The effects of Silicone hydrogel lenseson 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 Departmentof Ophthalmology, UT Southwestern medical center, Dallas.He received his optometric degree in 1995 from theHogeschool van Utrecht, the Netherlands and workedone year in private practice prior to enrolling inthe graduate program of the University of Houston,College of Optometry, Texas. Professors H. Dwight CavanaghM.D. Ph.D. (Dallas) and Jan P.G. Bergmanson O.D., Ph.D.(Houston) co-chaired his Ph.D. dissertation on ‘Cornealepithelial homeostasis during extended contact lenswear’. He is fellow of the American Academy ofOptometry and a past William C. Ezell fellow of theAmerican Optometric Foundation. He was recently awardedthe 2002-2003 Vistakon AOF research grant at the annualAAO meeting in San Diego to study the long-term effectsof extended contact lens wear on the corneal epithelium.

Introduction

The corneal epithelium is only 50 microns thick, about 1/10 thethickness of a credit card, yet it plays a pivotal role inprotecting the eye against mechanical damage and the penetrationof infectious organisms into the cornea. Furthermore, the cornealepithelium provides a stable underground for the anchoringof the tear film, which contains additional defensive agentsagainst infection. Every day, cells on the surface of the epitheliumexfoliate into the tear film and are replaced by younger underlyingcells. To maintain this continuous process of renewal, a nonstopneed for new cells (proliferation) is required. Proliferationexclusively occurs in the basal cell layer. In addition, thereis slow movement of cells towards the center (centripetal)and/or the tear film; in this regard, the corneal epitheliumcan be seen as a slow moving river of epithelial cells. Thecontinuous production and flow of epithelial cells is of vitalimportance for the maintenance of the corneal epithelium andits protective functions. It is not surprising therefore thata partial breakdown of the corneal epithelium or a seriousalteration of its normal physiology may lead to a decreasein effectiveness against infection.

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


Changes of the corneal epithelium during EW

Silicone-hydrogel lenses


Central thickness

In a prospective, randomized, double masked study it was shownthat DW with silicone hydrogel test lenses (Balafilcon A) andcontrol lenses (Etafilcon A) do not significantly thin the centralcorneal epithelium.¹A similar study on daily wear with theLotrafilcon A silicone hydrogel lens and the Etafilcon A lensrevealed the same result.²EW however, is capable of causingsignificant thinning of the central corneal epithelium (figure1).^{2, 3}The Etalfilcon A lens, worn on a weekly disposablebasis, thinned the corneal epithelium -6.8% following the firstsix months of EW. Thereafter, the corneal epithelium had partiallyrecovered as it was -4.6% thinner than baseline at conclusionof the study. The Balafilcon A lens produced less thinning thanthe control lens with overall thinning after 1 year of -2.9%and -3.2% in the monthly and weekly replacement of BalafilconA lenses respectively. Importantly, there was no statisticallysignificant difference between the 6N and 30N groups. Comparableconclusions were reported with the Lotrafilcon A silicone hydrogellens.²In summary, lens oxygen transmissibility and not wearingschedule seems to control the thinning response during hydrogellens wear.

Figure1 - click to enlarge

Surface cell size

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


Pseudomonas aeruginosa (PA) - binding

Using an eye irrigation chamber, it is possible to collect surfaceepithelial cells from human corneas. In a laboratory, these cellscan then be mixed withPseudomonas aeruginosabacteriato assess bacterial adherence to individual cells (figure 2).As it turnsout, corneal epithelial cells collected from contact lens patientsbind significantly more PA bacteria than non-lens wearing controls.Silicone hydrogel lenses (DW and EW) have also shown increasesin PA-binding although not as great as current disposable hydrogellenses.^{2, 3}Interestingly, the highest PA-binding appeared tobe during the first 1-3 months of EW, thereafter, an adaptationof the epithelium with less PA-binding in all test lens groupsoccurred. Again, no significant difference between 6N and 30NEW of silicone hydrogels was noted. (figure 3)

Figure2 - click to enlarge	Figure 3 - click to enlarge

Exfoliation

The normal exfoliation rate of superficial corneal epithelialcells in Etalfilcon A, Balafilcon A and Lotrafilcon A contactlens wearing patients is known to decrease during both DW andEW with no perceptible differences between silicone hydrogel(6N and 30N) and control lenses (figure 4).^1-3These findingscorrelate well with the results of several animal studies inwhich similar decreases in surface cell death were observed withsilicone hydrogel and other test lenses.^4-6Figure 5 shows thedistribution of dead/dying epithelial cells on the rabbit cornealsurface following several modes of contact lens wear. Overall,it suggests that the physical presence of the contact lens ratherthan the oxygen transmissibility of the lens material causesthe down-regulation of surface cell exfoliation. However, itshould be noted that collected cells from silicone hydrogel lenswearers appear to be indistinguishable in size and viabilityfrom non-lens wearers while cells collected from disposable lowDk control lens wearers demonstrate a statistically significantincrease in diameter.⁷

