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Corneal topography, near work and eyelid forces Tobias F. Buehren Diplom Ingenieur (FH) Augenoptik A thesis in partial fulfilment of the requirements for the degree of Doctor of Philosophy Centre for Eye Research School of Optometry Queensland University of Technology Brisbane, Australia 2003

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Page 1: Corneal topography, near work and eyelid forceseprints.qut.edu.au/15882/1/Tobias_Buehren_Thesis.pdf · aberrations of the human eye has grown rapidly. Aberrations of the whole eye

Corneal topography, near work

and eyelid forces

Tobias F. Buehren

Diplom Ingenieur (FH) Augenoptik

A thesis in partial fulfilment of the requirements

for the degree of Doctor of Philosophy

Centre for Eye Research

School of Optometry

Queensland University of Technology

Brisbane, Australia

2003

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KEYWORDS

Videokeratoscope, Cornea, Corneal topography, reading, lid forces, aberrations,

refractive error, myopia

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ABSTRACT

The cornea is the most powerful refractive component of the eye and as such, subtle

changes in corneal shape can cause substantial changes in the optical characteristics of

the eye. Monocular diplopia has previously been linked to corneal distortion

following near work in various studies but has not been investigated in detail. The

work reported in this thesis has investigated the optical effects of corneal distortions

caused by eyelid forces and demonstrated that several corneal higher and lower order

Zernike wavefront aberrations can change following reading.

Measuring subtle changes in corneal topography requires the highest possible

instrument accuracy, while software analysis tools should be able to detect and

highlight those subtle changes with high reliability. The effect of ocular

microfluctuations on the qualitative and quantitative analysis of corneal topography

was investigated. A technique was developed to measure tilt, displacement, and

cyclotorsion in multiple videokeratographs from the same cornea. This information

was used to reposition each videokeratograph according to the average position of a

sample of multiple measurements. The corneal topography of ten subjects was

measured 20 times each, using videokeratoscopy. The RMSE calculated from

difference between single videokeratographs and the average videokeratograph

decreased by an average of 24.6 % for the ten subjects’ data. The method can improve

the precision performance of videokeratoscopy in multiple measurements of corneal

topography.

I

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A study was undertaken, to investigate whether there are significant changes in

corneal topography during accommodation in normal corneas and corneas that are

pathologically thinner due to keratoconus. This was done to eliminate the possibility

that changes in corneal aberrations associated with near work could be at least partly

due to corneal changes caused by the effects of accommodation. A videokeratoscope

was modified to present an accommodation stimulus that was coaxial with the

instrument’s measurement axis. Six subjects with normal corneas and four subjects

with keratoconus were studied. In the initial analysis it was found that a number of the

subjects showed significant changes in corneal topography as accommodation

changed. However further analysis showed a significant group mean excyclotorsion of

the topography maps for both accommodation stimuli compared with the 0 D

stimulus. When the excyclotorsion was accounted for, no clear evidence of

statistically significant changes in corneal topography as a result of accommodation

were found. A small ocular excyclotorsion typically accompanies accommodation and

this changes the relative orientation of the topography of the cornea.

To investigate the effects of eyelid pressure on corneal shape and corneal aberrations

during reading, twenty young subjects with normal ocular health were recruited.

Cornea1 topography of one eye was measured with a videokeratoscope prior to

reading and then again after a 60 minute reading task. Twelve of the twenty corneas

showed significant changes in central topography immediately following reading. The

location of the changes corresponded closely to the position and angle of the subject’s

eyelids during reading. Within the central region of the cornea there were significant

changes in corneal wavefront Zernike coefficients, the root-mean-square error, overall

refractive power and astigmatism. The changes observed in corneal topography

II

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appear to be directly related to the force exerted by the eyelids during reading. These

findings may have important implications for the definition of refractive status and

may also aid in the understanding of the relationship between reading and the

development of refractive errors.

To study whether corneal distortions after reading significantly differ between

refractive error groups, corneal aberrations were measured before and after a period of

reading, for a group of ten young progressing myopes and a group of ten young stable

emmetropes. The major difference between the two groups was the location and

magnitude of the corneal distortions, which had a significantly larger effect on central

corneal optics in the myopic group compared to the emmetropic group. A

significantly smaller palpebral aperture for the myopic group in the reading gaze

position was the cause of this difference.

The experiments described in this thesis have shown that numerous corneal

characteristics can change due to eyelid forces during near work. The eye was shown

to undergo a small cyclotorsion during higher levels of accommodation. There was a

shift in direction of against the rule astigmatism of the cornea following reading and a

change was found for primary vertical coma and trefoil. The changes in corneal shape

following reading appear to be different in myope versus emmetropic refractive error

groups. These findings are important for our understanding of the stability of the

refractive error of the eye and could have important implications for refractive error

development.

III

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CONTENTS

Abstract I

Contents IV

Statement of Authorship VIII

Acknowledgements X

Chapter 1:

1.1

1.2

1.3

1.4

1.5

Introduction

Videokeratoscopy

1.1.1 Placido-based Instruments

1.1.2 Technical requirements

1.1.3 Corneal topography reconstruction

1.1.4 Topographic displays

1.1.5 Limitations of videokeratoscopes

1.1.6 Accuracy and repeatability

Corneal shape

Corneal mechanics

1.3.1 Hydration effects

1.3.2 Tear instability

1.3.3 Mechanical properties

1.3.4 Stability of corneal shape

1.3.5 Diurnal variations

1.3.6 Corneal epithelia1 cell movement

The effect of lid pressure on corneal topography

1.4.1 Monocular diplopia associated

with near work

Eyelids and blinks

1.5.1 Blinking

1 .5.2 Eyelidpressure

Page

1

3

3

4

7

8

8

11

16

19

19

20

21

23

24

25

27

29

34

36

37

IV

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1.6

1.7

1.8

Wavefront aberrations of the human eye

1.6.1 Aberroscopy

1.6.2 Measurements of monochromatic

wavefront aberrations

1.6.3 Ocular wavefront aberrations and

accommodation

1.6.4 Cornea1 and total wavefront aberrations

of the eye

1.6.5 Wavefront aberrations and myopia

Myopia and refractive error development

1.7.1 Myopia prevalence

1.7.2 Myopia etiology

1.7.3 Emmetropisation

1.7.4 Near work related myopia studies

in humans

Attempts to prevent myopia progression 1.7.5

Rationale

Chapter 2: Ocular Microfluctuations and

Video kera toscopy

2.1 Introduction

2.2 Methods

2.2.1 Regression plane - to remove tilts

2.2.2 Sphere apex - to remove x,y,z, shifts

2.2.3 Best-fit sphero-cylinder - to remove

cyclo-deviations

2.2.4 Limitations

2.2.5 Protocol

2.3 Results

2.4 Discussion

40

40

41

44

44

46

47

47

49

50

52

54

56

59

59

62

63

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67

69

70

75

V

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Chapter 3:

3.1

3.2

3.3

3.4

Chapter 4:

4.1

4.2

4.3

4.4

4.5

Chapter 5:

5.1

5.2

5.4

5.5

Chapter 6:

6.1

6.2

6.3

6.4

6.5

Corneal Topography and

Accommodation

Introduction

Methods

Results

Discussion

Corneal Aberrations and Reading

Introduction

Methods

Analysis

Results

Discussion

Corneal aberrations following reading

in progressing myopes

Introduction

Methods

Results

Discussion

Conclusions

Ocular micro fluctuations

Accommodation and topography

Corneal aberrations, reading and myopia

Future directions

Summary

77

77

79

85

93

97

97

98

100

104

114

120

120

122

128

146

153

153

154

155

160

165

VI

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References: 166

Appendix 1: Publications from thesis A

VII

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STATEMENT OF ORIGINAL AUTHORSHIP

“The work contained in this thesis has not been previously submitted for a degree or

diploma at any other higher education institution. To the best of my knowledge and

belief, the thesis contains no material previously published or written by another

person except where due reference is made.”

Signed: ................................................

Date: .........................

VIII

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Authorship

AUTHOR’S STATEMENT

The research reported in this thesis was carried out by myself or under my direction.

The development of some techniques described in this thesis has involved

collaboration with other persons.

Chapter 2: Ocular microfluctuations and videokeratoscopy

The development and writing of the fixation error minimization algorithm described

in this thesis primarily involved collaboration of Brenden J. Lee and D. Robert

Iskander. The author was responsible for all other aspects of the study.

Chapter 3: Corneal topography and accommodation

In manufacturing the telescope system to present a target co-axial with the Keratron

videokeratoscope, the collaborator was the physics department at Queensland

University of Technology. Jim Loughridge provided assistance with the data

collection. The author was responsible for all other aspects of the study.

Chapter 4: Corneal aberrations and reading

Brett Davis, D. Robert Iskander and Mark Morelande assisted with the various aspects

of the data analysis. The author was responsible for all other aspects of the study.

Chapter 5: Corneal aberrations following reading in progressing myopes

D. Robert Iskander, Sigfried Mioschek, and Martin Trunk developed the digital image

analysis software. Stephanie Voetz provided assistance with the data collection. The

author was responsible for all other aspects of the study.

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ACKNOWLEDGEMENTS

My special thanks go to Michael J. Collins and Leo G. Carney for giving me the

opportunity to do a PhD at Queensland University of Technology and also for their

assistance and encouragement during my studies.

X

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CHAPTER 1

Introduction

In the last two decades, the development of new technologies has significantly

enhanced research achievements in the field of visual optics. Today we are able to

measure the optical performance of the human eye to a degree of sophistication that

often exceeds our ability to understand this complex optical system. The questions I

have investigated in this dissertation concern the accurate measurement of corneal

shape and aberrations, its stability and its potential role in the development of

refractive error.

Measurement and understanding of corneal topography has been significantly

improved by the introduction of videokeratoscopy. Information is available on a much

larger area of corneal data compared with keratometry and the ability to measure

small regional changes in corneal topography is enhanced. The term precision of an

instrument refers to the agreement between repeated observations with the given

device. Accuracy of a method refers to how closely a measured value agrees with the

true value. To reliably measure small changes in corneal shape one must understand

the repeatability and accuracy of videokeratoscopes.

While the normal corneal shape resembles an ellipsoid, variations in surface occur and

corneal stability has reported to be affected by various factors. Cornea1 changes can

occur due to a range of effects such as finger pressure, eye position, rubbing, eyelid

position, and eyelid pressure. A number of researchers have identified monocular

1

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diplopia as the consequence of lid pressure effects on the cornea1 shape following near

work.

With the introduction of wavefront sensing technology, research in the field of optical

aberrations of the human eye has grown rapidly. Aberrations of the whole eye as well

as for various ocular components and conditions can be measured in detail. These new

techniques have the potential to provide fresh insights regarding the optical

characteristics and also the optical development and function of the human eye.

Within the last two decades of human myopia research interest has shifted towards

retinal image quality and it is now widely believed that emmetropisation is a vision-

dependent phenomenon. It is thought that some form of visual feedback mechanism

regulates retinal image-mediated ocular growth. Within this context, the measurement

of the optical characteristics of the human eye using videokeratoscopy and wavefront-

sensing technologies may provide a significant new insight to this research field.

2

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1.1 VIDEOKERATOSCOPY

Since the development of computer-assisted videokeratoscopes in the mid- 1980s,

there has been a rapid increase in technical sophistication and features of the devices.

The Cornea1 Modelling System was the first commercially available

videokeratoscope, and incorporated the colour-coded contour map (Maguire et al.

1987). The basic principle of these instruments involves projection of a target light

source on the cornea and capturing of the reflection of this light from the cornea by a

video camera (Figure 1-1). This information is analysed by software and the data is

displayed in a variety of formats. Earlier forms of corneal measuring devices supplied

significantly less data points than current videokeratoscopes. This allows a much

more detailed description of corneal shape. The number of measurements obtained

from current videokeratoscopes range from 5000 up to more than 8000 discrete points

depending on the instrument.

1.1.1 Placido-based Instruments

Placido-based videokeratoscopes measure the angle of the corneal surface and use this

angular information to compute curvature and height. A conical Placido disc target

projects numerous concentric rings on the cornea and a virtual image located behind

the reflecting surface is detected by a video camera and analysed to determine the size

and shape of the rings (Sanders and Koch 1993). Each of the rings in the virtual image

is analysed at a certain angular interval (often 256 meridians) to allow computation of

topography for a total of many thousand points. On the optic axis of the

videokeratograph is a luminous fixation point that is centred with respect to the

concentric rings comprising the object target. Several algorithms for analysing ring

data are available (Keller and van Saarloos 1997). Local curvature algorithms are

3

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based on instantaneous radius of curvature along a particular meridian and essentially

utilises local changes in curvature to generate topography maps. Spherically biased

algorithms for this analysis assume that the cornea is spherical, and small errors are

introduced as a result. The third algorithm used is based on the posterior focal power

of the cornea and is calculated using Snell’s law. After the cornea1 surface is

reconstructed, a graphical picture of the patient’s topography is presented most

commonly in a colour-coded contour map. Other presentation forms include

difference maps, various contact lens fitting presentations, isometric displays, numeric

format, composite plot displays, and meridional displays.

1.1.2 Technical requirements

The improvements of computer hardware and software in terms of storage capacity

and processing speed led to a tremendously increased number of points that can be

analysed. Although many refinements have been made to focus techniques, alignment

systems, target designs, and algorithms, limitations arise from underlying assumptions

and several measurement errors still exist. Bibby described the technical requirements

for reliable topographic measurements as follows; “the instrument must be

independent from the shape being measured and should measure the total area of

shape (Bibby 1976). Furthermore, all information should be acquired simultaneously

with high accuracy and reproducibility.”

4

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Placido-rings

Figure 1 - 1 : Simple schematic model of Placido-based computer-assisted videokeratoscope

5

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With regards to working distance, two types of instruments can be distinguished.

Image capture can be either achieved by a small faceplate at short working distance

(e.g. Keratron) or a large faceplate at long working distance (e.g. EyeSys). The

smaller target design at short working distance is used to minimise unwanted

reflections of lashes and adnexa in the ring image (Mandell 1996).

These devices are more likely to have an area that is not interrupted by the ocular

adnexa. The instruments allow measurements to extend further into the cornea1

periphery and sometimes to the limbus (Mandell 1996). On the other hand, larger

targets have the advantage of allowing a longer object distance, which will

theoretically cause less error from any unwanted decentration or defocusing of the eye

during the measurement. Thereby long working distance systems should provide

higher reproducibility.

The image of the reflected target, which is located behind the cornea, should lie on a

flat plane however this is not possible for every cornea. Thus the reflected image

commonly lies on a curved image plane, which means that there is only one point of

focus on the flat plane of the photographic film (Dave et al. 1998). Different target

designs have been tested to minimise the problems encountered when focusing on a

curved image plane. Current obtainable faceplate geometry varies in features like

number of rings, their colour, brightness and spacing. Ring mires that are to closely

spaced might blur together when reflected off distorted corneas. Ring mires that are

too small in diameter are difficult to detect due to the limited pixel resolution of the

video camera.

6

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Focusing of the Placido-ring target on the cornea can be achieved either manually or

by an automatic focusing system. The image may be captured automatically when the

target disc is positioned in the correct distance from the cornea. In some instruments

automatic focusing systems have a setting, which may be varied to offer easier

capture or a higher accuracy. The automatic focusing systems may compensate focus

errors on actual corneas or use an out of focus detector and make adjustments in the

algorithm (Opticon 1997).

Most commercially available reflective videokeratoscopes are designed such that the

instrument axis is aligned normal to the corneal surface along a direction known as

the vertex normal. For measurements applied to visual problems such as refractive

surgery, the ideal would be a position when the videokeratoscope axis coincides with

the point where the line of sight intersects the cornea (Mandell 1992).

1.1.3 Cornea1 topography reconstructions

Most videokeratoscopes reconstruct the cornea using a two-dimensional coordinate

system known as a plane geometry model. The algorithm, which is spherically biased,

demands that the centre of curvature lies on the videokeratoscope axis. The instrument

has to be centred and placed at the correct focal distance and the algorithm (also

known as the axial solution), calculates corneal power at any point as the power of a

sphere, which would produce the same ring reflection as that of the cornea. This

approximation is accurate for axis-centred spheres only. For non-spherical surfaces,

the centre of curvature actually moves off the optical axis. Another method, the arc-

step algorithm is not spherically biased and reconstructs corneal surface composed of

several multiple arcs. This reconstruction technique can accurately describe aspheric

7

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corneal profiles because more peripheral arcs need not be centred on the instrument

axis. The corneal shape is reconstructed by adding adjacent arcs sharing a common

tangent where they meet (Tripoli et al. 1995; Mattioli and Tripoli 1997).

1.1.4 Topographic displays

A range of topographic displays is available to present corneal raw data (i.e. slope or

height data). Topographic displays can be divided into two main categories: corneal

function and corneal shape. The subgroup of corneal shape displays consists of three

different displays, axial curvature, tangential curvature, and surface height. The

refractive power map display is classified as a corneal function map (Roberts 1998).

Many devices supply other features like multiple images, profile plots, difference

maps, or contact lens software, which simulates the fluorescein pattern of rigid lenses

fitted to the corneal topography.

1.1.5 Limitations of videokeratoscopes

Videokeratographs are aligned along an axis that is slightly, but significantly

displaced from the line of sight. The videokeratoscope axis is aligned perpendicular to

the cornea and is thus directed towards the centre of curvature more than the centre of

the entrance pupil. This corneal position is more peripheral than the sighting centre,

which is the intersection of the line of sight with the corneal surface. The patient

views the fixation point inside the target cone while the operator carries out focusing

and alignment. When achieved it gives an individual position of the pupil centre, the

optic axis of the videokeratograph, and its distance from the vertex normal (Mandell

1996).

8

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The influence of defocus can have significant effects on corneal height measurement

error. Due to the relatively smaller amount of defocus with long working distance

devices compared to the same amount of defocus with short working distance devices,

the latter are particularly sensitive to this problem. Also an accurate camera to cornea

distance is very important, so that maximum contrast of the camera resolution can be

satisfied. Although Mandell demonstrated that longer working distance systems

provide higher reproducibility, they are more sensitive to shadowing from the

eyelashes and nose at the corneal surface (Mandell 1996).

Generally the corneal surface is described using a set of Cartesian coordinates (x, y,

and z) to define its profile. However the two-dimensional image in videokeratoscopy

has insufficient information on its own to enable a point-by-point localisation in three-

dimensional space. Therefore several assumptions must be made. Dave et al.

described, in general, the assumptions that needed to be made for the various

reconstruction techniques (Dave et al. 1998). The working distance from the target to

the image is a constant. The instrument axis is perpendicular to the corneal surface.

The light from one meridian of the target is reflected in the same meridian in the film

plane. There is no circumferential tilt of the corneal surface although for point targets,

this assumption is not required. The position of the image at the film plane is unique

for a particular surface. The image plane lies on a flat plane.

Incorrect or unsteady fixation of the luminous fixation point is a potential source of

error in videokeratoscopy. This error can become significant if patients have large

refractive error or another source of low visual acuity, which prevent them from

9

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maintaining fixation. Fixation errors are most noticeable in the cornea1 periphery and

produce effects similar to instrument misalignment.

Hubbe and Foulks assessed fixation error effects using five subjects who fixated in

certain angles from coaxial with the instrument (Hubbe and Foulks 1994). The I-S

value method was applied to compare the corresponding meridians. The I-S value is

the difference between the inferior (I) and superior (S) powers of the cornea. An I-S

value greater than 1.20 D suggests the presence of keratoconus. The I-S values

increased as fixation angle increased as expected. A mean value of 1.26 D, which is

the value used by Rabinowitz and McDonnell as the limit for early keratoconus

detection, was reached by three out of five normal corneas at 5". At 10" misalignment,

all of them easily reached that value (Rabinowitz and McDonnell 1989).

Using a radially aspheric surface, Roberts investigated the potential spherical bias of

the TMS- 1 (Roberts 1995). The instrument demonstrated increasing error from centre

to periphery for an ellipsoid with 7.5 mm apical radius of curvature and a value of 0.5

of eccentricity. Roberts presented an error of more than 3 D at 4 mm from apex. This

strong spherical bias was found to influence system performance by limiting the

ability of the device to detect subtle shifts in surface curvature. Compared to

misalignment errors, this inherent algorithm error in mapping a radically aspheric

surface was found to be relative high.

Tripoli et al. estimated the accuracy of Keratron's arc-step profile reconstruction

algorithm with four rotationally symmetric, radially aspheric test surfaces (Tripoli et

al. 1995). It was intended to distinguish between error caused by the algorithm and

10

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error from other sources. Keratron measurements were compared with the surface

formula and ray-traced simulations of the profile reconstruction algorithm.

Tripoli et al. concluded that Keratron’s arc-step algorithm measured height more

precisely than videokeratoscopes that use spherically biased algorithms.

Belin and Ratliff assessed smoothing functions of raw data acquisition (axial solution)

of seven commercially available videokeratographs (TMS, EyeSys, CAS, Master Vue,

CM-1000, Keratron, and TechnoMed C-Scan) (Belin and Ratliff 1996). Six calibrated

test objects to simulate clinical conditions such as myopic or hyperopic ablation,

simulated central islands and spherical or sphero-cylindrical shapes were used. It was

found that no system accurately measured all objects. Sources of error occurred with

excessive raw data smoothing, loss of accuracy in the periphery, poor central

coverage and the inability to read large transitions.

Mattioli and Tripoli assessed the accuracy of the profile reconstruction algorithm used

by the Keratron videokeratoscope (Mattioli and Tripoli 1997). The height of eight test

surfaces with central astigmatism ranging from 4 D to 16 D was measured. Keratron

measurements were compared with the surface formula and ray-traced simulations of

the profile reconstruction algorithm. The maximum height error ranged from 0.47 %

to 2.9 % of the total height, with the eight test surfaces.

1.1.6 Accuracy and repeatability

Topographers measure corneas less precisely than they measure artificial test surfaces.

Determination of statistically significant differences in corneal topography for clinical

applications demands a large amount of data processing. Regarding corneal

11

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topography measurements, videokeratoscopes are the most accurate devices and

collect significantly more data than other instruments such as keratometers. Test

surfaces such as perspex or steel balls of known surface shape determined using

standard surface metrology methods may be measured with videokeratoscopes and the

results compared. This is not possible for measurements of real corneas. To estimate

the accuracy of a videokeratoscope for cornea1 topography measurements it must be

compared with other models of videokeratoscopes taking the instruments’ accuracy

for artificial test surfaces into account.

A comparison of three videokeratoscopes (TMS-1, EyeSys, and the Visioptic EH-

270) in measurement of toric test surfaces was undertaken by Greivenkamp et al.

(Greivenkamp et al. 1996). They used precision diamond-turned toric surfaces, which

were independently measured. The results showed systematic performance differences

among the three instruments. The general characteristics that lead to potential

inaccuracies were overall high frequency noise in the power maps and surface height

maps (TMS-l), discontinuities in the centre of the power maps, and underestimation

of the amount of astigmatism because of excessive data smoothing (EyeSys and

Visioptics).

Dave et al. used 12 perspex convex surfaces of varying eccentricities and different

apical radii to evaluate the accuracy and repeatability of the EyeSys model II (Dave et

al. 1998). The sagittal radius of curvature for both central and peripheral known

points were measured twice on each surface. To evaluate accuracy and repeatability of

the points and the relationship between eccentricities, raw data tables were analysed.

The accuracy of the EyeSys model II decreased slightly as the p-value decreased.

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Repeatability for the aspheric surfaces was shown to be high (SD f 0.01 mm in all

quadrants).

A study from Hilmantel et al. determined the accuracy of the Tomey, Topographic

Modelling System to measure asymmetric surfaces (Hilmantel et al. 1999). The

characteristics of asymmetric surfaces were created through ellipsoidal test objects

tilted relative to the videokeratoscope axis. A Melles-Griot mini-goniometer was used

to permit accurate rotation of the test objects about its apex. Smooth, mildly

asymmetric surfaces were created with maximum tilts of up to 15". Root mean square

error (RMSE) of surface elevation for all objects at all tilts, varied from a low of

0.69 pm to a high of 11.32 pm. Hilmantel found the TMS-1 to be capable of

measuring with an accuracy of about 1 pm to 10 pm while the degree of asymmetry

did not have a statistically significant effect on accuracy.

