Optluil. Phy.siol. Opt. Vol, 17, No, 5, pp, 414- 420. 19971997 Tlie College of Optometrists, Published by Elsevier Science Ltd

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PII: S0275-5408(97)00023-9

RESEARCH NOTE

The effect of an artificially-elevatedintraocular pressure on corneal thicknessin Chinese eye

Andrew K. C. Lam' and William A. Douthwaite^

'Department of Optometry and Radiography, Hong Kong Polytechnic University, Hong Kong and^Department of Optometry, University of Bradford, Bradford, UK

Summary

We measured the central corneal thickness and the applanation intraocular pressure (IOP) on45 Hong Kong Chinese. There was no obvious relationship between these two parameters, asdifferent from other literatures. It could be due to either a limited number of subjects with a highlOP level (only six subjects with IOP > 22 mmHg), or Chinese has a thicker central cornea ingeneral. The mean central cornea of our subjects was thicker (566 + 36//m) than some pre-vious findings. Thirty subjects had their intraocular pressure further increased by adopting a 40head-down posture. Their IOP and topographic corneal thickness were measured again. Therewas no significant change in the central corneal thickness even though the IOP was elevatedby 11.7 mmHg. However the nasal cornea demonstrated a thinning effect (by some 18/(m)during the IOP elevation but it returned to the pre-inverted level after returning to a sitting pos-ture for 5 min. Further investigation with more corneal regions being measured would be valu-able to evaluate the in vivo effect of IOP elevation from glaucoma attack on corneal thickness.Copyright < 1997 The College of Optometrists. Published by Elsevier Science Ltd

Introduction

Applanation tonometry has been considered as a stan-dard method in measuring intraoeular pressure (IOP).The basic concept is by modifying the Imbert-FickLaw

from ^= P..A (I)

where W is the external force against a sphere. P[ isthe pressure in the sphere and A is the applanatedarea by the external force

to B (2)

where S is the surface tension, Aj is the inner cor-neal surface area and B is the internal force from thecornea due to lack of corneal flexibility (Shields. 1992).

Receheii: 12 November 1996Revised form: 4 March 1997

Other referenee may use another formula to indicatethe influence of these two factors such as

= P, (3)

where M and N are the surface tension and theforce needed to deform the cornea, respectively (Hart.1992). Thus, the surface tension (either S or M) andthe spring force (either B or N) just indicate the direc-tion of the forees or pressures in which the surface ten-sion is acting towards the cornea and the spring forceis acting from the cornea. We do not need to addthese two factors in the calculation because the surfacetension balances the spring force and the measuredpressure Pi approximates to the actual iOP P̂ , whenthe region of eorneal applanation is 3.06 mm in diam-eter (area = 7.35 mm").

Previous investigations have found that the applana-tion tonometry result was afiected by corneal thick-

414

Elevated IOP and corneal thickness: A. K. C, Lam and W. A. Douthwaite 415

ness. A thiek eornea results in an overestimation of theIOP and vice versa (Hansen and Ehlers, 1971; Ehlersct at,. 1975: Johnson ei at.. 1978: Whitacre ct at.. 1993:Argus. 1995). Ehlers et at. (1975) derived an equationfor applanation tonometry and central corneal thick-ness as follows,

applanation tonometry (mmHg) — 2.43 -I- 24.90

X central corneal thickne.ss {mm) (4)

Thus, a variation of 0.2 mm in corneal thicknesswould cause a 5 mmHg change in the IOP. Whitacreet al, (1993) found a 0.2 mm varialion of eorneal thick-ness would cause an erroneous IOP estimation from3.6 to 4.6 mmHg, dependent on the IOP level. Ehlerset al. (1975) suggested that the Goldmann tonometercould give accurate readings when the central cornealthickness was 0.52 mm. For the Perkins tonometer,they considered that a corneal thickness of 0.54 mm to0.55 mm would allow accurate tonometry readings.

