Corneal and Epithelial Thickness Changes After 4
Weeks of Overnight Corneal Refractive Therapy
Lens Wear, Measured With Optical
Sameena Haque, B.Sc., M.C.Optom., Desmond Fonn, Dip.Optom., M.Optom.,
Trefford Simpson, Dip.Optom., M.Sc., Ph.D., and Lyndon Jones, Ph.D.
Purpose. To investigate thickness changes of the total cornea and
epithelium across the horizontal corneal meridian after 4 weeks of
overnight corneal refractive therapy (CRT) rigid contact lens
(Paragon Vision Sciences, Mesa, AZ) wear. Methods. Thirty
subjects were fitted with CRT contact lenses (Dk/t ? 67), which
were worn overnight for 4 weeks. Corneal thickness was measured
at nine locations along the horizontal meridian by using optical
coherence tomography (OCT) before lens insertion in the evening.
Corneal thickness was measured the next morning immediately
after lens removal and 1, 3, 7, and 14 hours later. This was
repeated on days 4, 10, and 28 of the study and then 3 days after
discontinuing lens wear. Results. Twenty-three subjects com-
pleted the study. At lens removal on day 1, the central and
paracentral cornea swelled by 4.9% and 6.2%, respectively (both
P ? 0.000). The central epithelium thinned by 7.3%, and the mid
peripheral epithelium thickened by 13% (both P ? 0.000). Corneal
swelling recovered throughout the day, with most of the deswell-
ing taking place within the first 3 hours after lens removal.
Maximal central epithelial thinning reached 13.5% by day 4. Three
days after the study completion, corneal and epithelial thickness
had recovered to baseline values. Conclusions. This study shows
that CRT lenses induce differential overnight swelling across the
cornea, with rapid deswelling during the day. Central epithelial
thinning and paracentral thickening occurs, with recovery 3 days
after discontinuation of lens wear.
Key Words: Corneal refractive therapy—Corneal swelling— Ep-
ithelium—Optical coherence tomography—Orthokeratology.
Corneal refractive therapy (CRT) is a term that has been used to
describe a modern form of orthokeratology. Rigid gas-permeable
contact lenses are worn overnight to flatten the central cornea and
temporarily reduce myopia.1Experience with daily wear of or-
thokeratology lenses has shown that myopia reduction is reversible
and recovers slowly throughout the day after removal of the lens.2
Other studies have shown that there is less myopic regression with
overnight wear of orthokeratology and CRT lenses.3–5
Several investigators have examined the degree to which the
cornea and its epithelium respond to modern orthokeratology
lenses. Wang et al.6found central corneal swelling of 4.9% and
central epithelial thinning of 5.1% after a single night of CRT lens
wear. Alharbi and Swarbrick4and Soni et al.7reported 33% central
epithelial thinning and insignificant stromal thickness changes in
patients wearing reverse-geometry lenses for 3 months.
The three studies described in the preceding paragraph differed
experimentally and used different lens designs and equipment to
measure corneal and epithelial thickness. Although there is good
agreement regarding central epithelial thinning in the studies by
Alharbi and Swarbrick4and Soni et al.,7there is a scarcity of
information on the diurnal and temporal effects of overnight wear
of reverse-geometry and CRT lenses. Further work is also required
to determine the recovery capacity of the cornea. The purpose of
this study was to measure corneal and epithelial thickness changes
using optical coherence tomography (OCT) across the horizontal
corneal meridian after overnight wear of CRT lenses for 4 weeks.
Optical coherence tomography is an in vivo technique for
high-resolution cross-sectional imaging of tissue in which optical
interferometry is used to determine the distance between reflective
structures within the eye.8It is a noninvasive procedure and
produces micrometer-scale resolution of the tissue in situ. Recent
studies6,9have used a modified version of this instrument to
measure corneal thickness. OCT has the ability to differentiate
between different layers of tissue within a structure (e.g., the
thickness of the epithelium within the cornea).
