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Vincent, Stephen, Collins, Michael, Read, Scott, Carney, Leo, & Yap, Mau-rice(2011)Interocular symmetry in myopic anisometropia.Optometry and Vision Science, 88(12), pp. 1454-1462.

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https://doi.org/10.1097/OPX.0b013e318233ee5f

1

Interocular Symmetry in Myopic Anisometropia 1

Stephen J Vincent BAppSc(Optom)(Hons)1 2

Michael J Collins PhD FAAO1 3

Scott A Read PhD1 4

Leo G Carney DSc PhD FAAO1 5

Maurice KH Yap PhD FAAO2 6

1 Contact Lens and Visual Optics Laboratory, School of Optometry, Queensland University of 7

Technology, Brisbane, Queensland, Australia 8

2 Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, 9

Hong Kong, PR China 10

11

Corresponding author: 12

Stephen Vincent 13

Contact Lens and Visual Optics Laboratory 14

School of Optometry 15

Queensland University of Technology 16

Room B556, O Block, Victoria Park Road, Kelvin Grove 4059 17

Brisbane, Queensland, Australia 18

Phone: 617 3138 5732, Fax: 617 3138 5665 19

Email: sj.vincent@qut.edu.au 20

21

Number of Tables: 6 22

Number of Figures: 2 23

Word count: 5038 (excluding abstract, figures and references) 24

Date submitted: May 12, 2011 25

26

2

Abstract 27

Purpose: To investigate the interocular symmetry of optical, biometric and biomechanical 28

characteristics between the fellow eyes of myopic anisometropes. 29

Methods: Thirty-four young, healthy myopic anisometropic adults (≥ 1 D spherical equivalent 30

difference between eyes) without amblyopia or strabismus were recruited. A range of biometric and 31

optical parameters were measured in both eyes of each subject including; axial length, ocular 32

aberrations, intraocular pressure (IOP), corneal topography and biomechanics. Ocular sighting 33

dominance was also measured. 34

Results: Mean absolute spherical equivalent anisometropia was 1.70 ± 0.74 D and there was a strong 35

correlation between the degree of anisometropia and the interocular difference in axial length (r = 36

0.81, p < 0.001). The more and less myopic eyes displayed a high degree of interocular symmetry for 37

the majority of biometric, biomechanical and optical parameters measured. When the level of 38

anisometropia exceeded 1.75 D, the more myopic eye was more likely to be the dominant sighting 39

eye than for lower levels of anisometropia (p=0.002). Subjects with greater levels of anisometropia 40

(> 1.75 D) also showed high levels of correlation between the dominant and non-dominant eyes in 41

their biometric, biomechanical and optical characteristics. 42

Conclusions: Although significantly different in axial length, anisometropic eyes display a high degree 43

of interocular symmetry for a range of anterior eye biometrics and optical parameters. For higher 44

levels of anisometropia, the more myopic eye tends to be the dominant sighting eye. 45

Key words: myopia, anisometropia, aberrations, biomechanics, dominance 46

47

3

Introduction 48

While there is evidence to suggest that both genetics and the environment may influence the 49

development of myopia, there is no theory which adequately explains the mechanisms underlying all 50

aspects refractive error development, including the refractive condition of anisometropia. Two 51

commonly proposed hypotheses include those where optical factors (such as ocular aberrations) or 52

mechanical factors (such as intraocular pressure (IOP) or forces generated during convergence) 53

promote excessive axial eye growth. 54

Anisometropia is a condition characterised by a difference in refractive error between fellow eyes 55

typically due to an interocular difference in axial lengths, in particular the depth of the vitreous 56

chamber.1 Hyperopic anisometropia that persists during early childhood is often associated with 57

amblyopia and strabismus due to the disruption of normal visual development.2 However, in myopic 58

anisometropia, in which the more myopic eye may still receive a clear image during close viewing, 59

amblyopia and strabismus are less likely to develop.3 Anisometropia may be used as an 60

experimental paradigm in refractive error research. Comparing the more and less ametropic eyes of 61

the same anisometropic subject allows for greater control of potential confounding inter-subject 62

variables (e.g. age, gender and ethnicity) compared to traditional cohort studies (i.e. myopes 63

compared to emmetropes). 64

If mechanical factors are primarily involved in anisometropic eye growth, then we would expect 65

differences in the biomechanical properties between the fellow eyes (such as corneal thickness, 66

corneal hysteresis, or IOP). Previous studies have confirmed that corneal thickness is similar 67

between the fellow eyes of anisometropes4, however recent studies have shown that the more 68

myopic eyes of anisometropes have slightly lower values of corneal hysteresis, suggesting a 69

reduction in mechanical strength of the cornea.4,5 70

4

Cross-sectional studies of IOP in anisometropic subjects using both contact and non-contact 71

applanation techniques have not consistently shown significant differences between the more and 72

less ametropic eyes.6-9 These studies suggest that axial elongation due to a simple IOP induced 73

expansion of the globe is unlikely to be involved in the development of myopia or axial 74

anisometropia. If a relationship does exist between IOP and axial elongation, we might expect that 75