Patients with marginally high IOP may be requestedto have their IOP measured again on a different oc-casion for the confirmation of such a high pressure.According to the suggested relationship describedabove, the measurement of corneal thickness couldprovide more information for a more effective diagno-sis. However, the question that arises is if a thick cor-nea is the cause or the result of high IOP. There hasbeen no study on the eorneal thickness pre- and post-IOP elevation. The relationship between elevated IOPand corneal thickness should be clearly known beforeany conclusion can be drawn.

ln view of the direct acting effect of the IOP on theposterior corneal surface, an increase in intraocularpressure may alTect the corneal thickness by eitherpressing the cornea physically to reduce its thickness,or physiologically impairing the active pumping of theendothelium to inerease the corneal thickness. Thisstudy investigated the effect of an alteration of theintraocular pressure on the corneal thickness.

Methods

A Nidek Echoscan US-2000 (Nidek Co., Ltd..Japan) ultrasound pachometer was used to measurethe corneal thickness. The pachometer probe has atransmission frequency of II MHz and a tip diameterof 1.5 mm. The ultrasound velocity was set at 1640 m/sec (Goss ('/ al.. 1980). The measurement range of thispachometer was from 200/mi to 1300/jm with a pre-cision of I /mi. This pachometer was first calibratedwith a test plate provided by the manufacturer.Measurements within 112+ 15/im were considered asaccurate. Then the instrument was assessed to deter-

mine how many readings should be taken for humancornea measurement. Nine subjects were recruited inthis pilot study.

The pachometer unit can store eight consecutivereadings at each of the 33 pre-determined locations.We measured the central cornea of each subject bytaking 24 readings. The corneal centre was judged bynaked eye with respect to the pupil centre, similar toother ultrasound pachometry studies (Siu and Horse,1993: Herse et al,. 1993). The subjects were requestedto stay on a head-rest to reduce any movement. Themean and S.D. of the first eight readings were com-pared with the first 16 readings and also the total 24readings to see if there was any difference in the meanresults.

The mean central comeal thicknesses by consideringthe first eight readings, the first 16 readings and thetotal 24 readings were 556 ftm, 558 /jm, and 558 fim.respectively. The standard deviations were 5.0 /im,5.9/(m, and 6.\ fim, respectively. A repeated measureanalysis of variance (ANOVA) did not show any sig-nificant difference in mean and standard deviation(mean: d.f\ = 2. F = 2.02, P = 0.16, S.D.: d.f. - 2,F= 1.42, P= 0.27). By considering the first set ofeight readings, the small S.D., as similar to other stu-dies (Salz ('/ al.. 1983; Nissen et al.. 1991; Giasson andForthomme, 1992). revealed a good repeatability fromthis pachometer. Thus only eight successive readingswith a S.D. less than \0 ptm was considered to be asuccessful measurement.

The main study involved an applanation tonometryand the assessment of corneal thickness at five lo-cations. The corneal health of each subject waschecked with a biomicroscope at the beginning. Theircorneal astigmatism was measured with a Topcon CK-1000 automatic keratometer (Tokyo Optical Co. Ltd.,Japan).

Each subject retained his/her sitting posture for5 min while the procedures were explained. Both eyeswere instilled with one drop of 0.4% Benoixnate HCL.Only the right eye was measured and the local anaes-thetics on the left eye was used to reduce the blinkingfrequency. The right eye was prepared for IOPmeasurement with fluorescein strips and saline sol-ution.

A Perkins tonometer (Clement Clarke InternationalLtd.. England) was used to measure the IOP. The cali-bration of the Perkins tonometer was carried out witha 20 g weight in a standard procedure as recommendedfrom various reference books (Cockburn, 1991).Before contacting the cornea with the tonometer, thetonometer was set to 10 mmHg to extend the ton-ometer head f\illy. After the tonometry, the cornealthickness was measured by the ultrasound pachometer.The central corneal thickness was measured first, fol-

416 Opthal. Physiol. Opt, 1997 17: No 5

lowed by the peripheral cornea on the temporal, nasal,inferior, and superior regions, all were around 2 mmfrom the limbus determined with naked eye. Thesequence of the peripheral measurements was either ina clockwise or counter-clockwise direction, in a ran-dom order for different subjects. Once a sequence ofmeasurement was decided, the same sequence was usedfor different postures on the same subject. Use of thelimbus as a landmark was believed to be a better wayof ensuring the continuance of a constant position

Initial sitting

40° head-down position

Final sitting

Figure 1. Intraocular pressure and keratometric measure-ments in three dierent postures: initial sitting, 40 head-down, final sitting

than comparing the position with respect to the pupilcentre.

