1. Contact Lens Interactions with the Tear Film Subcommittee Report Members: Jennifer Craig (Chair & SC Liason) Mark Willcox (Workshop Vice-Chair) Pablo Argueso Cecile Maissa Ulrike Stahl Alan Tomlinson Jianhua Wang Norihiko Yokoi Fiona Stapleton (Harmonization Subcommittee Member)

2. Interactions with the Tear Film Subcommittee The tear film is crucial to ocular surface health, and a contact lens, by its very presence, affects the tear film, and therefore has the potential to affect comfort

3. Interactions with the Tear Film Subcommittee Biophysical- changes to dynamics and quality Biophysical- Biochemical - compositional changes Biochemical Effects on the tear film

4. Interactions with the Tear Film Subcommittee Comprehensive review of the literature on each topic with respect to: – the pre-corneal (non-CL) tear film – the tear film in the presence of a CL – the impact of that aspect on discomfort in CL wear Evaluation of deficiencies in the current literature, together with suggestions for future research Biophysical & biochemical tear film aspects

5. Interactions with the Tear Film Subcommittee Tear film dynamics – Blink impact on tear film – Lipid layer quantity and quality – Evaporation – Stability – Temperature – Thickness – Turn over – Volume / CL edge profile – Exchange (post-lens) Tear film quality – Osmolality – Ferning – pH – Viscosity

6. Interactions with the Tear Film Subcommittee Biochemistry – Lipidome – Proteome – Mucins, glycocalyx and “mucin” balls – Other components Cellular content (PMNs) Contaminants

7. Interactions with the Tear Film Subcommittee Blink impact CL –  blink frequency to compensate for  TBUT Incomplete blinks in hydrogel CL wear linked to: – increased fluorescein staining – discomfort and increased lens deposition 1 Lipid layer (LL) Lipid layer   surface tension and  evaporation In CL wear, LL thickness and uniformity are  due to  aqueous layer thickness 2 No clear relationship with comfort

8. Interactions with the Tear Film Subcommittee Evaporation Non-CL: Evaporation  with incomplete lipid layer CL   evaporation (x 1.2 – x 2.6) associated with  stability, independent of lens material Under adverse conditions,  evaporation related to discomfort in hydrogel, but not SiHy, CL wearers 3 Temperature Surrogate measure for tear film evaporation and/or stability No clear relation with comfort

9. Interactions with the Tear Film Subcommittee Tear film stability Evaluated with TBUT / NIBUT tests or dynamic tests Lipid thickness closely associated with TBUT, thus, in CL:  Aqueous   lipid layer spread   TBUT *non-material specific Pre-corneal TBUT  initially but longer term changes in post-removal TBUT * not observed 5 Non-CL > 10sRigid CL 2 – 3 sHydrogel CL * 5 – 6 s 4

10. Interactions with the Tear Film Subcommittee Relation of stability to comfort With soft CL, discomfort is observed with  TBUT 6, 7 Pre-lens TBUT < 3 s predicts symptomatic CL wear 8 With CL, under adverse environmental conditions:  relative humidity   stability   symptoms 9 Wearers unable to tolerate 6 hrs CL wear have lower NIBUT than tolerant wearers (13s vs 20s) 10

11. Interactions with the Tear Film Subcommittee Tear film thickness Normal thickness around 3µm In CL, PLTF around 2µm on stabilisation 11 PoLTF approximately 1 – 3µm 11 No established association with discomfort Tear turnover rate No consistent change in TTR with CL wear However, immediately post lens removal, TTR in symptomatic individuals is less than that in asymptomatic individuals 12

12. Interactions with the Tear Film Subcommittee Tear volume Total volume in non-CL eye around 2 to 4µl 11 In CL, meniscus volume  from around 1.5 to 1.0µl 11 Limited but significant effect of tear volume on comfort 10, 13 Meniscus profile Altered in soft CL wear 13 No association with CL discomfort established

13. Interactions with the Tear Film Subcommittee Tear Exchange  with  lens size, 14 but not linked with discomfort Osmolarity No consistent effect of adapted CL wear on osmolarity 15 Relation to discomfort equivocal 15, 16 Ferning Ferning grade increases with CL wear 17 Can differentiate CL and non-CL wearers, but ability to predict intolerance not currently confirmed 17, 18

14. Interactions with the Tear Film Subcommittee pH  by 0.27 – 0.53 units in CL wear 19 but is not clearly related to comfort 20 Viscosity effects of CL unknown Surface tension no studies specific to CL wear some biochemistry changes (lipids, sPLA2, lipocalin) may relate to changes to surface tension 21

15. Interactions with the Tear Film Subcommittee Changes in tear biochemistry Lipidome:  phospholipid levels (due to  sPLA2) 21 is conceivably a contributing factor in CL discomfort Proteome:Most major proteins unaffected by CL wear Possible increases in cytokines  lipocalin-1 in CL intolerance 21 Mucins: Relation to tolerance inconclusive 22, 23 Possible relation between pattern of mucin degradation and CL discomfort 24

16. Interactions with the Tear Film Subcommittee Summary CLs induce:  stability, lipid layer and volume  evaporation rate To date, the effect on comfort of many of these biophysical properties is unknown or inconclusive Link to discomfort ✔ Link to discomfort ? stabilitylipid layer thickness evaporationsurface tension tear turnoverosmolarity volumepH ferningtemperature

