Sustaining Limbal Health
Checking limbal redness, preventing hyperemia
and protecting stem cells for long-term wellness.
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
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
Hyperemia of the limbus is one of the earliest
detectable signs in the cascade that leads to neovascular response.
HOW CAN WE SUPPORT LIMBAL
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
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.
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
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