Each subject was then asked to lie on a tilting table2 m away from the chair. The end of the table was el-evated to give an inclination of 40 head-down. Thisposture was retained for 5 min and the subjects wereinstructed not to close the eye and keep blinking nor-mally. We used 5 min to ensure an elevated IOP levelwas obtained (Lam and Douthwaite, 1997a). The IOPand corneal thicknesses were measured again at theend of the 5 min period.

Thereafter, the tilt table was reset to a horizontalposition and the subject was requested to be seated onthe chair again. Another 5 min of adaptation wasgiven before the final measurements of IOP and cor-neal thickness in the sitting posture. It took less than3 min to finish the measurements for each posture. Thecorneal health was checked again with a biomicroscopebefore dismissing the subjects. Figure I shows the threemeasurement postures.

For those subjects with high initial IOP, or afraid ofthe discomfort induced by the tilting, we onlymeasured their centra! corneal thickness and the base-line IOP and did not proceed further because of safetyreasons. The relationship between the central cornealthickness and the IOP obtained in the initial sittingposture was plotted. Then the ehanges in the IOP andeorneal thickness during postural change were ana-lysed.

Results

Forty-five Chinese subjects had their central cornealthickness and intraocular pressure measured. No sub-ject had corneal astigmatism greater than 1.75 DC andtherefore the IOP was measured only with the appla-nation mire placed horizontally (Holladay et at,. 1983).Their baseline IOP ranged from 11.7 to 27 mmHg.There was no significant relationship between the cen-tral corneal thickness and the IOP {Figure 2;y - 1.99.Y + 529, /• - 0.18, P - 0.24).

Fifteen subjects did not proceed further because ofthe reasons mentioned above. Thirty subjects tookpart in the inversion study and had their peripheralcornea measured.

The IOP and topographic corneal thicknesses atdifferent postures were tabulated {Tabte I). There wasno significant difference in the initial corneal thick-nesses for the four peripheral regions (One-wayANOVA: d.f. = 3. 116. F= 2.29, P - 0.08). The su-perior cornea was the thinnest region compared withthe others. During the postural change, the intraocularpressure demonstrated a significant ehange (Repeatedmeasure ANOVA: d.f. = 1. F = 291.4. P < 0.01). Theaveraged inverted IQP was 28.6 mmHg (SD

Elevated IOP and corneal thickness: A. K. C. Lam and W. A. Douthwaite 417

cu

oocoo

"o

u

700

650

600

550

500

450

400

Table 2. Mean variation and standard deviation of intra-ocular pressure and corneal thickness from initial sitting toinverted posture (i.e. inverted posture - initial sitting)

10 15 20 25 30

Intraocular pressure (mmHg)

Figure 2. Relationship between the central corneal thick-ness and the intraocular pressure. Regression line:

29, r=0.18, P=0.24

3.7 mmHg). There was an averaged increase of11.7 mmHg from sitting to inverted posture {Tahte 2).For the corneal thickness, only the nasal corneademonstrated a significant change (Repeated measureANOVA: d.f. - 2, f = 34, P < 0.01). The variationwas less than 20 JXYO. while the mean change was evenless in other corneal regions [Table 2).

Discussion

This study is concerned with the relationshipbetween corneal thickness and the measured IOP andalso the change in corneal thickness when the IOP israised by an altered posture. There was no significantrelationship between the corneal thickness and theapplanation tonometry which may be, firstly, due to alimited number of subjects with a high IOP result.There were only six subjects with IOP of 22 mmHg orhigher and the greatest IOP was 27 mmHg. Subjects

Parameter MeanStandarddeviation

IOP (mmHg)Central corneal thickness {fin\)Superior corneal thickness (//m)Nasal corneal thickness (//m)Inferior corneal thicknessTemporal corneal thickness