MATERIALS AND METHODS
Thirty healthy subjects (20 women and 10 men) with a mean age
of 25.8 ? 6.9 years (range, 21–51 years) were enrolled. Informed
consent was obtained from each individual, and ethics clearance
was obtained from the Office of Research Ethics at the University
of Waterloo before commencement of the study. Each subject had
no history of ocular disease or surgery. Refractive error of partic-
ipants was restricted to a spherical correction of ?1.00 to ?6.00
diopters (D), with no more than ?1.75 D of cylindrical correction.
Supported by Paragon Vision Sciences and an equipment grant from the
Canada Foundation for Innovation.
From the Centre for Contact Lens Research, School of Optometry,
University of Waterloo, Waterloo, Ontario, Canada.
Address correspondence and reprint requests to Desmond Fonn, Centre
for Contact Lens Research, School of Optometry, University of Waterloo,
Waterloo, ON, N2L 3G1 Canada; e-mail: email@example.com
Accepted April 29, 2004.
Eye & Contact Lens 30(4): 189–193, 2004
© 2004 Contact Lens Association of Ophthalmologists, Inc.
Table 1 summarizes the corneal parameters of the group. Current
rigid gas-permeable lens wearers were excluded, and soft lens
wearers had to discontinue lens wear 2 weeks before the start of
Instrumentation and Lenses
A Humphrey-Zeiss OCT system (Humphrey Systems, Dublin,
CA) was used to measure corneal thickness across the horizontal
meridian. Images were taken at 10° intervals across a 10-mm chord
by using a fixation device mounted on the instrument. The device
used in this study differed slightly from the version used by our
group previously.6,10,11This version consisted of two sets of four
light-emitting diodes, located nasally and temporally to the central
fixation light approximately 0.8, 1.6, 2.7, and 3.6 mm from the
center (Fig. 1). Subjects were asked to fixate each illuminated
light-emitting diode in sequence with the eye that was being
measured. A video monitor enabled the observation of the incident
beam, which was aligned with the reflection of the fixation target
on the corneal surface. The image was captured when a specular
reflection was obtained and confirmed perpendicularity of the
incident beam to the cornea. Each cross-section of the cornea
scanned (Fig. 2) was 1.13 mm in length and enabled the compi-
lation of a thickness profile of the cornea along the horizontal
The CRT lenses used (Paragon Vision Sciences, Mesa, AZ;
Proximity Control Design) were manufactured from fluorosilicone
acrylate with an oxygen permeability (Dk) of 100 ? 10?11and
transmissibility of 67 ? 10?9. The lenses were fit using software
provided by the manufacturer. The computer program uses the flat
keratometry reading, sphere, and overrefraction values to calculate
the back optic zone radius, return zone depth, and landing zone
angle for the 10.5-mm diameter lens. The lenses selected by the
program were assessed on the eye to ensure that there was
appropriate apical touch (4 mm), mid peripheral clearance, ade-
quate edge lift, and proper centration. The lens parameters for the
23 subjects are listed in Table 2.
In the evening before the first night of the study (termed day 0),
baseline corneal thickness was measured. Both eyes were mea-
sured at all nine locations, as described earlier. The CRT lenses
were inserted, and the fit was assessed for adequate movement,
centration, and fluorescein pattern before sleep. Participants slept
at the Centre for Contact Lens Research; they retired at 10 PM and
awoke at 7 AM the next day for the day 1 measurements. On
awaking, the subjects kept their eyes closed until lenses were
removed for corneal measurements. The measurements were re-
peated 1, 3, 7, and 14 hours after lens removal. The entire
procedure was repeated on days 4, 10, and 28 of the study. At the
end of the 4-week period, lens wear was discontinued and corneal
thickness measurements were repeated 3 days later.
Raw data files captured by the OCT instrument were processed
by using custom software, as described previously.6,11Analysis of
these thickness measurements was performed using Statistica 6.0
(Statsoft, Inc., Tulsa, OK). Repeated-measures analysis of variance
and Tukey honestly significantly different post hoc testing were
used to analyze changes in corneal and epithelial thickness from
baseline levels during the study period. Corneal and epithelial thick-
ness changes were expressed as percentage change: ([thicknessbaseline
? thicknesstime] / [thicknessbaseline] ? 100). The chosen level for
significance was 0.05.
