1. Report of the Contact Lens Materials, Design & Care Subcommittee Members: Lyndon Jones (Chair & SC Liaison) Noel Brennan, Jose Gonzalez-Meijome, John Lally, Carole Maldonado-Codina, Tannin Schmidt, Lakshman Subbaraman, Graeme Young Jason Nichols (Harmonization Subcommittee Member)

2. Materials, Design & Care Subcommittee Workshop goals/mission related to our committee: – “To systematically examine the role of CL materials, design and the care system in the development of contact lens discomfort (CLD)” Issues to overcome with literature examined: – variability in questionnaires used across studies – subjects enrolled neophytes; asymptomatic; subjects who experience dryness – changing one parameter inevitably impacts another eg water content = thickness; design; Dk; modulus – variables across studies wearing modality (DW; EW; CW) wearing period (few hrs to many days) replacement period (1 day to 3 months or longer) care products used (preserved; non-preserved; none)

3. Materials

4. Hydrogels: water content & ionicity – HWC materials are associated with an increase in CLD compared with LWC 1-4 – no proven link with ionicity variations impossible to determine differences between FDA GII vs GIV of similar EWC – designs too dissimilar in studies published to-date SiHy: water content & ionicity – no studies yet conducted to examine these factors Materials, Design & Care Subcommittee

5. Dk/t – many studies listed as evidence for (or against) an influence of Dk/t on comfort were not designed with that specific purpose in mind 23 were identified – using these studies to infer CLD is linked to oxygen supply is fraught with difficulties most contain inappropriate masking or controls – CW/EW? 2 studies have shown improved comfort with SiHy CW vs hydrogel EW 5,6 Materials, Design & Care Subcommittee

6. Dk/t (DW) – at least 9 studies have reported switching hydrogel wearers into SiHy lenses many report improvements in subjective response – BUT studies showed consistent omission of a concurrent randomized, masked control (e.g. "switching" back into a hydrogel lens) that would enable confirmation of an improvement in comfort – properties other than Dk/t may impact comfort (surface and bulk properties; edge design) 7 – to-date, no level I studies have proven that Dk/t alone is linked with CLD Materials, Design & Care Subcommittee

7. Modulus & mechanical factors – early SiHy materials tensile moduli > most hydrogels adaptation period sometimes needed increased potential for mechanical complications – later SiHy materials have lower moduli through chemical structure modification and/or increased EWC – most studies reporting refitting hydrogel wearers into SiHy report similar or higher levels of comfort 8,9 even with a higher modulus Materials, Design & Care Subcommittee

8. Dehydration – initial temperature-induced dehydration – subsequent evaporative dehydration produces a water gradient that draws water through the lens and can result in desiccation staining this is localized and may result in only a small change in a given lens’ overall water content – bulk water loss is closely related to initial EWC – in vivo studies (16 identified) have evaluated dehydration and comfort ratings relationship not consistently shown Materials, Design & Care Subcommittee

9. Friction – emerging importance to CL field varied testing protocols unknown which best simulates in-eye performance – some recent evidence (albeit preliminary) does exist for an association between contact lens friction and comfort 10,11 Materials, Design & Care Subcommittee

10. Wettability – widely adopted by the CL industry to describe the ability of the tear film to spread and remain on the surface of a lens – no physical measurement exists that can completely quantify “wetting” – In vitro no relationship proven between in vitro measurements and on-eye wetting and whether these lab measurements are related to CLD – In vivo many methods described none conclusively link with CLD Materials, Design & Care Subcommittee

11. Design & Fit

12. Lens fit – increased movement for SCL results in reduced comfort 12-14 – thin, tapered edge designs interact less with the lids and may influence CLD 15,16 confounding roles of modulus – more complex, thicker designs are less comfortable and result in higher reports of CLD 17,18 also linked to greater drop-out 19 Tear exchange – increased tear exchange occurred with increased movement, which led to reduced comfort 20 no proven relationship Materials, Design & Care Subcommittee