Tang et al. investigated accuracy and precision performance of four

videokeratoscopes (Keratron, Medmont, and TMS) and the rasterstereogrammetry

based videokeratoscope (PAR-CTS) in measuring six test surfaces (Tang et al. 2000).

A Talysurf instrument was used to accurately quantify the topography of the test

surfaces that consisted of a sphere, an asphere, a multicurve and three bicurve (5.0,

6.5, and 8.5 mm radius of curvature) surfaces. The elevation errors were calculated by

subtracting the Talysurf readings from the instruments averaged data. The study

showed high accuracy of instruments on some but not all surfaces. Keratron and

Medmont showed the best accuracy on average for the sphere, asphere, and

multicurve followed by TMS, which showed slightly better performance for the 5.0

and 6.5 bicurve surfaces. The PAR-CTS had the poorest performance in precision of

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the four devices but was more accurate than the other three instruments for the 8.5

bicurve surface.

Jeandervin and Barr compared the accuracy and repeatability of three commercially

available videokeratoscopes for real eye measurements and four calibration spheres

respectively (Jeandervin and Barr 1998). Of the three instruments (Alcon EyMap EH-

290, EyeSys system 2000, Humphrey Mastervue topography system), the EyeSys

system 2000 was found to have best repeatability while the Humphrey Atlas was

shown to be the most accurate instrument based on the measurements of calibration

spheres. Hough and Edwards assessed reproducibility of four EyeSys systems for the

measurement of vertex radius and central topography (Hough and Edwards 1999). In

contrast to Jeandervin and Barr’s data, Hough and Edwards concluded that the EyeSys

system does not provide reproducible values of corneal dimensions at a level that

would normally be acceptable for the specification of rigid lens back surface radii. It

was pointed out that Jeandervin and Barr's results were based on two measurements

of twelve eyes only and therefore may have underestimated the extend of variation.

The Keratron was found to show high repeatability for corneal topography

measurement within the central 4 to 5 mm of the map (Buehren et al. 2001). The

standard deviation within most areas of this region showed *OS0 D of instantaneous

power and *0.25 D of refractive power. However at the edge of an 8 mm diameter,

instantaneous power maps frequently reached more than *1.00 D of standard

deviation.

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Cho et al. compared the performance of four videokeratoscopes (Humphrey Atlas

991, Orbscan 11, Dicon CT200, Medmont E300) in measuring topography of young

Chinese adults (Cho et al. 2002). Both the Humphrey Atlas and the Medmont

demonstrated high levels of performance, showing good agreement between elevation

values. Of the four videokeratoscopes tested, the Orbscan II showed the poorest

repeatability and reproducibility.

In summary, Placido-based videokeratoscopes provide an important tool for cornea1

topography analysis and diagnosis. Differences in accuracy and precision

performance exist between instruments due to various factors.

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1.2 CORNEAL SHAPE

Based on early studies using keratometers, a mean value of the central corneal radius

of curvature is 7.85 mm f0.25 mm (Clark 1973) with a difference in curvature

between the flattest and steepest meridian of 0.15 f 0.15 mm in normal Caucasian

populations (Guillon et al. 1986). Curvature usually flattens towards the periphery.

Kiely et al. found that an ellipsoidal surface best describes the asphericity of the

corneal shape (Kiely et al. 1982). The mean and standard deviation of the central

radius of curvature for 176 healthy eyes was 7.72 f 0.27 and the asphericity was

Q = -0.26 f 0.18. Kiely et al. pointed out that the cornea is significantly asymmetric

in both radius of curvature and asphericity (Kiely et al. 1982).

Features of normal corneal topography have been extensively characterized and

classified (Bogan et al. 1990; Rabinowitz et al. 1996). Bogan et al. qualitatively

classified the topography of 399 normal corneas based on computer-assisted

videokeratography (Bogan et al. 1990). They compared their descriptions of

topographic maps and identified five characteristic patterns: round, oval, symmetric

bow tie, asymmetric bow tie and irregular. Rabinowitz et al. divided

videokeratographs into 10 categories and included 10 analysis indices in order to

quantitatively describe phenotypic features (Rabinowitz et al. 1996). Indices provide

an objective measure and reproducibility of videokeratoscope analysis, which can be a

useful tool in the interpretation of pathological conditions such as keratoconus;

contact lens induced corneal warpage, or surgically altered corneas.

Wilson et al. suggested standardisation of colour-coded scales, because the clinical

and research use of the instruments have increased enormously (Wilson et al. 1993). It

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was claimed that the so-called Klyce-Wilson scale (constant, 1.5 dioptre intervals)

provides the best combination of sensitivity and the best range of coverage on a wide

variety of corneas ranging from normal to surgically altered, and to those affected by

pathology.

Keratoconus is a pathological condition characterised by unusual corneal topography

that has been extensively investigated and a number of videokeratographic methods

for the detection of keratoconus have been developed (Dingeldein et al. 1989;

Rabinowitz and McDonnell 1989; Maeda et al. 1994). Smolek and Klyce proposed a

neural network approach, which was found to outperform several other methods in

distinguishing between keratoconus, keratoconus suspects, and topographies that are

similar to keratoconus (Smolek and Klyce 1997).

Various mathematical techniques have been used to categorize corneal topography.

Schwiegerling et al. presented a method to decompose corneal height data captured

with a videokeratoscope using a set of Zernike polynomials (Schwiegerling et al.

1995). The method provides a sophisticated technique for extracting high-order

corneal height variations such as those arising from disease or refractive surgery.

Decomposition overcomes the drawback that the spherical and cylindrical

components of the cornea obscure small variations in the surface. For applications like

refractive surgery the Zernike polynomials are a useful technique for determining the

shape of the aberrated cornea as well as the ablation pattern to convert the cornea into

an ideal shape (Greivenkamp et al. 1996; Schwiegerling and Greivenkamp 1996;

Schwiegerling et al. 1996; Schwiegerling 1997; Schwiegerling and Greivenkamp

1997; Langenbucher et al. 1999; Langenbucher et al. 1999).

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Oshika and co-authors applied the Zernike technique to measure corneal aberrations

as a function of aging in a large population of normal subjects (Oshika et al. 1999).

An increase in third order (coma like) cornea1 aberrations with age was found while

spherical-like aberrations did not vary with aging. These results are in agreement with

the results of McLellan et al. on changes in ocular aberrations with age (McLellan et

al. 2001).

In summary, the normal corneal shape resembles an ellipsoid. Using a set of

mathematical functions, corneal height data can be decomposed into distinct surface

components. Small variations in surface height can then be highlighted, which

otherwise would be obscured by spherical and cylindrical components.

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1.3 CORNEAL MECHANICS

The corneal surface is a dynamic structure affected by various factors such as

hydration, tear characteristics, hypoxia, lid pressure, blinking and external forces.

When determining accuracy and reproducibility of videokeratoscopes these factors

represent a source of variability and are sometimes difficult to quantify. The functions

of tear film, tear flow, tear chemistry, and tear film stability have been researched in

many studies. Much remains unknown about the influence of blink forces, lid

pressure, blink frequency, and tear layer dynamics on corneal topography

measurements.

1.3.1 Hydration effects

A study by Rom et al. describes the relationship between topography and corneal

oedema (Rom et al. 1995). Lack of corneal oxygen supply was created using a

nitrogen chamber goggle for one eye, while the other eye served as control.

Topographic measurement and baseline pachymetry of each eye from 10 subjects

were obtained. Thickness of all corneas exposed to the nitrogen chamber increased

but demonstrated no significant topographic changes, apart from the nasal area where

the corneal power lessened. There was no significant correlation between changes in

corneal topography and corneal thickening in any area measured.

Using de-epithelized eye-bank eyes at various stages of hydration, Ousley and Terry

evaluated hydration effects on the central and paracentral corneal topography (Ousley

and Terry 1996). The average central corneal steepening between pre-and post-

hydration conditions was 0.44 D, while the average paracentral steepening was

0.89 D.

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1.3.2 Tear instability

Using videokeratoscopy, Pavlopoulos et al. examined the effect of artificial tears

applied to normal and post-keratoplasty eyes (Pavlopoulos et al. 1995). In normal

eyes, the application of artificial tears showed increasing corneal asymmetry and

changes to the location of the steepest point of the cornea. For eyes that had

undergone keratoplasty, the artificial tears created a more regular and symmetric

surface and significantly altered the simulated keratometry values. It was

recommended that corneal topography be performed before the application of

artificial tears.

Novak et al. analysed the effect of six artificial tear preparations on videokeratoscopic

measurements with the EyeSys (Novak et al. 1997). All preparations except two

induced significant, time-dependent changes in mean corneal power in the central

five-millimetre zone compared with baseline measurements. The mean induced

change was less than 0.5 D. When performing repeated measurements, the highest

consistency was achieved when no tears were instilled.

Licznerski et al. introduced a new method for evaluating tear film stability in the

human eye, using the lateral shearing interference technique (Licznerski et al. 1998).

The lateral shearing interferometer allows non-invasive testing of the human tear film

with a high accuracy. They presented sequences of shearing interferograms showing

the development of break-up on the normal eye during the inter-blink period. The tear

layer distribution process was clearly visible through the interference fringes that

become more and more distorted due to the evaporation of the tears and formation of

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break-up sites. Nemeth et al. used high-speed videokeratography to detect tear film

regularity changes following blinking (Nemeth et al. 2002). It was found that the

corneal surface becomes more regular in the first few seconds after a blink.

In summary it appears unlikely that hydration effects in the in-vivo human cornea

have a significant impact on corneal topography. The tear film represents a significant

source of variability during corneal topography measurements with tear-break-up

being capable of substantially distorting the local surface. Artificial tear preparations

do not appear to be beneficial in improving the videokeratoscope precision

performance. Following a blink, it takes the tear film a few seconds to reach the most

regular and stable state.

1.3.3 Mechanical properties

The mechanical properties of the in vivo human cornea are difficult to determinate. In

materials like metals, the relationship between stress and strain is a simple linear one.

Young’s modulus (E) is the constant parameter, which characterizes the elastic range

of those materials. Biological materials show a more complex behaviour. Constant

increasing stress might be followed by a non-linear decrease of strain, which is known

as ‘stress stiffening.’ Nyquist and Nash et al. have demonstrated that the mechanical

properties of the cornea are viscoelastic (Nyquist 1968; Nash et al. 1982). This means

that additionally to the elastic behaviour, a retarded strain component occurs without

further increasing the stress. This behaviour is called creep. Furthermore the cornea

consists of different layers each showing different mechanical characteristics.

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Many investigations concerning Young’s modulus of the cornea have been performed

using stress-strain tests on strips of excised cornea (Nyquist 1968; Andreassen et al.

1980; Nash et al. 1982). While Andreassen et al. found differences in stress strain

parameters between normal and keratoconic corneas (Andreassen et al. 1980),

Nash et al. found no correlation between elastic parameters and age, or a measurable

difference in the elastic behaviour of normal and keratoconus corneas under

physiologically relevant stress levels (Nash et al. 1982).

Other researchers used whole eyes in vitro to measure the displacement of mercury

drops that had been placed on the cornea1 surface, while inducing an increase of intra

ocular pressure (Hjortdal and Jensen 1995; Shin et al. 1997). For intra ocular

pressures of physiological relevance, Shin et al. reported small values of average

strain for the central region of the cornea but indicated that the strain distribution

throughout the entire cornea was unexpectedly non-uniform. Wang et al. applied an

ultrasonic technique for the measurement of elastic moduli of the human cornea

(Wang et al. 1996). The results of Young’s moduli (5 to 20 x 106Nm-2) compare with

those testing the stress-strain relationship on strips of cornea (Nyquist 1968;

Andreassen et al. 1980; Nash et al. 1982).

Hjortdal and Jensen studied the regional performance of the cornea and limbus in

vitro by pressure loading of 18 intact human cadaver eyes (epithelium removed)

(Hjortdal and Jensen 1995). Circumferential as well as meridional deformation with

pressure varied between the centre, para-centre, periphery, and limbus. Meridional

strains were smallest at the para-centre and periphery, and largest at the limbus

suggesting reinforcing para-central and peripheral structures in the meridional

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direction. Circumferentially, strains were smallest at the limbus, suggesting

reinforcing limbal structures in the circumferential direction.

In summary, the mechanical properties of the cornea are viscoelastic. Quantification

of corneal mechanics is a difficult and complex problem. Various techniques have

been applied to measure elastic moduli of the in-vitro cornea and regional differences

in strains of corneal structures have been found.

1.3.4 Stability of corneal shape

Mandell and St Helen investigated the influence eye position, accommodation,

convergence, pupil size, lid position and closure, miotics, and rubbing on stability of

the corneal contour (Mandell and St Helen 1968). Cornea1 curvature was found to

change significantly as a result of digital pressure, lid forces, and rubbing.

In 1972, Carney and Clark investigated experimental deformation of the in vivo

cornea (Carney and Clark 1972). Corneas of two subjects were flattened by pressing a

flat surface against the corneal apex over five different time periods. The recovering

cornea was measured along a horizontal or vertical meridian before and during a 10-

min period after applanation. In the experiment, for the human in vivo cornea, at least

99 % of the central displacement had been recovered within 8 sec after retraction of

the tonometer probe. Carney and Clark therefore concluded that the delayed response

in the recovery of the in vivo cornea from deformation is much faster than expected

compared with previous studies on deformation of post-mortem corneas (Carney and

Clark 1972).

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Knoll summarized the cause of “unnatural” effects on corneal shape changes, the

magnitude of the effects on the corneal shape, and how quickly the corneal shape is

restored (Knoll 1976). Concentrating on short-term effects, factors such as finger

pressure and tugging on the lids, eye position, rubbing, application of an applanation

tonometer, changes in corneal astigmatism induced by retracted lids and lid pressure

that causes bilateral monocular diplopia following near work were identified.

Studies that have investigated the effect of accommodation on the corneal shape have

been limited by the available technology. Investigations of the more central regions of

the cornea using keratometers (Fairmaid 1959; Lopping and Weale 1965) and

photokeratoscopes (Mandell and St Helen 1968) have created contradictory findings.

Fairmaid showed meridional changes in corneal curvature with convergence but

found no shape changes in the accommodating but non-verging eye (Fairmaid 1959).

Lopping and Weale also reported that significant changes occur in corneal shape

during ocular convergence (Lopping and Weale 1965). Mandell and St Helen did not

find any changes in topography with either convergence or accommodation (Mandell

and St Helen 1968). Using a modified keratometer, Pierscionek et al. found changes

in corneal topography with accommodation in at least one of the principal meridians

for most of the subjects tested (Pierscionek et al. 2001).

1.3.5 Diurnal variation

The cornea has also been observed to have diurnal variations in thickness and

topography (Reynolds and Poynter 1970; Rengstorff 1972; Kiely et al. 1982).

Kiely et al. measured corneal topography and thickness during a period of 12 hr of

one day in hourly intervals (Kiely et al. 1982). Instrumentation comprised an auto-

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collimating photokeratoscope, a keratometer, and a pachometer attached to a slitlamp.

In agreement with other studies a significant overall steepening of corneal curvature

throughout the day was observed (Reynolds and Poynter 1970; Kiely et al. 1982).

Thickness at five locations was shown to be greatest immediately after awakening and

became thinner at all locations as time during the day elapsed.

1.3.6 Corneal epithelial cell movement

The corneal epithelium consists of five to seven layers of cells and has an overall

thickness of 50 to 52 pm (Smolin and Thoft 1994). It has a complete cell turnover in

5 to 7 days (Hanna and O'Brien 1960). Davanger and Evensen discovered the

migration of epithelial cells from the corneal limbus towards the centre (Davanger and

Evensen 1971). They found evidence that the limbal structure can produce cells that

migrate over the cornea. Corneal epithelial stem cells have shown to be located at the

palisades of Vogt at the limbo-cornea1 junction and have been found to proliferate

epithelium cells from the limbal region (Kinoshita et al. 1982; Schermer et al. 1986;

Kinoshita et al. 2001). Schermer et al. and Cotsarelis et al. confirmed that the source

of cell proliferation and migration is epithelial cells from the sclero-cornea1 limbus

(Schermer et al. 1986; Cotsarelis et al. 1989).

Thoft and Friend proposed the X, Y, Z hypothesis of corneal epithelial maintenance.

It basically expresses the relationship between epithelial cell proliferation and

epithelial cell loss; where X is the proliferation of basal epithelial cells; Y, the

contribution to the cell mass by centripetal movement of peripheral cells; and Z, the

epithelial cell loss from the surface (Thoft and Friend 1983). Hence corneal epithelial

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maintenance can be defined by the equation: X + Y = Z, which simply states that cell

loss must be balanced by cell replacement.

In summary, various factors affect the stability of the corneal shape. Factors such as

diurnal variations in thickness and cell movements can change the structure and

thereby the shape of the cornea. While various short-term effects such as mechanical

pressure from lids or applanation tonometry can change corneal shape due to

mechanical deformation.

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1.4 THE EFFECT OF LID PRESSURE ON CORNEAL

TOPOGRAPHY

Several factors indicate that lid forces may be capable of influencing corneal shape.

Grosvenor’s theory of with the rule astigmatism development says that small forces

(long term pressure) of the eyelids, in the area where they cover the corneal surface,

could gradually cause steeping of the superior and inferior regions of the cornea

(Grosvenor 1978). Furthermore indirect evidence comes from case reports of

monocular diplopia (Fincham 1963; Mandell 1966; Knoll 1975; Bowman et al. 1978;

Carney et al. 1981; Kommerell 1993; Ford et al. 1997; Campbell 1998; Golnik and

Eggenberger 2001) associated with near work. In most of these cases the eyelids were

thought to be responsible for the changes in corneal curvature.

Kiely and Carney examined corneal topography in a series of trials involving blinking

and lid retraction (Kiely and Carney 1978). The corneal topography of eight subjects

was monitored with the auto-collimating photokeratoscope of Clark (Clark 1972). The

effect on corneal topography of normal blinking, lid retraction and hard forced

blinking were determined. For each condition, photokeratograms were taken before

and immediately after the trial, while in the case of the forced blink trials,

photokeratograms were taken additionally at two and five minutes after the trial. No

significant changes were found in this study except in one isolated case.

The effect of lifting the lids away from the globe has been shown to change the

measured toricity in the direction of less with the rule astigmatism (Wilson et al.

1982; Grey and Yap 1986). Keratometric measurements served to determine corneal

changes in 36 eyes with normal lid position and after retraction with a lid speculum.

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The results showed a significant increase of steepness in the horizontal corneal

meridian while the vertical meridian didn’t show significant changes. For high

astigmats the changes were systematically in the direction of less with the rule

astigmatism while low astigmats showed no systematic trends.

Vihlen and Wilson investigated whether the pressure of the eyelids influences corneal

astigmatism (Vihlen and Wilson 1983). Lid tension and corneal curvature of 100

subjects was compared. It was hypothesised that if lid forces are involved in the

shaping of the cornea, then senile changes leading to a decrease of lid tension with

age should be a factor in corneal changes with age. However, there was no

experimental evidence found that lid tension between individuals is responsible for

differences in corneal toricity.

Grey and Yap measured corneal astigmatism in connection with three different

narrowed lid positions (Grey and Yap 1986). They found a statistically significant

increase of corneal with the rule astigmatism when the lid aperture was narrowed to

leave uncovered only a central vertical area of 2.0 to 2.5 mm of the cornea. In this

position, corneal astigmatism changed by about 2 D. Widening of the palpebral

aperture didn’t cause significant change in corneal astigmatism.

Lieberman and Grierson investigated central corneal shape with and without the

eyelids touching the corneal surface using a stereogrammetry based device

(Lieberman and Grierson 2000). Difference maps between the two conditions

revealed significant central corneal distortion with the lids in their normal position

touching the cornea. In a preliminary study leading to this dissertation, Buehren et al.

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found statistically significant corneal power changes within a few seconds of the post-

blink interval in the upper and lower regions of the topography maps (Buehren et al.

2001). The location of the band-like distortions correlated well with the subjects’

natural position of the eyelids in primary gaze.

In summary, several studies have found short-term effects of eyelid forces on corneal

astigmatism and corneal distortion. However there has been no conclusive evidence

that long-term effect of lid forces are involved in the shaping of the cornea.

1.4.1 Monocular diplopia associated with near work

Morgan first reported a single case of monocular diplopia (i.e. double images in one

eye) and Fincham observed slight doubling of monocular vision by a large proportion

of subjects with good visual acuity (43% of 70 eyes) (Morgan 1955; Fincham 1963).

Usually one image was fainter than the other and hence was often unnoticed.

Frequently only one eye was affected. It was interesting that all these cases were

similar in that the doubling was almost always approximately in the vertical direction

and homonymous. Fincham assumed that refractive index differences in the

crystalline lens are responsible for the diplopia since he didn’t detect any changes in

corneal topography.

Between 1966 and 1992 three case reports of monocular diplopia are noteworthy.

Mandell reported of a single case of monocular diplopia associated with near work.

The patient complained about blur and vertically double images after reading

(Mandell 1966). The pinhole and the stenopaic slit (placed in the horizontal meridian)

were used to test visual acuity and clearly identified the source of diplopia as optical

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in origin. When placing the stenopaic slit in the vertical meridian the diplopia

persisted. Furthermore, the retinoscopic reflex revealed dark lines approximately in

the horizontal direction that had not been observed when the patient didn’t experience

diplopia. Finally, keratometer readings exhibited mire distortions that occurred just

after reading. Mandell therefore concluded the cause of the monocular diplopia was

due to changes in the corneal contour.

The second case report of Bowman et al. presented quantitative results of corneal

deformation associated with monocular diplopia following near work (Bowman et al.

1978). Using the autocollimating photokeratoscope of Clark, corneal asphericity from

a reference sphere in any number of meridians were calculated. Across an area about

1.5 mm radially from the ophthalmometric axis, a shift in direction of positive

asphericity (more oblate) was measured in the superior temporal, superior and

superior nasal semi-meridians.

The third study by Goss and Criswell concerned a case report of a 36 year old male

with bilateral monocular polyopia following television viewing (Goss and Criswell

1992). Apparently the monocular polyopia resulted from corneal surface changes

induced by narrowing of the lid aperture. This narrowing was associated with the

supine posture, which was used by the patient to watch television. It seemed logical to

assume that it was the upper eyelid that was distorting the cornea in this case, because

of its lowered position associated with the downgaze position. In photokeratograms

taken before watching television, the rings where smooth and regular, while numerous

irregularities were present afterwards.

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Knoll described his personal experience of bilateral monocular diplopia following

near work (Knoll 1975). Photokeratograms verified that the upper lids were producing

furrows in the corneas near the upper edge of the pupil, since reading with one eye

closed prevented the closed eye from developing diplopia. Knoll also found a

vertically shifted and homonymous ghost image and likened the effect of it to having

a prism placed base down on the upper part of the pupil.

Carney et al. predicted the angular positions of any secondary image resulting from

corneal distortion. Nine subjects viewed monoculary through a microscope while

keeping the other eye forcibly closed (Carney et al. 1981). Five of the subjects

reported the presence of secondary images in the closed eye after 15 min of the task.

Tracing rays from a distant object point through the distorted cornea could plot the

angular displacement of each ray as a function of its distance from the

ophthalmometric axis. The results showed that the predicted angles of the secondary

images correlated well with the measured angular positions.

Based on retinoscopic characteristics, Kommerell described his findings of monocular

diplopia in 20 patients with ghost images as the “Venetian blind phenomenon”

(Kommerell 1993). Abnormal pressure from the upper eyelid was explained to be the

cause for the phenomenon.

Ford et al. investigated monocular diplopia associated with near work and

hypothesized that the corneal alterations are primarily related to the position of the

lids and tear film interaction with the corneal surface (Ford et al. 1997). Six subjects

that complained of monocular diplopia were examined and compared with a control

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group of 20 patients without such complaints. A preliminary full ophthalmological

examination for each subject was carried out. Before and after a reading task of 30

minutes, videokeratographs were acquired using the Topographic Modeling System 1

(TMS). In addition, the red reflex using direct retinoscopy was observed and the lid

position in relation to the pupil in primary gaze and during the reading task was noted.

Each of the six subjects showed a horizontal band in the red reflex and developed

diplopia, whereas two controls also showed a faint band but did not complain about

optical effects. Further analysis of corneal topography was undertaken using the

difference map. The difference maps of the six subjects showed horizontal bands of

steepening and flattening of approximately 2.5 D of axial power.

