Lyndon Jones - PhD FCOptom DipCLP DipOrth FAAO (Dip CL) FIACLE

Associate Professor, School of Optometry
Associate Professor, Departments of Physics,
Chemistry & Chemical Engineering (cross-appointed)
Associate Director, Centre for Contact Lens Research

School of Optometry
University of Waterloo, Waterloo, Canada

Adaptive Effects of 30-night Wear of Hyper-O2 Transmissible Contact Lenses on Bacterial Binding and Corneal Epithelium.

DH Ren, K Yamamoto, PM Ladage, M Molai, L Li, WM Petroll, JV Jester, HD Cavanagh
Ophthalmology 2002: 109: 27 - 40.

In the early to mid-1980's millions of patients in the United States wore their lenses on an extended wear (EW) modality, for periods often in excess of one-month and not infrequently for three months at a time. By 1986, hundreds of patients were being seen with contact lens related corneal ulcers and reports concerning the potential impact of the problem were increasingly appearing in the professional and lay press. In March of that year representatives from many interested parties, including the FDA, major contact lens manufacturers and the National Eye Institute gathered to discuss this crucial issue. The result of these and subsequent discussions were two independent studies that were published in the New England Journal of Medicine in 1989 that defined the risks of contact lens wear. ^{1, 2} These studies clearly indicated that the risk of developing ulcerative keratitis was some 10-15 times greater for a patient if they slept in a contact lens, compared with using identical lenses on a daily-wear basis. Further European studies confirmed this fact. ^{3, 4} As a result, practitioners became wary of recommending such a modality and the number of patients being fitted with EW lenses reduced across the globe though-out the ensuing years.

During the early 1990's, manufacturers and clinicians alike became attracted by the concept that the major reason behind the development of corneal ulcers was related to poor hygiene and compliance and that the incidence of corneal ulceration could be reduced by using an EW lens that was worn once and then discarded. This attractive philosophy was adopted fairly universally and the concept of disposable EW lenses became popular. However, early reports questioned the fact that disposability impacted on the incidence of ulcerative keratitis ^{5, 6} and a 1999 conducted in the Netherlands 7 confirmed that the wearing of disposable lenses on an EW basis had no impact on the incidence of ulcerative keratitis, with an incidence of approximately 20 cases per 10,000 wearers being seen in users of hydrogel EW lenses, regardless of whether the lens was disposed of regularly or not.

The recent launch of two novel silicone-hydrogel (SH) contact lenses, with oxygen transmissibilities (Dk/t) of 4-6 times that obtained with conventional hydrogels, has provided practitioners with a new alternative to fit patients who wish to sleep in their contact lenses. Bausch & Lomb's PureVision and CIBA Vision's Focus Night&Day have recently received FDA approval for use as 30-day EW or "continuous wear" (CW) lenses. However, based on the fact that the concept of "safe" lenses for EW has failed twice in the last 15 years, the key question that remains is whether these highly oxygen permeable lenses will result in a reduction in the incidence of ulcerative keratitis.

Initial results appear quite promising, in that major research centers involved in the original studies to validate the use of SH lenses have yet to see any cases of microbial keratitis in their controlled clinical studies. To some extent, it will take several years of the lenses being available in clinical practice before a true incidence can be established. However, in the meantime, some recently published laboratory-based work by Dwight Cavanagh's group in Texas provides an interesting perspective on what the likely future holds for wearers of SH lenses used on an EW basis.

The paper published by David Ren et al in the January issue of Ophthalmology builds on work conducted by the Cavanagh group over the last 6-7 years, in which binding of Pseudomonas aeruginosa to exfoliated corneal epithelial cells is quantified and correlated with the degree of oxygenation afforded them by various contact lens materials. The hypothesis put forward by the group is that in order that microbial keratitis occur the cornea must bind bacteria and that subsequent infection is dependent upon the bound bacteria being able to invade the cornea to infect the corneal stroma. If the epithelium binds less bacteria then subsequent infection should be less likely.

The group's initial work in this area began with rabbit-based models, in which the rabbits were fitted with contact lenses of various Dk/t's and, after a period of time of wearing the lenses on an EW basis, the binding of Pseudomonas to the corneal epithelial cells was determined. ⁸ This study proved that bacterial binding was inversely proportional to the Dk/t of the lens, a finding that was confirmed in human studies in 1999. 9 These two studies also indicated that the use of high Dk/t SH lenses on an overnight basis reduced bacterial binding to epithelial cells, compared with conventional lens materials.

As a result, a large-scale, one-year in vivo study was conducted, in which 178 neophyte patients were randomly fitted with lenses on an EW basis. The lenses consisted of either a conventional 6-night EW material, high Dk/t SH lens (worn on a 6-night or 30-night regimen) or high Dk/t rigid gas permeable (RGP) material. The lenses were worn for one year, during which tear samples and epithelial cells were sampled at various time-points. The binding of Pseudomonas to the collected epithelial cells was quantified and the tear samples were analysed for levels of lactate dehydrogenase (LDH), which was used as a marker of epithelial cell irritancy.

