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Increased Corneal Thickness in Patients With Ocular Hypertension
David C. Herman, MD;
David O. Hodge, MS;
William M. Bourne, MD
Arch Ophthalmol. 2001;119:334-336.
ABSTRACT
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Background Central corneal thickness greater than 0.520 mm causes true intraocular
pressure to be overestimated when the technique of applanation tonometry is
used to measure intraocular pressure.
Objective To compare the corneal thickness measurements of patients enrolled in
a study of ocular hypertension with those of age-matched control subjects
with normal intraocular pressure.
Methods Central corneal pachymetry using an optical pachymeter was performed
on each study subject (n = 55) at baseline and in an independent sample of
control subjects. A 2 sample, 2-tailed t test was
used to compare the 2 populations.
Results The patients with ocular hypertension had significantly higher mean
corneal thickness measurements (mean ± SD, 0.594 ± 0.037 mm)
than the control group (0.563 ± 0.027 mm) (P<.001).
Conclusion Corneal thickness may be a confounding factor in the measurement of
intraocular pressure, and this may modify the risk for progression to glaucoma
in patients with ocular hypertension.
INTRODUCTION
OCULAR hypertension (OHT) is a diagnosis based primarily on the results
obtained from the clinical measurement of intraocular pressure (IOP). The
diagnosis of OHT is made when a patient has consistently elevated IOP, open
angles by gonioscopy, and no clinical signs of optic nerve damage, such as
pathologic cupping, disc asymmetry, or visual field changes associated with
the diagnosis of glaucoma. Because the major diagnostic criterion for OHT
is based primarily on the clinical measurement of IOP, any variable that can
affect the measurement of IOP could lead to an errant diagnosis of OHT.
The most universally applied clinical measurement of IOP is applanation
tonometry performed as first described by Goldmann and Schmidt.1
Although less likely to be affected by scleral rigidity, applanation tension
can be affected by corneal thickness, a limitation recognized by Goldmann
and Schmidt. They believed that significant variations in corneal thickness
were uncommon and assumed a corneal thickness of 520 µm in calibration
of the applanation tonometer. As clinical measurement of corneal thickness
has become widely available, several studies have found a positive correlation
between corneal thickness and applanation pressure.2-4
Manometric studies performed in animals and humans have found that pressures
measured with applanation tonometry are likely to overestimate the true IOP
as the central corneal thickness increases in the nonedematous cornea and
underestimate the true IOP as central corneal thickness decreases.5-6
The Ocular Hypertension Treatment Study (OHTS) is an National Eye Institute–sponsored
prospective multicenter randomized study designed to determine the efficacy
of early pressure-lowering intervention in patients with OHT. Mayo Clinic
in Rochester, Minn, was approved by the OHTS Data and Safety Monitoring Committee
and the National Eye Institute to undertake this ancillary study to investigate
the corneal changes, if any, associated with OHT or its treatment.
PATIENTS AND METHODS
One hundred sixty-one patients were evaluated for participation in the
OHTS by one of us (D.C.H.). The protocols of the OHTS and this ancillary study
were reviewed and approved by the institutional review board of Mayo Clinic
and informed consent was obtained for all subjects for each study before enlistment
in the study. Entry criteria for the OHTS included the following7:
best-corrected visual acuity of 20/40 or better in both eyes; normal and reliable
visual fields in both eyes as confirmed by the Visual Field Reading Center;
no anterior segment abnormalities; IOP measured by Goldmann applanation tonometry
with mean pressures greater than or equal to 24 mm Hg, but less than or equal
to 32 mm Hg in one eye and greater than or equal to 21 mm Hg but less than
or equal to 32 mm Hg in the other eye; no history of ocular trauma or surgery;
no topical or systemic corticosteroid use; no ocular condition that may lead
to increased IOP or cause visual field loss; and normal optic nerve appearance
as confirmed by the Optic Disc Reading Center.
Of these patients, 55 were found to meet the entry criteria of the OHTS
and agreed to participate in the OHTS. In addition to the studies performed
for the OHTS, each subject underwent endothelial photography and central corneal
pachymetry with a contact specular microscope (Keeler Instruments, Inc, Broomall,
Pa) on enlistment in the study, then annually thereafter. Corneal thickness
measurements of the OHTS subjects' left eye were compared with the corneal
thickness measurements of the left eyes of an age-matched (±3 years)
control group with normal IOP. For each patient with OHT enrolled in the study,
we selected consecutive controls from an existing group of subjects previously
enlisted in another study. All 55 control subjects had been carefully examined
and found to have normal ophthalmic findings in all clinical respects, including
anterior segment examination and dilated fundus examination. No attempt was
made to match the sex, race, or refractive error of control and study subjects.
To be eligible to serve as a control, the subject had to have an IOP of less
than or equal to 21 mm Hg in each eye on a single applanation tonometry measurement,
which was recorded by the operator of the tonometer. A single corneal pachymetry
measurement was made in a similar manner of control and study subjects using
the same contact specular microscope. The corneal endothelium was visualized
and the corneal thickness corresponding to the point of best endothelial cell
mosaic focus was recorded as the corneal thickness measurement. All IOP measurements
in the OHTS group were made at the study randomization visit by certified
study personnel, the operator, and the recorder, using a calibrated Goldmann
applanation tonometer to reduce potential measurement bias. The operator adjusts
the dial and the recorder writes down the results. The IOP is measured twice.
If the 2 readings are within 2 mm Hg, the mean of the 2 measurements is used.