More recently Golnik and Eggenberger published a study which investigated

symptomatic corneal topographic changes induced by reading in downgaze (Golnik

and Eggenberger 200 1). Three symptomatic cases of monocular diplopia following

reading and a control group of nine subjects were studied. The three symptomatic

cases showed changes of up to 2.5 D in the topography difference maps following

reading. The non-symptomatic controls also showed central refractive power change

of up to 1.5 D, however they did not experience monocular diplopia following

reading. Golnik and Eggenberger reported that 30 to 60 minutes is needed to resolve

visual symptoms after cessation of reading.

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Chapter 1

N

Summary of monocular diplopia studies

Method Decay Finding/Conclusion

30 - 60 min

Study

Corneal topographic change

Task Instrument

Fincham (1 963) 70 Illuminated cylinder vessel

Refractive index difference in lens

Mandell (1 966) Keratometer Reading Change in cornea1 shape Pinhole Stenopaic slit Case report

Knoll (1975) Photokeratoscope Reading 30 - 60 Furrows in the cornea min Own experience

Bowman (1 978)

Carney (1 98 1)

Photokeratoscope Reading Microscope (15 min)

Corneal deformation

Corneal distortion

Case report

9 I Case report Cross and

Criswell(l992) Kommerell (1993) 20

Television viewing Photokeratoscope

Retinoscope Abnormal eyelid pressure

Ford (1 997) Videokeratoscope Reading for (30 min)

Horizontal bands of distortion 6 and 20 controls

Golnik and Eggenberger (2001)

3 symptomatic and 9 controls Videokeratoscope Reading

Table 1-1 : Summary of studies reporting monocular diplopia following near work activities, which have been published within the last 40 years.

33

Corneal surface changes

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1.5 EYELIDS AND BLINKS

The major tasks of the eyelids are to protect the eye from injury or excessive light by

closure and to spread a film of tears over the cornea by blinking (Wolff 1968). The

upper eyelid is larger and more mobile than the lower eyelid and they meet at the

medial and lateral angles (canthi). The lateral canthus is about 2 to 3 mm higher than

the medial (Dutton 1994; Snell and Lemp 1998). Interpalpebral fissure measures of

the adult range from 8 to 1 1 mm, whereas the horizontal length is 30 to 31 mm (Snell

and Lemp 1998).

There has been conjecture that only a limited area of the conjunctiva of the upper

eyelid is in close contact with the eyeball (Parsons 1904; Ehlers 1965). Kessing, using

tomography, provided the only direct demonstration of the contact of the eyelids with

the ocular surface (Kessing 1967). He concluded that only a marginal area of the

upper eyelid, while in the lower lid the entire tarsal area, is in close contact with the

globe. More recently Korb et al. described the marginal conjunctiva of the upper

eyelid as a wiping surface to spread the tear film over the ocular surface and therefore

named this area the “lid wiper” (Figure 1-2) (Korb et al. 2002). Korb and co-authors

found characteristic staining with fluorescein of that portion of the marginal

conjunctival epithelium in contact lens wearers suffering from dry eye symptoms. The

clinical condition was described as lid-wiper epitheliopathy.

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Figure 1-2: The area of the lid-wiper starts posterior to the Meibomian glands, where the

stratified squamous epithelium changes from keratinised to non-keratinised tissue, and

extends superiorly to the subtarsal fold (Figure courtesy of Korb et al. 2002).

35

halla
This figure is not available online. Please consult the hardcopy thesis available from the QUT Library
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1.5.1 Blinking

King and Michels measured a blink rate of about 12 blinks/min, while Abelson and

Holly reported blink frequencies of 16 to 17 blinks per minute (King and Michels

1957; Abelson and Holly 1977). However substantial differences in blink rate

between individuals have been reported by York et al., Carney and Hill (York et al.

1971; Carney and Hill 1982), who found typical blink rates of 13 blinks per minute

with marked individual variations. Furthermore, a variety of factors have been shown

to influence blink frequency. Decreased blink rates were observed with subjects

during difficult visual tasks (York et al. 1971) and with soft contact lens wearers that

seemed to subconsciously develop a blinking strategy to suppress blinking during

critical tasks (Pointer et al. 1985). In general, anxiety increases the blink rate, while

increased attention decreases the blink rate (King and Michels 1957).

Types of blinks are frequently divided into three categories: spontaneous blinks,

reflex blinks and voluntary blinks (Guitton et al. 1991; Kaneko and Sakamoto 1999).

Abelson and Holly classified spontaneous blinks into three types: twitch blink,

consisting of a small movement of the upper eyelid (-2%) ; incomplete blink, in which

the descending upper eyelid covered less than two third of the cornea (-17%); and

normal complete blinks (-80%); and voluntary or forced blinks that included an

upward movement of the upper lids (Abelson and Holly 1977).

A mean value of maximum velocity for the closing phase of a typical spontaneous

blink of 8 to 10 mm amplitude is 280 mdsec reached within 70 msec (Collewijn et

al. 1985). Total duration of the down phase is -100 to 150 msec. Average values of

maximum velocity for the opening phase corresponds to 150 mm/sec (Guitton et al.

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1991) with 200 to 300 msec of total blink duration (Collewijn et al. 1985; Guitton et

al. 1991).

1.5.2 Eyelid pressure

A few researchers have attempted to measure eyelid pressure. Moller conducted two

studies in 1954 and 1955 using a modified Hansen manometer, which enabled direct

measurement of the change in pressure that accompanied blinking (Moller 1954;

Moller 1955). The results showed 10, 20 and 50 (mm water) of lid pressure for gentle

(natural closure), full (deliberate blink), and forced (hard squeeze) blinks,

respectively.

Miller developed a scleral lens and balloon system to measure lid pressure (Miller

1967). His results for the different kinds of blink types showed 38 for gentle, 140 for

full and 693 for forced blinks (pressure in mm water), which differed significantly

from the results of Moller. The eyes were first anaesthetised and then a 0.84 mm thick

scleral contact lens was inserted. The scleral lens and lens-balloon combination

measured a total thickness of 2.5 mm at the apex. After insertion, the combination was

attached to a pressure transducer and lid pressure was determined on ten normal

subjects. Because of the unnatural thickness of the lens-balloon system the results

obtained by Miller are questionable.

Lydon and Tait applied a special lens pressure transducer and used a thin (0.1 mm)

modified scleral shell to measure lid pressure (Lydon and Tait 1988). The transducer

was connected via a valve to a manometer. Before insertion of the scleral lens and

performance of blinking manoeuvres, the subjects’ corneas were anaesthetized. The

37

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results of lid pressure measurement under normal conditions showed small pressure

values. In cases of forced blinks, a significantly higher pressure was reached.

In order to measure lid tension, Kennard and Smyth glued a perspex saddle to the lid

sulcus from which various weights were hung (Kennard and Smyth 1963). The

tension of the upper lid was found to not be constant. Vihlen and Wilson derived the

passive spring constant of the upper lid by pulling it away from its rest position

(Vihlen and Wilson 1983). The method involved a small clamp, which was attached

to the upper lid and displaced in a direction normal to the cornea. A range of 1.2 to

6.8 g/mm was measured (mean 3.2 g/mm, SD = f 1.1). The results correlated well

with earlier findings (Hung et al. 1977). Evinger et al. applied weight to the eyelid

while attaching a silk suture to the outer surface of the lid so that the suture pulled

almost straight down on the eyelid (Evinger et al. 1984). Applications of weight to the

lid caused a displacement of the lid that was recorded by a lid monitor. Lid tension of

10 g/mm was measured in primary gaze but was only about 2.5 g/mm in a gaze

direction of 40 degree below horizontal.

Bilateral eye globe retraction occurs during blinking (Evinger et al. 1984; Collewijn et

al. 1985; Riggs et al. 1987). The globe retraction occurs due to co-contraction of the

extraocular muscles, rather than lid forces driving the globe back into the orbit. Lydon

and Tait found that the eye retracts about 0.5 mm on normal blinking and twice as

much on forced blinking (Lydon and Tait 1988). The most plausible explanation for

this effect is the co-contraction of the extraocular muscles on normal blinking while

the lids may contribute some additional force under forced blinking conditions.

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The magnitude of retraction (interquartile range: gentle and full 0.4 - 0.7 mm, forced

0.7 - 1.3 mm) was in agreement with the results of Doane and Riggs et al. (Doane

1980; Riggs et al. 1987).

In summary, the eyelids protect the eye and spread the tear film over the cornea. It has

been shown that just a portion of the upper eyelid, the marginal conjunctival

epithelium, acts as a lid wiper to spread the tear film over the corneal surface. Mean

blink rate is around 12 to 17 blinks per minute, showing large individual variability.

Blink rate is affected by contact lens wear, level of attention, anxiety, and corneal

sensitivity. Characteristics of blinks have been identified, measured, and types of

blinks have been divided into several categories. Eyelid pressure has not been

measured with high reliability. In cases of forced blinks, significantly higher pressures

may be reached compared to normal blinking conditions. Lid tension was found to not

be constant and lower in the direction of downward gaze. A bilateral eye globe

retraction occurs during blinking, which is due to co-contraction of extraocular

muscle rather than eyelid forces.

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1.6 WAVEFRONT ABERRATIONS OF THE

HUMAN EYE

1.6.1 Aberroscopy

In 1893, using a grid, a blurring lens and a viewing point source, Tscherning

subjectively quantified aberrations and thereby described the first aberroscope

(Tscherning 1893). Howland and Howland later applied the cross cylinder

aberroscope technique invented by Howland to the measurement of monochromatic

aberrations of the human eye (Howland 1968; Howland and Howland 1976; Howland

and Howland 1977). The technique relied on the subject drawing a grid shadow

formed on the retina, which was then analysed to derive a Taylor polynomial to

quantify the aberrations of the eye. In 1984 Walsh et al. presented an objective

technique for the determination of monochromatic aberrations of the human eye

(Walsh et al. 1984). In agreement with previous findings using the subjective method,

Walsh and co-workers confirmed that third order aberrations are typically larger than

fourth order aberrations in the total wavefront error (Walsh et al. 1984).

Almost parallel to Tscherning’s work in the late nineteenth century, Hartmann used

the Scheiner principle to measure the aberrations of mirrors and lenses (Hartmann

1900). A perforated opaque screen was used to isolate numerous light bundles. Any

deviation of the propagating light bundle then can be measured with a sensor. Shack

and Platt improved the idea of the Hartmann screen by using an array of small lenslets

that focuses light into an array of spots (Shack and Platt 1971). Liang and co-authors

first applied the Hartmann-Shack wavefront technology to measure aberrations of

human eyes (Liang et al. 1994). Today the technique represents the most widely used

objective method to assess the aberrations of human eyes.

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1.6.2 Measurements of monochromatic wavefront aberrations

In order to characterise the wavefront of an eye it is useful to analyse the aberrations

based on a set of mathematical functions. It is possible to describe aberrations with a

Taylor series expansion. Each term represents aberrations of a particular order. Seidel

used a better approximation and derived five components now known as Seidel

aberrations (spherical aberration, coma, astigmatism, Petzval curvature of field and

distortion) (Freeman 1990). Zernike polynomial series offer an advantage due to their

orthogonality for continuous curves. Therefore Zernike polynomials are most suitable

for optical applications and have been used to estimate ocular (Liang et al. 1994) and

cornea1 aberrations (Schwiegerling et al. 1995). Today Zernike polynomials are the

standard method for describing monochromatic aberrations of the human eye.

There are different conventions of Zernike polynomial presentations in use (No11

1976; Kim and Shannon 1980; Tyson 1982; Conforti 1983; Born and Wolf 1985;

Malacara et al. 1990). This has led to difficulties within the vision research

community when comparing the result of ocular aberrations that have used different

Zernike conventions. In response, the OSA (Optical Society of America) taskforce

was formed in 1999 to establish standards for reporting of optical aberrations in visual

optics research and related clinical disciplines (Thibos 2000). In Table 1-2 the first 20

Zernike terms according to the OSA convention are presented. Within this thesis any

presentation of wavefront aberrations with Zernike polynomials uses the OSA

convention.

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ZERNIKE POLYNOMIALS ACCORDING TO OSA CONVENTION

J N m Orthonormal Zernikes Description

Table 1-2: The first 20 Zernike terms according to the OSA (Optical Society of America)

convention are presented, with Z," (n = order, m = frequency).

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After Liang et al. first presented aberrations of the human eye using the Hartmann-

Shack wavefiont sensor technology, this research field has grown rapidly (Liang et al.

1994). First results showed large subject-to-subject variations however some

correlation was found between right and left eyes of the same subject (Liang and

Williams 1997). Marcos and Burns found little symmetry between left and right eyes

(Marcos and Burns 2000) however three large population based studies confirmed the

findings (Porter et al. 2001; Castejon-Mochon et al. 2002; Thibos et al. 2002).

Castejon-Mochon et al. reported of a tendency for mirror symmetry between eyes

while Thibos et al. also indicated the presence of significant bilateral symmetry

(Castejon-Mochon et al. 2002; Thibos et al. 2002).

Thibos et al. showed an exponential decline of aberrations with increasing Zernike

order and a linear increase of the wavefiont error with increasing pupil area (Thibos et

al. 2002). Castejon-Mochon et al. found that 99% of the root-mean square wavefront

error is contained in the first four orders of a Zernike expansion (Castejon-Mochon et

al. 2002). Changes in monochromatic aberrations with age have shown that

aberrations of the cornea and eye increase with age (Guirao et al. 2000; McLellan et

al. 2001).

Recently Carkeet et al. presented monochromatic aberration data from a population of

Singaporean school children (Carkeet et al. 2002). The results revealed significant

differences between refractive error groups as well as between racial groups. Chinese

subjects showed significantly higher amounts of aberrations than Malay subjects.

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1.6.3 Ocular wavefront aberrations and accommodation

Before the introduction of Hartmann-Shack wavefront technology, changes in

spherical aberration with accommodation have been reported (Koomen et al. 1949;

Ivanoff 1956; Jenkins 1963). Eyes generally decrease from positive spherical

aberration and changed to negative values with increasing levels of accommodation.

Atchison et al. first characterized the wave front aberration as a function of

accommodation of the eye in detail (Atchison et al. 1995). It was found that third

order (coma and coma-like) aberrations were dominant for most people which was in

agreement with earlier findings (Howland and Howland 1976; Howland and Howland

1977; Walsh et al. 1984; Walsh and Charman 1985). Also the classical trend towards

negative spherical aberration with increasing accommodation was found for about

half of the subjects. Ninomiya et al. confirmed the change in spherical aberration

towards negative dioptric values in young adults (He et al. 2000; Ninomiya et al.

2002). He et al. found a trend of increasing wavefront aberrations with increasing

levels of accommodation (He et al. 2000).

1.6.4 Corneal and total wavefront aberrations of the eye

The anterior corneal surface is the eyes’ most powerful refractive component and

therefore is a major contributor to the eyes’ total wavefront aberrations.

Videokeratoscopes capture several thousand raw data points from the corneal surface.

In order to investigate individual corneal surface characteristics, the corneal shape can

be decomposed using a set of mathematical functions. Corneal wavefront information

and knowledge about its contribution to the total aberrations of the eye can be

obtained using a ray trace technique.

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Guiaro and Artal first demonstrated a procedure to calculate the wavefront aberrations

of the human cornea from its surface shape measured by videokeratoscopy (Guirao

and Artal 2000). The method describes the procedure to calculate the wavefront

aberration of a refracting surface from the elevation data. In order to characterise the

exact wavefront aberration values at each point of the surface, it may be fitted with

Zernike polynomials using the same method used for fitting the corneal surface

(Schwiegerling et al. 1995).

Applegate et al. calculated corneal wavefiont variance and compared the results with

various contrast sensitivity and acuity measurements (Applegate et al. 2000).

Wavefiont variance was defined as the difference between a reference wavefront and

the actual corneal wavefront. A statistically significant correlation between visual

performance and corneal wavefront variance was found. Marcos et al. suggested that

corneal irregularities are a major contributor to the variability of monochromatic and

transverse chromatic aberrations of the eye (Marcos et al. 2001).

The amount of total versus corneal wavefront aberrations was found to be larger in the

cornea than for the complete eye, indicating a partial compensation of corneal

aberrations by internal optics of the eye (Artal et al. 2001; Mrochen et al. 2003).

Barbero et al. compared corneal and total optical aberrations in both eyes of a

unilateral aphakic patient (Barbero et al. 2002). Cornea1 wavefiont aberration was

calculated using videokeratoscopic elevation data. The aphakic eye showed a 98.4 %

correspondence between the corneal and total aberrations. For the normal eye, the

corneal spherical aberration was higher than the total spherical aberration indicating a

45

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compensatory role of the crystalline lens in total spherical aberration of the normal

eye.

1.6.5 Wavefront aberrations and Myopia

The relationship between monochromatic aberrations and refractive error has also

been investigated. Collins et al. first objectively measured monochromatic aberrations

in the eyes of young myopic and young emmetropic subjects using the modified

Howland and Howland aberroscope technique (Atchison et al. 1995; Collins et al.

1995). Myopes showed higher levels of negative spherical aberration relative to the

emmetropic subjects for both non-accommodated and accommodated conditions. A

high proportion of the aberroscope grids in the myopic eyes were too highly aberrated

to permit analysis indicating higher levels of aberrations in the myopic eyes. Collins

et al. suggested that high amounts of wavefront aberrations might play a role in

myopia development (Collins et al. 1995).

Several studies confirmed that myopes have significantly larger wavefront aberrations

than emmetropes (Cheng et al. 2000; He et al. 2000; Marcos et al. 2000) although

there has been some diversity of findings. Greater root mean square (RMS) errors of

wavefront aberrations have been found for myopes compared with emmetropes

(He et al. 2002). While Marcos et al. found significantly increased 3rd order

components in myopes, He et al. reported of significantly greater 2nd and 4* order

components (He et al. 2000; Marcos et al. 2000). Paquin et al. found a quasi-linear

relationship between increasing aberrations and refractive error (Paquin et al. 2002).

Based on the results found for different racial background and refractive error,

Carkeet et al. found no evidence for aberration-driven form-deprivation as a major

46

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mechanism of myopia development (Carkeet et al. 2002). More recently Cheng et al.

found no correlation between total higher order aberrations and refractive error in

myopic and hyperopic eyes but a tendency towards larger higher-order aberrations for

astigmats as compared with non-astigmats (Cheng et al. 2003).

1.7 MYOPIA AND REFRACTIVE ERROR DEVELOPMENT

While there is evidence that refractive error is partly genetically determined, there is a

growing body of evidence that the type of visual tasks undertaken also influence

refractive error development. The observed increase in myopia prevalence over recent

decades has increased debate regarding the relative contribution of environmental and

genetic factors to myopia development. In Singapore, for instance, within a decade the

prevalence of myopia in young adults has increased from 26% to 65% in university

graduates (Tay et al. 1992). Today it is generally accepted that the risk factors for

myopia development are both genetic and environmental (Mutti et al. 1996; Pacella et

al. 1999; Wu and Edwards 1999).

1.7.1 Myopia prevalence

Many Asian populations are reported to have significantly higher rates of myopia than

western populations (Chandran 1972; Lin et al. 1988; McCarty et al. 1997; Wong et

al. 2000). For comparable young age ranges the prevalence of myopia in populations

in Taiwan is 84% (Lin et al. 1995), in Japan 65.6% it is amongst students (Matsumura

and Hiroaki 1999), and it is 50% to 70% in Hong Kong (Lam and Goh 1991). For

Australia a myopia prevalence of 17% has been reported (Wensor et al. 1999). In the

United States myopia prevalence of 25% has been found (Sperduto et al. 1983),

although more recently McCarty et al. reported more than 40% prevalence in the US

47

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(McCarty et al. 1997). These differences in myopia prevalence between different

ethnic groups with similar living standards seem to underscore the relevance of

genetic factors in refractive error development.

More evidence to support the importance of genetics in myopia comes from twin

studies (e.g. (Teikari et al. 1989; Hammond et al. 2001) and links between parental

history and the myopia development in children (Gwiazda et al. 1993; Yap et al.

1993; Zadnik et al. 1994; Goss and Jackson 1996; Edwards 1998; Pacella et al. 1999;

Hammond et al. 200 1 ; Lee et al. 200 1). Gwiazda et al. reported a myopia prevalence

of 43% in children with two myopic parents, 22.5% when only one parent is myopic

and 8% with neither parent myopic (Gwiazda et al. 1993). Zadnik and co-workers

found that even before juvenile myopia onset, children of myopic parents have longer

eyes (Zadnik et al. 1994).

On the other hand numerous investigators have noted an association between near

work activities and myopia (Parssinen and Lyyra 1993; Goss and Rainey 1998; Tan et

al. 2000). A number of reports of a high prevalence of myopia among student

populations comes from Norway (Midelfart et al. 1992; Kinge and Midelfart 1999;

Kinge et al. 1999; Kinge et al. 2000), indicating that intensive near work may initiate

or lead to myopia progression in young adults. Other examples reported to show high

myopia prevalence and progression related to intense near work are Orthodox Jewish

male students (Zylbermann et al. 1993), and law students (Zadnik and Mutti 1987;

Loman et al. 2002).

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Further support for environmental factors playing a role in myopia comes from

studies of some occupational groups. Adams and McBrien reported a prevalence of

refractive errors in a population of clinical microscopists of 71% with 49% reporting

onset or progression of myopia after entry into the profession (Adams and McBrien

1992). The incidence of myopia progression in a follow up study in this occupational

group was 45% (McBrien and Adams 1997).

1.7.2 Myopia etiology

The etiology of myopia is not fully understood, however many theories have been

proposed. The biological theory explains the distribution of refractions with a natural

variation (Gaussian distribution) between individuals in the growth of the eye. This

early theory by Steiger implies that myopia is not preventable (Steiger 19 13).

Use-abuse theories state that intensive near work, such as reading, cause myopia due

to tensing of muscles in or around the eye, which over a period of time makes the eye

permanently more myopic (Angle and Wissmann 1980). Angle and Wissmann

showed an association between education and the tendency of myopia appearance and

progression among 12 to 17 year olds, concluding that at least some of the variance of

myopia can be explained by the use-abuse theory (Angle and Wissmann 1978; Angle

and Wissmann 1980). Van Alphen has supported the theory showing a potential

significance of ciliary muscle tone on choroidal tension and scleral stretch following

inflation of in vitro eyes (van Alphen 1986).

The hypothesis suggesting that emmetropisation is a vision-dependent phenomenon

(Rabin et al. 198 1) has shifted researchers interest towards retina1 image quality rather

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than tensing of muscles in or around the eye as possible etiological risk factor of

myopia. Goss and Wickham proposed that retinal image-mediated ocular growth is a

possible etiological factor in juvenile-onset myopia (Goss and Wickham 1995). The

hypothesis is consistent with animal models (Wallman et al. 198 1 ; Raviola and

Wiesel 1985; Schaeffel et al. 1988; Wildsoet 1997) and is supported by numerous

human infant refraction data taken early in life (Howland et al. 1978; Ingram and Barr

1979; Atkinson et al. 1980; Howland and Sayles 1984; Ehrlich et al. 1997)

1.7.3 Emmetropisation

Emmetropisation is the process by which the normally distributed refractive error of

infants changes towards a narrower distribution, showing a marked peak about

emmetropia. The proposal finds support from several studies that have reported of

high incidence of astigmatism within the first months after birth followed by a

significant decrease of astigmatism within year one to six (Howland et al. 1978;

Ingram and Barr 1979; Atkinson et al. 1980; Howland and Sayles 1984; Ehrlich et al.

1997). Gwiazda et al. conducted a study of noncycloplegic refractions of 1000

children between the age of 0 to 6 years showing a large reduction in the amount of

cylindrical error accompanied by an astigmatic change from against-the-rule

astigmatism before age 4.5 years to with-the-rule astigmatism thereafter (Gwiazda et

al. 1984).

Hyperopia (Mayer et al. 2001; Pennie et al. 2001) and myopia (Ehrlich et al. 1995)

have also been found to decline significantly with increasing age. Ehrlich et al.

showed significant emmetropisation of the mean spherical equivalent towards low

hyperopia in a group of infant myopes from 8.5 to 38.5 months of age and

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furthermore found a significant decline for both with-the-rule astigmatism and

against-the-rule astigmatism (Ehrlich et al. 1995).