IOP would be higher in the more myopic eye of anisometropes, at least during myopia development 76

or progression. 77

If optical factors contribute to asymmetric eye growth, we might anticipate differences in the optical 78

properties of the two eyes. However, previous studies have found only small or non-significant 79

differences between the fellow eyes of anisometropes for corneal10-12 or crystalline lens power.1 80

Tian et al13 investigated the interocular symmetry of ocular aberrations in myopic anisometropes (> 81

1.00 D spherical equivalent {SEq}) and found no significant interocular differences in individual 82

Zernike terms, 3rd, 4th and 5th order aberrations or total higher order aberrations. Kwan et al11 also 83

examined the interocular symmetry and magnitude of total ocular aberrations in myopic 84

anisometropia (> 2.00 D SEq) and observed a strong correlation between fellow eyes for a range of 85

Zernike terms but significantly higher levels of aberrations in the less myopic eyes (total, 3rd order 86

and 4th order root mean square (RMS) values and spherical aberration). 87

Previous biometric studies have examined the interocular symmetry of moderate to high degrees of 88

anisometropia including subjects with amblyopia, structural ocular abnormalities or pathology. In 89

this study we have examined the interocular differences in the fellow eyes of axial myopic 90

anisometropes without amblyopia, strabismus or ocular disease for a comprehensive range of 91

biometric, biomechanical and optical parameters. While we cannot rule out the influence of genetic 92

or environmental factors in the development of myopic anisometropia, we have compared the two 93

eyes within the one subject in an attempt to minimise the inter-subject variations in such variables. 94

5

Our hypothesis was that the more and less myopic eyes may exhibit biometric or optical differences 95

which may provide insight into the mechanism underlying asymmetric refractive error development. 96

Methods 97

Subjects and screening 98

Thirty-four young, healthy adult subjects aged between 18 and 34 years (mean age 24 ± 4 years) 99

with a minimum of 1.00 D of spherical-equivalent myopic anisometropia were recruited for the 100

study (mean anisometropia 1.70 ± 0.74 D). Subjects were recruited from the staff and students of 101

QUT (Queensland University of Technology, Brisbane, Australia) (n = 10) and HKPU (Hong Kong 102

Polytechnic University, Hong Kong, PR China) (n = 24). Twenty-two of the 34 subjects were female 103

and 31 of the subjects were of East Asian descent, with the remaining three subjects of Caucasian 104

ethnicity. 105

Before testing, subjects underwent a screening examination to determine subjective refraction, 106

binocular vision and ocular health status. Ocular sighting dominance was assessed using a forced 107

choice method (a modification of the hole-in-the-card test).14 Stereopsis was assessed using a 108

random dot stereo test (TNO test). All subjects were free of ocular or systemic disease and had no 109

history of ocular surgery or trauma. Subjects with best corrected visual acuity worse than 0.10 110

logMAR, strabismus, unequal visual acuities (interocular difference of greater than 0.10 logMAR) or a 111

history of rigid contact lens wear were excluded from the study. Fourteen soft contact lens wearers 112

were included in the study, but ceased contact lens wear for 36 hours prior to participation. 113

Approval from both the QUT and HKPU human research ethics committees was obtained before 114

commencement of the study and subjects gave written informed consent to participate. All subjects 115

were treated in accordance with the tenets of the Declaration of Helsinki. 116

Data collection procedures 117

A range of biometric and optical measurements were collected from the more and less myopic eye 118

of each subject including axial length, corneal topography, corneal biomechanics, intraocular 119

6

pressure and ocular aberrations. Measurements were taken using the same instruments 120

(manufacturer and model) at both sites and by the same author (SJV) to minimise the potential for 121

inter-operator variability. In order to standardise measurement conditions at both sites, the lighting 122

conditions were kept at mesopic levels for all ocular measures. 123

Axial length 124

Axial length (defined as the distance from the anterior corneal surface to the retinal pigment 125

epithelium) was measured using the IOLMaster (Carl Zeiss Meditec, Inc., Jena; Germany). The 126

IOLMaster is a non-contact instrument based on the principle of partial coherence laser 127

interferometry and has been found to provide precise, repeatable measurements of axial length in 128

children15 and adults.16,17 Five measures of axial length with a signal-to-noise ratio of greater than 129

2.0 were taken and averaged for each eye. 130

Corneal topography 131

Corneal topography was measured using the E300 videokeratoscope (Medmont Pty. Ltd., Victoria, 132

Australia) based on the Placido disc principle. Four measurements, captured according to the 133

manufacturers recommendations, were performed on each eye. 134

Ocular biomechanics 135

Corneal biomechanics and intraocular pressure were measured using the Ocular Response Analyzer 136

