The effects of Silicone hydrogel lenses on the corneal epithelium

Patrick M. Ladage B.Optom., Ph.D., F.A.A.O. B.Optom. (Hogeschool van Utrecht, The Netherlands) Ph.D. (University of Houston, College of Optometry, Texas) Patrick is currently assistant-instructor at the Department of Ophthalmology, UT Southwestern medical center, Dallas. He received his optometric degree in 1995 from the Hogeschool van Utrecht, the Netherlands and worked one year in private practice prior to enrolling in the graduate program of the University of Houston, College of Optometry, Texas. Professors H. Dwight Cavanagh M.D. Ph.D. (Dallas) and Jan P.G. Bergmanson O.D., Ph.D. (Houston) co-chaired his Ph.D. dissertation on ‘Corneal epithelial homeostasis during extended contact lens wear’. He is fellow of the American Academy of Optometry and a past William C. Ezell fellow of the American Optometric Foundation. He was recently awarded the 2002-2003 Vistakon AOF research grant at the annual AAO meeting in San Diego to study the long-term effects of extended contact lens wear on the corneal epithelium.

Introduction

The corneal epithelium is only 50 microns thick, about 1/10 the thickness of a credit card, yet it plays a pivotal role in protecting the eye against mechanical damage and the penetration of infectious organisms into the cornea. Furthermore, the corneal epithelium provides a stable underground for the anchoring of the tear film, which contains additional defensive agents against infection. Every day, cells on the surface of the epithelium exfoliate into the tear film and are replaced by younger underlying cells. To maintain this continuous process of renewal, a nonstop need for new cells (proliferation) is required. Proliferation exclusively occurs in the basal cell layer. In addition, there is slow movement of cells towards the center (centripetal) and/or the tear film; in this regard, the corneal epithelium can be seen as a slow moving river of epithelial cells. The continuous production and flow of epithelial cells is of vital importance for the maintenance of the corneal epithelium and its protective functions. It is not surprising therefore that a partial breakdown of the corneal epithelium or a serious alteration of its normal physiology may lead to a decrease in effectiveness against infection.

Over the past three decades, we have learned a great deal about the effects of daily (DW) and extended contact lens wear (EW) on the corneal epithelium, as both wearing modalities are capable of inducing various epithelial changes; some are minor, others seem more serious. How does the new generation of soft lenses, silicone-hydrogel lenses, fit into this picture? Do silicone-hydrogel lenses affect the corneal epithelium? If yes, how do they compare to conventional soft lenses? Does it make a difference whether patients sleep 6 nights or 30 nights in silicone hydrogel lenses? The aim of this editorial is to review our current understanding of the effects of silicone hydrogel contact lens wear on the corneal epithelium.


Changes of the corneal epithelium during EW

Silicone-hydrogel lenses


Central thickness

In a prospective, randomized, double masked study it was shown that DW with silicone hydrogel test lenses (Balafilcon A) and control lenses (Etafilcon A) do not significantly thin the central corneal epithelium. ¹ A similar study on daily wear with the Lotrafilcon A silicone hydrogel lens and the Etafilcon A lens revealed the same result.² EW however, is capable of causing significant thinning of the central corneal epithelium (figure 1). ^{2, 3} The Etalfilcon A lens, worn on a weekly disposable basis, thinned the corneal epithelium -6.8% following the first six months of EW. Thereafter, the corneal epithelium had partially recovered as it was -4.6% thinner than baseline at conclusion of the study. The Balafilcon A lens produced less thinning than the control lens with overall thinning after 1 year of -2.9% and -3.2% in the monthly and weekly replacement of Balafilcon A lenses respectively. Importantly, there was no statistically significant difference between the 6N and 30N groups. Comparable conclusions were reported with the Lotrafilcon A silicone hydrogel lens.² In summary, lens oxygen transmissibility and not wearing schedule seems to control the thinning response during hydrogel lens wear.

Figure 1 - click to enlarge

Surface cell size

Unlike DW with silicone hydrogel lenses¹, EW causes a significant increase in cell size of the superficial epithelial cells in the central cornea. This cell enlargement over time appears to be equal in patients wearing silicone and conventional hydrogel lenses.^{2, 3} Analogous to the corneal epithelial thickness measurements, there did not seem to be any difference in cell size changes between 6N and 30N silicone hydrogel lens wear.