The most compelling evidence for a process of active emmetropisation comes from

animal studies that have shown compensatory eye growth in response to focusing

errors imposed by lenses (Schaeffel et al. 1988; Troilo and Wallman 1991; Norton

and Siegwart 1995; Wildsoet 1997). Schaeffel et al. raised chickens with defocusing

lenses of different power in front of their eyes (Schaeffel et al. 1988). A consistent

shift in the chickens' refractive state in a direction to compensate for the lens was

found. Schaeffel et al. discuss the findings in the context of a closed-loop feedback

system acting to regulate eye growth (Schaeffel et al. 1988).

Rabin et al. based their suggestion of emmetropisation being a visually dependent

phenomenon, on a retrospective analysis of refractive error among humans subjected

to various ocular anomalies which disrupt vision (Rabin et al. 198 1). A link between

increasing incidence of ametropia and visual anomalies such as ptosis or congenital

aphacic eyes was identified. In human infants, a degradation of retina1 image quality

due to various pathological conditions has been shown to result in high myopia (Robb

1977; O'Leary and Millodot 1979; Hoyt et al. 1981; Nathan et al. 1985; Miller-Meeks

et al. 1990). Several authors have reported an association between congenital ptosis

and increased presence of astigmatism, myopia, or amblyopia (O'Leary and Millodot

1979; Ugurbas and Zilelioglu 1999; Gusek-Schneider and Martus 2000). Temporal

and manifest changes in spectacle or contact lens correction after ptosis surgery has

been found in adults (Cadera et al. 1992; Holck et al. 1998; Brown et al. 1999).

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1.7.4 Near work related myopia studies in humans

The literature of myopia studies in humans is immense. Within this thesis, just near

work related studies that might be of importance in association with cornea1 distortion

during reading are summarized. Since prolonged near work is thought to be an

environmental risk factor associated with myopia development, one possibility is

related to the accuracy of accommodation during near viewing. A typical

accommodation stimulus-response curve (ASRC) shows a lead of accommodation for

far objects, a crossing point possibly close to the eyes’ tonic level, and

accommodative lag at the near point (Morgan 1944).

A widely discussed hypothesis is that accommodative lag during near work results in

a blurred retinal image (hyperopic defocus), which in turn triggers eye growth. A

large number of studies have investigated whether accommodative stimulus/response

behaviour differs with refractive error (McBrien and Millodot 1986; Rosenfield and

Gilmartin 1988; Gwiazda et al. 1993; Gwiazda et al. 1995; Abbott et al. 1998).

Despite considerable methodological differences, reduced accommodation stimulus

responses in myopes have been reported in many studies (i.e. lags of accommodation

tend to be higher in myopes) (McBrien and Millodot 1986; Rosenfield and Gilmartin

1988; Gwiazda et al. 1993; Gwiazda et al. 1995). Abbott et al. observed a greater lag

of accommodation in progressing myopes compared to those whose myopia was

stable (Abbott et al. 1998). Conflicting reports however have found that an increased

lag of accommodation accompanies rather than precedes the development of myopia

(Rosenfield et al. 2002).

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A related research area, which has been extensively investigated, is near work induced

transient myopia (NITM), a short-term myopic shift of the far point immediately

following a sustained near visual task (Ong and Ciuffieda 1995). NITM is thought to

be the effect of a prolonged accommodation response time to a far target following

extending near viewing tasks, but has also been found over a range of accommodative

stimulus levels (Owens and Wolf-Kelly 1987) and for the near point of

accommodation value (Fisher et al. 1987). Some researchers have attributed this

refractive shift to an actual change in tonic accommodation (Ehrlich 1987; Owens and

Wolf-Kelly 1987). NITM has shown a dependency of ethnicity (Wolffsohn et al.

2003) and time of the visual near task (Ehrlich 1987; Rosenfield et al. 1992) on decay

characteristics and is manifest during the progressive phase of myopia development

(Vera-Diaz et al. 2002). Since myopes show particularly striking near work after-

effects, it has been speculated that NITM may cause or be a precursor to permanent

myopia or myopic progression (Ciuffieda and Wallis 1998).

Some researchers hypothesized that uncorrected astigmatism may play a role in the

development of school-age myopia (Fulton et al. 1982; Grosvenor and Goss 1998;

Gwiazda et al. 2000) and against-the rule astigmatism has been associated with faster

myopic progression rates in children (Hirsch 1964; Grosvenor et al. 1987; Gwiazda et

al. 1993). Although there is general agreement that axial elongation is the most

obvious cause of school-age myopia progression, myopes have steeper corneas (Scott

and Grosvenor 1993; Carney et al. 1997; Goss et al. 1997) and myopia progression

has been shown to correlate with steepening of the principal meridian nearest to

vertical (Goss and Erickson 1987) (i.e. with-the-rule cornea1 astigmatism).

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1.7.5 Attempts to prevent myopia progression

Methods that have been used to prevent myopia progression have shown limited

success (Grosvenor 1989). Theories that sustained accommodation promotes myopia

progression in humans have led to the use of bifocal or progressive spectacle lenses in

children to reduce the progression of childhood myopia. Earlier clinical trials with

bifocal lenses have been inconclusive (Goss 1982). More recently, Edwards and co-

workers have found no difference in the increase in myopia between a matched

treatment group wearing progressive lenses and control group (Edwards et al. 2002).

However there are several studies that have noted a link between esophoria and

reduced myopia progression following bifocal lens wear in children (Oakley and

Young 1975; Goss 1986; Fulk et al. 2000; Brown et al. 2002).

Clinical procedures involving the treatment of myopia with cycloplegia such as

atropine, in combination with bifocal lenses appear to be effective in preventing

myopia progression (Bedrossian 1979; McBrien et al. 1993; Chou et al. 1997; Lin et

al. 1999). However myopia progresses when atropine is discontinued and problems of

the treatment comprise various side effects and patients’ compliance (Woo and

Wilson 1990).

There have been a number of studies reporting that rigid contact lenses may slow the

progression of myopia in children (Stone 1976; Grosvenor et al. 1987; Grosvenor et

al. 1989; Khoo et al. 1999). Stone performed the first major clinical study in which a

significant annual reduction of myopia progression in the contact lens wearers

(0.17 D) as compared with the control group (0.38 D) was found (Stone and Powell-

Cullingford 1974). Cornea1 flattening accounted for only about half of the reduction in

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myopia. Therefore it was concluded that rigid lenses might have an effect on the axial

growth of the eye. A clinical trial, the contact lens and myopia progression (CLAMP)

study, is under way to further clarify the effect of rigid gas-permeable contact lenses

on myopia progression in children (Walline et al. 2001).

In summary, based on numerous studies in the field of myopia prevalence and

progression, the risk factors for myopia development can be broadly divided into a

combination of both genetic and environmental factors. The most widely accepted

theory regarding the etiology of myopia suggests that retinal image quality is an

etiological risk factor in juvenile-onset myopia. The hypothesis is supported by

various animal studies, the process of emmetropisation observed early in life and

pathological conditions that degrade retinal image quality that have been shown to

disrupt infant emmetropisation.

An increased lag of accommodation during near work, which would result in a blurred

retinal image, has been suggested to trigger eye growth. Near work induced transient

myopia (NITM) has been speculated to be a precursor to manifest myopia since it has

been shown to accompany the progression of myopia, while against-the-rule

astigmatism has been associated with faster myopia progression rates. Bifocal lenses

in combination with cycloplegia are effective in preventing the progression of myopia

during the therapy, while rigid contact lenses have shown to slow down myopia

progression in children and have been speculated to have an effect on axial length.

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1.8 RATIONALE

Videokeratoscopes provide a sophisticated description of the corneal shape. Accuracy

and repeatability of the instruments have been investigated and show that several

sources of error impose limits to corneal topography measurement. There have been

numerous studies concerning the stability of corneal shape and lid force induced

corneal distortions following reading. One of the major environmental risk factors for

myopia development is reading and near work. However the cornea is not thought to

play a major role in refractive error development, maybe because too little is known

about corneal stability during near work and the optical effects of corneal distortions

on visual performance of the eye. In a series of experiments described in this thesis,

several of these issues were addressed, and potential interactions between corneal

optics and refractive error are discussed.

One of the sources of error in videokeratoscope measurement is the stability of the

eye being measured. Chapter 2 describes a method which was developed to minimize

the effect of ocular microfluctuations during videokeratoscopy to improve the

qualitative and quantitative analysis of corneal topography. A technique was

developed to measure tilt, displacement, and cyclotorsion in multiple

videokeratographs from the same cornea. This information was used to reposition

each videokeratograph according to the average position of a sample of multiple

measurements. The method provided an improvement to the precision performance of

videokeratoscopy in multiple measurements of corneal topography.

One factor that could have an effect on the corneal shape during near work is

accommodation. Previous studies regarding the effect of accommodation on corneal

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curvature on normal corneas have been restricted by the available technology.

Chapter 3 reports a study that was undertaken to determine if there are significant

changes in corneal topography during accommodation in normal corneas and corneas

that are pathologically thinner due to keratoconus. A videokeratoscope was modified

to present an accommodation stimulus that was coaxial with the instrument’s

measurement axis. The effects of ocular micromovements on multiple topography

maps were minimized using the technique described in Chapter 2. Using this

experimental set up, the accuracy of corneal topography measurement should

substantially improve compared with previous studies that have used keratometers or

photokeratoscopes to measure corneal topography during accommodation.

Monocular diplopia has been linked to corneal distortion following near work in

various studies, however the optical cause of the distortions have never been analysed

in detail. To investigate the effects of eyelid pressure on corneal shape and corneal

aberrations during reading, a detailed objective analysis using traditional sphero-

cylinder and corneal higher order aberrations was performed in Chapter 4. Twenty

young subjects with normal ocular health were recruited for the study. The experiment

was conducted early in the morning, with subjects instructed not to perform any

prolonged reading prior to the experiment. Significant changes in corneal root-mean-

square error, overall corneal refractive power, and corneal astigmatism were found

after reading.

Since these findings may have important implications for the relationship between

reading and the development of refractive errors, the question arises whether the

optical characteristics of the cornea following reading differ between different

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refractive error groups. In the experiment described in Chapter 5, cornea1 distortions

following reading were studied in a group of young progressing myopes and a group

of young stable emmetropes.

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CHAPTER 2

Ocular Microfluctuations and

Video keratoscopy

2.1 INTRODUCTION

The measurement of subtle changes in corneal topography requires the highest

possible instrument accuracy and also requires software analysis tools that can detect

and highlight those subtle changes with high reliability. The work described in this

chapter addresses the issue of the statistical significance of change in corneal

topography and describes methods to improve the estimation of topography change.

Videokeratoscopes provide sophisticated qualitative and quantitative descriptions of

the cornea. While currently available videokeratoscopes incorporate a number of

important improvements compared to older instruments (Dave 1998), there are still

significant differences between instruments in terms of precision (Binder 1995;

Jeandervin and Barr 1998; Moura et al. 1998; Tang et al. 2000). For all

videokeratoscopes, the precision with inanimate test surfaces (Potvin et al. 1995;

Greivenkamp et al. 1996; Dave et al. 1998; Priest and Munger 1998; Hilmantel et al.

1999; Tang et al. 2000) is expected to be higher than the performance on real eyes

(Wilson et al. 1992; Kanpolat et al. 1997; Jeandervin and Barr 1998; Hough and

Edwards 1999), since natural dynamics of the eye and anterior ocular surface are

likely to decrease the instruments’ precision. Studies on real eyes have found that the

tear layer (Cronje-Dunn and Harris 1996; Licznerski 1998; Thibos and Hong 1999;

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Nemeth et al. 2001), and lid forces (Wilson et al. 1982; Ford et al. 1997; Lieberman

and Grierson 2000) can contribute to increased topographical variability. It has also

been shown that poor fixation is a potential source of measurement variability (Hubbe

and Foulks 1994; Mandell 1996; Keller et al. 1997; Douthwaite and Pardhan 1998).

Errors may occur in videokeratoscopy as a result of variations in the measurement

axis. Chan and Mandell showed that decentration of the corneal apex can produce

significant videokeratograph errors when using standard alignment, rather than

alignment with the apex (Chan and Mandell 1997). Eccentric subject fixation

produces changes such as corneal asymmetry (Douthwaite and Pardhan 1998) or

irregular astigmatism similar to that seen in cases of keratoconus (Silverman 1994;

Keller et al. 1997). Hubbe and Foulks also observed these pseudokeratoconus patterns

with fixation deviations of less than 5 degrees in some patients with normal corneas

(Hubbe and Foulks 1994).

A normal fixation pattern is characterised by miniature eye movements such as micro-

saccades, drifts, and tremor (Riggs and Ratliff 195 1; Steinman et al. 1973 (28)). These

microfluctuations are typically 5 to 7 minutes of arc in magnitude (Steinman et al.

1973 (28); Tulunay-Keesey 1976 (29); Dell'Osso and Dardoff 1983 (30); Ferman et

al. 1987 (3 1)). Dell'Osso and Dardoff reported that they can range from 1 to 25

minutes of arc (Dell'Osso and Dardoff 1983 (30)), and the direction of eye movements

varies considerably from subject to subject (Steinman et al. 1973(28)). When visual

acuity is diminished through factors such as amblyopia or uncorrected refractive

errors, these microfluctuations are thought to increase in magnitude (Srebro 1983;

Westall and Aslin 1984). More recently Jampel and Shi have measured retina1

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micromovements of a mean of about 3 minutes of arc, ranging from less than 1 to 24

minutes of arc within 33.3 msec (Jampel and Shi 2000 (34)). A succession of

micromovements caused the visual line to trace a zigzag pathway across the foveola.

Difference maps are useful to investigate changes in corneal topography. Changes can

occur as a consequence of contact lens wear (e.g. orthokeratology), refractive surgery,

or pathological changes. One of the problems associated with interpreting difference

maps is the uncertainty regarding the significance of changes apparent in the

difference map. This problem can be largely overcome by averaging multiple

videokeratographs taken for both the first and second measurement conditions. Such

an approach requires interpolation of the topography data into a common coordinate

system for all points in all of the maps. This allows not only an average

videokeratograph map to be derived for each condition, but also a standard deviation

to be calculated for all points in the map (Buehren et al. 2001).

One of the factors that are likely to make a major contribution to the standard

deviation (variance) associated with multiple videokeratoscope measurements is the

small variation in fixation due to natural microfluctuations in eye position. This

results in the measurement points from two videokeratographs being captured at

slightly different point locations of the cornea relative to the videokeratoscope axis

(VK axis). Thus each measurement is slightly displaced and the corresponding

corneal locations are no longer at the same position relative to the instrument axis.

This displacement decreases precision of repeated videokeratographs and will also

result in errors when two videokeratographs are subtracted from each other (i.e.

difference map).

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In this study, a technique was developed to use videokeratoscope data to minimise

lateral shifts, tilts and cyclo-deviations caused by fixation errors and cyclo-rotations.

We investigated the apparent amount of these deviations in the data from ten subjects

and calculated the effects of these errors on difference maps and Zernike polynomials

derived from videokeratographs.

2.2 METHODS

The Keratron videokeratoscope, based upon the Placido disk principle, was used for

all corneal topography measurements. Across a range of inanimate test surfaces, the

Keratron has been shown to have an accuracy between < 0.25 and 1 micron centrally,

about 3 to 5 microns at 3.5 mm from centre, and precision of 5 f 1 micron of standard

error (Tripoli et al. 1995; Tang et al. 2000). Before the study, the instrument

calibration was checked according to the manufacturer’s instructions. Twenty

measurements were taken from each subject. Cornea1 height data from the Keratron

software and the corresponding radial data files were exported and then changed into

Cartesian coordinates (the Keratron samples the data at 256 equally spaced semi-

meridians). The videokeratograph that showed the smallest available number of

complete Placido rings, within a sample of twenty videokeratographs captured from

one subject, was used for analysis of all twenty videokeratographs, omitting the

incomplete ring data at the edges of the map. In this way the same corneal diameter

was used for each of the maps during the correlation procedure.

The technique of minimizing fixation errors is based on a number of assumptions that

can be made when taking multiple measurements of the same cornea within a short

time period. If we assume that corneal topography does not change during the

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measurement period, then within the limitations of the videokeratoscope's precision,

there is only one unique shape for an individual cornea. By extracting some of these

unique characteristics, such as tilt, shift, and cylinder axis, it should be possible to

reposition a single measurement with respect to the average of multiple

measurements of the same cornea. This should not only improve the interpretation of

difference maps but also increase the precision associated with multiple

measurements. The principle of the method we describe here should be applicable to

any cornea1 height data derived from any type of videokeratoscope.

2.2.1 Regression plane - to remove tilts

A two-dimensional regression plane, fitted into a set of three-dimensional data points,

gives a measure of the tilt of this set of data points with respect to the coordinate

system (Figure 2-1). We collect the discrete videokeratoscope height data C(x,, y,) ,

d = 1,. . . , D , into a column vector C, and form a linear regression C=AP, where A is

the column vector of the parameters, P=[X Y I ] is a (D x 3) matrix of the plane, and

D denotes the number of sample points. We use the least squares (LS) method to

estimate the parameters of the fitted plane a= (PTP)-'PTC, and calculate the best

plane fit using eP=h.

The angle of tilt shown by the plane relative to the coordinate system (i.e. VK axis)

represents the sum of the inherent surface tilt due to the surface asymmetry and the

additional tilt induced by fixation errors. The above procedure is applied to all

multiple measurements of the same cornea and an average tilt, eP(+ of the plane is

calculated. Then, every map is rotated into this average tilt. Since the timing of

multiple videokeratoscope measurements is random, there is no way of knowing the

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true tilt of the corneal surface. However, the greater the number of multiple

measurements, the more likely it becomes that the average tilt is accurate, because

less bias is present.

2.2.2 Sphere apex - to remove x, y, z shifts

In the next step, spheres are fitted to each of the 20 tilt adjusted maps using the LS

method since the corneal apices have moved away from the VK axis following tilt

adjustment. The apices of the fitted spheres are assumed to find corresponding

locations on each surface since there are no more tilts between maps and the sphere

fit is unaffected by potentially inherent cyclo-deviations between measurements.

Now, the apices of the spheres are shifted to the centre of the coordinate system (i.e.

VK axis) as they are assumed to represent the same location on the cornea. These

shifts have no effect on the angles of the regression planes (tilts), which are now also

the same in each map. Hence, the maps are now correlated with respect to map tilts

and surface shifts along the x-, y-, and z-axis. Since the cornea is not perfectly

rotationally symmetric, it can’t be assumed that the new corneal apices are equivalent

to the apices found by the spheres. Hence the corneal apices are yet not shifted into

the mean corneal apex (i.e. VK axis). Subtracting the average amount of shifts that

were applied to a sample of maps from each individual shift of a map achieves this

aim. Now, the sum of all remaining shifts shows the smallest possible amount

relatively to the VK axis. Hence no more bias from the sphere fit is apparent. The

locations of the new corneal apices are now at the mean corneal apex (i.e. VK axis).

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-4 -4 Y X

Figure 2-1 : 2-D linear regression plane fit to a set of raw data points of cornea1 height

measurement. Cornea1 height data is shown in Placido rings. Scale for x, y, and z is in mm.

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2.2.3 Best-fit sphero-cylinder - to remove cyclo-deviations

In general, cyclo-deviations are associated with cyclophoria. Wick and Ryan

measured cyclophoria on 100 consecutive non-strabismic patients and found a mean

value of 0.78 degree (Wick and Ryan 1982 (37)). Additional variability is likely to

come from differences in head positioning in the videokeratoscope’s headrest. Ferman

repeatedly measured ocular torsion in four subjects and found deviations of

approximately 1.5 to 5 degrees in static primary positions while the subjects viewed a

central target (Ferman et al. 1987 (3 1)).

Astigmatic corneas will show toric (saddle) shape in the difference map, if a cyclo-

deviation is present between two videokeratographs. To find the best-fit sphero-

cylinder to the corneal surface, the technique proposed by Maloney was applied

(Maloney et al. 1993). This method was used to determinate the orientation of corneal

astigmatism in each videokeratograph (i.e. axis of astigmatism). Then an average

value of the corneal astigmatic axis for the sample of multiple measurements was

calculated and all maps rotated accordingly around the z-axis.

In Figure 2-2 (top) a difference map is shown from two videokeratographs of subject

4. The map indicates asymmetric infero-temporal changes (2-D plot) reaching slightly

more than 5 microns at the edge of a 6 mm zone (profile plot). After the two

videokeratographs were tilt-reduced and apex matched (centre), a toric (saddle) shape

difference comes to light (2-D plot), leaving infero-temporal and supero-nasal

changes of approximately 3 microns in magnitude (profile plot). The RMSE is slightly

decreased from 1.25 microns to 1.02 microns. Figure 2-2 (bottom) shows the result

when the full procedure is applied (i.e. tilt reduced, apex matched, and cyclo-rotation

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reduced). The RMSE decreased by 45.4 % from the original 1.25 microns to 0.68

microns. The maximum value in the difference map is just slightly above 2 microns

and most data points lie within a difference off 1 micron (profile plot). The 2-D plot

shows a relatively symmetric increase in differences from the centre to the edge of the

map. These differences are now approaching the level of the instrument’s precision

performance for inanimate test surfaces (Tripoli et al. 1996; Tang et al. 2000).

2.2.4 Limitations

The procedure for minimization of fixation errors has been derived with certain

assumptions that ultimately limit the accuracy of the outcomes. Firstly, the technique

does not take into account that, concomitant with slight gaze changes, the area of

measurement also slightly changes. This means that at the edges of the maps, along

the direction of the deviation, slightly more or less data will be captured in the

videokeratograph. No matter which diameter is chosen to correlate a set of multiple

measurements, these data points at the edge of the map represent slightly different

areas between maps. However since the gaze changes and thus the difference between

cornea1 areas are very small (approximately -0.4 %), this problem should have little

effect on the methods’ accuracy. Secondly, the technique cannot exceed the

measurement precision of the instrument itself. This means that measurement errors

other than caused by ocular micromovements (e.g. instrument errors, tear layer

variability, or lid force effects) decrease the accuracy of the regression plane, the

sphere, as well as the cyclo-rotation procedure, in finding the same characteristic from

each videokeratograph.

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Figure 2-2: Difference map (top) of two successively captured videokeratographs of subject 4

(data untreated). The same difference map after tilt reduction and apex matching (centre) and

additional cyclo-deviation correction (bottom) was applied.

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Thirdly, the effectiveness of the procedure in fmding the average spatial position of

the cornea is dependent on the number of measurements. In this study we have used

20 measurements as a basis for the mean, however it is obvious that the larger the

sample of measurements, the more reliable the average becomes. Finally, for a

perfectly rotationally symmetric cornea, the technique of fmding the axis of corneal

astigmatism would not apply. However such a cornea would be rare and small

amounts of corneal astigmatism would cause relatively small cyclo-torsional precision

errors.

2.2.5 Protocol

Ten subjects took part in this study. Mean age was 29 years ranging from 22 to 43

years. None of the subjects had significant corneal disease. Three subjects were

emmetropes, two were myopes, and five had myopic astigmatism.

Videokeratographs of all 10 subjects were captured with the instruction to the subjects

to fixate the videokeratoscope target and just prior to image capture, to blink and then

open the eyes wide (i.e. normal image capture procedure). For the 20 measurements

taken from each subject, the root mean square error (RMSE) of corneal height

difference maps between each single videokeratograph and the averaged

videokeratograph of the 20 measurements was compared before and after fixation

error minimization. Cornea1 height data was fitted with the first 11 Zernike

polynomials according to the Zernike convention of No11 (No11 1976). This is

equivalent to taking terms up to the third radial and azimuthal order plus the fourth

order radial term (Thibos et al. 2000). After the data was corrected for fixation errors,

the procedure was repeated, fitting the first 11 Zernike terms. The mean and standard

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deviation of the two terms was compared for the normal videokeratographs and the

videokeratographs corrected for fixation errors. The analysis for both RMSE

calculation and Zernike polynomial fit was performed in a 5 mm pupil area for all

subjects’ data.

2.3 RESULTS

Across the group, microfluctuations derived from the repositioned videokeratographs

showed an average value of 5.8 minutes of arc f 2.2 (SD), which was in general

agreement with the values reported by studies of these eye movements (Table 2-1).