(ORA; Reichert Ophthalmic Instruments, Buffalo, New York, USA). The ORA is a non-contact 137

tonometer that uses an air impulse to take two pressure measurements; one while the cornea is 138

moving inward, and the other as the cornea returns. The average of these two pressure values 139

provides a Goldmann-correlated IOP measurement (IOPg). The difference between these two 140

pressure values is corneal hysteresis (CH), or the viscoelasticity of the corneal tissue.18 The CH 141

measurement also allows the calculation of the corneal-compensated intraocular pressure (IOPcc), 142

which is less affected by corneal properties than other methods of applanation tonometry.19 The 143

7

ORA also provides a measure of the corneal resistance to deformation, the corneal resistance factor 144

(CRF). Four measurements were performed and the mean for each parameter was calculated for 145

each eye. 146

Ocular aberrations 147

Total ocular monochromatic aberrations of each eye were measured using a Complete Ophthalmic 148

Analysis System (COAS) wavefront aberrometer (Wavefront Sciences, New Mexico, USA). The 149

system was modified to allow fixation of an illuminated external target at 6 metres via a beam 150

splitter between the eye and the wavefront sensor. The subject’s distance prescription was inserted 151

into a lens holder outside of the path of the COAS beam (after taking into account the change in 152

vertex distance) to allow a clear view of the fixation target. The eye not being measured was 153

occluded. Subjects had natural pupil sizes without pharmacological dilation during COAS 154

measurements. Room illumination was kept in the mesopic range to maximize the pupil size and to 155

optimise the visibility of the externally illuminated distance target during measurements. One 156

hundred wavefront measurements (4 x 25 frames) were taken for each eye and later averaged. 157

Data analysis 158

Corneal topography 159

Following data collection, corneal refractive power and height data were exported from the 160

videokeratoscope. Topography maps that displayed poor focus or local irregularities such as tear 161

film instability were excluded from analysis. Topography data were analysed using customised 162

software. Refractive power maps and corneal height data were averaged using an established 163

technique20 assuming a corneal refractive index of 1.376. This analysis was conducted for right and 164

left eye data, taking into account midline symmetry (enantiomorphism). 165

A best-fit sphero-cylinder was calculated from each subject’s mean refractive power maps.21 The 166

sphero-cylindrical analysis was calculated around the line of sight. Corneal height data were used to 167

8

calculate the corneal wavefront error using a ray tracing procedure described by Buehren et al22. 168

Zernike wavefront polynomials were fitted to the wavefront error (up to and including the eighth 169

radial order) and expressed using the double index notation (Optical Society of America [OSA] 170

convention).23 The image plane was at the circle of least confusion and the wavelength used was 171

555 nm. The wavefront was centred on the line of sight by using the pupil offset value from the 172

pupil detection function in the Medmont videokeratoscope as the reference axis for the wavefront. 173

This procedure was conducted for 4 measurements per eye and the mean and standard deviations 174

were calculated. Corneal diameters of 4 and 6 mm were chosen for analysis purposes to 175

approximate mean pupil sizes in photopic and mesopic conditions respectively. Simulated 176

keratometry readings and corneal asphericity values (Q) were recorded for the principal corneal 177

meridians. The Medmont E300 software calculates the best fit ellipse at a specified chord (6 mm 178

diameter was chosen). 179

Ocular aberrations 180

Wavefront data from the COAS was fitted with an 8th order Zernike expansion and exported for 181

further analysis. Using customised software, the 100 wavefront measurements were rescaled to set 182

pupil diameters of 4 and 6 mm using the method of Schwiegerling24 and then the coefficients of the 183

Zernike polynomials were averaged. Pupil size scaling was only conducted to convert from a larger 184

natural pupil size to a smaller pupil which has been shown to be associated with only very small 185

errors that are not expected to be optically significant.24 This analysis was conducted for right and 186

left eye data, taking into account enantiomorphism. Although corneal and ocular wavefronts were 187

fit with 8th order Zernike expansions, given that the predominant higher order aberrations are 3rd 188

and 4th order terms25,26 we limited our analysis up to and including the 4th order. 189

190

9

Statistical analysis 191

Two tailed paired t-tests were used to assess the statistical significance of the mean interocular 192

difference between the more and less myopic eyes of the anisometropic subjects. Pearson’s 193

correlation coefficient was used to quantify the degree and statistical significance of the interocular 194

symmetry between the more and less myopic eyes. Pearson’s correlation coefficient was also used 195

to examine the relationship between the magnitude of refractive anisometropia and the interocular 196

difference of a range of parameters. Interocular differences were calculated by subtracting the less 197

myopic eye from the more myopic eye. Chi-square tests of independence were used to examine the 198

distribution of proportions. 199

Results 200

The mean components of subjective refraction, best corrected visual acuity and axial length of the 201

anisometropic subjects are presented in Table 1. The subjects’ mean spherical equivalent refraction 202

was -5.35 2.74 D for the more myopic eye and -3.64 ± 2.61 D for the less myopic eye. There were 203

statistically significant differences between the more and less myopic eyes for the spherical 204

component and spherical equivalent of the refractive error, however, the magnitude of refractive 205

astigmatism (cylinder) was similar between the two eyes. Mean best corrected visual acuity was not 206

significantly different between fellow eyes. The magnitude of spherical equivalent anisometropia 207

was significantly correlated with the interocular difference in axial length between fellow eyes (r = -208