Twenty-three subjects completed the study, and their data are
reported below. Two subjects withdrew because of lens discom-
fort, three because of poor vision, one because of conjunctivitis,
and one because of a corneal abrasion.
The cornea showed maximal swelling immediately on lens
removal, which reduced rapidly (Figs. 3 and 4). Figure 3 shows the
extent of central and paracentral corneal swelling from the time of
lens removal to the 14-hour measurement after a single night of
CRT lens wear (day 1). The paracentral curve is represented as the
mean of the first two nasal and temporal positions (N1, N2, T1, and
T2) from the center. These results show that the paracentral swelling
was significantly greater than the central swelling (F[4, 88] ? 1.15,
P ? 0.000). Immediately after lens removal, central corneal swelling
was 4.9%, compared with 6.2% in the paracentral region. The corneal
swelling pattern remained the same for days 4, 10, and 28 (Fig. 4), but
Summary of Corneal Parameters Before Study
Baseline corneal parameters (mean ? SD)
Refractive error, sphere (D)
Refractive error, cylinder (D)
Keratometry, flat K (D)
Keratometry, cylinder (D)
Central corneal thickness (?m)
Central epithelial thickness (?m)
?2.77 ? 1.19
?0.49 ? 0.39
43.73 ? 1.57
?0.64 ? 0.40
508 ? 28.3
52 ? 2.6
?2.54 ? 1.11
?0.53 ? 0.41
43.71 ? 1.54
?0.67 ? 0.43
506 ? 26.2
52 ? 3.1
strument with fixation target, as viewed by the subject.
The Humphrey-Zeiss optical coherence tomography in-
Corneal Refractive Therapy Lens Parameters
Total diameter (mm)
Back optic zone radius (mm)
Back optic zone diameter (mm)
Center thickness (mm)
Return zone depth
Landing zone angle
8.4 ? 0.38
67 ? 10?9
0.526 ? 0.03
33.08 ? 1.09
190 S. HAQUE ET AL.
Eye & Contact Lens, Vol. 30, No. 4, 2004
it appears that central and paracentral swelling decreased from day 1,
although this change was not statistically significant (F[96, 1728] ?
1.22, P ? 0.08). It also appears that central deswelling (overshoot)
increased from day 1 to day 28.
Figure 5 shows the change in epithelial thickness from lens
removal to the end of the day (F[32, 704] ? 38.3, P ? 0.000),
measured on four different study days during the 4 weeks. There
was no significant difference among days. The central epithelium
thinned by 7.3% immediately after lens removal, whereas the
paracentral epithelium thickened by approximately 13% (averaged
over T1, T2, N1, and N2 locations). The pattern of epithelial
thickness change was consistent for the remaining measurement
days, but central epithelial thinning increased (P ? 0.05 for days
4, 10, and 28 compared with day 1) and paracentral thickening
decreased after day 4. Maximal epithelial thinning after lens
removal (13.5%) occurred on day 4 and progressed to 15.0%
thinning by hour 14. The absence of recovery to baseline thickness
was evident on all four measurement days.
After 72 hours without lens wear after day 28 (Fig. 6), the
cornea recovered to baseline thickness (99.7% recovery centrally
and 98.5% recovery paracentrally, an average of T3 and N3
locations). Epithelial thickness also recovered to original values.
The center was approximately 2 ?m (3.8%) thinner, and the mid
periphery (average of T2 and N2 locations) remained 3.5% thicker
than baseline values.
Optical coherence tomography has been shown to be a reliable
instrument for measuring corneal and epithelial thickness.6,8–11In
this study, there were significant amounts of corneal swelling and
epithelial thickness changes after overnight CRT lens wear. The
meridional corneal swelling pattern showing greater paracentral
than central swelling immediately after lens removal was similar to
that reported by Wang et al.6The swelling patterns induced by
CRT lenses in these studies are different to that induced by
conventional rigid designs6,11,12and soft lenses,11,13,14in which
the reverse is true, whereby swelling is greater centrally than
The degree of central corneal swelling reported in this study
differs from the results of Alharbi and Swarbrick,4who showed no
central stromal thickness changes. It has been estimated that to
prevent lens-induced corneal swelling after overnight lens wear,
the oxygen transmissibility of a contact lens must be at least 87 ?