This corresponds to an average apex shift from the mean of 10 microns f 3.5 SD. This

apex shift was calculated by deriving the hypotenuse of x-shifts and y-shifts, which

were effectively applied to a single videokeratograph after sphere bias correction. To

compare this value with the angles of miniature eye movements reported in the

literature (5 to 7 minutes of arc), it has to be doubled (i.e. 20 microns f 7 SD) and

then the angle between this distance and the centre of eye rotation has to be

calculated. Doubling is necessary because the distance of a single apex from the

average apex represents just half the distance of an equivalent eye movement from a

start point to an end point. Gullstrands’ eye-model was used to determinate the

distance between cornea1 apex and the centre of eye rotation. Subject 2 showed the

largest eye movement of the group with 23 min of arc (apex displacement

82 microns). Cyclo-deviations were estimated to average 2.4 degrees f 1.1 (SD)

between maps, with a maximum value of 4.6 degrees shown by subject 6.

The RMSE shows an average decrease of 24.6% after minimization of fixation errors

ranging from 14.3 % to 43.2 %. In Figure 2-3 the average decrease of the RMSE in

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percentage for each of the ten subjects are shown. The absolute values appear to be

small in magnitude (all averages less than 1 micron) however this value has to be

analysed with caution. Videokeratoscopes capture several thousand data points on the

cornea, which are unequally distributed within the measurement area (i.e. more data

points are close to the centre). Thus, the amount of the RMSE for the entire map is

biased to the smaller measurement errors occurring in more central areas.

As expected, the standard deviation of the horizontal and vertical prism components

derived from the Zernike polynomial expansion decreased considerably following

minimization of fixation errors. There was an 82.3 % decrease of the 2,' (p, (3)

1 vertical prism term and 73.8 % decrease of 2, (p, 0) horizontal prism term (Figure 2-

4). Also the standard deviation of zi2 (p, primary astigmatism (45 degrees)

decreased substantially by 43.8 %. Since the oblique astigmatism term 2,' (p, is

likely to be the smaller primary astigmatism component for most people, small

cyclotorsional corrections of the cornea are expected to show larger effects on the

standard deviation of this term compared with 2: (p, primary astigmatism

(90 degrees). The remaining Zernike terms showed little decrease of standard

deviations.

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Ocular Microfluctuations

Average

eye rotation

Average

apex movement

Average

cyclo-deviation

Maximum

eye rotation

Maximum

apex movement

Maximum

cyclo-deviation

This study based on

corneal topography

5.8 min of arc

f 2 (SD)

20 pm f 7 pm

2.4"

f 1.1 (SD)

23 min of arc

82 pm

4.6"

Other studies based on

eye movements

(28 - 31,34,37)

6 min of arc (28,30)

5 min of arc (29)

7 min of arc (3 1)

3 min of arc in

33.3 msec intervals (34)

Range 1.5" to 5" (37)

f 1.2 to f 2.07 (SD)

Range

1-25 min of arc (30)

1-24 min of arc in

33.3 msec intervals (34)

5" (37)

Table 2-1: Comparison of miniature eye movements between measurements based on corneal

topography and conventional measurement techniques.

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2.4 DISCUSSION

When we compare the eye movements calculated in this study with the values

reported for ocular microfluctuations, the results agree surprisingly well. This

indicates that the technique we have developed to reposition videokeratographs is

capable of detecting the topographical effects of these small eye movements. We have

not analysed the directions of eye movements because the 20 separately captured

videokeratographs did not measure eye movements at specific time intervals. The

videokeratographs were captured at irregular intervals and therefore represent a

random sample of eye movements that have occurred within a longer time period.

The average value for cyclo-deviations lies within the range of deviations reported by

Ferman (Ferman et al. 1987 (3 1)). Our mean value is calculated from 200

measurements that were captured from 10 subjects. Ferman described the range of 88

displacements taken from both eyes of 4 subjects. The maximum cyclo-deviation

measured in this study was 4.6 degrees, which is close to the 5 degrees of Ferman’s

study. These cyclo-deviations contributed significantly to increased variability

between measurements.

Following minimization of the effect of eye movements, the RMSE clearly showed a

decrease of variability between measurements with an average decrease of 24.6 %

across the group. This increase in precision will allow better analysis of the quality of

real changes between measurements, since the color-coding of difference maps is less

biased by differences due to eye movements (e.g. tilts). However, there was still a

significant amount of remaining variability between measurements even after fixation

error minimization. These differences are presumably due to tear layer instability and

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lid force effects. Variability was also evident in overall curvature (i.e. steeper or

flatter), which probably results from small defocus errors (i.e. instrument to cornea

distance). More sophisticated range finder systems might be able to decrease these

measurement errors resulting from defocus.

Fitting the surface with the Zernike polynomial expansion showed that some terms are

particularly vulnerable to eye movements. The variability of prism terms as well as

astigmatism components could be decreased considerably following minimization of

fixation errors. This will aid procedures that aim to correct refractive errors, based on

corneal or total wavefront information. However, it should be emphasized that the

methodology does not improve the instruments accuracy. It only improves the

instruments precision performance leading to a more reliable estimate of change. For

example in the topographical diagnosis and monitoring of keratoconus, small changes

over time could be measured with greater sensitivity and certainty. Analyses such as

corneal height difference maps from multiple measurements, or changes in Zernike

polynomials between visits could also be evaluated with higher precision.

This study revealed that the precision performance of videokeratoscopes for

measurements of corneal topography could be improved. The RMSE analysis, the

Zernike analysis, and the changes shown in the difference maps, indicate that the

algorithm developed in this study helps to decrease the standard deviation of multiple

measurements from corneal topography.

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Chapter 3

CHAPTER 3

Cornea1 Topography and Accommodation

3.1 INTRODUCTION

Changes in corneal aberrations associated with near work could not only be due to

corneal distortions caused by eyelid forces (Mandell 1966; Knoll 1975; Bowman et

al. 1978; Carney et al. 198 1 ; Goss and Criswell 1992; Kommerell 1993; Ford et al.

1997; Campbell 1998; Golnik and Eggenberger 2001) but also due to changes in

corneal topography caused by accommodation. The ocular forces generated during

accommodation and convergence can be substantial. It is feasible that forces arising

during accommodation could lead to changes in corneal topography given the

proximity of the ciliary muscle to the limbus and the forces exerted onto the eye

globe by the extraocular muscles during convergence.

The optical characteristics of the human eye change during accommodation. The term

accommodation implies a change in the spherical refractive power of the eye.

Changes in astigmatism with accommodation are known as near, dynamic, or

accidental astigmatism (O'Brien and Bannon 1947; Fletcher 1954; Rabbetts 1972;

Brzezinski 1982; Millodot and Thibault 1985; Ukai and Ichihashi 1991; Byakuno et

al. 1994). It is thought that near astigmatism originates from meridional changes of

the crystalline lens during accommodation. Various studies have shown that the

unaccommodated eye normally has positive spherical aberration, which changes to

become negative spherical aberration as the level of accommodation increases

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(Koomen et al. 1949; Ivanoff 1956; Jenkins 1963; Lu et al. 1993; Atchison et al.

1995; Collins et al. 1995). There is some evidence to suggest that asymmetric

aberrations of the eye (eg. coma) may also change in type and magnitude as a

function of accommodation (Lu et al. 1993; Atchison et al. 1995; Collins et al. 1995).

It is reasonable to assume that changes in crystalline lens features such as shape,

position or refractive index distribution are the most likely causes of these changes in

monochromatic aberrations associated with accommodation. However as the cornea

is the major refracting surface of the eye, small changes in its topography due to the

forces associated with accommodation could contribute to changes in the optics of the

eye.

Previous studies of the effect of accommodation on the corneal topography of normal

eyes have been limited by the available technology. Studies of the more central

regions of the cornea with keratometers (Fairmaid 1959; Lopping and Weale 1965)

and photokeratoscopes (Mandell and St Helen 1968), have produced contradictory

findings. Fairmaid reported meridional changes in curvature with convergence but

found no corneal shape changes in the accommodating but non-verging eye (Fairmaid

1959). Lopping and Weale also reported that significant changes occur in corneal

topography during ocular convergence (Lopping and Weale 1965). However Mandell

and St Helen did not find any changes in topography with either convergence or

accommodation (Mandell and St Helen 1968). More recently, using a modified

keratometer, Pierscionek et al. found changes in topography with accommodation in

at least one of the principal meridians for most of the subjects tested (Pierscionek et

al. 2001).

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Chapter 3

The hypothesis that we investigated in this study is that the forces exerted upon the

cornea during accommodation are sufficient to alter the shape of the human cornea.

We measured changes in topography of normal corneas and corneas that were

pathologically thinner due to keratoconus. We reasoned that corneas weakened

through keratoconus might be more susceptible to these potential changes.

Any changes that occur in corneal shape associated with accommodation were

expected to be relatively small, compared to the overall topography. Therefore the

method we employed for the detection of these changes must have the highest

possible accuracy and precision and be statistically verifiable.

3.2 METHODS

The Keratron videokeratoscope was used for all corneal topography measurements.

For normal eyes, the instrument’s standard deviation for the central 4 mm diameter

has shown to be in the order o f f 0.25 D of refractive power ( f 2 microns) (Buehren

et al. 2001). We modified the Keratron to measure the topography of the anterior

corneal surface while accommodation demand was varied. The modification allowed

the accommodation stimulus to be induced coaxially with the instrument’s

measurement axis (Figure 3-1). The amount of accommodation could be varied while

the subject directly fixated the target inside the cone of the instrument. Previous

studies used one or more semi-transparent mirrors in order to align a peripherally

located target with the instrument axis. However great care needs to be taken to

avoid the possibility of alignment errors.

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Our modification involved the replacement of the standard light emitting diode (LED)

fixation target within the Keratron with a telescope focussing system. The new

fixation target was a black cross hair on a diffuse white background at the end of a

perspex rod. The rod is able to slide within a hollow metal tube, which fits into the

position of the original LED fixation target. The accommodation control system

contained two lenses of appropriate power to allow the fixation cross to be focussed

with a precisely defined accommodation demand. The operator adjusted the required

accommodation demand by moving of the perspex rod within the tube according to

the calibrated dioptric scale etched onto the side of the rod.

Calibration of the rod was checked using an emmetropic subject and cycloplegia was

induced to prevent the subject from accommodating. Lenses of known power were

inserted at the spectacle plane of the observer while the perspex rod was moved until

the black cross was in sharp focus. Vertex distance was taken into account when

calculating the appropriate accommodation stimulus to lens power relationship.

Results showed that the accommodation demand 'error' was within f 0.50 D of the

amount of accommodation 'set' on the fixation tube scale (Figure 3-2). Given the

levels of accommodation tested in the study (0 D, 4 D and 9 D) we considered this

degree of error to be acceptable.

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Chapter 3

k I I I I

A <AT. I I I I I I I I

1 I

Figure 3-1: Telescope system consisting of a cross-hair target and a two-lens system

projecting the virtual target “2” at distances between -3 D and +9 D of accommodation

demand, coaxially with the videokeratoscope axis.

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Chapter 3

For the main experiment, ten young subjects were recruited to fulfil the following

criteria. Six were emmetropic to mildly myopic subjects with normal corneas and

four subjects had mild to moderate degrees of keratoconus. The University Human

Research Ethics Committee approved the study and informed consent was obtained

for all subjects. None of the subjects were regular contact lens wearers to avoid

potential confounding effects of the lenses on corneal function. The normal subjects

had no history of significant corneal or ocular pathology. All subjects were able to

achieve sharp focus of the crosshair for maximum amplitudes of accommodation of

up to 9 D. The subjects’ eye that showed the smaller amount of refractive error was

chosen for measurement. Individual variability of refractive errors led to individual

differences in the maximum amplitude of accommodation demand that could be

induced with the telescope system. This resulted in maximum effective

accommodation amplitudes ranging between 6.75 D and 9 D (mean 8 D). For the 4 D

accommodation stimulus, individual refractive errors were taken into account by

changing the tube setting accordingly (e.g. for a -2 D myopic subjects the tube setting

was + 6 D of accommodation stimulus; i.e. - 2 D + 6 D = + 4 D effective

accommodation demand).

Data collection was performed in the following order. Six measurements were

collected for 0 D accommodation demand, then six measurements for 4 D demand,

then again 0 D demand, thereafter 9 D demand, and finally again six measurements

for 0 D demand (i.e. 18 measurements of 0 D accommodation demand and six

measurements for each of the two accommodation stimuli of 4 D and 9 D demand).

Any maps where the lid position was too close to the topography measurement area

were discarded in order to minimize measurement variability from eyelid forces

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(Buehren et al. 2001). This reduced the total number of measurements per condition

slightly (i.e. 17.2 f 1.7 SD measurements of 0 D accommodation demand and 5.4 f

1.1 SD measurements for each of the two accommodation stimuli of 4 D and 9 D

demand). A one minute break was taken between testing at each accommodation

demand level as a precaution against residual effects.

After collection of the data, each map was exported using the Keratron export utility.

For the different stimulus conditions (i.e. 0 D, 4 D, 9 D), height data maps were

correlated and repositioned to best approximate the average spatial position of the

cornea based on the number of measurements taken for each stimulus level

(Chapter 2). This procedure minimizes the effects of ocular micromovements on

multiple topography maps. The technique is based on the assumption that corneal

topography does not change when taking multiple measurements of the same cornea

within a short time period, provided that the conditions between measurements are

the same. The correlation between maps takes into account corneal tilt, apex

movement, and cyclotorsion, all relative to the average of the set of maps being

correlated.

The average map at each accommodation demand, standard deviation map, and

number of valid measurement points at each point location were calculated. The

average maps of the 4 D and 9 D accommodation stimuli were subtracted from the 0

D accommodation stimulus average. A two-tailed t-test was applied to the differences

at each point location within the maps and p-value maps were plotted along with the

relevant topography difference maps. The diameter of the central corneal area, which

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Chapter 3

was used for analysis, varied depending on the number of complete Placido-ring data

available from the videokeratoscope measurements (mean 6.2 mm f 0.4 mm).

3.3 RESULTS

Five out of the ten subjects showed areas of significant (p < 0.001) change in corneal

height within the measurement area as a result of changing accommodation. The

subjects showing changes were the four keratoconic subjects as well as one normal

subject. Two keratoconic corneas (subjects 9 and 10) showed local flattening at about

3 mm distance from pupil center. These changes were significant for both the 4 D

accommodation stimulus and the 9 D stimulus. The other two keratoconics also

revealed significant changes in topography with accommodation. Subject 8 showed

corneal elevation changes between -6 and +13 microns with greater changes for the

9 D stimulus (

Figure 3-3). Subject 7 showed smaller areas of change for the 9 D stimulus, but not

for the 4 D stimulus. For the one normal eye (subject 2), the 9 D accommodation

stimulus caused a corneal steepening in some local areas at the edge of a 6 mm pupil.

The remaining five normal eyes mostly showed smaller changes up to f 3 microns,

however none of those changes were statistically significant in the t-test maps. An

example of the height differences for subject 1 is shown in Figure 3-4.

Apart from the changes in the topography difference maps, we also observed changes

in the corneal astigmatic axis in many of the subjects. For the 4 D stimulus, 3 subjects

(subjects 3, 8, and 10) showed significant excyclotorsion of the axis of corneal

astigmatism (p < O.Ol), while subject 7 showed significant incyclotorsion (p < 0.05).

For the 9 D stimulus, five (1,2,3, 8, and 10) out of ten subjects showed significant

85

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excyclotorsion (p < 0.05). Furthermore, for the group as a whole there was a

significant shift towards excyclotorsion for both the 4 D stimulus (p = 0.03) and the

9 D stimulus (p = 0.01). The magnitude of cyclotorsion of the axis of corneal

astigmatism was in the order of 1 O to 2" f 2". Cyclotorsion results for individual

subjects are shown in Table 3-1.

In view of the changes in corneal astigmatic axis, we hypothesised that the changes in

the topography difference maps we had observed between the various levels of

accommodation could be due to differences in eye position (cyclotorsion) relative to

the instruments' measurement axis rather than being due to real corneal shape

changes. In order to investigate this hypothesis we reanalysed the data. This time we

applied the fixation error minimization technique based on the grouped average

corneal position for all conditions (i.e. 0 D, 4 D and 9 D demand combined). This

means that the repositioning of each single map was based on the mean corneal

spatial position of all 30 measurements (i.e. 18 measurements for the 0 D demand

plus 6 measurements for each of the 4 D and 9 D accommodation stimuli). We

anticipated that if the accommodation-related changes we found were actually due to

differences in eye rotation, the changes in topography between accommodation levels

should disappear following the procedure. However if the changes were real corneal

shape changes, the fixation error minimization algorithm would not change the

outcomes.

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The corneal topography height differences associated with accommodation for

subject 8 and subject 1 are shown in Figure 3-3 and Figure 3-4 respectively. The

height difference, the p-value map and profile plot are shown before maps had been

repositioned using the fixation error minimization algorithm. The same data is also

plotted after the corneas were repositioned using the fixation error minimization

algorithm. The normal cornea of subject 1 (Figure 3-4) shows little effect of

accommodation on topography height difference either before or after cyclotorsion

correction. But the cyclotorsion correction for the keratoconic cornea of subject 8

(Figure 3-3) shows much less variation in the height difference map and only very

small regions of significant change within the p-value map. For all four keratoconic

corneas the height differences decreased after cyclotorsion correction and the highly

significant areas within the differences maps disappeared almost entirely. However

subject 2 (normal cornea) who showed corneal steepening for the 9 D stimulus still

showed significant change after fixation error minimization procedure. We decided to

repeat our full protocol with subject 2. When we combined the data from the original

and second trials for subject 2 and reanalysed the effects of accommodation, there

were few areas of significant change apparent in the topography difference maps.

In order to verify the cyclotorsional changes we found in topography, we identified

blood vessels on the conjunctiva in the area surrounding the limbus in our

videokeratographs. We then looked at the angle of a blood vessel relative to the

videokeratoscope axis for each accommodation stimulus level and compared this

angle to that of the corneal astigmatic axis at the same accommodation stimulus level.

The result for subject 8 is presented in Figure 3-5, showing about four degrees of

excyclotorsion for both, cylinder axis (indicated by dark arrow) and blood vessel

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Chapter 3

(indicated by bright arrow). These results support eye rotation as the primary cause

for the changes in cornea1 shape which we found as a result of different

accommodation demands.

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Chapter 3 _

90

Figure 3-3: Top panel: Shows the height difference map between 7 D and 0 D of

accommodation stimulus for subject 8 (left), along with the 3-D difference map plot (right)

and the relevant p-value map showing areas of statistical significance (p < 0.001) in black.

Bottom panel: Shows the same height difference map after the maps had been repositioned to

minimize fixation errors. Bottom panel (right): 3-D difference plot and relevant p-value map

(p < 0.001).

Height difference 0D v 7D

Height difference 0D v 7D

Cyclotorsion corrected

P-value map

Height difference 0D v 7D

P-value map

Height difference 0D v 7D

P-value

P-value

Subject 8

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Chapter 3

91

Figure 3-4: Top panel: Shows the height difference map between 8.75 D and 0 D of

accommodation stimulus for subject 1 (left), along with the 3-D difference map plot (right)

and the relevant p-value map showing areas of statistical significance (p < 0.001) in black.

Bottom panel: Shows the same height difference map after the maps had been repositioned to

minimize fixation errors. Bottom panel (right): 3-D difference plot and relevant p-value map

(p < 0.001).

Height difference 0D v 8.75D

Cyclotorsion corrected

P-value map

Height difference 0D v 8.75D

P-value map

Height difference 0D v 8.75D

Height difference 0D v 8.75D

P-value

P-value

Subject 1

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Chapter 3 _

92

Figure 3-5: Example of refractive power map output for subject 8, for a 0 D accommodation stimulus (left) and a 7 D accommodation stimulus (right).

Differences in corneal astigmatic axis are shown along with the displacement of blood vessels (indicated by arrows; white for blood vessels and grey for

astigmatic axis) relative to the videokeratoscope coordinate system. The magnitudes of both are similar and approximately 4°.

0 D 7 D

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Chapter 3

3.4 DISCUSSION

We did not find clear evidence of statistically significant changes in corneal

topography as a result of accommodation in the subjects examined in this study. This

was the case for both the subjects with normal corneas and those with keratoconic

corneas. These results are consistent with previous studies on central regions of the

cornea (Fairmaid 1959; Lopping and Weale 1965; Mandell and St Helen 1968).

We did however find a significant cyclotorsion of corneal topography of many of the

eyes when changing focus from far to near distances and this may explain the

apparently contradictory findings in the literature in this field.

During fixation the amount of torsion is fixed for each eye position (Listing’s law)

(Fetter and Haslwanter 1999). In our study we induced convergence in the presence

of a deliberate head turn and therefore our results may not be directly comparable to

the findings of Fairmaid, or Lopping and Weale on corneal changes associated with

natural convergence (Fairmaid 1959; Lopping and Weale 1965). Fairmaid reported an

increase of curvature in the horizontal meridian and a decrease of curvature in the

vertical meridian while Lopping and Weale found flattening in the horizontal

meridian associated with convergence.

As in our experiment, Pierscionek et al. induced accommodation in the measured eye,

while the other eye was covered (Pierscionek et al. 2001). This produces

asymmetrical convergence (i.e. a different head position relative to normal

convergence). Pierscionek et al. found differences in central corneal curvature in at

least one principal meridian in most of the subjects tested (Pierscionek et al. 2001).

However the results of the study, which also measured accommodation stimuli of up

93

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to 9 D, may have been affected by the cyclotorsional variations, which have been

reported by other authors (Allen and Carter 1967; Bannon 1971; Enright 1980) and

which also have been found in our study. Allen and Carter have shown that even with

an experimental procedure that produces asymmetrical convergence, excyclotorsion

can arise in the non-verging eye (Allen and Carter 1967).

The technique, which was used to confirm that cyclotorsional changes had caused the

apparent changes in the topography difference maps was initially developed in order

to remove ocular micromovements during videokeratoscopy (Chapter 2). By applying

the method across all accommodation conditions not only cyclotorsion was corrected

but also lateral shifts and tilts between corneal topography measurements were

minimized. It was previously shown that cyclotorsional fluctuation is a substantial

contributor to micromovements during steady fixation (Chapter 2). The order of

magnitude (2.4" f 1.1) is similar to what was found for the different accommodation

conditions in this study.

In some of my subjects, these ocular microfluctuations may have masked

cyclotorsional changes related to the different accommodation conditions. However,

within the group it still was possible to show statistically significant cyclotorsional

differences between the 0 D demand condition and the 4 D or 9 D demand conditions.

Furthermore, the comparison between the location of limbal blood vessels and the

changes in corneal astigmatic axis also supported the role of ocular cyclotorsion in

causing apparent changes in corneal shape with accommodation.

94

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Chapter 3

Along with others (Allen and Carter 1967; Bannon 1971) it was found that

excyclotorsion occurred with accommodation for most of the subjects. When it was

not accounted for cyclotorsional effects, the keratoconic corneas showed the greatest

changes with accommodation due to higher levels of corneal asymmetry. In the case

of a cyclotorsion occurring between far and near viewing conditions, this would

clearly lead to larger differences occurring in keratoconic corneas rather than more

rotationally symmetric “normal” corneas. The two examples shown in

Figure 3-3 and Figure 3-4 confirm this effect. Both eyes show a significant amount of

cyclotorsion between the different accommodation conditions (Table 3-1). The

excyclotorsion in case of the keratoconic cornea of subject 8 (showing 4 D of corneal

astigmatism) caused significant height changes in the difference map. However, the

excyclotorsion in case of the normal cornea of subject 1 (showing only 0.5 D of

corneal astigmatism) did not lead to such significant changes in the difference map.

The rotation of corneal topography during accommodation has significant

implications for the accuracy of results obtained from optometers or wavefront

sensors that measure the optical characteristics of eyes during near versus far viewing

conditions and pre- versus post operative refractive surgery. As a result of

accommodation, small changes in ocular astigmatism may occur and also asymmetric

higher order aberrations such as coma will be affected. For example, ocular

cyclotorsion while fixating a near target during refractive surgery procedures may

contribute to residual astigmatism outcomes. Furthermore, analyses such as

videokeratoscope difference maps and wavefront analyses of pre- versus post-

operative refractive surgery will be affected if the change in the eye’s refractive status

leads to a change in accommodative status during the image capture procedure.

