Volume 197, August 2011, p. 295-303. (PDF)
Lin MC, Yeh T, Graham AD, Truong TN, Hsiao C, Wei G, Louie A. Factors Affecting Ocular Surface Health During 30-day Continuous Wear: Rigid Gas Permeable vs. Silicone Hydrogel Hyper-O2 Transmitted Contact Lenses. Invest Ophthalmol Vis Sci. 2011 Jun 1;52(6):3530-8. (PDF)
Han S, Graham AD, Lin MC. Clinical Assessment of a Customized Free form Progressive Add Lens Spectacle. Optom Vis Sci. 2011. Feb/March 88(2/3). (PDF)
Liu WC, Lee SM, Graham AD, Lin MC. Effects of Eye-Rubbing and Breath-Holding on Corneal Biomechanical Properties and Intraocular Pressure. Cornea. 2011 Aug;30(8):855-60. (PDF)
Lin MC & Svitova TF. Contact Lenses Wettability In Vitro: Effect of Surface-Active Ingredients. Optom Vis Sci. 2010. Jun;87(6):440-7. (PDF)
Svitova TF & Lin MC. Tear Lipids Interfacial Rheology: the effect of Lysozyme and Multi-Purpose Lens Care Solutions. Optom Vis Sci. 2010. Jan 87(1). (PDF)
Graham AD, Truong TN, Lin MC. Conjunctival Epithelial Flap in Continuous Contact Lens Wear. Optom Vis Sci. 2009. April ;86(4):e324-31. (PDF)
Lin MC & Polse KA. Hypoxia, Overnight Wear, & Tear Stagnation Effects on the Corneal Epithelium. Data and Proposed Model. Eye & Contact Lens. 2007. Nov; 33(6 Pt 2):378-81; discussion 382. (PDF)
Lin MC, Soliman GN, Lim V, Giese ML, Wofford LE, Marmo C, Radke C, Polse KA. Scalloped-channels enhance tear mixing under hydrogel contact lenses. Optom Vis Sci. 2006. Dec; 83(12). (PDF)
Lin MC, Soliman, GN, Song MJ, Smith JP, Lin CT, Chen YQ, Polse KA. Soft contact lens extended wear affects epithelial permeability: hypoxic or mechanical mechanism? Contact Lens & Anterior Eye. 2003. Mar; 26(1):11-6. (PDF)
Lin MC, Chen YQ and Polse KA. The effects of soft lens and ocular characteristics on the post-lens tear thickness. Eye & Contact Lens. 2003. Jan;29(1Suppl):S33-6; discussion S57-9, S192-4. (PDF)
Lin MC, Graham AD, Polse KA, Fusaro RE. The impact of rigid contact lens extended wear on corneal epithelial barrier function. Invest Ophthalmol Vis Sci. 2002. 43(4): 1019-24. (PDF)
Graham AD, Fusaro RE, Polse KA, Lin MC, Giasson CJ. Predicting extended wear complications from overnight corneal swelling. Invest Ophthalmol Vis Sci. 2001. 42: 3150-3157. (PDF)
Polse KA, Fusaro RE, Graham MS, Gan CM, Rivera RK, Lin MC, Sanders TL, McNamara NA, Chan JS.The Berkeley Contact Lens Extended Wear Study: Part II – Clinical Results. Ophthalmol. 2001. 108 (8):1389-99. (PDF)
Polse KA, Graham MS, Fusaro RE, Gan CM, Rivera RK, Lin MC, Sanders TL, McNamara NA, Chan JS. The Berkeley Contact Lens Extended Wear Study: Part I – Study Design. Ophthalmol. 2001. 108 (8): 1381-88. (PDF)
Lin MC, Graham AD, Polse KA, McNamara NA, Tieu TG. The effects of one-hour wear of high oxygen permeable soft lenses on corneal pH and epithelial permeability. CLAO. 2000. 26(3): 130-133. (PDF)
Lin MC, Graham AD, Polse KA, Mandell RB, McNamara NA. Measurement of post contact lens tear thickness. Invest Ophthalmol Vis Sci. 1999. 40: 2833-2839. (PDF)
Lin MC, Snyder C. Comparison of flexure and residual astigmatism with RGP lenses of low, medium and high oxygen permeability. ICLC. 1999. 26: 5-9. (PDF)
Gordon A, Bartlett JD, Lin MC: The effect of diclofenac sodium on the initial comfort of RGP contact lenses: a pilot study. J Am Optom Assoc. 1999 Aug; 70(8):509-13. (Abst)
Miller KL, Lin MC, Radke CJ, Polse KA: Tear mixing under soft contact lenses. In Silicone Hydrogels. Butterworth-Heinemann Oxford, D.F. Sweeney, Ed., 2003