Figure4 - click to enlarge	Figure5 - click to enlarge

Proliferation

Cell Division in the corneal epithelium is greatly inhibitedduring short-term low Dk EW. A contact lens with a Dk=15 forexample causes an average suppression of about -80% (figure 6).⁸Figure 7 shows that of all test lenses worn continuously for48-hours, silicone hydrogel lens wear (Balafilcon A) reducednormal corneal epithelial cell division the least.⁹The differencein proliferation rates between low and high oxygen transmissiblehydrogel lenses may explain why central epithelial thinning ismore pronounced in the lower oxygen transmissible soft lensesseen in clinical studies.^{2, 3}Preliminary, long term data however,shows an increase in corneal epithelial proliferation duringcontinuous silicone hydrogel lens wear, suggesting a possibleadaptation of the corneal epithelium to the new conditions.⁹It is not known yet if this also takes place with lower oxygentransmissible lenses.

Figure6 - click to enlarge	Figure7 - click to enlarge

Clinical, non-inflammatory observations:mucin balls and microcysts

Epithelial microcysts and mucin balls have been described extensivelyon this website. Briefly, the presence of epithelial microcystsin the corneal epithelium is a good clinical indicator of chronichypoxia. Unlike disposable contact lenses, silicone hydrogellenses do not induce an increase in epithelial microcysts whenworn on EW basis.^10-12This is another piece of strong evidencein favor of silicone hydrogel lenses suggesting that the problemof hypoxia in the clinical practice can be referred to our contactlens history books.

One clinical observation that appears to beon the rise with silicone hydrogel lens wear is/are localizeddepression(s) inthe corneal epithelium, associated with mucin balls.^{11, 13-17}It is believed that from time to time mucin balls can form andbecome trapped between the corneal epithelium and the contactlens (in the post-lens tear film). These ball-like structuresmay then press themselves partially into the easily moldableepithelial layer, causing spherical indentations as seen withbiomicroscopy^{13, 14}and in vivo confocal microcopy (figure 8).^{16, 17}In an animal model it was shown that these spherical indentationsare distinct holes in the corneal epithelium lacking epithelialcell nuclei.¹⁶Care should be taken not to confuse these indentationswith other forms of epithelial disorders.^{13, 14}Mucin balls seemto be patient and contact lens dependent. Although the patientsare asymptomatic and no relationship between significant cornealcomplications and mucin ball indentations have been observedor reported, clinical action should be taken for safety purposesin severe cases with excessive and frequently recurring mucinballs.

Figure8 - click to enlarge

Summary

The corneal epithelium needs adequate amounts ofoxygen to function optimally and to maintain its normal homeostaticdynamics. Untilnow, contact lenses have not been able to provide the cornealepithelium with sufficient amounts of oxygen, leading to severalminor and major epithelial changes and complications. Siliconehydrogel lenses, together with hyper Dk oxygen transmissiblerigid gas permeable lenses, have now virtually eliminated theproblem of hypoxia. This exciting and significant advancementshould certainly benefit the overall health of the corneal epithelium,even though the elimination of hypoxia may not be the end ofthe story. Consequently, a healthy and functional corneal epithelium,would be expected to be more effective in fighting off infectiousorganisms. Does this mean that hyper Dk lenses will entirelyeliminate corneal infection? Unfortunately, the answer is no.Infections can still occur with silicone hydrogel lenses, albeita steep decline in incidence rates is anticipated based on encouragingclinical data.¹⁸Future epidemiological studies willreveal the exact incidence rates, nonetheless, careful selectionof EW patientsand adequate clinical monitoring, even with silicone hydrogellenses, should still apply in today’s contact lens practice.


Figureslegend

1. Corneal epithelial thickness prior to contact lens wear (0=baseline)and at several time-points during extended wear. (6N= weeklyreplacement; 30N=monthly replacement).³
2. Pseudomonas aeruginosabinding to exfoliated human cornealepithelial 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 contactlens wear (0=baseline) and at several time-points during extendedwear.³
5. Number of dead/dying cells on the rabbit corneal epitheliumfollowing short-term EW and eyelid suturing.⁴
6. Proliferating cells in the rabbit corneal epithelium aftershort-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 corneafollowing short-term silicone hydrogel and other types of lenswear.⁹
8. A. Severe case of mucin ball related spherical indentationsin the human corneal epithelium as seen by in vivo confocal microscopy.B. Rabbit model shows distinct holes in the corneal epitheliumwith 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 epithelialcells 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.
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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.
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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.
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18. Holden BA. Microbial keratitis and Vision Loss with contact lenses. Eye and Contact lens 2003;29:S131-S134.