95

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In summary it appears unlikely that changes occur in central corneal shape during

accommodation up to a level of 9 D. Therefore, the changes in corneal topography

that have been reported to occur in some individuals following reading can be

ascribed to lid force effects as suggested by most of these authors (Mandell 1966;

Knoll 1975; Bowman et al. 1978; Carney et al. 1981; Goss and Criswell 1992;

Kommerell 1993; Ford et al. 1997; Campbell 1998; Golnik and Eggenberger 200 1)

rather than due to forces caused by accommodation. However, we found a significant

excyclotorsion of the eye globe during accommodation, which in turn caused a

rotation of corneal topography relative to the instrument’s measurement axis. While

the amount of this cyclotorsion is small, it should be taken into account when

considering the optical characteristics of the eye for different levels of

accommodation.

96

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CHAPTER 4

Corneal Aberrations and Reading

4.1 INTRODUCTION

The anterior surface of the eye is its most powerful refractive component and as such,

subtle changes in corneal shape can cause substantial changes in its optical

characteristics. Monocular diplopia has been linked to corneal distortion following

near work in various studies dating back over 35 years (Mandell 1966; Knoll 1975;

Bowman et al. 1978; Carney et al. 1981; Goss and Criswell 1992; Kommerell 1993;

Ford et al. 1997; Campbell 1998; Golnik and Eggenberger 2001). The corneal

distortions that have been observed in these studies have been explained by sustained

(Mandell 1966; Knoll 1975; Bowman et al. 1978; Carney et al. 1981) or abnormal lid

pressure (Kommerell 1993), lid position (Goss and Criswell 1992; Ford et al. 1997),

and tear film interactions with the corneal surface during sustained close work (Ford

et al. 1997; Golnik and Eggenberger 2001). During routine topography measurements,

lid pressure effects on corneal topography have been observed in the central and

peripheral corneal shape (Lieberman and Grierson 2000; Buehren et al. 2001).

There has been conjecture that lid pressure may cause corneal astigmatism (Wilson et

al. 1982; Grey and Yap 1986). Vihlen and Wilson found no significant association

between the tension of the eyelids and the amount of corneal toricity (Vihlen and

Wilson 1983). Grey and Yap measured ocular astigmatism in subjects with three

deliberately narrowed lid positions and found a statistically significant increase of

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ocular with-the-rule astigmatism when the lid aperture was narrowed (Grey and Yap

1986). There is also evidence that astigmatism can be induced by chalazion (Nisted

and Hofstetter 1974; Cosar et al. 2001), lid-loading procedures used in the treatment

of lagophthalmos (Kartush et al. 1990; Brown et al. 1999; Goldhahn et al. 1999), and

after ptosis surgery (Holck et al. 1998).

While studies on monocular diplopia after near work provide useful information about

the subjectively perceived optical effects of corneal distortion, there hasn’t been a

detailed objective analysis regarding the optical characteristics of corneal distortions

following near work. In this study we have investigated the effect of one hour of

reading on corneal topography. The position of eyelids during reading, relative to the

location and size of the pupil, was measured and compared with corneal topography

changes. We have analysed the optical consequences of the changes that were

observed using traditional sphero-cylinder and corneal higher order aberrations.

4.2 METHODS

Twenty subjects (age range 20 to 37 years, mean 27 years) with healthy eyes were

recruited for the experiment, and one eye was randomly chosen for analysis. Informed

consent was obtained for all subjects. The twenty eyes had a range of refractive errors

(mean –1.6 D, range +0.25 to –6.00 D); five were emmetropic (i.e. ≤ 0.5 D in the

worst meridian), five were primarily astigmatic (i.e. ≤ 0.5 D of spherical component

and > 0.5 D of astigmatic component), five had simple myopia (i.e. ≤ 0.5 D of

astigmatism and > 0.5 D of myopic component), and five had myopic astigmatism

(i.e. > 0.5 D of myopic and astigmatic component).

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The experiment was always conducted early in the morning, approximately 2-3 hours

after the subjects woke. All subjects were given the instruction not to perform any

sustained reading (e.g. newspaper) prior to the experiment. For each subject, six

baseline videokeratographs were taken prior to reading and six videokeratographs

were again taken immediately after the 60 minutes reading task.

The Keratron videokeratoscope (EyeQuip Division, Alliance Medical Marketing,

Jacksonville, FL) was used for all corneal topography measurements. The Keratron

has been shown to have high accuracy and precision performance for inanimate test

objects (Tripoli et al. 1995; Tang et al. 2000). Prior to the study, the instrument

calibration was checked according to the manufacturer’s instructions. The

videokeratoscope is based on the placido-disk principle and enables the capture of six

consecutive videokeratographs without the requirement for immediate data

processing.

The subjects were seated and asked to read from a novel for 60 minutes. During this

time the subjects were allowed to adopt whatever head posture was comfortable.

Photopic lighting conditions were used during the reading task. The subjects’ pupil

size was measured in the photopic room condition with the subjects focused at a

distance of 33 cm.

Prior to the reading experiment, digital photography was used to document the

external ocular features using a high-resolution digital camera (Kodak DC260).

Photography was conducted with: (1) the eyes in reading gaze posture, and (2) the

subject positioned in a headrest with eyes in primary gaze. A ruler with millimetre

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100

increments was placed in the peripheral field of the captured images to allow

calibration of subsequent measurements.

To determine the approximate position of the eyelids during reading in relation to the

corneal topography, we identified iris features in the digital photographs of the eye

taken during both reading and in the headrest. We then assumed that the relative

position of the eye during videokeratoscopy was the same as that photographed when

the subject was in the headrest. This allowed us to superimpose the approximate

position of the eyelids during reading onto the corneal topography measurements

taken after reading (Figure 4-1). In this way, we could investigate the potential

association between lid position during reading and changes in topography.

After 30 minutes of reading, the subjects’ blink frequency was measured over a time

period of 3 minutes and mean blink rate per minute was later calculated. The subjects

were not informed that blink frequency was being monitored, since this may cause a

change in blink characteristics (Zaman and Doughty 1997; Cho et al. 2000).

4.3 ANALYSIS

Corneal instantaneous power, height data, and refractive power were exported from

the videokeratoscope for analysis. The instantaneous power maps were chosen to

compare corneal topography with the subject’s natural lid position during reading,

because the instantaneous power maps are most sensitive to local power changes

caused by slight variations in slope.

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To study the potential effect of reading on topography, height difference maps were

calculated. For each set of six baseline measurements and six post-reading

measurements, the effect of ocular microfluctuations were minimized using the

method described in Chapter 2. The methodology repositions a given

videokeratograph map to best approximate an “average” videokeratograph based on a

set of multiple measurements of the same cornea. This procedure involves

interpolating (bilinear) the topography data to a common grid format (256 meridians

and point spacing along the meridian of ~0.15 mm) and subsequent calculation of an

average height map for each set of maps (i.e. before and after reading).

From the six refractive power maps for each condition (i.e. pre- and post-reading) we

calculated the average, standard deviation, and the number of valid measurements at

each grid location within the map. Difference maps of pre- versus post-reading

topography were calculated along with the t-test maps showing significant areas of

change (Buehren et al. 2001). The root mean square error (RMSE) between corneal

refractive power and best-fit sphero-cylinder before and after reading was calculated

and t-tests were applied to measure the significance of changes in refractive power

between the averages of the two conditions.

This was performed for each individual’s photopic pupil size and also for fixed pupil

sizes of 2.5, 3, 4, 5, and 6 mm. For the 4 mm fixed pupil size, power matrices (Harris

2000) were used to average individual best-fit sphero-cylinders for each condition and

again to calculate the corneal changes in sphere, cylinder and astigmatic axis pre

versus post-reading. A multivariate test (Hotelling’s T2) representing a generalisation

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of the t statistic was used to test the significance of overall change in corneal sphero-

cylinder.

The anterior surface of the cornea was modelled as a single surface optical system in

order to derive the corneal wavefront error using a method similar to that described by

Guirao and Artal (Guirao and Artal 2000). Optical path distance (OPD) for each point

on the surface was calculated using 3-D ray tracing and the wavefront was fitted using

a set Zernike terms of up to the fourth order polynomial expansion according to the

Optical Society of America convention (OSA convention) (Thibos 2000) for pupil

sizes of 2.5 mm, 4 mm, and 6 mm (image plane at circle of least confusion, wavefront

error scaled by λ = 555 nm, refractive index n = 1.376, and midline symmetry taken

into account (Smolek et al. 2002). All wavefront coefficients were normalized to a

unit circle to enable quantitative comparison between different pupil sizes. The

wavefront was centred on the line of sight. To achieve this we calculated the average

pupil offset derived from the pupil detection system provided by the Keratron

videokeratoscope for each subject and used this offset as the new principle axis

reference point. A full 3-D ray-trace technique was applied to calculate the wavefront

error along the line of sight. T-tests were used to identify statistically significant

changes in corneal wavefront Zernike coefficients after reading.

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Figure 4-1: Method for overlaying eyelid features onto corneal topography maps. Iris features (indicated by arrows) are used in each of the images to record relative

lid position. Subject 13 (top left), lid position in primary gaze, lid position during reading (bottom left), baseline corneal topography overlaid with lid position in

primary gaze (top right), and post-reading corneal topography overlaid with lid position during reading (bottom right).

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4.4 RESULTS

In twelve of the twenty subjects we studied, the instantaneous power maps after

reading showed distinct band-like distortions in the superior region of the maps,

which correlated closely with the subject’s natural lid position during reading. In

Figure 4-2, two examples of videokeratograph comparisons before and after reading

for subject 1 and 15 are shown, with the overlay of the subjects’ lid position during

reading. These topography changes were often encroaching within the boundary of

the subjects’ upper pupil margin. Topography changes were also often evident in the

inferior cornea associated with the position of the lower lid margin during reading

(see subject 1, Figure 4-2). However these inferior distorted regions generally did not

encroach within the pupil zone.

Analysis of the corneal wavefronts revealed that seven wavefront coefficients were

significantly changed after one hour of reading (Figure 4-3). The terms that changed

significantly for all pupil sizes were 22Z primary astigmatism (p < 0.05 at 2.5 mm and

p < 0.01 at 4 mm and 6 mm), 13−Z primary vertical coma (p < 0.01 at 2.5 mm and

p < 0.001 at 4 mm and 6 mm), and 33−Z trefoil 30° (p < 0.05 at 6 mm and p < 0.01 at

2.5 mm and 4 mm). The change of the primary astigmatism terms was in the direction

of against-the-rule (i.e. with-the-rule astigmatism decreased or against-the-rule

astigmatism increased).

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Figure 4-2: Examples of the effect of lid position during reading upon corneal topography. Subject 1 (left) and subject 15 (right), corneal topography pre-reading

(top) versus pos-reading (bottom) is shown overlaid with the subjects’ lid position in primary gaze and during reading respectively.

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Other changes in Zernike terms were limited to certain pupil sizes (i.e. corneal

regions). For the 2.5 mm pupil size, the term 13Z primary horizontal coma (p < 0.05)

changed significantly. The defocus term 02Z changed for the 4 mm and 6 mm pupil

sizes (p < 0.01 at 4 mm and 6 mm). The vertical prism term 11−Z changed for the 6

mm pupil size (p < 0.05) and the secondary astigmatism component 24Z changed for

the 4 mm pupil size (p < 0.05).

There was a significant association between changes occurring in the wavefront for

the 13−Z vertical coma and the 3

3−Z trefoil 30° terms after reading. Most subjects (15

of 20) showed positive vertical coma and negative trefoil 30°, or negative vertical

coma and positive trefoil 30° in the baseline (pre-reading) measurements and this

trend was increased after reading (18 of 20). Both of these combinations of coma and

trefoil terms represent a wave-like shape (Figure 4-4 bottom) but they are opposite in

direction. After reading, there was a trend for the vertical coma term to shift in the

negative direction, whereas the trefoil 30° term generally shifted in the positive

direction. The changes in the vertical coma and trefoil 30° coefficients after reading

are shown in Figure 4-4 (top). These wave-like shape changes in the wavefront are

consistent with the changes in instantaneous power maps associated with the effect of

the upper lid margin.

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* * ** * * * * *

* * * * *

-0.15

-0.12

-0.09

-0.06

-0.03

0

0.03

0.06

0.09

Zernike Coefficients (OSA convention)

Cha

nge

in W

avef

ront

Err

or C

oeff

icie

nt V

alue

(

)

2.5mm P upil4.0mm P upil6.0mm P upil

1- 1 Z

1 1 Z

-22Z

02Z

22Z

-33Z

-13Z

1 3 Z

3 3 Z

-44Z

-24Z

0 4 Z

24Z

44Z

* = t-test significant at (p < 0.05)

Figure 4-3: The group mean change (±SE) of normalized Zernike wavefront coefficients after reading (post minus pre) for three pupil sizes (2.5 mm, 4 mm, 6 mm) is

shown. The Zernike polynomials are vertical prism 1

1−Z , horizontal prism

11Z , primary astigmatism along 45°

22−Z , defocus

02Z , primary astigmatism

22Z ,

trefoil along 30° 3

3−Z , primary vertical coma

13−Z , primary horizontal coma

13Z , trefoil

33Z , tetrafoil along 22.5°

44−Z , secondary astigmatism along 45°

24−Z ,

spherical aberration 04Z , secondary astigmatism

24Z , and tetrafoil

44Z .

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Chapter 4 _

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Correlation between Change in vertical Coma and Trefoil along 30° after reading

y = -0.8739x - 0.0056R = 0.8121

-0.06

-0.04

-0.02

0

0.02

0.04

0.06

0.08

0.1

-0.1 -0.08 -0.06 -0.04 -0.02 0 0.02 0.04

Change in primary vertical ComaWavefront Coefficient Value (λ)

Cha

ng

e in

Tre

foil

alo

ng

30°

W

ave

fro

nt

Co

eff

icie

nt

Val

ue

()

Negative Coma Positive Trefoil Negative Coma + Positive Trefoil

Figure 4-4: Correlation between change in primary vertical coma and trefoil along 30° (4 mm pupil)

following reading. Bottom panel shows the combination of negative vertical coma and positive trefoil

30° coefficients producing a “wave-like” distortion.

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An example of the optical changes in corneal refractive power following reading is

presented for subject 8 in Figure 4-5. In the difference map (pre-versus post-reading

refractive power), the superior semi-meridian shows values of up to -1.34 D change.

These changes are highly statistically significant as shown by the p-values of the t-test

map (Figure 4-5). Within a 4-mm pupil, thirteen of the twenty subjects showed

statistically significant (p < 0.001) areas of change in refractive power (Table 4-1, last

column). These significant regions of change were mostly located in the upper, and/or

the lower pupil areas. Some subjects showed small randomly distributed points of

statistically significant change, however these areas were considered to be non-

systematic and probably related to local tear instabilities rather than true changes in

corneal topography and were not classified as representing statistically significant

change (in Table 4-1, last column).

The group mean RMSE deviation from the best-fit sphero-cylinder was slightly larger

for the post-reading corneas (Table 4-1). This difference was statistically significant

when calculated for the individuals’ photopic pupil size (pre 0.23 D versus post 0.28 D,

p = 0.013) as well as for fixed pupils of 5 mm and 6 mm (pre 0.31 D versus post 0.35

D, p = 0.036 and pre 0.38 D versus post 0.42 D, p = 0.022 respectively). The increased

RMSE was not statistically significant for the 2.5, 3 and 4 mm pupils (p = 0.66, p =

0.28, and p = 0.09 respectively).

In Table 4-1 individual subject data for various refractive power changes following

reading are summarized. This includes the total refractive error, corneal best-fit sphero-

cylinder power pre and post-reading and the change in corneal sphero-cylinder for the

twenty subjects.

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Across the group, lid fissure width decreased from a mean of 9.4 mm (SD ± 0.9) in

primary gaze to 6.8 mm (SD ± 1.0) in the reading position. Average pupil size of the

subject group during reading in the photopic condition was 3.3 mm (SD ± 0.7). Blink-

frequency showed large variability between individuals, with an average value of 8.3

blinks/minute (range 2 to 26 blinks per minute). There was no significant correlation

between blink rate and corneal RMSE differences (R2 = 0.10).

The changes in corneal aberrations that we measured following reading were clearly

associated with forces applied by the eyelid margin to the surface of the eye. However

the role of eye movements during reading was unknown. To investigate this we

recruited one subject (subject 9) who showed obvious corneal topography changes

following the reading trial. The subject was retested on a separate morning, but this

time the subject had to stare (fixed gaze) at a single word on a page for 60 minutes in

normal reading gaze. The changes in refractive power following the fixed gaze trial

along with the results from the initial reading trial of the same subject are shown in

Figure 4-6. The corneal changes after 60 minutes of staring are less pronounced, with

values approximately half those found after 60 minutes of reading. The locations of

changes shown after both trials indicate that a similar lid position was adopted during

the two experiments. Although it is not clear whether other factors may also have

influenced these two trials, it may be speculated that eye movements during reading

contribute to the forces applied to the cornea.

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Corneal Refractive Power Analysis (Subject 8)

Figure 4-5: Average baseline refractive power map (top left) and average post-reading refractive

power map (top right) for a 6-mm pupil zone of subject 8. Bottom left: Refractive power difference

map of post-reading minus baseline refractive power for a 4 mm pupil zone. Bottom right:

Significance map based on t-tests at all points within the map. The regions where p values < 0.001 are

in black, 0.001< p < 0.05 are in grey and p values > 0.05 are in white.

60 Min Read

RMSE = 0.30 D RMSE = 0.42 D

Baseline

Difference in 4 mm Pupil P-values

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Table 4-1: The changes in corneal refractive power (sph, cyl, and axis) are presented as refractive error, not correction. The RMSE is the difference between the

corneal refractive power and the best-fit corneal sphero-cylinder. The topographic refractive power changes illustrate those subjects where statistically significant

areas of change occurred in refractive power within the central 4 mm of the cornea following reading (see Figure 5 example). Because of potential type 1 errors

associated with repeated statistical testing, we have chosen to highlight only corneal changes where p < 0.001 (i.e. * = p < 0.05; ** = p< 0.01; *** = p < 0.001).

Subject RMSE 4mm (D)

RMSE 4mm (D)

Subjective Refractive Error (Correction)

Corneal Refractive Power Pre-reading

(4mm)

Corneal Refractive Power Post-reading

(4mm)

Changes in Corneal Best-fit Sphero-cylinder

(4mm)

Region/s of Refractive

Power Change (4mm)

Pre-read. Post-read. Sph Cyl Axis Sph Cyl Axis Sph Cyl Axis Sph Cyl Axis

1 0.19 0.29 *** -3.00 -0.25 168° +46.60 +1.40 4° +46.56 +1.34 179° -0.14 +0.23 128° *** ***

2 0.31 0.21 * -4.00 -0.5 178 +46.00 +0.40 6° +46.10 +0.41 7° +0.09 +0.02 33°

3 0.29 0.36 -0.75 -0.75 180° +48.33 +1.50 183° +48.19 +1.52 188° -0.25 +0.25 49° **

4 0.43 0.43 -3.25 -0.25 160° +50.37 +0.98 176° +50.42 +0.80 174° -0.14 +0.20 97°

5 0.12 0.17 0.00 0.00 -- +47.94 +0.15 139° +48.03 +0.18 156° -0.05 +0.10 5° **

6 0.20 0.25 * -2.75 -0.25 20° +48.30 +1.48 169° +48.56 +1.56 169° +0.26 +0.08 167° *** ***

7 0.34 0.26 * 0.00 0.00 -- +47.91 +1.38 173° +48.11 +1.45 173° +0.19 +0.09 150° ** ***

8 0.30 0.42 *** -0.25 -0.75 115° +50.38 +0.33 151° +50.39 +0.28 121° -0.17 +0.30 87° * ***

9 0.22 0.41 *** -0.75 -0.75 20° +47.46 +1.67 180° +47.40 +1.37 181° -0.37 +0.31 90° ** ***

10 0.29 0.28 0.00 0.00 -- +48.38 +0.67 153° +48.41 +0.69 155° +0.02 +0.05 12° ***

11 0.22 0.36 * 0.00 -0.25 180° +47.39 +0.78 173° +47.78 +0.60 166° +0.19 +0.23 99° ***

12 0.18 0.16 -5.00 -1.25 163° +48.70 +1.91 179° +48.75 +2.02 180° +0.04 +0.13 17°

13 0.32 0.48 *** +0.25 -1.25 17° +49.05 +2.20 5° +49.14 +1.85 8° -0.28 +0.41 81° *** ***

14 0.19 0.25 -0.75 -0.75 9° +47.28 +0.89 20° +47.24 +0.92 16° -0.08 +0.11 161°

15 0.22 0.36 *** -0.50 -1.00 6° +49.70 +2.07 1° +49.73 +1.83 4° -0.24 +0.30 73° *** ***

16 0.43 0.40 0.00 -2.25 82° +49.59 +1.90 86° +49.62 +1.82 82° -0.14 +0.28 31° ** ***

17 0.22 0.29 0.00 0.00 -- +49.42 +0.87 9° +49.40 +0.88 11° -0.05 +0.07 53° ***

18 0.32 0.29 -5.25 -0.25 5° +48.26 +1.00 180° +48.34 +1.12 2° +0.06 +0.15 18° ***

19 0.33 0.37 * -6.00 -1.75 35° +47.79 +2.06 8° +47.69 +2.02 10° -0.20 +0.18 61° ** ***

20 0.20 0.32 *** 0.00 -1.25 84° +49.48 +0.30 82° +49.36 +0.66 83° -0.12 +0.36 81° *** ***

Mean 0.27 0.32 ** -1.83 -0.22 20° +48.56 +0.92 91° +48.62 +0.85 92° -0.06 +0.07 74°

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Figure 4-6: Top: Refractive power difference map for an 8 mm pupil zone of subject 9 after 60

minutes of reading. Bottom: Refractive power difference map for a 8 mm pupil zone of subject 9 after

60 minutes of staring (fixed gaze) at a single word on a page for 60 minutes in normal reading gaze.

RMSE = 0.41

RMSE = 0.27

Refractive power difference after 60 min. fixed gaze (Subject 9)

Refractive power difference after 60 min. reading (Subject 9)

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4.5 DISCUSSION

We have shown that some individuals have significant changes in the topographical

and optical characteristics of the cornea following one hour of reading. The

topographical changes showed a clear association with the position of the eyelids

during the reading task. The upper eyelid in particular, caused a wave-like distortion

that was evident in the topography and corneal wavefront post-reading.

Corneal distortions have been previously reported in cases associated with monocular

diplopia following reading (Mandell 1966; Knoll 1975; Bowman et al. 1978; Carney

et al. 1981; Goss and Criswell 1992; Kommerell 1993; Ford et al. 1997; Campbell

1998; Golnik and Eggenberger 2001). Most of these studies have reported that

subjects perceive vertical doubling of images. The wave-like aberration change that

we found in many subjects, related to the vertical coma and trefoil Zernike terms

(Figure 4), is the likely optical explanation for this perception of vertical doubling.

The significant wave-like aberration changes we found following reading were

oriented vertically and would have the effect of blurring the retinal image along the

vertical axis.

The magnitude of change and the time course of remission of corneal changes

following reading are probably influenced by various factors. These may include the

time spent reading, the visual tasks undertaken after reading, the subject’s blink

frequency, individual corneal tissue characteristics, and the effect of age on both lid

tension and corneal tissue characteristics. To gain an impression of this time course,

we continued to measure corneal topography after the 60-minute reading task for one

subject (subject 9). A large proportion of the corneal changes had disappeared at ten

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minutes post-reading, however it required 120 minutes before the topography was

approaching pre-reading shape. Knoll found that the perception of double images

caused by corneal distortions after reading can last several hours, as long as no further

near work is done (Knoll 1975). Golnik have recently reported that 30 to 60 minutes

is needed to resolve visual symptoms after cessation of reading (Golnik and

Eggenberger 2001). Since the time period of the experimental reading task in this

experiment extended over only 60 minutes, longer periods of reading may intensify

the degree of corneal changes that occur and the recovery of normal topography may

take substantial time.