0.81, p < 0.001) (Figure 1). However, given the r-value of -0.81, it appeared that for some subjects 209

there were various factors contributing to the magnitude of anisometropia other than an interocular 210

difference in axial length (e.g. interocular asymmetry in corneal or lenticular power, crystalline lens 211

position or retinal thickness). 212

213

10

Ocular biomechanics 214

Valid measurements were obtained for 31 subjects with the ORA. Measurements for 3 subjects 215

were excluded due to poor fixation or eyelash interference during data collection. A high degree of 216

symmetry was observed between the fellow eyes for all measures of intraocular pressure and 217

corneal biomechanics (Table 2). There were no statistically significant correlations between the 218

degree of anisometropia and the interocular difference in IOPg (r = 0.12), IOPcc (r = 0.19), CRF (r = -219

0.16) and CH (r = -0.16) (p > 0.05 for all parameters). 220

Corneal topography 221

Various measures of corneal shape were captured using the Medmont E300 videokeratoscope. One 222

subject was excluded from the Medmont data analysis due to substantial missing data due to 223

eyelash interference and reduced palpebral aperture size. The group mean and standard deviations 224

for the more and less myopic eyes are displayed in Table 3. 225

There was a high degree of interocular symmetry for all the corneal parameters that were measured 226

(p < 0.0001). The magnitude of refractive astigmatism was not statistically different between the 227

more and less myopic eyes (Table 1). However, examination of the principal corneal meridians 228

revealed that on average, the more myopic eyes were slightly more powerful in both the flattest and 229

steepest corneal meridians compared to fellow eyes. The average interocular difference between 230

the more and less myopic eyes was 0.19 ± 0.57 D for the steepest meridian (p = 0.06), 0.15 ± 0.37 D 231

for the flattest meridian (p = 0.03) and 0.17 ± 0.32 D for the average of the two principal meridians 232

(p < 0.01). 233

Average corneal asphericity (Q) values were slightly more prolate (greater peripheral flattening) in 234

the more myopic eyes in both the steepest and flattest meridians. This interocular difference was 235

statistically significant for the mean Q value (average of the steepest and flattest meridians) and for 236

the steepest corneal meridian, with Q values of -0.14 ± 0.09 in the less myopic eyes and -0.19 ± 0.12 237

in the more myopic eyes (p = 0.001). 238

11

The group mean and standard deviations for corneal sphero-cylinder and refractive power vectors M 239

(spherical corneal power), J0 (90/180 astigmatic power) and J45 (45/135 oblique astigmatic power) 240

in the more and less myopic eyes are displayed in Table 4. The more myopic eyes had a significantly 241

higher M for both 4 and 6 mm corneal diameters, however, the mean astigmatic vectors and 242

spherocylinder were not significantly different between fellow eyes. 243

Corneal aberrations 244

There was a high degree of interocular symmetry for corneal higher order aberrations up to the 245

fourth order, in particular within the 6 mm analysis diameter. On average, there were no 246

statistically significant differences between the more and less myopic eyes for third, fourth and 247

higher order RMS values (Table 5). There were few significant correlations between the interocular 248

difference in corneal aberrations for individual Zernike coefficients up to the fourth order and the 249

degree of spherical equivalent anisometropia. The strongest correlations for the interocular 250

difference in Zernike coefficients and the magnitude of anisometropia were observed for fourth 251

order terms Z (4,-2) secondary astigmatism (r = -0.35, p = 0.06) and Z (4,-4) tetrafoil along 22.5˚ (r = 252

0.41, p = 0.03) over a 4 mm corneal diameter. These correlations were relatively weak for the 4 mm 253

diameter and were weaker for the 6 mm analysis diameter. Correlation analysis for spherical 254

aberration revealed no significant relationship between the interocular difference in Zernike 255

coefficient Z (4,0) and the degree of anisometropia. 256

Total ocular monochromatic aberrations 257

Due to inter-subject variation in natural pupil sizes during data collection, some subjects were 258

excluded from analysis when examining aberrations over larger pupil diameters. Here we present 259

data for 31 subjects over a 4 mm pupil diameter and 19 subjects for a 6 mm diameter. A high degree 260

of interocular symmetry of Zernike coefficients was observed between the more and less myopic 261

eyes over both pupil sizes. There were no statistically significant differences between mean 262

individual Zernike coefficients for the more and less myopic eyes. The less myopic eyes had slightly 263

12

greater mean RMS values of 3rd, 4th and total higher order aberrations compared to more myopic 264

eyes. However, these interocular differences were small in magnitude and did not reach statistical 265

significance (Table 5). There were no significant correlations between the interocular difference in 266

individual Zernike coefficients up to the 4th order and the magnitude of anisometropia. 267