10?9(cm ? mL O2) / (sec ? mL ? mm Hg).15In this study, the
central Dk/t was 67 ? 10?9(cm ? mL O2) / (sec ? mL ? mm
Hg), which explains the 4.9% central and 6.2% paracentral corneal
swelling compared with the 2% to 4% typically seen centrally after
overnight eye closure without lens wear.15–17
Three hours after lens removal, full return to baseline central
corneal thickness occurred. The speed at which the cornea recov-
ered strengthens the notion of measuring thickness as soon as
(right) as captured by optical coherence tomography
and its axial reflectivity profile (left). Corneal thick-
ness was calculated from the distance between
peak A (the anterior corneal surface) and peak C.
Epithelial thickness was obtained as the distance
between peak A and peak B.
Single scan image of the central cornea
corneal swelling and deswelling after
the first night of corneal refractive ther-
apy lens wear. Vertical bars denote
0.95 confidence intervals.
Mean central and paracentral
191 CORNEAL AND EPITHELIAL THICKNESS CHANGES
Eye & Contact Lens, Vol. 30, No. 4, 2004
possible after lens removal after eye opening, which was the case
in this study.
The central cornea continued to deswell beyond baseline toward
the end of the day (Fig. 4). This has been termed overshoot and has
been described previously.17–19It is known to occur after lens-
induced hypoxic stress, although the causes are not entirely clear.
The cause of the deswelling differences between central and
paracentral cornea in this study may also be influenced by the
central mechanical pressure induced by the CRT lenses.
After the first night of CRT lens wear, central epithelial thinning
and mid peripheral epithelial thickening was observed immedi-
ately after lens removal. It was surprising that the central epithe-
lium, which had thinned by 7.3% showed little recovery after 14
hours, yet most of the paracentral thickening decreased with time.
The epithelial thickness changes followed a consistent pattern for
the duration of the study, although there was greater central
thinning and less paracentral thickening from day 4 onward. We
found approximately 12% thinning after 1 month, but this is
substantially less than the 30% reported by others.4,7Possible
explanations for these differences include lens design variations
and the difference in technique of epithelial measurement. We
used Paragon CRT lenses and OCT for corneal and epithelial
measurements. Alharbi and Swarbrick4and Soni et al.7used lenses
from two other manufacturers (BE and Contex designs, respec-
tively) and the use of optical pachometry and confocal microscopy,
respectively, to measure epithelial thickness.
swelling pattern after 4 weeks of cor-
neal refractive therapy lens wear with
measurements obtained on four sep-
arate study days.
Corneal swelling and de-
weeks of corneal refractive therapy
lens wear measured on 4 study days.
Data points for hours 3 and 7 have
been omitted for clarity.
Epithelial changes during 4
192 S. HAQUE ET AL.
Eye & Contact Lens, Vol. 30, No. 4, 2004
Central corneal swelling decreased from 4.9% after the first Download full-text
night of CRT lens wear to 3% on subsequent study days. Paracen-
tral swelling also decreased (Fig. 4). This indicates a possible
adaptation effect. Neophyte contact lens wearers have a higher
initial swelling response than adapted lens wearers,20–22hence the
greater central corneal swelling seen on day 1. Adaptation to
contact lens wear is believed to down-regulate the overnight
corneal swelling response.21
Reversibility has been touted as an advantage of corneal refrac-
tive therapy. Although the duration of this study was relatively
short (28 days), Figures 6 and 7 are good examples of how the
cornea is able to recover from 4 weeks of overnight CRT lens
In summary, overnight CRT lens wear induced corneal thick-
ness changes. The central epithelial thinning found was probably
the result of compression induced by the relatively flat-fitting CRT
lenses. The paracentral thickening may be the result of the negative
pressure of the tear film induced by localized lens clearance, with
redistribution of the epithelial tissue being partly responsible for
the thickness changes. Central corneal swelling recovers rapidly
after lens removal, and it appears that there is adaptation to
overnight lens wear.