The changes we observed in the corneal topography following reading are probably

the result of displacement of epithelial tissue, although this assumption needs to be

confirmed by pachometry of the epithelium. The magnitude of the height changes

observed in post-reading topography were in the order of 4 microns (range 3 to 7),

which would suggest that only a few superficial epithelial cells would need to be

displaced for this topographical change to occur.

Since reading in some individuals can significantly change the corneal shape, this

raises the question of the true refractive error of these eyes. It could be argued that a

refractive correction for reading/close work might be best derived after a period of

reading in these individuals. In terms of the best-fit sphero-cylinder to corneal

topography, this result changed by up to 0.37 D in spherical component, up to 0.41 D

in cylinder component, and up to 30 degrees in cylinder axis when comparing pre- to

post-reading topography.

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In another scenario, the question of the appropriate refractive correction of an

individual arises in corneal refractive surgery. The appropriate sphero-cylinder

correction in procedures such as laser in situ keratomileusis (LASIK) and

photorefractive keratectomy (PRK) may be altered if the individual has undertaken

significant reading prior to corneal topography measurement. Potentially more

problematic is the case of customized LASIK, where the higher order wavefront

aberrations of the eye are also corrected by a corneal ablation (Alessio et al. 2000;

Knorz and Neuhann 2000; Mrochen et al. 2000). We have shown that a number of

higher order Zernike aberration terms of the corneal wavefront are significantly

changed by 60 minutes of reading.

The anterior corneal surface is the eyes’ most powerful refractive component and

therefore is a major contributor to the eyes’ total wavefront aberrations. In general,

third-order (coma and coma-like) aberrations are the dominant aberrations for most

eyes (Howland and Howland 1977; Liang and Williams 1997). In this study, corneal

coma and trefoil have changed substantially after reading in both magnitude and

direction. Our results suggest that studies of the eyes’ total aberrations should account

for the visual tasks undertaken prior to total wavefront aberration measurement.

Various studies of the eyes’ total wavefront aberrations have found that higher order

aberrations change with increasing levels of accommodation (Atchison et al. 1995; He

et al. 2000). Since the changes we observed in the corneal wavefront following

reading were related to lid position, we expect that previous studies of aberrations and

accommodation have been measuring the effects of changes in the optical

characteristics of the crystalline lens and not the cornea, because wavefront sensors

typically induce accommodation with the subject in primary gaze (not downward

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reading gaze). To fully understand the optical characteristics of the eye during reading

it would be necessary to measure the eye’s total wavefront during reading (or

downgaze).

The results of studies that have measured accommodation (refractive status) of the eye

pre- versus post-reading tasks may have been influenced by the temporary optical

changes that we have found to occur in the corneas of some subjects. The exact effect

of these corneal changes upon total refractive error (accommodative status) is difficult

to predict, but would depend on the method of refractive measurement used by the

optometer (Collins 2001).

It is generally accepted that the risk factors for myopia development can be broadly

classed as genetic and environmental factors (Mutti et al. 1996). One of the major

environmental factors which have been shown to have an association with myopia

development is reading and near work (Adams and McBrien 1992; Goss and Rainey

1998; Hepsen et al. 2001) and there has been considerable speculation about the role

of retinal image quality in myopia development (Rabin et al. 1981). The results of our

study suggest that in some individuals the corneal optics change during reading in a

variety of ways that influence retinal image quality. Corneal sphero-cylinder can

change, individual aberrations change (eg. vertical coma and trefoil) and the total

corneal root-mean-square error (i.e. variation from a perfect sphero-cylinder) can

change.

When we studied the interaction between corneal root-mean-square error (i.e.

variation from a perfect sphero-cylinder) and pupil size, we found that the group mean

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RMSE became significantly higher after reading for pupil sizes of 5 and 6 mm,

showed borderline significance for a 4 mm pupil, and was not statistically significant

for pupil sizes of 2.5 and 3 mm. For many individuals within the group, this increased

RMSE was significant at all pupil sizes and if we analysed the increase in RMSE

post-reading for each individuals’ photopic pupil size, the effect was again significant.

This suggests that there is a small, but significant overall loss in retinal image quality

for some individuals during reading.

Studies of myopia development in various animals show that the overall sign of

defocus can regulate eye growth (Schaeffel et al. 1988; Troilo and Wallman 1991;

Norton and Siegwart 1995). In our subjects, the optical changes induced by the

eyelids during reading did not typically have a rotationally symmetrical form. We

described the most common change in shape of the corneal wavefront as “wave-like”

accompanied by an astigmatic shift in direction of against-the-rule. When we

examined the group mean change in the corneal wavefront defocus, there was a small

change indicating slight central steepening of the cornea for pupil sizes of 4 mm and

6mm.

Lid related forces could play a role in refractive error development. O’Leary and

Millodot reported that subjects with ptosis were more likely to develop myopia and

speculated palpebral aperture may be a factor in the aetiology of myopia (O'Leary and

Millodot 1979). Many Asian populations are reported to have significantly higher

rates of myopia than western populations (Chandran 1972; Lin et al. 1988; McCarty

et al. 1997; Wong et al. 2000). Compared with western populations it is well known

that Asian eyes have smaller vertical palpebral apertures (Lam and Loran 1991) and

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different anatomical characteristics resulting in a thickened upper eyelid and

overlying fold of skin (Doxanas and Anderson 1984), all of which may serve to

increase the optical effects of lid forces during reading. A number of studies have

reported that rigid contact lenses may slow the progression of myopia in some

children (Stone 1976; Grosvenor et al. 1987). We might expect that rigid contact

lenses would absorb much of the force of the eyelids during reading. These potential

interactions are speculative, but we believe are worthy of further investigation.

During reading, corneal topography can change and this effect appears to be directly

related to the force exerted by the eyelids. As a consequence, the optical

characteristics of the eye can be significantly altered during and after reading. This

leads to questions of how we define the refractive status of the cornea and eye, which

may need to be qualified in terms of the visual tasks undertaken prior to the refractive

and corneal topography measurements. These findings may also lead to a better

understanding of the relationship between reading and the development of refractive

errors.

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CHAPTER 5

Corneal aberrations following reading in progressing myopes

5.1 INTRODUCTION

It was shown that the optical characteristics of the cornea can change following reading

(Chapter 4). It was therefore of interest to examine whether corneal distortions after

reading might represent a factor in refractive error development by studying the

response of different refractive error groups.

Studies on monocular diplopia after near work provide useful information about the

subjectively perceived optical effects of corneal distortion. The most common

description is that of monocular vertical doubling (Mandell 1966; Knoll 1975; Bowman

et al. 1978; Carney et al. 1981; Goss and Criswell 1992; Kommerell 1993; Ford et al.

1997; Campbell 1998; Golnik and Eggenberger 2001). In Chapter 4, a detailed objective

analysis of the optical characteristics of corneal distortions after reading has been

performed in which it is shown that several lower and higher order Zernike wavefront

coefficients significantly change.

The introduction of ocular wavefront technology has enabled such detailed analysis of

the eyes’ optical characteristics. Several studies that have measured ocular wavefront

aberrations as a function of refractive error found that myopes have significantly larger

wavefront aberrations than emmetropes (Collins et al. 1995; Cheng et al. 2000; He et al.

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2000; Marcos et al. 2000). Paquin found a quasi-linear relationship between increasing

aberrations and refractive error (Paquin et al. 2002). Collins suggested that high

amounts of wavefront aberrations might play a role in myopia development (Collins et

al. 1995).

The changes of optical characteristics during reading raise the question of how to define

refractive status and, more importantly, whether corneal distortions during reading

might be linked to refractive error development. Based on a retrospective analysis of

refractive error among humans subjected to various ocular anomalies disrupting pattern

vision, Rabin suggested emmetropisation to be a vision-dependent phenomenon (Rabin

et al. 1981). Goss proposed that retinal image-mediated ocular growth is a possible

etiological factor in juvenile-onset myopia (Goss and Wickham 1995). The hypothesis is

consistent with animal models based on various studies (e.g. (Wallman et al. 1981;

Raviola and Wiesel 1985; Schaeffel et al. 1988) and supported by human infant

refraction data taken early in life (Howland et al. 1978; Ingram and Barr 1979; Atkinson

et al. 1980; Howland and Sayles 1984; Ehrlich et al. 1997).

Several authors have reported an association between congenital ptosis and increased

presence of astigmatism, myopia, or amblyopia (O'Leary and Millodot 1979; Ugurbas

and Zilelioglu 1999; Gusek-Schneider and Martus 2000). Experimentally induced

congenital ptosis in chicks produces regional axial myopia (Langford et al. 1998).

Changes in refractive error after ptosis surgery have been found in humans (Cadera et

al. 1992; Holck et al. 1998; Brown et al. 1999). O’Leary pointed out that in the normal

reading posture the palpebral aperture is reduced and that many races prone to myopia

have a narrow palpebral aperture (O'Leary and Millodot 1979).

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In this study we have investigated corneal topography, corneal aberrations, and

palpebral aperture before and after a period of up to two hours of reading, for a group of

young progressing myopes and a group of young stable emmetropes. The aim was to

study whether corneal distortions after reading significantly differ between the two

groups and whether lid position during reading differs between the two groups.

5.2 METHODS

Ten young progressing myopic subjects and ten young emmetropic subjects participated

in the experiment. The subjects were recruited mostly from optometry students at the

Queensland University of Technology. The mean age of the myopic group was 22 years

ranging from 19 to 27 years. Average best sphere refraction was –3.13 D with a range of

–1.00 D to –6.00 D of myopia. The mean cylindrical refraction was –0.30 D ± 0.28 D

(SD). Mean myopia progression rate was -0.6 D over the last two years (varying from

–0.50 to –1.00 D). Subjects who were regular contact lens wearers were asked not wear

the lenses for at least 40 hours prior to the experiment to avoid potential confounding

effects of the lenses on corneal function. There were no rigid gas permeable contact lens

wearers amongst the myopic subjects. As a control group, ten young emmetropic

students were recruited. The mean age was 22 years ranging from 19 to 28 years.

Average best spherical refraction was –0.03 D range +0.25 to –0.25 D. The mean

cylindrical refraction was –0.05 D ± 0.18 D (SD). The emmetropic group did not show

any significant refractive error shift within the last two years (–0.05 D varying from

0.00 to –0.25 D).

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For all subjects the left eye was used for measurements. The subjects had no history of

significant corneal or ocular pathology and achieved 0 logMAR, or better, corrected

vision. The experiment was always conducted in the morning between 9.00 and

12.00 am. All subjects were given the instruction not to perform any significant near

tasks prior to the experiment. Informed consent was obtained for all subjects.

The protocol and data collection procedures were similar to those described in the

“Corneal aberrations and reading” study (Chapter 4). The Keratron videokeratoscope

(EyeQuip Division, Alliance Medical Marketing, Jacksonville, FL) was used for all

corneal topography measurements. Prior to the study, the instrument calibration was

checked according to the manufacturer’s instructions. For both the myopic and

emmetropic groups, six baseline videokeratographs were taken prior to a 1-hour reading

task and again immediately after 1-hour of reading and after a further 1-hour reading

task (i.e. after a total of 2 hours of reading). Reading distance for each individual was

measured at the beginning of the reading trials and compared as a function of refractive

error group.

Digital photography was used to document the external ocular features with the eyes in

reading gaze posture, and also with the subject positioned in a headrest with eyes in

primary gaze focusing on a 5-m distant Bailey-Lovie Chart. For subsequent analysis, a

calibration scale was placed within the frame of the images taken in the headrest with

eyes in primary gaze. The subjects were informed that at some stage during the reading

protocol, a photo of the left eye would be taken. The subjects were instructed, when

approached, not to change their reading posture as a consequence of the photography.

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A software program for digital image processing measurement was used for analysis of

the external eye images (Iskander et al. 2003). Utilising several customised image-

processing techniques the software allowed automatic analysis of the pupil, limbus, and

palpebral fissure parameters. After acquisition of eye biometrics from the photographs

taken in the headrest with eyes in primary gaze, the horizontal limbus diameter was used

as a reference for calibration and subsequent analysis of the digital photographs taken

with the eye in natural reading gaze posture.

Corneal instantaneous power and height data were exported from the videokeratoscope

for analysis. For the instantaneous power maps, the six corneal measurements taken

from each subject for each of the pre- and post-reading conditions were averaged. Then

the individually averaged pre- and post-reading maps were used to calculate the group

mean instantaneous power and standard deviation map for both the emmetropic group

and the myopic group. To study the potential effect of reading on topography, the

average difference map of pre- versus post-reading topography was calculated for each

reading period and refractive error group along with the t-test maps showing significant

areas of change within the maps.

The corneal wavefront was calculated using the same methods as in Chapter 4, but this

time Zernike terms of up to the sixth radial order (OSA convention) were fitted to the

corneal wavefront. For the two post-reading conditions the wavefront was calculated at

the baseline circle of least confusion in order to highlight potential changes in corneal

spherical power. The lower order Zernike wavefront coefficients were used to calculate

corneal sphero-cylinder power (Salmon 1999) at the pre-reading circle of least

confusion before and after reading for pupil sizes of 3, 4, and 5 mm. Power matrices

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(Harris 2000) were applied to calculate the group mean best-fit sphero-cylinder for each

condition and again to calculate the corneal changes in sphere, cylinder and astigmatic

axis pre versus post-reading. The Hotelling’s T2 multivariate test was used to test the

significance of overall change in corneal sphero-cylinder between the emmetropic and

myopic groups. For the 3, 4, and 5 mm pupil sizes, the group mean corneal wavefront,

root mean square error RMS was calculated as total wavefront RMS change, total higher

order wavefront RMS change, 3rd order, 4th order, 5th order, and 6th order wavefront

RMS change. T-tests were applied to investigate the significance of change of the

various wavefront RMS components between the emmetropic and myopic subjects.

After the subjects had finished the reading experiment, they were asked complete a near

task activity questionnaire (Table 5-1). The questionnaire was based on the

questionnaire reported by Walline, but was adapted for the near work activity of a

university student population (Walline et al. 2001). Questions included the number of

hours per week of university classes, how many hours per week outside of university

classes students do study or read for assignments, use a computer, read for pleasure, and

do intensive near work activities (e.g. model building, sewing etc.).

A point system was developed to characterise the relevance of different visual near task

activities with respect to its potential to affect corneal shape and optics. It has been

shown that different visual near tasks such as computer work, reading, and microscopy

have different effects on the corneas’ optical changes within the central pupil area

(Collins et al. 2003). Furthermore, eye movements during reading appear to play an

important role in intensifying these effects (Chapter 4). Therefore, near tasks that are

usually performed in downward gaze and are accompanied by systematic eye

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movements such as “study or read for assignment” or “reading for pleasure” were

assigned factor 3 = high relevance. Other near work activities that are usually performed

in downward gaze but are not typically associated with systematic eye movements such

as model building were assigned factor 2 = medium relevance, while computer work

was given a factor of 1 = low relevance because of the relatively horizontal gaze

direction during computer work. For the hours of weekly university classes a medium

relevance factor of 2 was assigned. Each subject’s weekly hours for each of the near

work activities were multiplied with its weighting factor and then added to a total value

representing the weekly near work activity as a function of its potential effect corneal on

shape and optics.

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CORNEAL ABERRATIONS FOLLOWING READING REPORT OF NEAR WORK ACTIVITY

Patient Age Gender

Sph Cyl Axis Myopia progression within the last 2 years How many hours per week of university classes do you have?

How many hours per week outside of university classes do you: Study or read for assignments? Hours

Use a computer? Hours Read for pleasure? Hours

Do intensive near work activities (e.g. model building, sewing etc.)

Hours

Table 5-1: Near work activity questionnaire for a university student population. Near work

activities are categorised in relevance levels according to the near task’s potential to change

corneal shape and optics. Study or read for assignment and reading for pleasure = factor 3: high

relevance. Intensive near work activities such as model building and university classes = factor

2: medium relevance, while computer work = factor of 1: low relevance.

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5.3 RESULTS

Both emmetropic and myopic groups showed corneal shape and optics changes

following 1-hour and 2 hours of reading. The main difference between the two groups

was the location and magnitude of the corneal distortions, which had a significantly

larger effect on central corneal optics in the myopic group compared to the emmetropic

group.

The average baseline (pre-reading) corneal instantaneous power maps (Figure 5-1) for

the ten emmetropes (left) and the ten myopes (right) show higher corneal astigmatism in

the myopic group (emmetropes: cyl –0.56 D axis 27º; myopes: cyl –1.03 D axis 3º)

indicating that the higher total astigmatism amongst the myopes is primarily of corneal

origin. The relevant standard deviation maps were calculated at each point of the

average maps for each of the two groups (bottom panel). Particularly in the upper semi-

meridian toward the 12 o’clock position, the myopic group shows increasing standard

deviation indicating larger variability of slope of the myopic “baseline” (pre-reading)

corneas within this region. There is also a small, but less distinctive, increase of the

standard deviation within the emmetropic corneas in this area. After one hour of

reading (Figure 5-2) the corneas of myopes become increasingly asymmetrical due to a

flattening of the central upper semi-meridian, as can be seen in the difference map

(centre right). P-values within the t-test maps (bottom panel) show little to no statistical

significance of the changes.

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BASELINE CORNEAL TOPOGRAPHY

Emmetropes (n = 10) Myopes (n = 10)

Figure 5-1: Average baseline instantaneous power map of emmetropic group (top left) and myopic

group (top right) for a 6 mm pupil zone. Bottom left: Standard deviation map calculated at each point

of the average map based on the emmetropic group (n = 10). Bottom right: Standard deviation map

calculated at each point of the average map based on the myopic group (n = 10).

Instantaneous Power Instantaneous Power

Standard Deviation Standard Deviation

* = t-test significant at (p = 0.05)

Sph +0.32 Cyl –0.56 Axis 27 Sph +0.59 Cyl –1.03 Axis 3

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POST-1HR-READING CORNEAL TOPOGRAPHY

Emmetropes (n = 10) Myopes (n = 10)

Figure 5-2: Average post 1-hour reading instantaneous power map of emmetropic group (top left) and

myopic group (top right) for a 6 mm pupil zone. Centre: Instantaneous power difference map of post

reading minus baseline instantaneous power for emmetropic group (center left) and myopic group

(center right). Bottom right: Significance map based on t-tests at all points within the map for

emmetropic group (bottom left) and myopic group (bottom right).

Instantaneous Power Instantaneous Power

Difference Map Difference Map

P-value map P-value map

* = t-test significant at (p = 0.05)

Sph +0.61 Cyl –0.92 Axis 6 Sph +0.31 Cyl –0.63 Axis 29

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POST-2HR-READING CORNEAL TOPOGRAPHY

Emmetropes (n = 10) Myopes (n = 10)

Figure 5-3: Average post 2-hour reading instantaneous power map of emmetropic group (top left) and

myopic group (top right) for a 6 mm pupil zone. Centre: Instantaneous power difference map of post

reading minus baseline instantaneous power for emmetropic group (center left) and myopic group

(center right). Bottom right: Significance map based on t-tests at all points within the map for

emmetropic group (bottom left) and myopic group (bottom right).

Instantaneous Power Instantaneous Power

Difference Map Difference Map

P-value map P-value map

* = t-test significant at (p = 0.05)

Sph +0.62 Cyl –0.86 Axis 7 Sph +0.25 Cyl –0.57 Axis 28

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After two hours of reading (Figure 5-3 top) the mean corneal map of the myopic group

shows a distinct band like distortion at less than 2 mm from the pupil centre. The mean

corneal map of the emmetropes also shows more asymmetry due to distortions in the

upper cornea at about 2.5 mm from the pupil centre. The changes are highlighted in the

difference maps showing a similar but larger and more complex distortion pattern in the

myopic group. The distortions in the myopes are more closely located to the pupil centre

and show higher statistical significance (bottom right) than in case of the emmetropic

group (bottom left).

The change of corneal wavefront RMS error after two hours of reading is shown in

Figure 5-4. What becomes evident from this analysis is that a large proportion of the

increased total wavefront RMS error change in the myopic group comes from the lower

order defocus and primary astigmatism components. In comparison, the emmetropic

group does not show such a distinct difference between total RMS and higher order

RMS changes. For a 5 mm pupil, the amount of the total higher order RMS changes in

both groups are very similar. When the RMS error is analysed in terms of the Zernike

higher order components, a more complex distortion pattern within the myopic group is

indicated by larger 4th order RMS changes and significantly larger 5th order RMS

changes (p = 0.008) in the myopes, while the 3rd order components are larger in the

emmetropes. For the smaller pupil regions of 4 mm and 3 mm, the magnitude of change

in the Zernike 4th, 5th, and 6th order terms became less significant in myopes and

emmetropes. As a consequence, within a 3 mm pupil zone the myopes show increased

higher order RMS changes. In the 3 mm pupil these changes are primarily due to the 3rd

order components in the myopes resulting in a statistically significant increase of the

total wavefront RMS error (p = 0.029) in this pupil size.

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Analysis of the corneal wavefronts revealed significantly changed wavefront

coefficients for both groups after one and two hours of reading. For a 5 mm pupil the

corneal wavefront coefficients before and after 2 hours of reading for the emmetropic

group and the myopic group are shown in Figure 5-5 and Figure 5-6 respectively. As in

Chapter 4, for the myopic group the changes in primary vertical coma and trefoil along

30º were similar in magnitude and as such that primary vertical coma shifted in negative

direction while the trefoil component shifted in positive direction. Statistical significant

corneal wavefront coefficients for emmetropes and myopes for all pupil sizes are

summarized in Table 5-2.

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-0.08

-0.04

0

0.04

0.08

0.12

0.16

0.2

0.24

0.28

0.32

0.36

0.4

0.44

Cha

nge

in W

avef

ront

RM

S V

alue

(mic

rons

)Myopic GroupEmmetropic Group

Figure 5-4: Group mean change (±SD) in wavefront root mean square error (RMS) after 2 hours of reading for myopes and emmetropes for three different

pupil sizes (3, 4, and 5 mm) is shown. Corneal wavefront RMS is presented as total RMS, higher order RMS, 3rd order, 4th order, 5th order, and 6th order RMS

components along with the relevant significance values for the t-test comparison between the change in value for the myopic versus emmetropic groups.

5 mm Pupil 4 mm Pupil 3 mm Pupil

Total RMS

Higher Order

3rd Order

4th Order

5th Order

6th Order

p-Value 0.079

0.726

0.212

0.076

0.008

0.404

p-Value 0.114

0.229

0.633

0.321

0.221

0.488

p-Value 0.029

0.052

0.079

0.083

0.269

0.173

Total RMS

Higher Order

3rd Order

4th Order

5th Order

6th Order

Total RMS

Higher Order

3rd Order

4th Order

5th Order

6th Order

Corneal Wavefront RMS change after 2 hours of Reading (OSA convention)

*

*

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Chapter 5 _

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Figure 5-5: Group mean wavefront coefficients (±SD) of emmetropes before and after 2 hours of reading for a 5 mm pupil sizes is shown. Zernike terms

according to OSA convention of up to the 6th order polynomial expansion are presented. Piston and the prism coefficients are excluded.

-0.5

-0.45

-0.4

-0.35

-0.3

-0.25

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

Zernike Coefficients (OSA convention)

Cha

nge

in W

avef

ront

Err

or C

oeff

icie

nt V

alue

(mic

rons

)BaselinePost 2-h read

* = t-test significant at (p < 0.05)

13−Z 3

3−Z 4

4−Z 1

3Z

33Z

24Z

04Z

24−Z 4

4Z

55−Z 3

5−Z 1

5−Z 1

5Z 35Z

55Z

66−Z 4

6−Z 2

6−Z 0

6Z

26Z

46Z

66Z

22Z

22−Z 0

2Z

* * *

Emmetrope Group: Baseline and post 2-hours reading Zernike wavefront coefficients (5 mm pupil)

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Figure 5-6: Group mean wavefront coefficients (±SD) of myopes before and after 2 hours of reading for a 5 mm pupil sizes is shown. Zernike terms

according to OSA convention of up to the 6th order polynomial expansion are presented. Piston and the prism coefficients are excluded.