13. Deposits

14. – many studies rely on visible deposition rather than biochemically measuring the degree of deposition ~50% of those published linking deposits and comfort – known that visible and measured deposition show a poor correlation 21,22 – studies conducted using visible methods to determine CL deposition have provided poor evidence that comfort and deposits are linked particularly over the one month or less that lenses are now typically worn – future studies would be ill advised to rely on visible assessment of deposition to relate to CLD Materials, Design & Care Subcommittee

15. Protein deposits – Hydrogel materials 9 studies investigated a link between protein deposits and CLD – 8 unable to show a link between protein quantity and CLD 1 study has shown a link between CLD and denatured protein – over an 8 hr period 23 – SiHy materials 3 studies have investigated a link between protein deposits and CLD most recent study showed a weak correlation (r = -0.13) with comfort on insertion 24 Materials, Design & Care Subcommittee

16. Lipid & mucin deposits – mucin deposits (2) no link with CLD – lipid deposits (3) 1 study investigating lipid deposition on a variety of SiHy materials was able to show weak correlations for both overall comfort (r = -0.13; p=0.03) and comfort on insertion (r = -0.16; p=0.008) 24 – future work may be better directed at investigating mucin or lipid breakdown products rather than total lipid or mucin Materials, Design & Care Subcommittee

17. Wearing Period & Replacement

18. Wearing schedule – several studies have looked at DW vs overnight wear masking obviously impossible – apart from relatively minor dryness upon waking, individuals who sleep in lenses are not at a disadvantage (and may benefit) in terms of comfort compared to DW – inadequacies of study designs prevent more definitive conclusions Materials, Design & Care Subcommittee

19. Lens age and replacement frequency – several studies have reported improved comfort with disposable/frequent replacement reusable lenses and improvement is linked with increasing frequency of lens replacement – important to remember that the lenses used are not necessarily the same material, design or cared for with the same care system or are exposed to no care system in the case of DD Materials, Design & Care Subcommittee

20. Lens age and replacement frequency – overall, there is almost a complete absence of masked, randomized, controlled studies that consider the impact of replacement schedule on CLD particularly for SiHy materials – tendency for studies to suggest that more frequent replacement is conducive to greater comfort Materials, Design & Care Subcommittee

21. Time of day – evidence in support of decreased comfort toward the end of the day cannot arise from Level I studies impossible to conduct a controlled, masked, randomized study where time of day is the key independent variable – large number of studies provide data to support the hypothesis that comfort decreases during the day and is exacerbated by contact lens wear Materials, Design & Care Subcommittee

22. Care System

23. Care solutions – systematic analysis of the literature shows that many studies exist reporting variations in CLD between care products – products are complex in their composition and no studies to date have been conducted to relate specific components within a care system and their impact on CLD – therefore, it cannot be concluded that a specific biocide, wetting agent or other single component alone will provide improved comfort Materials, Design & Care Subcommittee

24. Care solutions – two large-scale retrospective studies conducted extensive regression analysis to investigate any link between CLD and care solutions 2,18 no significant association between CLD and any CL care system was apparent – recent study has shown that subjective satisfaction (particularly in symptomatic wearers) can be influenced by the combination of lens/solution prescribed 25 Materials, Design & Care Subcommittee

25. Rewetting drops – a number of studies demonstrate some level of symptom-relief for CL wearers – evidence would suggest relatively little advantage over the use of saline Blister-pack solution – no published study has systematically examined whether a modified BPS has a direct impact on CLD Materials, Design & Care Subcommittee

26. Summary

27. – much of the published work has been poorly conducted, with inappropriate or missing controls – future work must be conducted using well controlled, randomized, cross-over studies in which all variables (replacement period, care system, wearing time etc.) are considered – requires some fundamental studies in which the isolation of a single change in a material, design or solution characteristic is investigated can only be conducted with the close cooperation of industry Materials, Design & Care Subcommittee

28. Donald Rumsfeld "Simply because you do not have evidence that something does exist, does not mean that you have evidence that it doesn't exist."

29. Thank you! QUESTIONS?