Manuscript Review by Kathy Dumbleton

Corneal epithelial homeostasis following daily and overnight contact lens wear
Ladage,P.M. Yumamoto,K. Li,L. Ren,D.H. Petroll,W.M. Jester,J.V. Cavanagh,H.D. Contact Lens and Anterior Eye 2002/00/00//;25(1):11-21.

This important paper summarizes the results from a series of human and rabbit studies which were conducted to investigate the effect of contact lens wear on corneal epithelial homeostasis. The authors introduce the subject by explaining the role of the corneal epithelium in defence against infection. Epithelial renewal is vital to the maintenance of corneal health. Cell proliferation, migration and exfoliation are the three crucial mechanisms involved in this process.

Two experimental and one control lens types were worn in the human studies reported; the experimental lenses were a hyper Dk/t silicone hydrogel (SH) lens (balafilcon A, Dk/t = 110) and a hyper Dk/t RGP lens (tisilfilcon A, Dk/t = 97); the control soft lens was etafilcon A (Dk/t = 32.5). Lenses were worn on either a daily wear (DW) or extended wear (EW, 6 nights or 30 nights) basis in order to assess the effects of DW and EW on corneal epithelial thickness, cell surface size, exfoliation rates and Pseudomonas aeruginosa (PA) binding to exfoliated cells.

In these studies the authors reported that RGP lens wear had more of an impact on epithelial thickness and enlargement of surface cells than soft lens wear. EW was found to result in epithelial thinning and surface cell enlargement, with relatively more thinning occurring following low Dk soft lens wear than SH lens wear. Epithelial thickness did recover partially with longer term RGP EW. Exfoliation of epithelial cells decreased with EW to a similar degree regardless of oxygen transmissibility. While PA binding increased with both soft lens types regardless of wearing schedule (DW or EW), only EW with RGP lenses resulted in a slight increase in PA numbers. A recovery in epithelial exfoliation and a return to lower levels of PA binding were reported over time. The length of EW with SH lenses (6 versus 30 nights) was found to have no effect on the epithelial homeostasis assessed in these studies.

In addition to the materials worn in the human studies, two RGP materials were worn in the rabbit studies, a low Dk/t material (DK/t = 10) and a medium Dk/t material (Tolofocon A, Dk/t = 43). Rabbits wore a lens in one eye only for a period of 24 hours or had one eyelid sutured for 24 hours during these studies. All rabbits were sacrificed after treatment and the results from the experimental eyes were compared with the contralateral control eyes. A series of experiments were conducted on the rabbit eyes to investigate the life cycle of corneal epithelial cells from the proliferation of basal cells, their vertical migration, the progressive signs of apoptosis and exfoliation of the cells.

In these studies, short term contact lens wear with all materials or eyelid closure resulted in a significant suppression of central epithelial basal cell proliferation. Cell proliferation at the limbus was similarly suppressed following RGP lens wear, but remained unaffected by soft contact lens wear or eyelid suturing. RGP contact lens wear also resulted in a delay in the cell differentiation rate and upward migration of the epithelial cells. Normal apoptosis and exfoliation was suppressed by eyelid suturing and with all lens types worn by the rabbits regardless of oxygen transmissibility.

These results support the hypothesis that corneal epithelial homeostasis resulting in exfoliation is an apoptopic regulated process. The studies also confirm that epithelial surface cells migrate centripetally and die principally in the central cornea. This may be attributed to the strong sweeping action of the eyelid creating high shearing forces at the corneal apex resulting in increased apoptosis in this region. This theory is further supported by the results from the rabbit suturing experiments when the action of blinking was eliminated.

Contact lens wear and eyelid suturing were shown to suppress apoptosis and in the central cornea to allow a concomitant increase in surface epithelial cell size. Despite these restraints to normal cell turnover, epithelial thickness is known to decrease with overnight contact lens wear, in all probability as a result of the effect of decreasing cell proliferation in the basal layers being greater than the diminished cell loss at the surface of the epithelium. Results from these studies indicate that the depression of cell proliferation also appears to be both oxygen and lens dependent.

In summary, the authors conclude that while epithelial homeostasis appears to be suppressed by contact lens wear in general, the effects appear to be diminished to some extent with hyper Dk/t lens materials (RGP and SH). Further research is however required to gain a deeper understanding of the mechanisms involved and chronic and adaptive effects which may occur.