-0.5

-0.45

-0.4

-0.35

-0.3

-0.25

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

Zernike Coefficients (OSA convention)

Cha

nge

in W

avef

ront

Err

or C

oeff

icie

nt V

alue

(mic

rons

)BaselinePost 2-h read

* = t-test significant at (p < 0.05)

13−Z 3

3−Z 4

4−Z 1

3Z

33Z

24Z

04Z

24−Z 4

4Z

55−Z 3

5−Z 1

5−Z 1

5Z 35Z

55Z

66−Z 4

6−Z 2

6−Z 0

6Z

26Z

46Z

66Z

22Z

22−Z 0

2Z

Myopic Group: Baseline and post 2-hours reading Zernike wavefront coefficients (5 mm pupil)

* * * *

* *

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Chapter 5 _

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Summary of significant corneal wavefront changes after 2 hours of reading for various pupil sizes:

Table 5-2: The change of various normalised corneal Zernike wavefront coefficients in microns (OSA convention) along with the relevant p-values for the

emmetropic and myopic group respectively is shown.

Emmetropic Group Myopic Group

Zernike Pupil Pupil Pupil Pupil Pupil Pupil

Microns 3 mm p-value 4 mm p-value 5 mm p-value 3 mm p-value 4 mm p-value 5 mm p-value

11−Z -0.031 0.006 -0.049 0.003 -0.064 0.041 -0.086 0.018 -0.10 0.006 2

2−Z -0.008 0.031 -0.009 0.042 22Z 0.036 0.040 0.039 0.004 3

3−Z 0.020 0.017 0.015 0.017 0.010 0.023

13−Z -0.007 0.010 -0.014 0.010 -0.019 0.003 -0.022 0.020 -0.017 0.002 -0.014 0.012 13Z -0.004 0.047 -0.005 0.011 -0.007 0.027 -0.008 0.018 2

4−Z 0.004 0.049 0.005 0.049

44−Z 0.003 0.044 04Z 0.002 0.036

55−Z -0.002 0.030 0.004 0.035 66Z -0.003 0.039

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The difference in corneal wavefront error coefficient changes after two hours of reading

between the myopic and emmetropic groups revealed a significantly larger change of

the 22Z primary astigmatism term in direction of against-the-rule in the myopic group

(p < 0.05 at 5 mm) (Figure 5-7). The 02Z defocus term shifted toward corneal flattening

(hyperopia) in myopes (see Figure 5-6) while emmetropes tended to show slightly

steeper corneas following reading (see Figure 5-5). This led to a significant 02Z defocus

term difference (p < 0.05 at 3, 4, and 5 mm) between emmetropes and myopes. There is

little statistically significant change within the 3rd order terms, however several 4th and

higher order terms changed significantly different, confirming the more complex

distortion pattern of the instantaneous power maps in the myopes.

The effect on corneal higher order RMS of time spent reading revealed a linear trend

towards more significant changes for longer reading periods and larger pupils (4 mm

and 5 mm pupil) within the emmetropic group (Figure 5-8). After one hour of reading

the higher order wavefront RMS values show larger increases in the myopic group,

reaching statistically significant differences compared with the emmetropic group for

the three pupil sizes analysed. After two hours of reading the mean corneal higher order

wavefront RMS for myopes decreases slightly relative to the 1-hour reading trial while

emmetropes continued to increase. However, for the 4 mm and 5 mm pupils the

difference still was significantly larger in myopes. The mean corneal higher order

wavefront RMS in microns for a 3, 4, and 5 mm pupil at the baseline condition was not

significantly higher in the myopic group compared with the emmetropic group

(emmetropes: 0.07 µm, 0.11 µm, and 0.19 µm ; myopes: 0.08 µm, 0.16 µm, and 0.26

µm for a 3, 4, and 5 mm pupil respectively).

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-0.15

-0.125

-0.1

-0.075

-0.05

-0.025

0

0.025

0.05

0.075

0.1

Zernike Coefficients (OSA convention)

Cha

nge

in W

avef

ront

Err

or C

oeff

icie

nt V

alue

(mic

rons

) 3mm Pupil4mm Pupil5mm Pupil

Figure 5-7: Group mean difference in wavefront coefficient change (±SD) between myopes and emmetropes after 2 hours of reading for three different pupil

sizes (3, 4, and 5 mm) is shown. Zernike terms according to OSA convention of up to the 6th order polynomial expansion are presented. Piston and the prism

coefficients are excluded.

* = t-test significant at (p < 0.05)

13−Z 3

3−Z 4

4−Z 1

3Z

33Z

24Z

04Z

24−Z 4

4Z

55−Z 3

5−Z 1

5−Z 1

5Z 35Z

55Z

66−Z 4

6−Z 2

6−Z 0

6Z

26Z

46Z

66Z

22Z

22−Z 0

2Z

* * * * *

* *

* *

* * *

Corneal wavefront error change after 2 hours of reading (Difference for Myopic minus Emmetropic Group)

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0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

Hig

her

orde

r wav

efro

nt R

MS

(mic

rons

)

Emmetrope

Myope

Figure 5-8: Higher order corneal wavefront RMS (±SD) before and after 1-hour and 2 hours of reading for myopic group and emmetropic group. The increase for various pupil sizes is shown.

pre-read post 1-h post 2-h

pre-read post 1-h post 2-h

pre-read post 1-h post 2-h

3 mm pupil 4 mm pupil 5 mm pupil

*

*

* *

*

* = t-test significant at (p < 0.05)

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Chapter 5 _

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The group mean characteristic shape difference between emmetropes and myopes of the

total corneal wavefront in a 5 mm pupil zone after 2 hours of reading, show increased

differences in the upper region of the wavefront (Figure 5-9 top left). The higher order

Zernike wavefront (top right) as well as 4th and 5th order components (centre right and

bottom left) show the characteristic band like distortion pattern following reading with

the 4th order component (centre right) making up for most (RMS = 0.0595 µm) of the

differences in higher order wavefront error change between the myopes and the

emmetropes.

In Table 5-3 the group mean corneal sphero-cylinder and corneal best sphere lens

(sphero-cyl and BSL measured at pre-reading circle of least confusion) before and after

1 hour and 2 hours of reading are shown along with the differences, and the statistical

significance of the changes (Hoteling T2). For the myopes, within the 3 and 4 mm pupils

the group mean sphere and cylinder after 2 hours of reading show the largest changes

with sph +0.22 (±0.35) and cyl –0.21 (±0.32) for a 3 mm pupil, while for a 4 mm pupil a

change of sph +0.22 (±0.27) and cyl –0.23 (±0.23) is shown. However only within the 3

mm pupil, the sphero-cylinder change at 1 hour after reading in the myopic versus the

emmetropic group is significantly different (Hoteling T2, p = 0.049). The changes in

corneal wavefront RMS are shown in Table 5-2 along with the t-test results for each

group. For both myopic and emmetropic groups there is a trend towards more

significant changes for larger pupils and longer reading periods.

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Wavefront Error Difference (Myopic minus Emmetropic Group)

All Coefficients Higher Order

3rd order 4th order

5th order 6th order

Figure 5-9: Group mean difference in wavefront root mean square error (RMS) between myopes

and emmetropes (myopes minus emmetropes) is shown. Corneal wavefront RMS difference is

presented as total RMS (top left) along with the sphero cylinder change, higher order RMS (top

right), 3rd order (centre left), 4th order (centre right), 5th order (bottom left), and 6th order RMS

components (bottom left).

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Emmetropic and myopic group data of sphero-cylinder changes

Emmetropes (n = 10) Myopes (n = 10)

Pupil 3mm Pupil

3mm

Baseline Sph Cyl A BSL HO RMS Baseline Sph Cyl A BSL HO

RMS Mean

SD 0.32

(±0.19) -0.56

(±0.39) 27 0.040 (±0.07)

0.067 (±0.013)

Mean SD

0.59 (±0.38)

-1.03 (±0.75) 3 0.070

(±0.047) 0.081

(±0.03)

Post1-h read Sph Cyl A BSL HO RMS Post1-h read Sph Cyl A BSL HO

RMS Mean

SD 0.31

(±0.18) -0.63

(±0.39) 29 0.000 (±0.08)

0.071 (±0.012)

Mean SD

0.61 (±0.38)

-0.92 (±0.70) 6 0.148

(±0.184) 0.104

(±0.04) Difference

SD 0.00

(±0.07) -0.09

(±0.07) 46 -0.040 0.004 Difference SD

0.15 (±0.24)

-0.14 (±0.18) 78 +0.079 0.023

T-Test T-Test T-Test T-Test P=0.095 p=0.229

P=0.165 p=0.043

Difference in Sphero-Cylinder change between Emmetropic and Myopic Groups Hoteling T2: p = 0.049

Post2-h read Sph Cyl A BSL HO RMS Post2-h read Sph Cyl A BSL HO

RMS Mean

SD 0.25

(±0.24) -0.57

(±0.38) 28 -0.033 (±0.129)

0.069 (±0.012)

Mean SD

0.62 (±0.34)

-0.86 (±0.71) 7 0.187

(±0.232) 0.099

(±0.05) Difference

SD -0.06

(±0.15) -0.04

(±0.05) 61 -0.07 0.005 Difference SD

0.22 (±0.35)

-0.21 (±0.32) 76 +0.117 0.018

T-Test T-Test T-Test T-Test P=0.126 p=0.365

P=0.115 p=0.356

Difference in Sphero-Cylinder change between Emmetropic and Myopic Groups Hoteling T2: p = 0.165 Pupil 4mm Pupil

4mm

Baseline Sph Cyl A BSL HO RMS Baseline Sph Cyl A BSL HO

RMS Mean

SD 0.36

(±0.19) -0.59

(±0.42) 26 0.068 (±0.051)

0.107 (±0.028)

Mean SD

0.58 (±0.40)

-1.01 (±0.76) 1 0.076

(±0.026) 0.158

(±0.08)

Post1-h read Sph Cyl A BSL HO RMS Post1-h read Sph Cyl A BSL HO

RMS Mean

SD 0.34

(±0.16) -0.63

(±0.38) 27 0.029 (±0.06)

0.120 (±0.028)

Mean SD

0.58 (±0.38)

-0.85 (±0.78) 4 0.15

(±0.14) 0.191

(±0.094) Difference

SD -0.01

(±0.07) -0.06

(±0.06) 46 -0.039 0.012 Difference SD

0.16 (±0.22)

-0.18 (±0.20) 78 +0.076 0.034

T-Test T-Test T-Test T-Test P=0.07 P=0.10

P=0.120 p=0.101

Difference in Sphero-Cylinder change between Emmetropic and Myopic Groups Hoteling T2: p = 0.110

Post2-h read Sph Cyl A BSL HO RMS Post2-h read Sph Cyl A BSL HO

RMS Mean

SD 0.28

(±0.24) -0.62

(±0.41) 27 -0.029 (±0.143)

0.128 (±0.028)

Mean SD

0.59 (±0.37)

-0.81 (±0.78) 5 0.1833

(±0.168) 0.177

(±0.065) Difference

SD -0.08

(±0.17) -0.04

(±0.05) 54 -0.097 0.021 Difference SD

0.22 (±0.27)

-0.23 (±0.23) 77 +0.108 0.019

T-Test T-Test T-Test T-Test P=0.086 p=0.067

p=0.074 p=0.46

Difference in Sphero-Cylinder change between Emmetropic and Myopic Groups Hoteling T2: p = 0.088 Pupil 5mm Pupil

5mm

Baseline Sph Cyl A BSL HO RMS Baseline Sph Cyl A BSL HO

RMS Mean

SD 0.42

(±0.21) -0.61

(±0.43) 25 0.112 (±0.048)

0.186 (±0.05)

Mean SD

0.62 (±0.41)

-1.02 (±0.76) 1 0.112

(±0.029) 0.260

(±0.11)

Post1-h read Sph Cyl A BSL HO RMS Post1-h read Sph Cyl A BSL HO

RMS Mean

SD 0.39

(±0.20) -0.63

(±0.41) 26 0.07 (±0.06)

0.202 (±0.04)

Mean SD

0.60 (±0.39)

-0.91 (±0.78) 2 0.15

(±0.08) 0.314

(±0.12) Difference

SD -0.03

(±0.08) -0.03

(±0.06) 44 -0.04 0.017 Difference SD

0.09 (±0.13)

-0.18 (±0.10) 79 +0.035 0.054

T-Test T-Test T-Test T-Test p=0.076 p=0.112

p=0.246 p=0.005

Difference in Sphero-Cylinder change between Emmetropic and Myopic Groups Hoteling T2: p = 0.167

Post2-h read Sph Cyl A BSL HO RMS Post2-h read Sph Cyl A BSL HO

RMS Mean

SD 0.33

(±0.26) -0.61

(±0.40) 27 0.02 (±0.14)

0.219 (±0.06)

Mean SD

0.615 (±0.39)

-0.86 (±0.74) 3 0.19

(±0.11) 0.30

(±0.10) Difference

SD -0.06

(±0.17) -0.05

(±0.06) 71 -0.09 0.06 Difference SD

0.16 (±0.16)

-0.18 (±0.10) 80 +0.073 0.041

T-Test T-Test T-Test T-Test p=0.106 p=0.048

p=0.073 p=0.049

Difference in Sphero-Cylinder change between Emmetropic and Myopic Groups Hoteling T2: p = 0.054

Table 5-3: The best sphere lens (BSL) change is calculated from the difference between the

baseline corneal wavefront circle of least confusion and post reading circles of least confusion at

various pupil sizes. HO RMS = Higher order wavefront root mean square error.

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Analysis of digital image processing measurement revealed a significantly smaller

palpebral aperture for the myopic group in the reading gaze position (emmetropic group

= 8.15 mm (±1.91); myopic group = 6.74 mm (±1.21); p = 0.042) but not in primary

gaze position (emmetropic group = 10.72 mm (±1.44); myopic group = 10.21 mm

(±1.61); p = 0.47). Also the distance from the upper lid margin to the pupil centre in the

myopic group was significantly smaller in reading gaze position (emmetropic group =

3.38 mm (±1.50); myopic group = 2.14 mm (±1.0); p = 0.028) but not in primary gaze

position (emmetropic group = 4.52 mm (±1.04); myopic group = 4.08 mm (±0.73); p =

0.29). No statistical significant difference was found for the distance from the lower lid

margin to the pupil centre either in primary gaze position (emmetropic group = 6.20 mm

(±0.82); myopic group = 6.13 mm (±1.00); p = 0.87) or in reading gaze position

(emmetropic group = 4.77 mm (±1.07); myopic group = 4.6 mm (±0.59); p = 0.63). A

typical example of reading gaze ocular biometrics for an emmetropic subject and a

myopic subject (Figure 5-10) is shown.

Average horizontal limbus diameter was 12.36 mm (±0.48) for the emmetropic group

and for the myopic group 11.97 mm (±0.61) (p = 0.13). The average reading distance

for emmetropes was 42.80 cm ranging from 30 to 52 cm, while myopes showed a mean

reading distance of 36.60 cm ranging from 23 to 48 cm (p = 0.087). Near work activity

scores showed 82 (±26) for the emmetropes and 97 (±31) for the myopes (p = 0.24)

respectively.

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Chapter 5 _

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Figure 5-10: Ocular biometrics data in reading gaze position using automatic image

measurement techniques for an emmetropic subject (left) and a myopic subject (right)

respectively. The information extracted from digital photographs is PUPIL d = pupil diameter,

LIMBUS d = limbus diameter, APERTURE UP = distance from limbus centre to upper lid

margin, and APERTURE DOWN = distance from limbus centre to lower lid margin.

PUPIL d = 4.13 mm LIMBUS d = 12.00 mm Aperture UP = 3.38 mm

Aperture DOWN = 4.89 mm

PUPIL d = 3.79 mm LIMBUS d = 10.79 mm Aperture UP = 2.26 mm

Aperture DOWN = 4.69 mm

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5.4 DISCUSSION

The major difference between the two groups of emmetropes and myopes found in this

study was the location and magnitude of corneal distortions following reading. This was

most noticeable in the instantaneous power difference maps and supported by the digital

image analysis of lid position during reading. For the myopic group, the location and

magnitude of distortions caused larger central corneal optical changes as compared with

the emmetropes, which was most clearly highlighted by the total RMS error changes.

Almost all subjects showed some changes in the corneal instantaneous power

topography after two hours of reading. The exception was one emmetropic subject in

whom there was virtually no change in topography apparent after two hours of reading.

This emmetropic subject also showed the largest palpebral aperture in the reading gaze

position (12.3 mm) and this provides a likely explanation for the lack of central (>5mm)

corneal topography changes.

Corneal wavefront RMS analysis revealed that distortions closer to the pupil centre not

only have a larger impact on higher order Zernike term components but also

significantly change the lower order astigmatism and defocus components. Analysis of

corneal wavefront error confirmed several of the previously reported results (Chapter 4),

which were found to be associated with the band like distortions related to lid forces.

For the myopic group an astigmatic shift in the direction of against-the-rule, as well as

significant changes of the primary vertical coma and trefoil along 30° terms were found.

While the link between lid force effects on the cornea and the changes of coma and

trefoil components is interesting, it may not always be a precise description for these

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corneal distortions. As distortions become more complex, a combination of secondary

astigmatism and tetrafoil components in addition to some 5th and 6th order terms may

provide a more accurate description. For larger pupils in particular, several 5th and 6th

order Zernike coefficients changed significantly in both groups indicating that Zernike

terms up to the 4th order may not always be enough to adequately describe the changes

in the corneal surface associated with lid forces.

Due to the 1 hour and 2 hour time periods the participants spent on reading, it was

possible to gain an impression of the effect of time on distortions, which showed a

group mean increase in magnitude of distortions and optical effects with increasing

time. Some subjects did not show increased higher order aberration changes after 2

hours, but rather showed a slight decrease relative to the 1-hour trial. While there was a

group mean increase in lower order terms, the change in higher order components did

not always lead to an increased higher order wavefront RMS. In one myopic subject the

corneal changes after reading even lead to a decrease in wavefront RMS error compared

with the subject’s baseline RMS. The differences between the 1-hour and 2 hour trial

might also be affected by a change in reading strategy (i.e. a change in body or head

posture or a change in book position) after a certain period of reading. To further

investigate this effect, continuous or periodic digital photos of lid and eye position

during the entire reading period would need to be taken. Reading a book for 2 hours

without any breaks is probably uncommon. In our experiment there was a short break of

just a view minutes between the 1-hour and 2 hour reading trials to collect corneal data

after the first hour of reading.

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Averaging of individuals’ corneal instantaneous power maps (Figure 5-1 to Figure 5-3)

may have resulted in distortions being masked due to differences in location on the

corneal surface. However the aim of this analysis was to illustrate the group mean trend

for emmetropes and myopes. A more accurate analysis is provided by the corneal

wavefront Zernike coefficients and RMS data.

The most commonly reported subjective visual observation that has been reported

following reading is monocular vertical doubling (Fincham 1963; Mandell 1966; Knoll

1975; Bowman et al. 1978; Carney et al. 1981; Kommerell 1993; Ford et al. 1997;

Campbell 1998; Golnik and Eggenberger 2001). Some studies have estimated the time

course of remission of distortions after reading based on subjective perception of

remission of the vertical doubling (Knoll 1975; Golnik and Eggenberger 2001). When

objectively measuring the time course of remission of the lid induced changes on the

corneal surface, there appears to be a non-linear decrease in the distortion with a large

proportion of the effect disappearing within a short time period after cessation of

reading, followed by a continuous slowing down of the process that may take more than

120 minutes after 60 minutes of reading (Chapter 4). It has also been shown that lid

related distortions in the periphery of the cornea change within seconds during the post-

blink interval (Buehren et al. 2001).

The optical effects during reading with the eyelids in reading gaze posture are likely to

be larger, taking into account short term changes that have been reported within the

post-blink interval (Buehren et al. 2001). In order to allow individual statistical analysis

to be drawn from our data and to improve accuracy, we have collected six corneal

topography measurements for each subject and each of the pre- and post reading

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conditions. After reading, several subjects’ data showed a small trend towards

decreasing distortions even within the short time frame it took to capture the six images

(approximately 30 sec). Furthermore, the effect of the tear meniscus at the lid margin in

cases where the upper lid position is near the upper pupil edge could also contribute to

changes in optical characteristics during reading. In order to capture the full magnitude

of the optical changes of eyes during reading it would be necessary to measure the eye’s

corneal and total wavefront aberrations after a period of reading with the eye in the

reading gaze position.

The exact mechanism of how the changes on the corneal surface occur is not clear. The

pattern of remission could indicate cell displacement similar to the mechanism that has

been proposed in orthokeratology (Swarbrick et al. 1998). However this assumption

needs to be confirmed by pachometry of the epithelium.

The likelihood of corneal distortions effecting overall visual performance during the day

will be significantly influenced by the time spent on near work activities. The sample of

myopes in this study reported that they spend about 20 % more time on near work

activities than the sample of emmetropes, although the difference was not statistically

significant. The myopes also used smaller reading distances than emmetropes, which is

likely to have an influence on eye movements during reading.

The issue of labelling subject groups as emmetropic and progressing myopes in this

study is not straightforward. If changes in topography associated with lid forces during

reading lead to myopia progression then the amount of time spent reading is an

important factor influencing myopia progression. It is conceivable that a subject

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classified as emmetropic might have significant corneal changes associated with lid

forces following reading. However if this subject performs little habitual reading, then

there would be no stimulus for myopia progression. On the other hand a subject with

lesser lid force, who reads often, could become a progressing myope. Therefore the

possible influence of lid forces during reading on myopia progression cannot be

considered in isolation from the amount of time spend reading.

Prolonged near work, which is a well established environmental risk factor associated

with myopia development (Tan et al. 2000; Hepsen et al. 2001; Saw et al. 2002) has

drawn researchers attention in the field of ocular wavefront aberrations. Changes in

spherical aberration with accommodation have been reported to decrease from positive

spherical aberration and changed to negative values with increasing levels of

accommodation (Koomen et al. 1949; Ivanoff 1956; Jenkins 1963; Atchison et al. 1995;

Ninomiya et al. 2002). Third order (coma and coma-like) aberrations are dominant for

most people (Howland and Howland 1976; Howland and Howland 1977; Walsh et al.

1984; Walsh and Charman 1985) and also have found to change with accommodation

(Atchison et al. 1995; He et al. 2000; Ninomiya et al. 2002).

One of the main interests in the field of myopia research is the mechanism of

accommodation and its possible relationship to myopia development. Using auto-

refractometers, a large number of studies have investigated whether accommodative

stimulus/response behaviour differs with refractive error (McBrien and Millodot 1986;

Rosenfield and Gilmartin 1988; Gwiazda et al. 1993; Gwiazda et al. 1995; Abbott et al.

1998). A common hypothesis is that accommodative lag results in a blurred retinal

image (hyperopic defocus), which in turn triggers eye growth. This is consistent with

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the results of animal studies (Schaeffel et al. 1988; Wildsoet 1997) that have

demonstrated that in the presence of artificially imposed hyperopic retinal defocus (with

negative lenses), the axial length of the eye increases, presumably to compensate for the

induced retinal defocus, and myopia develops. Reduced accommodation stimulus

responses in myopes have been reported in many studies (i.e. lags of accommodation

tend to be higher in myopes) (McBrien and Millodot 1986; Rosenfield and Gilmartin

1988; Gwiazda et al. 1993; Gwiazda et al. 1995). Conflicting reports have found that an

increased lag of accommodation accompanies rather than precedes the development of

myopia (Rosenfield et al. 2002).

Considering the various factors that can affect visual performance during the reading

process, much remains unknown. The complex optical characteristics shown by corneal

distortions and their interaction with internal ocular aberrations have not been

investigated. Studies that use wavefront sensors to investigate far and near viewing

conditions have the potential to provide more detailed information about the eye’s

optical characteristics during and after reading. While there is ongoing research

concerning the accommodation system, little is known about how corneal distortions

might affect accommodation. Furthermore the question must be raised of how much of

the apparent differences found in accommodation behaviour in myopes might have their

origin in the changes in corneal aberrations associated with reading in downgaze.

The hypothesis that corneal distortions during reading may contribute to juvenile-onset

myopia is consistent with the hypothesis of retinal image-mediated ocular growth.

Congenital ptosis has been associated with higher incidence of refractive error. In this

study it is shown that the optical effects of prolonged narrowing of the palpebral

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aperture is likely to compromise retinal image quality during reading and thereby could

have an effect on retinal image-mediated ocular growth. The results of this study have

also shown that the distance from pupil centre significantly influences optical changes

due to corneal distortion. In the group of myopes in this study, corneal distortions

following reading tended to be larger and occur closer to the central corneal area

compared with the emmetropic group.

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