Sighting ocular dominance 268

The more myopic eye was the sighting dominant eye in 22 subjects (65%). However, when the level 269

of anisometropia exceeded 1.75 D (the approximate mean level of anisometropia in the subject 270

group), the more myopic eye was the dominant eye in 90% of subjects (Table 6, Figure 2). Although 271

two thirds of the subjects had anisometropia ≤ 1.75 D, there was a statistically significant difference 272

in the proportion of more myopic dominant eyes between the “low” (≤ 1.75 D) and “high” (> 1.75 D) 273

anisometropia groups (p = 0.002, Table 6). The more myopic eye was always the dominant sighting 274

eye when the level of anisometropia exceeded 2.25 D. 275

Stereoacuity was not significantly different between subjects with less myopic dominant 276

eyes (55 ± 64 seconds of arc) or more myopic dominant eyes (57 ± 31 seconds of arc) (p > 277

0.05, unpaired t-test). Although the “high anisometropia” group displayed a slightly 278

reduced level of mean stereopsis (72 ± 67 seconds of arc) compared to the “low 279

anisometropia” group (49 ± 28 seconds of arc), this difference did not reach statistical 280

significance (p > 0.05, unpaired t-test). 281

Given the significantly higher proportion of more myopic dominant sighting eyes in the subjects with 282

greater levels of anisometropia, we examined the interocular symmetry between the dominant and 283

non-dominant eyes of both the low and high anisometropia groups. On average, dominant eyes 284

were more myopic with greater axial lengths (-4.86 ± 2.80 D, 25.42 ± 1.01 mm) compared with non-285

dominant eyes (-4.13 ± 2.77 D, 25.15 ± 0.90 mm) (all p < 0.05). This was most evident for the high 286

13

anisometropia group (dominant: -6.70 ± 2.77 D and 25.69 ± 0.57 mm, non-dominant: -4.56 ± 3.51 D 287

and 24.93 ± 0.71 mm) (p < 0.0001). 288

There was no difference in best corrected visual acuity between the dominant and non-dominant 289

eyes. There were also no statistically significant differences between the dominant and non-290

dominant eyes for all measures of IOP, corneal biomechanics and corneal refractive power vectors 291

M, J0 and J45. Non-dominant eyes had larger RMS values for third, fourth and higher order corneal 292

and total aberrations compared to the dominant eyes in each anisometropic cohort examined, 293

however, these interocular differences were not statistically significant. 294

Discussion 295

This study provides a comprehensive examination of the optical and biomechanical properties of 296

anisometropic eyes not associated with pathology, amblyopia or strabismus. Since this was a cross 297

sectional study and not longitudinal, we cannot be certain if differences between the eyes represent 298

a possible cause or consequence of myopic eye growth. We observed a high degree of interocular 299

symmetry in myopic anisometropia. Aside from the interocular difference in axial length, there were 300

few significant differences between the more and less ametropic fellow eyes for a range of ocular 301

parameters. But interestingly, for higher levels of anisometropia (> 1.75 D), the more myopic eye 302

was typically the ocular sighting dominant eye. 303

A high degree of symmetry exists between fellow eyes for corneal power in both isometropic eyes 304

measured with slit scanning topography27 and anisometropic eyes measured with 305

keratometry.28,11,12,10 Although there is significant variability in corneal power in emmetropia and 306

myopia29, several studies have shown greater corneal power30-32 and a less prolate corneal shape33 307

(less peripheral flattening) in myopes compared to emmetropes. In our population of 308

anisometropes, our corneal measures with videokeratoscopy revealed, small interocular differences 309

between the flat and steep corneal meridians of fellow eyes. Also, the mean refractive corneal 310

14

power (average of the steep and flat corneal meridians) was significantly greater (steeper) in the 311

more myopic eyes. To our knowledge, this has not been observed in previous biometric studies of 312

anisometropic subjects. The more myopic eyes also exhibited more prolate corneas (flattening more 313

rapidly in the periphery), which is in contrast to previous studies which have shown that corneas 314

tend to become less prolate with increasing levels of myopia.34,35 315

We observed a high degree of interocular symmetry for measures of corneal resistance and 316

hysteresis. Hysteresis is positively correlated with central corneal thickness and is reduced in 317

conditions associated with corneal thinning such as advanced keratoconus, Fuch’s endothelial 318

dystrophy and the post LASIK cornea.18 Xu et al4 observed a small but statistically significant 319

reduction in corneal hysteresis in the more myopic eye compared to the fellow eye in a study of high 320

myopic anisometropia. A stretched or weakened sclera may be related to these lower values of 321

corneal hysteresis in high myopia. We found no such relationship in our cohort of anisometropes, 322

possibly due to the difference in the magnitude of anisometropia in our subjects (mean 1.70 D) 323

compared to those of Xu et al4 (mean 10.82 D). 324

The measurement of intraocular pressure may be influenced by variables such as age, blood 325

pressure, gender, corneal thickness and curvature and diurnal variation. We minimised the potential 326

confounding effect of such variables by comparing the fellow eyes in anisometropia and measured 327