The results of this study revealed that wearing SH lenses on an EW basis results in significantly less binding of Pseudomonas to epithelial cells that is found when conventional lens materials are worn overnight. Interestingly, there was no significant difference with SH lenses worn for 30-nights versus those worn for 6-nights. Of striking note was that an adaptive effect appeared to occur, with a return to pre-lens wear levels of bacterial binding after a six-month period, suggesting that an adaptive effect occurs to bacterial binding sites on the corneal epithelium after a period of use. Of further significance was that RGP lens-wear did not affect bacterial binding at any point, indicating that not only is there an oxygen effect on bacterial binding to epithelial cells but also a lens-type effect. Tear LDH levels increased in all groups from baseline levels and no adaptation occurred over the period of the study. Similar trends to that seen with bacterial binding were observed, with a greater increase in tear LDH with EW of conventional soft lenses compared with higher Dk/t materials, regardless of whether they were soft or rigid.

Based on this study, plus numerous other publications concerning their clinical performance, ^{10, 19} there is good reason to suppose that EW of new high Dk/t SH lens materials will result in fewer short and long-term clinical complications than those seen with conventional low Dk/t EW lenses. Will the incidence of microbial keratitis be reduced? Whilst the initial results are encouraging, ²⁰ the jury is still out, as currently no epidemiological study has been undertaken to prove the case either way. Plans are underway for a definitive study to be conducted, in a similar way to the studies published in 1989 ² and 1999 ⁷ that indicated the extent of the problem with conventional EW lenses. However, for this to occur a defined population needs to be wearing the lenses and it may take some time for the penetration of these lenses to achieve a critical mass that such a study becomes feasible.

In summary, the future for EW looks promising and practitioners interested in fitting such lenses should review the literature on a regular basis and continue to attend continuing education seminars to obtain the latest information concerning the use of SH lenses. The silicone-hydrogel website (www.siliconehydrogels.com) will continue to play its part by regularly providing summaries such as this of important papers to draw practitioners attention to new developments concerning their use.

1. Schein OD, Glynn RJ, et al.: The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group. N Engl J Med 1989; 321;12: 773-8.
2. Poggio EC, Glynn RJ, et al.: The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. N Engl J Med 1989; 321;12: 779-83.
3. Dart JK, Stapleton F, et al.: Contact lenses and other risk factors in microbial keratitis. Lancet 1991; 338;8768: 650-3.
4. Nilsson SE, Montan PG: The annualized incidence of contact lens induced keratitis in Sweden and its relation to lens type and wear schedule: results of a 3-month prospective study. CLAO J 1994; 20;4: 225-30.
5. Schein OD, Buehler PO, et al.: The impact of overnight wear on the risk of contact lens-associated ulcerative keratitis. Arch Ophthalmol 1994; 112;2: 186-90.
6. Matthews T, Frazer D, et al.: Risks of keratitis and patterns of use with disposable contact lenses. Arch Ophthalmol 1992; 110 1559-1562.
7. Cheng KH, Leung SL, et al.: Incidence of contact-lens-associated microbial keratitis and its related morbidity. Lancet 1999; 354;9174: 181-5.
8. Imayasu M, Petroll W, et al.: The relation between contact lens oxygen transmissibility and binding of Pseudomonas aeruginosa to the cornea after overnight wear. Ophthalmol 1994; 101;2: 371-388.
9. Ren DH, Petroll WM, et al.: The relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa to human corneal epithelial cells after overnight and extended wear. CLAO J 1999; 25;2: 80-100.
10. Papas E, Vajdic C, et al.: High oxygen-transmissibility soft contact lenses do not induce limbal hyperaemia. Curr Eye Res 1997; 16;9: 942-948.
11. Dumbleton KA, Chalmers RL, et al.: Changes in myopic refractive error with nine months' extended wear of hydrogel lenses with high and low oxygen permeability. Optom Vis Sci 1999; 76;12: 845-9.
12. Fonn D, du Toit R, et al.: Sympathetic swelling response of the control eye to soft lenses in the other eye. Invest Ophthalmol Vis Sci 1999; 40;13: 3116-21.
13. Keay L, Sweeney DF, et al.: Microcyst response to high Dk/t silicone hydrogel contact lenses. Optom Vis Sci 2000; 77;11: 582-5.
14. Lin MC, Graham AD, et al.: The effects of one-hour wear of high-Dk soft contact lenses on corneal pH and epithelial permeability. CLAO J 2000; 26;3: 130-3.
15. Long B, Robirds S, et al.: Six months of in-practice experience with a high Dk Lotrafilcon A soft contact lens. Contact Lens & Ant Eye 2000; 23;4: 112 - 118.
16. Covey M, Sweeney DF, et al.: Hypoxic effects on the anterior eye of high-Dk soft contact lens wearers are negligible. Optom Vis Sci 2001; 78;2: 95-9.
17. du Toit R, Simpson TL, et al.: Recovery from hyperemia after overnight wear of low and high transmissibility hydrogel lenses. Curr Eye Res 2001; 22;1: 68-73.
18. Dumbleton KA, Chalmers RL, et al.: Vascular response to extended wear of hydrogel lenses with high and low oxygen permeability. Optom Vis Sci 2001; 78;3: 147-51.
19. Montero Iruzubieta J, Nebot Ripoll JR, et al.: Practical experience with a high Dk lotrafilcon A fluorosilicone hydrogel extended wear contact lens in Spain. CLAO J 2001; 27;1: 41-6.
20. Edmunds F, Comstock T, et al.: Cumulative experience of extended wear clinical trials of a silicone hydrogel contact lens. Optom Vis Sci 2001; 78;12s: 202.