11.70.13.9-18.06.65.9

3.13.917.417.419.620.1

with a corneal thickness thicker than 600 ^m were not,in general, in the high IOP region {Figure 2). Thisresult may also be due to the Chinese eye having agreater central corneal thickness. The central cornea ofour sample was thicker than some previous studies(Giasson and Forthomme, 1992; Herse et al.. 1993;Patel and Stevenson, 1994) but close to studies using asimilar sample base (Lam and Douthwaite. 1997b),even the instrument used was different. Lam andDouthwaite (1997b) found the central eorneal thick-ness of their Chinese samples was around 550 }.im(S.D. = 34/mi). The averaged centra! corneal thick-ness of those 45 Chinese subjects in the current studywas 566/(m (S.D. - 36/im). Tanaka et al. (1996)reported that cornea was thicker in low ametropes(spherical equivalent from -3,30 D to +3.20D) thanin high myopes (spherical equivalent from —9.00 D to—25.50 D) both at central and peripheral regions. Themean spherical equivalent of our sample was —4.35 D(-0.50 D to —I1.75D) which could be considered asmoderate myopia.

Whitaere et at. (1993) considered a corneal thicknessof 540/(m to be the value allowing an accurate Perkinstonometry result and 200/im of corneal thicknesschange would cause around 4 mmHg variation in theIOP result (Ehlers et at., 1975; Whitacre et ai. 1993).If we use these figures as a reference, those subjects inthe current study with a central corneal thickness of640 /(m should have their IOP result decreased by2 mmHg. The IOP for subjects with a thicker centralcornea should be decreased more.

Table 1. Mean ± standard deviation of intraocular pressure and comeal thickness in different postures

Parameter Initial sitting Inverted Final sitting

IOP (mmHg)Central corneal thicknessSuperior corneal thicknessNasal corneal thicknessInferior corneal thickness (/im)Temporal corneal thickness (/im)

16.9 ±2.2565 + 40674 + 41698 + 45696 + 41683 + 39

28.6566678680703688

+ 3.7+ 40+ 42+ 44+ 47+ 42

18.0 ±3.2567 ± 40678 ± 44702 ± 46697 ± 44681 + 41

418 Opthal, Physiol, Opt. 1997 17: No 5

The Perkins tonometer was used because it is por-table and can be used in different postures (Dunnand Brubaker. 1973). A non-contact tonometer canalso achieve this purpose but non-contact tonometersare reported to be influenced by anomalous cornea]thickness more than conventional applanation tono-metry (Graf, 1991). The trend for non-contact ton-ometer was found to be the same as conventionalapplanation tonometry by underestimating the IOPfor thin corneas and overestimating it in case of thickcorneas.

The corneal thickness at the different peripheral pos-itions varied slightly. The superior region was thinnerthan the other regions but the difference was not sig-nificant. Our result is opposing to the results obtainedby Li et at. (1994). We don't know if this thinning atthe superior region is due to a tight eyelid which putsexcessive pressure on the cornea. It is difficult to con-firm this suspicion concerning the effect from tight eye-lids when there is no accurate method for quantifyingthe lid tension. The corneal thickness at other regionswere similar to those in a recent study by Herse et al.(1993), mean peripheral corneal thickness of 709/im(S.D. ^ 56 fim). However, the corneal thickness at theperiphery in their study was an average of the su-perior, nasal, inferior, and temporal regions.

The average increase in the IOP from an initial sit-ting to the 40 head-down inversion was 11.7 mmHg(S.D. - 3.1) which was greater than other similar stu-dies with only 30' of inversion (Tarkkanen andLeikola. 1967; Lam and Douthwaite. 1997a). Draegerand Hanke (1986) studied the effect of postural changeon the IOP and found an increase in IOP from11.6 mmHg initially (90 upright) to 34.3 mmHg (com-plete head-down tih). The net increase reduced to15 mmHg from upright to 45- head-down. Friberg andWeinreb (1985) (bund a similar change of IOP fromsitting to complete inversion, 14.1 mmHg and35.6 mmHg. respectively. Klatz et al. (1983) alsoreported a 16 mmHg increase during a complete inver-sion procedure.

Postural change is a safe and quick procedure toincrease the IOP (Feldman et al.. 1989). An inversionof 40" was used in this study because it could generatean [OP elevation which is greater than by lying supine(Weber and Price, 1981; Buchanan and Williams.1985) and is more comfortable than completely invert-ing the subjects.