Pseudomonas aeruginosa (PA) - binding

Using an eye irrigation chamber, it is possible to collect surface epithelial cells from human corneas. In a laboratory, these cells can then be mixed with Pseudomonas aeruginosa bacteria to assess bacterial adherence to individual cells (figure 2). As it turns out, corneal epithelial cells collected from contact lens patients bind significantly more PA bacteria than non-lens wearing controls. Silicone hydrogel lenses (DW and EW) have also shown increases in PA-binding although not as great as current disposable hydrogel lenses.^{2, 3} Interestingly, the highest PA-binding appeared to be during the first 1-3 months of EW, thereafter, an adaptation of the epithelium with less PA-binding in all test lens groups occurred. Again, no significant difference between 6N and 30N EW of silicone hydrogels was noted. (figure 3)

Figure 2 - click to enlarge	Figure 3 - click to enlarge

Exfoliation

The normal exfoliation rate of superficial corneal epithelial cells in Etalfilcon A, Balafilcon A and Lotrafilcon A contact lens wearing patients is known to decrease during both DW and EW with no perceptible differences between silicone hydrogel (6N and 30N) and control lenses (figure 4).^1-3 These findings correlate well with the results of several animal studies in which similar decreases in surface cell death were observed with silicone hydrogel and other test lenses.^4-6 Figure 5 shows the distribution of dead/dying epithelial cells on the rabbit corneal surface following several modes of contact lens wear. Overall, it suggests that the physical presence of the contact lens rather than the oxygen transmissibility of the lens material causes the down-regulation of surface cell exfoliation. However, it should be noted that collected cells from silicone hydrogel lens wearers appear to be indistinguishable in size and viability from non-lens wearers while cells collected from disposable low Dk control lens wearers demonstrate a statistically significant increase in diameter.⁷

Figure 4 - click to enlarge	Figure 5 - click to enlarge

Proliferation

Cell Division in the corneal epithelium is greatly inhibited during short-term low Dk EW. A contact lens with a Dk=15 for example causes an average suppression of about -80% (figure 6).⁸ Figure 7 shows that of all test lenses worn continuously for 48-hours, silicone hydrogel lens wear (Balafilcon A) reduced normal corneal epithelial cell division the least.⁹ The difference in proliferation rates between low and high oxygen transmissible hydrogel lenses may explain why central epithelial thinning is more pronounced in the lower oxygen transmissible soft lenses seen in clinical studies.^{2, 3} Preliminary, long term data however, shows an increase in corneal epithelial proliferation during continuous silicone hydrogel lens wear, suggesting a possible adaptation of the corneal epithelium to the new conditions.⁹ It is not known yet if this also takes place with lower oxygen transmissible lenses.

Figure 6 - click to enlarge	Figure 7 - click to enlarge

Clinical, non-inflammatory observations: mucin balls and microcysts

Epithelial microcysts and mucin balls have been described extensively on this website. Briefly, the presence of epithelial microcysts in the corneal epithelium is a good clinical indicator of chronic hypoxia. Unlike disposable contact lenses, silicone hydrogel lenses do not induce an increase in epithelial microcysts when worn on EW basis.^10-12 This is another piece of strong evidence in favor of silicone hydrogel lenses suggesting that the problem of hypoxia in the clinical practice can be referred to our contact lens history books.

One clinical observation that appears to be on the rise with silicone hydrogel lens wear is/are localized depression(s) in the corneal epithelium, associated with mucin balls.^{11, 13-17} It is believed that from time to time mucin balls can form and become trapped between the corneal epithelium and the contact lens (in the post-lens tear film). These ball-like structures may then press themselves partially into the easily moldable epithelial layer, causing spherical indentations as seen with biomicroscopy ^{13, 14} and in vivo confocal microcopy (figure 8).^{16, 17} In an animal model it was shown that these spherical indentations are distinct holes in the corneal epithelium lacking epithelial cell nuclei.¹⁶ Care should be taken not to confuse these indentations with other forms of epithelial disorders.^{13, 14} Mucin balls seem to be patient and contact lens dependent. Although the patients are asymptomatic and no relationship between significant corneal complications and mucin ball indentations have been observed or reported, clinical action should be taken for safety purposes in severe cases with excessive and frequently recurring mucin balls.

Figure 8 - click to enlarge

Summary

The corneal epithelium needs adequate amounts of oxygen to function optimally and to maintain its normal homeostatic dynamics. Until now, contact lenses have not been able to provide the corneal epithelium with sufficient amounts of oxygen, leading to several minor and major epithelial changes and complications. Silicone hydrogel lenses, together with hyper Dk oxygen transmissible rigid gas permeable lenses, have now virtually eliminated the problem of hypoxia. This exciting and significant advancement should certainly benefit the overall health of the corneal epithelium, even though the elimination of hypoxia may not be the end of the story. Consequently, a healthy and functional corneal epithelium, would be expected to be more effective in fighting off infectious organisms. Does this mean that hyper Dk lenses will entirely eliminate corneal infection? Unfortunately, the answer is no. Infections can still occur with silicone hydrogel lenses, albeit a steep decline in incidence rates is anticipated based on encouraging clinical data.¹⁸ Future epidemiological studies will reveal the exact incidence rates, nonetheless, careful selection of EW patients and adequate clinical monitoring, even with silicone hydrogel lenses, should still apply in today’s contact lens practice.


