Article Date: 8/1/2005

Sustaining Limbal Health
Checking limbal redness, preventing hyperemia and protecting stem cells for long-term wellness.

Dr. Fonn: As practitioners, we understand the importance of preventing limbal hyperemia. Dr. Papas, do you think limbal redness is a better index of corneal oxygenation than corneal swelling or oxygen consumption?

Dr. Papas: It's perhaps even more immediate and important to wearers than it is to practitioners as it's cosmetically evident. Older soft lenses cause demonstrable redness around the limbus, and both patients and practitioners noticed that problem. It's a better index from that perspective, but I'm not sure whether it discriminates as well as some other indices.

Dr. Fonn: We think limbal redness is a precursor to more serious vascular complications of the eye from wearing contact lenses in the long term, and we've seen studies showing that limbal neovascularization eventually occurs.1 Is this conclusive? Should practitioners be aware of the relationship between limbal hyperemia and corneal vascularization?

Dr. Papas: Hyperemia of the limbus is one of the earliest detectable signs in the cascade that leads to neovascular response. I'm always asked, "Does that mean if we prevent limbal hyperemia, we prevent neovascularization?" Of course, many other problems have the potential to cause neovascularization, and the limbus may be responding to something other than hypoxia. But anything that prevents hyperemia is likely to reduce the risk of a neovascular response.

Dr. Fonn: Dr. Papas, you've done a great deal of research in this area. Your work suggests that 125 Dk/t is the critical value needed to detect changes in limbal redness. Is this a number we can use to define and prevent limbal hyperemia induced by oxygen deprivation?

Dr. Papas: We built a model that describes the relationship between observable changes in limbal redness and the corresponding oxygen transmissibility of the lenses on the eye. The model predicts the level of Dk/t you'd need to see the same change as that which occurs in normal, lens-free eyes during the day. To produce a change that small, according to the model, we need 125 Dk/t. Of course, as with all models, there is a range of uncertainty around that number.

 

 
 

Hyperemia of the limbus is one of the earliest detectable signs in the cascade that leads to neovascular response.

–Dr. Papas

HOW CAN WE SUPPORT LIMBAL HEALTH?

Dr. Fonn: Dr. Papas, colleagues have noted the importance of your work in part because you've studied the limbus, which is the only source of stem cells in the eye. In an effort to support limbal health and, thus, good long-term eye health, what factors should we consider?

Dr. Papas: It's important to look at the limbus when we assess contact lens wear. The lens periphery that overlies the limbal region plays a critical role in oxygen transmissibility, particularly among myopes, whose lenses are thickest in this region. Certainly studies have shown changes in epithelial cell function that we think are related to changes in the limbal stem cells.2 My colleague Dr. Isabelle Jalbert has shown differences in basal cell regularity between high-Dk and low-Dk lens wearers, which could point to the role of oxygen in cellular growth and epithelial turnover.

Dr. Cavanagh: This is the key issue. We just don't know what the right numbers are for the limbus, but the higher we start, the better our chance of keeping the limbus healthy over 40 or 50 years. Unless we're starting with hyper-Dk hydrogels, the numbers we read can be very deceptive as they relate to limbal stem cell issues.

HOW MUCH DO WE KNOW ABOUT LIMBAL STEM CELLS?

Dr. Fonn: Very little has been written about stem cells related to contact lens wear. What impact do you think contact lenses have in terms of everyday growth and repair, as well as long-term health?

Dr. Wilson: Limbal stem cells are slow-cycling cells, unlike the basal cells of the corneal epithelium, which divide fairly frequently. They're very hard cells to work with, which is why it's taken us so long to learn about them. We know these cells become active when the epithelium has become deficient in some way and needs new cells. But because their blood supply and activity rate are so difficult to understand at this point, we don't know if they're susceptible to the oxygen level at the anterior surface.

Dr. Cavanagh: That's absolutely true. That's why I don't put a number on the limbus — just "the higher, the better." I don't want to challenge the limbus over 30 years of lens wear. The data3 suggest several potential problems: The cell division rate, corneal thickness, and upward movement go down. And fascinating evidence suggests that the limbal proliferation rate goes up.

I think of it as an air-conditioned room, where we set the thermostat at 65 degrees and leave the doors open. The system uses more energy to maintain the temperature. The limbus uses more cells to try to repair the cornea that's constantly thinning in the center. It seems possible to exhaust the limbus, just as we might wear out the air conditioner. The limbal cells have a vast potential — they're estimated to divide 1,079 times! — but there's evidence of problems. According to Ed Holland's book4 on limbal stem cell transplantation, the second most common reason for the transplant is previous contact lens wear.

These cases are few, and many have been blamed on toxic solution responses, but it's something we need to keep in mind. This isn't a theoretical argument. It gets back to what Dr. Holden said: Why make the cornea live in adverse conditions if it doesn't have to?

REFERENCE

1. Dumbleton KA, Chalmers RL, Richter, DB, Fonn D. Vascular response to extended wear of hydrogel lenses with high and low oxygen permeability. Optom & Vis Sci. 2001;78:147-151.

2. Ladage PM, Jester JV, Petroll WM, et al. Role of oxygen in corneal epithelial homeostasis during extended contact lens wear. Eye & Contact Lens: Science & Clinical Practice. 2003;29(1 Suppl):S2-S6; discussion S26-S29, S192-S194.

3. Ladage PM, Yamamoto K, Ren DH, et al. Proliferation rate of rabbit corneal epithelium during overnight rigid contact lens wear. Invest Ophthalmol Vis Sci. 2001;42:2804-2812.

4. Holland EJ, Mannis MJ, eds. Ocular Surface Disease: Medical and Surgical Management. Springer-Verlag; 2002.



Contact Lens Spectrum, Issue: August 2005