IOP using a technique less influenced by corneal characteristics in comparison to applanation 328

tonometry. Our findings were similar to those of previous studies examining IOP in 329

anisometropia.6,36,8,9 We found no significant differences in IOP between the more and less 330

ametropic eyes and no correlation between the interocular difference in IOP and the magnitude of 331

anisometropia. Our results do not support a simple mechanical model of increased IOP leading to 332

axial elongation and myopia. However, it is possible that anisometropia may develop through an 333

IOP dependant mechanical mechanism with symmetrical IOPs, if there are interocular differences in 334

scleral biomechanics as suggested by Lee and Edwards8. The findings from our study and previous 335

15

studies of IOP in anisometropia are cross sectional in nature, which leaves open the possibility that 336

short term (e.g. diurnal variations) or longer term fluctuations in IOP may vary with anisometropia. 337

Plech et al37 observed that corneal higher order aberrations were similar between the fellow eyes of 338

anisometropes with amblyopia, however, to our knowledge our study is the first to report the 339

interocular symmetry of corneal aberrations in anisometropic eyes without amblyopia or strabismus. 340

We observed a high degree of interocular symmetry for corneal aberrations, which suggests that the 341

optical quality of the cornea is similar between the two eyes of myopic anisometropes. These 342

findings are in agreement with previous studies of between eye symmetry of corneal aberrations in 343

isometropic populations.38,26 344

A high degree of interocular symmetry also exists for total ocular monochromatic aberrations in 345

various isometropic populations.39-41,25 We observed a high level of symmetry between the fellow 346

eyes of anisometropes for Zernike coefficients up to the fourth order and higher levels of 3rd, 4th and 347

total RMS errors in the less myopic eyes. Although these differences were small and statistically 348

insignificant, our findings are in agreement with Kwan et al11 who also noted significant interocular 349

symmetry of higher order aberrations in anisometropes (> 2.00 D SEq) and significantly higher levels 350

of third order and total higher order aberrations in less myopic eyes. Tian et al13 also investigated 351

the interocular symmetry of ocular aberrations in ten myopic anisometropes (> 1.00 D SEq) similar to 352

the cohort in our study and found no significant interocular differences in individual Zernike terms, 353

3rd order, 4th order and 5th order aberrations or total higher order aberrations. 354

Since biometric or optical parameters may vary with ethnicity, we conducted an additional analysis 355

after removal of the three Caucasian subjects. Analysis of the 31 Asian subjects alone revealed 356

similar trends and p-values for the analysis of axial length, visual acuity, corneal topography, corneal 357

biomechanics, IOP and corneal and total ocular aberrations. 358

Our findings suggest that a high degree of symmetry exists between the fellow eyes of myopic 359

anisometropes for both corneal and total ocular higher order aberrations. Given the cross sectional 360

16

nature of our study we are unable to conclude whether higher order aberrations contribute to the 361

development of myopic anisometropia (i.e. an interocular difference in higher order aberrations 362

which diminishes over time may influence asymmetric axial elongation during refractive 363

development). Additionally, we cannot rule out the possibility that higher order aberrations during 364

accommodation (due to an unequal accommodative response between the eyes), following near 365

work (due to asymmetric palpebral aperture morphology and unequal eyelid pressure during 366

downward gaze) or that the sign of the aberrations may play a role in asymmetric refractive 367

development. 368

Along with the extensive range of optical and anterior biometric properties that we 369

examined in this study, there are many other factors that may be associated with the 370

development of anisometropia that we did not measure. Animal models have shown that 371

peripheral optics may play a role in the regulation of eye growth and refractive error 372

development.42,43 Asymmetries in retinal contour have also been reported between the two 373

eyes of myopic anisometropes.12 There is increasing evidence that orthokeratology, which 374

focuses light centrally at the fovea but induces peripheral myopic blur, slows the rate of axial 375

elongation during myopia development.44-46 Our current study limited its measurements to on 376

axis refraction, aberrations, biomechanics and biometrics, however given the potential role 377

of peripheral optics in refractive error development, investigations of peripheral refraction, 378

aberrations and biometrics in anisometropia are areas worthy of future study. 379

Developmental abnormalities of the optic nerve may also be associated with anisometropia. 380

Lempert47 reported that in hyperopic anisometropes, with or without amblyopia, the optic disc of 381

the more hyperopic eye is significantly smaller or underdeveloped in comparison to the fellow eye. 382

In myopes, asymmetric optic nerve head morphology due to unilateral tilted disc syndrome may 383

potentially result in differences in astigmatism between the fellow eyes and could initiate axial 384

17

anisometropic development. Examination of optic disc parameters in myopic anisometropes may 385

therefore provide more information regarding asymmetric axial elongation. 386

We observed that as the degree of anisometropia increased, the sighting dominant eye was more 387

often the more myopic of the two eyes. When anisometropia exceeded 1.75 D (n = 10), the more 388

myopic eye was the dominant eye in 90% of subjects. When greater than 2.25 D, the more myopic 389

eye was always the dominant eye. Our findings are in agreement with those of Cheng et al48 who 390

examined ocular dominance in 55 adults with spherical equivalent anisometropia ranging from 0.5 - 391