1. Dave T, Ruston D. Current trends in modern orthokeratology. Oph-
thalmic Physiol Opt 1998;18:224–233.
2. Polse KA, Brand RJ, Vastine DW, et al. Corneal change accompany-
ing orthokeratology. Plastic or elastic? Results of a randomized con-
trolled clinical trial. Arch Ophthalmol 1983;101:1873–1878.
3. Nichols JJ, Marsich MM, Nguyen M, et al. Overnight orthokeratology.
Optom Vis Sci 2000;77:252–259.
4. Alharbi A, Swarbrick HA. The effects of overnight orthokeratology
lens wear on corneal thickness. Invest Ophthalmol Vis Sci 2003;44:
5. Mountford J. An analysis of the changes in corneal shape and refrac-
tive error induced by accelerated orthokeratology. Int Contact Lens
6. Wang J, Fonn D, Simpson TL, et al. Topographical thickness of the
epithelium and total cornea after overnight wear of reverse-geometry
rigid contact lenses for myopia reduction. Invest Ophthalmol Vis Sci
7. Soni PS, Nguyen TT, Bonanno JA. Overnight orthokeratology: Visual
and corneal changes. Eye Contact Lens 2003;29:137–145.
8. Hrynchak P, Simpson T. Optical coherence tomography: An introduc-
tion to the technique and its use. Optom Vis Sci 2000;77:347–356.
9. Feng Y, Varikooty J, Simpson TL. Diurnal variation of corneal and
corneal epithelial thickness measured using optical coherence tomog-
raphy. Cornea 2001;20:480–483.
10. Wang J, Fonn D, Simpson TL, et al. The measurement of corneal
epithelial thickness in response to hypoxia using optical coherence
tomography. Am J Ophthalmol 2002;133:315–319.
11. Wang J, Fonn D, Simpson TL. Topographical thickness of the epithe-
lium and total cornea after hydrogel and PMMA contact lens wear with
eye closure. Invest Ophthalmol Vis Sci 2003;44:1070–1074.
12. Fonn D, Holden BA, Roth P, et al. Comparative physiologic perfor-
mance of polymethyl methacrylate and gas-permeable contact lenses.
Arch Ophthalmol 1984;102:760–764.
13. Fonn D, du Toit R, Simpson TL, et al. Sympathetic swelling response
of the control eye to soft lenses in the other eye. Invest Ophthalmol Vis
14. Holden BA, McNally JJ, Mertz GW, et al. Topographical corneal
oedema. Acta Ophthalmol (Copenh) 1985;63:684–691.
15. Holden BA, Mertz GW. Critical oxygen levels to avoid corneal edema
for daily and extended wear contact lenses. Invest Ophthalmol Vis Sci
16. Mertz GW. Overnight swelling of the living human cornea. J Am
Optom Assoc 1980;51:211–214.
17. du Toit R, Vega JA, Fonn D, et al. Diurnal variation of corneal
sensitivity and thickness. Cornea 2003;22:205–209.
18. Odenthal MT, Nieuwendaal CP, Venema HW, et al. In vivo human
corneal hydration control dynamics: A new model. Invest Ophthalmol
Vis Sci 1999;40:312–319.
19. O’Neal MR, Polse KA. In vivo assessment of mechanisms controlling
corneal hydration. Invest Ophthalmol Vis Sci 1985;26:849–856.
20. Armitage BS, Schoessler JP. Overnight corneal swelling response in
adapted and unadapted extended wear patients. Am J Optom Physiol
21. Ichikawa H, Kozai A, MacKeen DL, et al. Corneal swelling responses
with extended wear in naive and adapted subjects with Menicon RGP
contact lenses. CLAO J 1989;15:192–194.
22. Cox I, Zantos S, Orsborn G. The overnight corneal swelling response
of non-lens wear, daily wear and extended wear soft lens patients.
International Contact Lens Clinic 1990;17:134–137.
Corneal thickness at baseline and after 72 hours of no lens
Epithelial thickness at baseline and after 72 hours of no
193 CORNEAL AND EPITHELIAL THICKNESS CHANGES
Eye & Contact Lens, Vol. 30, No. 4, 2004