If the 2 readings are separated by more than 2 mm Hg, a third measurement
is made, and the median becomes the recorded IOP. A 2 -sample, 2-tailed t test was used to compare the 2 samples. The correlation between corneal
thickness and IOP was analyzed using the Pearson correlation coefficient.
RESULTS
Results of pachymetry are shown in Figure 1. Mean ± SD left eye corneal thickness in the OHT
group was 0.594 ± 0.037 mm (range, 0.470-0.670 mm) and 0.563 ±
0.027 mm (range, 0.510-0.650 mm) in the control subjects (P<.001). The results were similarly statistically significant when
comparing the right eye between groups. Mean ± SD left eye IOP in the
OHT group was 25.2 ± 2.0 mm Hg (range, 21.0-29.0 mm Hg) and 15.4 ±
2.9 mm Hg (range, 9.0-21.0 mm Hg) in the control group. A comparison between
corneal thickness and IOP for each group is illustrated in Figure 2. The correlation between corneal thickness and IOP was
significant in the OHT group (r = 0.28, P = .04). There was no correlation between corneal thickness and IOP
in the control group (P = .99). When the groups are
pooled, the correlation between corneal thickness and IOP is also significant
(r= 0.37, P<.001).
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Figure 1. Corneal thickness measurements
for the Ocular Hypertension Treatment Study (OHTS) group and the control group.
Mean corneal thickness in the OHT study group was 0.594 mm, mean corneal thickness
for the control group was 0.563 mm (P<.001).
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Figure 2. Plot of corneal thickness vs intraocular
pressure (IOP) for the Ocular Hypertension Treatment Study (OHTS) group and
the control group. Correlation between corneal thickness and IOP for the 2
groups together is statistically significant. (r
= 0.37, P<.001). Correlation for the OHTS group
is also significant (r= 0.28, P= .04). There is no correlation between corneal thickness and IOP
in the control subjects (P= .99).
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The pharmacological reduction of IOP by at least 20% in the treatment
group did not affect the corneal thickness of these subjects (P = .25), when pretreatment corneal thickness was compared with posttreatment
corneal thickness.
COMMENT
Ocular hypertension is a condition for which the major diagnostic criterion
is IOP. Previous studies have demonstrated the correlation between increased
corneal thickness and IOP as measured by applanation tonometry. Subjects with
OHT have statistically greater mean corneal thickness than matched control
subjects and subjects with the diagnosis of glaucoma.2-4
Results of the present study, performed on a group of carefully selected subjects
with OHT, confirm those of prior investigations. These studies taken together
suggest that corneal thickness may be a significant confounding factor in
the diagnosis and classification of OHT.
Most studies of OHT have assumed that, after careful examination and
testing, the measured IOP is one of the primary determinants of risk for progression
to glaucoma. However, clinical experience with these patients has shown that
it is difficult to accurately predict which patients will eventually develop
field loss and optic nerve changes, qualifying them for the diagnosis of glaucoma.8-10 Studies of early treatment
of subjects with OHT have had varying results, with some suggesting that early
pressure-lowering intervention was beneficial, while others demonstrated no
clinical effect of intervention.11-15
None of these studies have considered corneal thickness as a factor, which,
depending on the corneal thickness distribution of the sample studied, may
have allowed the selection of nonhomogeneous groups with respect to the true
IOP. Increased corneal thickness may also have allowed some subjects to be
classified as OHT when in fact their true IOP may have been less than the
entry criteria for the study. This would have decreased the statistical power
of the study to show a difference between treated and untreated subjects.
The OHTS will be measuring the corneal thickness in all enrolled subjects.
Several authors, through manometric studies, have devised nomograms
for correcting a pressure measured by Goldmann applanation tonometry to true
manometric IOP.5-6 These studies,
individually and collectively, measured a relatively small number of eyes,
and it is difficult to determine whether these conversion factors can be applied
to the individual patient with accuracy. Experiments by Ehlers and colleagues5 suggest that a central corneal thickness of 0.59 mm
may cause IOP measured by applanation tonometry to overestimate true IOP by
as much as 5 mm Hg. Eyes previously studied by manometric IOP manipulation
were known to have increased corneal thickness at normal IOPs. The role of
increased true IOP as a cause of increased corneal thickness in the normal
cornea has not been determined, although corneal thickness is unchanged in
the patients in our study whose pressures have been reduced pharmacologically
by at least 20%. Corneal thickness measurements in a large group of patients
with OHT may help to determine whether corneal thickness plays a clinically
significant role in OHT and the progression to glaucoma in some subjects.16
In summary, a sample of carefully selected subjects with OHT was found
to have greater average corneal thickness than a sample of age-matched controls.
Further study is needed to determine what role, if any, corneal thickness
plays in the conversion of OHT to glaucoma.
AUTHOR INFORMATION
Accepted for publication August 5, 2000.
This work was supported in part by research grants EY02037 and EY10406
from the National Institutes of Health, Bethesda, Md; an unrestricted grant
from Research to Prevent Blindness Inc, New York, NY; and the Mayo Foundation,
Rochester, Minn.
Corresponding author: David C. Herman, MD, Mayo Clinic, 200 First
St SW, Rochester, MN 55905 (e-mail: herman.david{at}mayo.edu).
From the Departments of Ophthalmology (Drs Herman and Bourne) and Biostatistics
(Mr Hodge), Mayo Clinic and Mayo Foundation, Rochester, Minn.
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