Report of the Contact Lens Materials, Design & Care Subcommittee Members :

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

3. Materials, Design & Care Subcommittee • 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

4. Materials, Design & Care Subcommittee • 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

5. Materials, Design & Care Subcommittee • 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

6. Materials, Design & Care Subcommittee • 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

7. Materials, Design & Care Subcommittee • 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

8. Materials, Design & Care Subcommittee • 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

9. Deposits

10. Materials, Design & Care Subcommittee • Deposits • 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

11. Materials, Design & Care Subcommittee • 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

12. Materials, Design & Care Subcommittee • 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

13. Wearing Period & Replacement

14. Materials, Design & Care Subcommittee • 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

15. Materials, Design & Care Subcommittee • 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

16. Materials, Design & Care Subcommittee • 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

17. Materials, Design & Care Subcommittee • 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

18. Care System

19. Materials, Design & Care Subcommittee • 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

20. Materials, Design & Care Subcommittee • 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

21. Summary

22. Materials, Design & Care Subcommittee • Summary • 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

23. Thank you! QUESTIONS?