Figures legend

1. Corneal epithelial thickness prior to contact lens wear (0=baseline) and at several time-points during extended wear. (6N= weekly replacement; 30N=monthly replacement).³
2. Pseudomonas aeruginosa binding to exfoliated human corneal epithelial cells (arrow heads).
3. Bacterial binding prior to contact lens wear (0=baseline) and at several time-points during extended wear.³
4. Corneal epithelial surface cell exfoliation prior to contact lens wear (0=baseline) and at several time-points during extended wear.³
5. Number of dead/dying cells on the rabbit corneal epithelium following short-term EW and eyelid suturing.⁴
6. Proliferating cells in the rabbit corneal epithelium after short-term contact lens wear: A. Low Dk RGP, B. hyper Dk RGP, C. Non-lens wearing control. Bar=50mµm.⁸
7. Proliferation rate central epithelium in the rabbit cornea following short-term silicone hydrogel and other types of lens wear.⁹
8. A. Severe case of mucin ball related spherical indentations in the human corneal epithelium as seen by in vivo confocal microscopy. B. Rabbit model shows distinct holes in the corneal epithelium with no cell nuclei. (Red staining=cell nuclei)¹⁶

References

1. Ladage PM, Yamamoto K, Ren DH, et al. Effects of rigid and soft contact lens daily wear on corneal epithelium, tear lactate dehydrogenase, and bacterial binding to exfoliated epithelial cells. Ophthalmology 2001;108:1279-1288.
2. Cavanagh HD, Ladage PM, Li L, et al. Effects of daily and extended wear of a novel hyper O2 transmissible soft contact lens on bacterial binding and corneal epithelium: a 1 year clinical trial. Ophthalmology 2002;109:1957-1969.
3. Ren DH, Yamamoto K, Ladage PM, et al. Adaptive effects of 30-night wear of hyper-O(2) transmissible contact lenses on bacterial binding and corneal epithelium: a 1-year clinical trial. Ophthalmology 2002;109:27-39; discussion 39-40.
4. Yamamoto K, Ladage PM, Ren DH, et al. Effect of eyelid closure and overnight contact lens wear on viability of surface epithelial cells in rabbit cornea. Cornea 2002;21:85-90.
5. Yamamoto K, Ladage PM, Ren DH, et al. Effects of low and hyper Dk rigid gas permeable contact lenses on Bcl-2 expression and apoptosis in the rabbit corneal epithelium. Clao J 2001;27:137-143.
6. Li L, Ren DH, Ladage PM, et al. Annexin V binding to rabbit corneal epithelial cells following overnight contact lens wear or eyelid closure. Clao J 2002;28:48-54.
7. Stapleton F, Kasses S, Bolis S, Keay L. Short term wear of high Dk soft contact lenses does not alter corneal epithelial cell size or viability. Br J Ophthalmol2001;85:143-146.
8. Ladage PM, Yamamoto K, Ren DH, et al. Proliferation rate of rabbit corneal epithelium during overnight rigid contact lens wear. Invest Ophthalmol Vis Sci2001;42:2804-2812.
9. Ladage PM, Jester JV, Petroll WM, Bergmanson JPG, Cavanagh HD. Eyelid closure, soft and silicone hydrogel contact lens wear: effects on the proliferation rate of the rabbit corneal epithelium. Invest Ophthalmol Vis Sci in press.
10. Keay L, Sweeney DF, Jalbert I, Skotnitsky C, Holden BA. Microcyst response to high Dk/t silicone hydrogel contact lenses. Optom Vis Sci 2000;77:582-585.
11. Sweeney DF, Keay L, Jalbert I, et al., Clinical performance of silicone hydrogel lenses, in Silicone hydrogels - the rebirth of continuous wear contact lenses, D.F. Sweeney, Editor. 2000, Butterworth-Heinemann: Oxford. p. 90-150.
12. Covey M, Sweeney DF, Terry R, Sankaridurg PR, Holden BA. Hypoxic effects on the anterior eye of high-Dk soft contact lens wearers are negligible. Optom Vis Sci 2001;78:95-99.
13. Pritchard N, Jones L, Dumbleton K, Fonn D. Epithelial inclusions in association with mucin ball development in high-oxygen permeability hydrogel lenses. Optom Vis Sci 2000;77:68-72.
14. Dumbleton K, Jones L, Chalmers R, Williams-Lyn D, Fonn D. Clinical characterization of spherical post-lens debris associated with lotrafilcon high-Dk silicone lenses. Clao J 2000;26:186-192.
15. Morgan PB, Efron N. Comparative clinical performance of two silicone hydrogel contact lenses for continuous wear. Clin Exp Optom 2002;85:183-192.
16. Ladage PM, Petroll WM, Jester JV, Fisher S, Bergmanson JP, Cavanagh HD. Spherical indentations of human and rabbit corneal epithelium following extended contact lens wear. Clao J 2002;28:177-180.
17. Craig JP, Sherwin T, Grupcheva CN, McGhee CNJ. An evaluation of mucin balls associated with high Dk silicone-hydrogel contact lens wear. Advances In Experimental Medicine And Biology 2002;506:917-923.
18. Holden BA. Microbial keratitis and Vision Loss with contact lenses. Eye and Contact lens 2003;29:S131-S134.