The average final IOP was slightly higher than thepre-inverted level even after 5 min of recovery time.This result is similar to another study using a similarsample base (Lam and Douthwaite, 1997a). Other stu-dies (Tarkkanen and Leikola, 1967; Jain andMarmion. 1976) reported the same or even lower post-inversion IOP, which is different from our findings.

There were only six subjects in the current study witha fmal IOP the same or less than the pre-inverted level.Since the IOP decreases for repeated applanation tono-metry measurements (Moses and Liu, 1968; Andersonand Grant, 1973; Motoiko et al.. 1982). the actual IOPin the final sitting position could be even higher thatour results suggest.

Whitacre ct al, (1993) compared the IOP obtainedfrom applanation tonometry and the IOP set withmanometry. After a baseline measurement, theyincreased the patients' IOP with the manometer andthen measured it with an applanation tonometer.Applanation tonometry was found to be affected bycorneal thickness. It underestimated the IOP for thincorneas and overestimated it for thick corneas, asreported from some earlier studies (Hansen andFhlers. 1971; Ehlers ct al.. 1975; Johnson et at.. 1978).However, they did not measure the corneal thicknesswhile the iOP was maintained at an elevated level.

The current study measured the applanation IOPand corneal thickness while the eye was maintainingan elevated pressure situation. There was no significantchange in the central corneal thickness with theinverted posture. Lam and Douthwaite (1997a) using asimilar inversion procedures did not find any signifi-cant change in the central corneal curvature arisingfrom the postural change. It appears that the centralcornea is able to resist any change in corneal curvatureor corneal thickness during a short-term elevation o^the IOP.

There appears to be no previous investigation intothe effect of !0P on the corneal thickness in vivo.Table 2 shows that the S.D. was similar at all the per-ipheral regions (17 to 20/mi). However, the smalleramount of mean change at the temporal, superior andinferior regions indicates that some subjects showingcorneal thickening while the others showing thinningand they cancelled out each other. Whereas the nasalcornea demonstrated a significant thinning in theinverted posture and returned to the pre-inverted levelafter resumption to the sitting posture. The mean re-duction in thickness was 18/(m (S.D. = \1 fim). Therewere 27 subjects demonstrating corneal thinning. Wewere surprised by this thinning effect on the nasal cor-nea arising from an elevated IOP. Dislocation of theprobe on the cornea, if any, should not appear on thenasal side solely. Further investigation with more cor-neal regions being measured could be valuable.

In the current study, the ultrasound velocity wasassumed to be 1640m/sec. Generally, velocity of ultra-sound depends on the density and compressibility ofthe material. The ultrasound velocity in human corneawas reported from 1540m/sec to 1640m/sec (Goss etat.. 1978). We ignored any effect on ultrasound vel-ocity from the elevation of IOP. If there is any effect

Elevated IOP and corneal thickness: A. K. C. Lam and W. A. Douthwaite 419

on the corneal characteristics such as the density andstress inside the cornea, the resulting variation of ultra-sound velocity would affect the measurement of cor-neai thickness. Even the reported ultrasound velocity.1540 m/sec to 1640 m/sec, would cause a nearly 6%change in corneal thickness assessment. Therefore, athorough consideration of the ultrasound velocityunder an elevated IOP situation would be valuable. Asimilar study using an optical pachometer may also beworthy.

Three subjects did not feel any discomfort through-out the whole procedures and surprisingly, all werefemales. Perhaps females have a greater tolerance insuffering from unusual situation. Two male and twofemale subjects felt uncomfortable throughout thewhole inversion period but the condition was still tol-erable. All the others felt a bit discomfort in the firstminute and then adapted to it. They described it as•"filling up with blood on the head".

This study demonstrated the constancy of the cen-tral cornea thickness under an elevated IOP situation.The thinning of the nasal cornea under this pressurechange requires further investigation with more cornealregions being measured. This study may also help topostulate the effect of IOP elevation from glaucomaon corneal thickness, but for short term effect only.

Acknowledgements

We would like to thank the Physiotherapy Section forthe loan of a tilt table and the subjects for their for-bearance with the experimental conditions. This pro-ject is supported by Grant 0351/351/A3/520 from TheHong Kong Polytechnic University.

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