5.5 D and reported a threshold level of anisometropia (1.75 D), beyond which the more myopic eye 392

was always the dominant sighting eye. The authors hypothesised that during or following sustained 393

near work, the dominant eye may have a greater lag of accommodation in comparison to the non-394

dominant eye, resulting in greater axial elongation in the dominant eye. 395

Ibi49 examined the accommodative response in the dominant and non-dominant eyes of young 396

isometropic subjects and observed that the dominant eye showed a slight myopic shift at both 397

distance and near fixation following accommodation. The author speculated that the static tonus of 398

the ciliary muscle is increased in the dominant eye, which may explain why the dominant eye is 399

often the more myopic eye in non-amblyopic anisometropia. However, if the dominant eye shows a 400

slight lead of accommodation following near work, this myopic defocus would slow eye growth, 401

based on the theory of retinal image mediated eye growth. 402

In anisometropic amblyopia, the dominant sighting eye is typically the eye with better visual acuity, 403

although there may be exceptions in some cases with intermittent strabismus.50 We found no 404

significant difference in best corrected visual acuity between dominant and non-dominant eyes 405

(mean inter-eye difference ≤ 0.01 logMAR), or when dividing our subjects into low and high 406

anisometropia cohorts. We also examined the interocular difference between dominant and non-407

dominant eyes for a range of optical and biometric parameters including corneal power vectors M, 408

J0 and J45 and corneal and total higher order aberration RMS values, in order to provide insights 409

18

into the potential role of optical and mechanical factors in the interaction between ocular 410

dominance and anisometropia. Whilst some trends were observed for differences in ocular optics 411

(e.g. higher levels of 3rd, 4th and higher order corneal RMS values in non-dominant eyes) between the 412

dominant and non-dominant eyes, limited differences of statistical significance were found. These 413

data do not point to an obvious underlying optical or biomechanical reason for the more myopic eye 414

typically being the dominant eye for higher levels of anisometropia, however we cannot rule out the 415

possible role of optical or mechanical differences that are present at the time when ocular 416

dominance develops. The role of ocular dominance in refractive error development (or the role of 417

refractive error in relation to the determination of ocular dominance) remains unclear. Although 418

Yang et al51 reported no significant effect of ocular dominance on myopia development, given the 419

findings of this study and those of Cheng et al48, the association between myopic anisometropia and 420

ocular dominance requires further investigation. A more precise technique of measuring sensory 421

ocular dominance, described by Li et al52 may provide a clearer insight into this association. 422

Aside from an interocular difference in axial length, due to asymmetry in the posterior vitreous 423

chamber, anisometropic eyes display a high degree of interocular symmetry for a range of biometric 424

and optical characteristics. While we did not observe significant interocular differences for several 425

of the parameters investigated in this population of anisometropes (mean SEq anisometropia 1.70 426

D), this does not rule out the possibility that interocular differences may exist in more severe cases 427

of anisometropia (with or without amblyopia). 428

Unlike previous anisometropia studies, we observed that the more ametropic eye had a significantly 429

steeper mean corneal power in comparison to the fellow eye. There is a threshold level of 430

anisometropia, above which the more myopic eye is typically the dominant sighting eye. The 431

findings from our study do not support a single mechanical (IOP expansion) or retinal image 432

mediated (corneal or total monochromatic aberrations) mechanism in the unaccommodated eye in 433

the development of myopic anisometropia, however, longitudinal studies of myopes during (not 434

19

after) the development of anisometropia may shed more light on the possible role of mechanical 435

and optical factors. 436

Acknowledgements 437

The authors thank Po Wah Ng for his assistance with subject recruitment. Some aspects of this 438

study were presented at the American Academy of Optometry meeting, San Francisco, November 439

17-20, 2010. 440

441

20

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603

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Table 1. Overview of the subjective refraction, best corrected visual acuity and axial length for the

more myopic and less myopic eyes of the anisometropic population.

More myopic eyes Less myopic eyes Paired t-test

Parameter Mean ± SD Mean ± SD p

Subjective refraction sphere (D) -4.87 ± 2.59 -3.18 ± 2.49 < 0.0001

Subjective refraction cylinder (D) -0.95 ± 0.85 -0.96 ± 0.82 0.85

Spherical equivalent (D) -5.35 2.74 -3.64 ± 2.61 < 0.0001

Best corrected visual acuity (logMAR) -0.01 ± 0.04 0.00 ± 0.04 0.26

Axial length (mm) 25.57 ± 0.89 25.00 ± 0.95 < 0.0001

25

Table 2. Mean ocular biomechanical parameters of the more and less myopic eyes for the anisometropic

population.

