11_04 CLS_AMO SUPPLEMENT
Using Fluorometry to Assess Corneal Epithelial
diagnostic methods are helping researchers learn how lens care solutions affect
the ocular surface.
By Meng Lin, OD, PhD,
he corneal epithelium
is a critical part of the eye's defense system. The upward differentiation of
corneal epithelial basal cells to the superficial cells establishes tight junctions,
forming a barrier between the inner corneal structures and the outside environment
and preventing potentially harmful substances from entering the eye.
Clinical slit lamp examination provides qualitative
information about corneal integrity, but may not be sensitive enough to detect subtle
quantitative changes in corneal integrity induced by contact lenses or lens care
systems. A more sensitive tool for quantifying corneal integrity is a fluorometer,
which measures the rate at which topically applied fluorescein enters the cornea.
This simple technique can detect and quantify potentially critical changes in epithelial
integrity that are not detectable by standard slit lamp assessment.
ASSESSING CORNEAL PERMEABILITY
In a healthy eye, intact
epithelial cell membranes and tight intercellular junctions resist the passage of
fluorescein and other hydrophilic substances. Therefore, increased uptake in fluorescein
dye reflects increased corneal permeability and reduced epithelial barrier function.
At the University of California Berkeley
Clinical Research Center, my colleagues and I investigated how contact lenses
affect the corneal epithelium. In a series of 1-hour studies, we investigated the
effect of open- vs. closed-eye contact lens wear on epithelial permeability in normoxic
and hypoxic conditions. Our results suggest that 1 hour of contact lens wear with
low- or high-Dk/t materials in the open-eye condition does not alter corneal epithelial
permeability. However, closed-eye lens wear, along with lens-induced hypoxia, can
compromise corneal epithelial barrier function. To learn more about the mechanisms
behind altered epithelial barrier function, we used fluorometry to measure the effect
of extended lens wear between 8 hours and overnight on corneal permeability.1-4
Previous studies of the effect of 1-night
overnight silicone hydrogel lens wear on the corneal epithelium used conventional
lens materials as a control. One study5 showed that 43% of silicone hydrogel
and 57% of conventional soft lenses significantly increased corneal epithelial permeability
after only 1 night of overnight wear.
Another study6 compared
the effect of gas permeable (GP) siloxane-fluorocarbon polymer lenses with different
Dk/t values during 1 to 12 months of overnight wear. The data showed that increased
corneal epithelial permeability is directly proportional to the amount of lens-induced
hypoxia, and that epithelial barrier function is impaired after GP overnight lens
wear compared to no lens wear.
These studies suggest that dose-dependent
hypoxia contributes to increased epithelial permeability during closed–eye
contact lens wear, but isn't solely responsible. Despite their increased oxygen
transmissibility, ultra-high Dk/t silicone hydrogel lenses worn overnight also
can alter epithelial junction integrity.
COMPARING LENS CARE PRODUCTS
Additional study paradigms
developed at our lab examine how lens care products affect corneal epithelium integrity.
Recently, we compared the effect of Complete MoisturePlus multipurpose solution
(CMP) and Opti-Free Express (OFX) multipurpose solution on corneal permeability
in non-contact lens wearers.7 Our primary endpoint was to determine differences
between the mean permeability score of each solution at each visit, and the scores
between baseline and follow-up visits with each solution type.
We examined study participants at baseline
(day 1) and the following day (day 2). On day 1, eligible subjects came to the research
center after being awake for a minimum of 4 hours. After a baseline anterior segment
examination, we delivered 2 μL of 0.35% sodium fluorescein to the superior
bulbar conjunctiva of both eyes. Each eye was scanned immediately after instillation.
On day 2, we repeated the anterior segment
examination and instilled 40 μL
of CMP or OFX into the subjects' eyes over eight applications and repeated the fluorometry
Mean baseline permeability was similar
in both groups: –2.26 nm/sec in CMP and –2.28 nm/sec in OFX subjects
(P = 0.89). On day 2, we noted a statistically significant difference in
epithelial permeability between eyes exposed to different lens care solutions. Permeability
in the CMP group was –2.38 nm/sec, compared with –2.14 nm/sec in the
OFX group (P = 0.04). The overall difference between solutions was 27%, with
eyes exposed to OFX demonstrating a higher average epithelial permeability (weaker
The CMP eyes showed slightly less permeability
on day 2, but permeability in the OFX eyes increased within the same time frame.
Although neither change from baseline was statistically significant, the positive
direction in the OFX group indicated more disruption of the epithelium and decreased
barrier function, whereas the negative trend in the CMP group indicated less disruption
and increased barrier function. However, further investigation into the interaction
between soft contact lenses and lens care products is needed to illustrate the cumulative
effects of these solutions on corneal
epithelial barrier function and to understand
the clinical implications of fluorometry for measuring corneal epithelial integrity.
PROTECTING THE BARRIER
Fluorometry is a sensitive
and useful tool for quantifying the effects of contact lens wear and lens care solutions
on the corneal epithelium. This technology may help us understand the fundamental
factors that contribute to altered epithelial barrier function in contact lens patients.
Contact Lens Spectrum, Issue: November 2005