17. Interactions with the Tear Film Subcommittee Conclusions absence of a consistent definition has hindered the correlation of biophysical and biochemical tear film parameters with discomfort the close relationship that exists between tear film stability, ocular surface temperature, and tear evaporation suggests that interventions that modify one aspect will influence all consideration of tear type important in relating tear film biochemistry to discomfort

18. Interactions with the Tear Film Subcommittee Future directions to define the biophysical and biochemical properties inherent to the structural integrity of the normal non-CL tear film to develop lens materials, designs and surfaces that promote biocompatibility … and refine the wetting agents within CL care solutions for long-term wettability of the CL surface … … to a level that allows the tear film to remain stable over the CL surface and support an adequate lipid layer

19. Interactions with the Tear Film Subcommittee Thank you TFOS Contact Lens Interactions with the Tear Film Subcommittee Sponsors

20. Interactions with the Tear Film Subcommittee References 1.Collins M, J, Stahmer D, Pearson G. Clinical findings associated with incomplete blinking in soft lens wearers. Clin Exp Optom 1989;72:55-56. 2.Yokoi N, Yamada H, Mizukusa Y, et al. Rheology of tear film lipid layer spread in normal and aqueous tear-deficient dry eyes. Invest Ophthalmol Vis Sci 2008;49:5319-5324. 3.Kojima T, Matsumoto Y, Ibrahim OM, et al. Effect of controlled adverse chamber environment exposure on tear functions in silicon hydrogel and hydrogel soft contact lens wearers. Invest Ophthalmol Vis Sci 2011;52: 8811-8817. 4.Guillon JP, Guillon M. Tear film examination of the contact lens patient. Contax 1988;14-20. 5.Chui WS, Cho P, Brown B. Soft contact lens wear in Hong Kong-Chinese: predicting success. Ophthalmic Physiol Opt 2000;20:480-486. 6.Fonn D, Dumbleton K. Dryness and discomfort with silicone hydrogel contact lenses. Eye Contact Lens 2003;29:S101-104 7.Glasson MJ, Hseuh S, Willcox MD. Preliminary tear film measurements of tolerant and non-tolerant contact lens wearers. Clin Exp Optom 1999;82:177- 181. 8.Hom MM, Bruce AS. Prelens tear stability: relationship to symptoms of dryness. Optometry 2009;80:181-184.

21. Interactions with the Tear Film Subcommittee References 9.Maruyama K, Yokoi N, Takamata A, Kinoshita S. Effect of environmental conditions on tear dynamics in soft contact lens wearers. Invest Ophthalmol Vis Sci 2004;45:2563-2568. 10.Glasson MJ, Stapleton F, Keay L, Sweeney D, Willcox MD. Differences in clinical parameters and tear film of tolerant and intolerant contact lens wearers. Invest Ophthalmol Vis Sci 2003;44:5116-5124. 11.Chen Q, Wang J, Tao A, Shen M, Jiao S, Lu F. Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses. Invest Ophthalmol Vis Sci 2010;51:1988-1993. 12.Tomlinson A, Fagehi R, Manahilov V. Why do some contact lens wearers avoid contact lens dry eye symptoms?, 90th Annual Meeting of the American Academy of Optometry. Phoenix, AZ, USA; 2012:E-abstract 120286 13.Chen Q, Wang J, Shen M, et al. Tear menisci and ocular discomfort during daily contact lens wear in symptomatic wearers. Invest Ophthalmol Vis Sci 2011;52:2175-2180. 14.McNamara NA, Polse KA, Brand RJ, Graham AD, Chan JS, McKenney CD. Tear mixing under a soft contact lens: effects of lens diameter. Am J Ophthalmol 1999;127:659-665. 15.Stahl U, Willcox M, Naduvilath T, Stapleton F. Influence of tearfilm and contact lens osmolality on comfort in CL wear. Optom Vis Sci 2009;86:857-867.

22. Interactions with the Tear Film Subcommittee References 16.Stahl U, Willcox M, Naduvilath T, Stapleton F. Influence of tearfilm and contact lens osmolality on comfort in CL wear. Optom Vis Sci 2009;86:857-867. 17.Evans KS, North RV, Purslow C. Tear ferning in contact lens wearers. Ophthalmic Physiol Opt 2009;29:199-204. 18.Ravazzoni L, Ghini C, Macri A, Rolando M. Forecasting of hydrophilic contact lens tolerance by means of tear ferning test. Graefes Arch Clin Exp Ophthalmol 1998;236:354-358. 19.Chen FS, Maurice DM. The pH in the precorneal tear film and under a contact lens measured with a fluorescent probe. Exp Eye Res 1990;50:251-259. 20.McCarey BE, Wilson LA. pH, osmolarity and temperature effects on the water content of hydrogel contact lenses. Contact Intraocul Lens Med J 1982;8:158- 167. 21.Glasson MJ, Stapleton F, Willcox MD. Lipid, lipase and lipocalin differences between tolerant and intolerant contact lens wearers. Curr Eye Res 2002;25:227- 235. 22.Berry M, Pult H, Purslow C, Murphy PJ. Mucins and ocular signs in symptomatic and asymptomatic contact lens wear. Optom Vis Sci 2008;85:E930-938. 23.Pisella PJ, Malet F, Lejeune S, et al. Ocular surface changes induced by contact lens wear. Cornea 2001;20:820-825. 24.Berry M, Purslow C, Murphy PJ, Pult H. Contact lens materials, mucin fragmentation and relation to symptoms. Cornea 2012;31:770-776.