Biomechanical parameter

More myopic eyes Less myopic eyes Paired t-test Interocular symmetry

Pearson’s correlation coefficient

(mmHg) Mean ± SD Mean ± SD p r

p

IOPg 15.60 ± 2.98 15.66 ± 2.86 0.83 0.87 < 0.0001

IOPcc 15.05 ± 2.20 15.15 ± 2.14 0.66 0.66 < 0.0001

CRF 11.25 ± 1.80 11.11 ± 1.60 0.52 0.76 < 0.0001

CH 11.35 ± 1.37 11.30 ± 1.41 0.68 0.68 < 0.0001

IOPg – Goldman-correlated IOP, IOPcc- Corneal compensated IOP, CRF – corneal resistance factor, CH –

corneal hysteresis.

26

Table 3. Mean corneal parameters of the more and less myopic eyes for the anisometropic population.

Corneal parameter

More myopic eyes Less myopic eyes Paired t-test Interocular symmetry

Pearson’s correlation coefficient

Mean ± SD Mean ± SD p r p

Flat K (D) 42.91 ± 1.30 42.77 ± 1.30 0.03 0.96 < 0.0001

Steep K (D) 44.52 ± 1.78 44.32 ± 1.69 0.06 0.95 < 0.0001

Mean K (D) 43.72 ± 1.51 43.55 ± 1.43 < 0.01 0.98 < 0.0001

Astigmatism (D) -1.61 ± 0.81 -1.55 ± 0.93 0.70 0.71 < 0.0001

Flat Q -0.46 ± 0.17 -0.44 ± 0.15 0.21 0.92 < 0.0001

Steep Q -0.19 ± 0.12 -0.14 ± 0.09 0.001 0.71 < 0.0001

Mean Q -0.32 ± 0.13 -0.29 ± 0.10 < 0.001 0.91 < 0.0001

K - Simulated keratometric corneal power, Q - corneal asphericity (for 6 mm chord).

27

Table 4. Mean corneal refractive power vectors and sphero-cylinder for the more and less myopic eyes

over 4 and 6 mm corneal diameters.

Corneal parameter (D) Corneal diameter (mm) More myopic eyes Less myopic eyes

M 4 49.21 ± 1.8 * 49.06 ± 1.78

6 49.60 ± 2.13 ** 49.43 ± 2.06

J0 4 0.87 ± 0.48 0.85 ± 0.53

6 0.94 ± 0.55 1.05 ± 0.56

J45 4 0.09 ± 0.24 0.06 ± 0.29

6 0.14 ± 0.14 0.12 ± 0.35

Sphero-cylinder 4 50.08/-1.75 x 3 49.91/-1.70 x 2

6 50.55/-1.90 x 4 50.49/-2.11 x 3

All values mean ± SD

Corneal sphero-cylinder data presented as (Sphere/Cylinder x Axis)

* p < 0.01, ** p < 0.001 Paired t test (more vs less myopic eyes)

28

Table 5. Mean 3rd, 4th and total higher order RMS values up to 8th order for corneal and total ocular monochromatic aberrations in the more and less myopic

eyes of the anisometropic population.

Corneal aberrations Total monochromatic aberrations

Analysis diameter

More myopic eyes Less myopic eyes Paired t-test More myopic eyes Less myopic eyes Paired t-test

RMS (mm) Mean ± SD Mean ± SD p Mean ± SD Mean ± SD p

3rd

order 4 0.106 ± 0.043 0.132 ± 0.109 0.14 0.045 ± 0.021 0.048 ± 0.028 0.56

6 0.379 ± 0.279 0.435 ± 0.586 0.24 0.105 ± 0.047 0.107 ± 0.055 0.93

4th

order 4 0.055 ± 0.016 0.076 ± 0.079 0.16 0.019 ± 0.009 0.020 ± 0.009 0.26

6 0.266 ± 0.164 0.359 ± 0.455 0.10 0.083 ± 0.038 0.087 ± 0.035 0.50

Total higher order

4 0.130 ± 0.040 0.171 ± 0.151 0.12 0.115 ± 0.048 0.121 ± 0.052 0.49

6 0.498 ± 0.370 0.636 ± 0.845 0.13 0.313 ± 0.085 0.328 ± 0.113 0.55

Corneal aberrations: 4 and 6 mm analysis n = 33.

Total monochromatic aberrations: 4 mm analysis n = 31, 6 mm analysis n = 19.

29

Table 6. Distribution of ocular sighting dominance in more and less myopic eyes in the anisometropic

population.

Spherical equivalent anisometropia

(Mean ± SD) (D)

Sighting dominant eye Χ2 test

More myopic Less myopic p

“Low” ≤ 1.75 (1.30 ± 0.26)

13 11

0.002 “High” > 1.75 (2.53 ± 0.74)

9 1

30

Figure Legends

Figure 1. Interocular axial length difference versus spherical equivalent anisometropia. *More

myopic eye minus the less myopic eye.

Figure 2. Distribution of sighting dominance in more and less myopic eyes as a function of spherical

equivalent anisometropia. When anisometropia exceeded 1.75 D (dashed line) the dominant eye

was the more myopic eye in 90% of subjects. When greater than 2.25 D anisometropia was present

(solid line), the dominant eye was always the more myopic eye.

31

Figure 1.

32

Figure 2.