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Ocular Response Analyzer in Children Dr. Kaushik Hegde

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CORNEA SESSION - III<br />

<strong>Ocular</strong> <strong>Response</strong> <strong>Analyzer</strong> <strong>in</strong> <strong>Children</strong><br />

<strong>Dr</strong>. <strong>Kaushik</strong> <strong>Hegde</strong>, <strong>Dr</strong>. Rohit Shetty, <strong>Dr</strong>. Ajoy V<strong>in</strong>cent, <strong>Dr</strong>. Harsha K.<br />

(Present<strong>in</strong>g Author: <strong>Dr</strong>. <strong>Kaushik</strong> Hedge)<br />

Corneal biomechanics and its relevance <strong>in</strong> the<br />

diseases of the cornea1,2 keratorefractive<br />

surgeries3,4 and measurement of Intra ocular<br />

pressure (IOP) 4,5 is an area of <strong>in</strong>tense and ongo<strong>in</strong>g<br />

research. Various techniques have been<br />

235<br />

described to measure this parameter some of<br />

them be<strong>in</strong>g the dynamic corneal imag<strong>in</strong>g 6 , high<br />

speed optical tomography 7 and more recently the<br />

ocular response analyser 3 (ORA; Reichert<br />

Ophthalmic Instruments, Depew, New York,


236 AIOC 2010 PROCEEDINGS<br />

USA).<br />

The pr<strong>in</strong>ciple of the ORA is based on non-contact<br />

tonometry (a patented bidirectional applanation<br />

event). 1 In addition to the IOP, it gives the<br />

measure of biomechanical properties of the<br />

cornea referred to as corneal hysteresis.<br />

Hysteresis refers to the energy lost dur<strong>in</strong>g the<br />

stress-stra<strong>in</strong> cycle. As with most biological<br />

materials, collagen is a viscoelastic material and<br />

therefore the cornea exhibits hysteresis.<br />

The effect of central corneal thickness (CCT) on<br />

IOP measurement is well known8,9 Corneal<br />

hysteresis may more effectively describe the<br />

contribution of corneal resistance to IOP<br />

measurements than CCT alone. 1 Prelim<strong>in</strong>ary<br />

studies have reported reduced hysteresis <strong>in</strong><br />

keratoconus, fuch’s dystrophy3 , primary open<br />

angle glaucoma and normal tension glaucoma1.<br />

Biomechanical properties of the cornea <strong>in</strong><br />

children10,11 or its contribution to the<br />

measurement of IOP12 are be<strong>in</strong>g better<br />

established.<br />

The primary aim of this study is to measure<br />

corneal hysteresis <strong>in</strong> children us<strong>in</strong>g ORA, with<br />

the <strong>in</strong>tention to provide a reference to establish<br />

the normative values and ranges of the corneal<br />

biomechanical parameters. The secondary<br />

objective is to study the correlation between the<br />

various biomechanical parameters <strong>in</strong> refractive<br />

error subgroups, and discuss the scope of its<br />

utility as a cl<strong>in</strong>ical tool.<br />

Materials and Methods<br />

Study design: Prospective, non-<strong>in</strong>terventional,<br />

cross sectional case series.<br />

Subjects and exam<strong>in</strong>ations: Informed consent<br />

was taken from the accompany<strong>in</strong>g parent or<br />

guardian, and <strong>in</strong>stitutional ethical review board<br />

clearance was obta<strong>in</strong>ed. All children(less than 16<br />

years) underwent a complete eye exam<strong>in</strong>ation.<br />

Any child with a history of ocular <strong>in</strong>fection,<br />

ocular allergy, ocular surgery and other causes<br />

known to affect the corneal hysteresis, as well as<br />

children unable to cooperate with the procedure<br />

were excluded from the study. The child was<br />

comfortably seated and asked to fixate on the<br />

green light <strong>in</strong> the <strong>in</strong>strument. ORA recorded<br />

corneal hysteresis (CH), corneal resistance factor<br />

(CRF) and two <strong>in</strong>traocular pressure<br />

measurements: <strong>in</strong>traocular pressure corneal<br />

compensated (IOPcc), which is reportedly<br />

<strong>in</strong>dependent of corneal thickness3,4 and<br />

<strong>in</strong>traocular pressure Goldmann-correlated<br />

(IOPg), which is <strong>in</strong>fluenced by corneal thickness.<br />

A m<strong>in</strong>imum of 4 read<strong>in</strong>gs were taken per eye and<br />

the best of the 4 read<strong>in</strong>gs was selected for<br />

analysis. CCT was measured us<strong>in</strong>g the IOPac<br />

Hand-Held Pachymeter (Standard, Model: 16011,<br />

Heidelberg Eng<strong>in</strong>eer<strong>in</strong>g, Inc., Germany). The<br />

probe was gently placed on the cornea <strong>in</strong> the mid<br />

pupillary plane <strong>in</strong> a perpendicular orientation, a<br />

m<strong>in</strong>imum of 20 read<strong>in</strong>gs were taken and<br />

averaged out to get the mean CCT. The children<br />

were dilated with cyclopentolate (0.5%, twice at<br />

an <strong>in</strong>terval of 30 m<strong>in</strong>utes) and refracted (NIDEK;<br />

AR-600, Japan). The spherical equivalent was<br />

noted which was verified by objective refraction.<br />

For the purpose of analysis the children were<br />

categorized <strong>in</strong>to 3 subgroups based on the<br />

refractive error (spherical equivalent) 13: >-0.50D<br />

(myopic), +2.00D to -0.50D (emmetropic),<br />

>+2.00D (hyperopic).<br />

Statistical analysis: Statistical Analysis was<br />

performed us<strong>in</strong>g Stastical Package for Social<br />

Sciences (version 10.5, SPSS Inc). Group<br />

differences for cont<strong>in</strong>uous variables were tested<br />

us<strong>in</strong>g the unpaired student t tests and one-way<br />

analysis of variance (ANOVA) for normally<br />

distributed data. Results are presented as mean<br />

± standard deviation [SD]. All statistical tests<br />

were two-tailed, and P value less than 0.05 was<br />

considered to <strong>in</strong>dicate statistical significance.<br />

Correlations between sub-groups were analyzed<br />

us<strong>in</strong>g the Pearson correlation coefficient.<br />

Results<br />

A total of 150 eyes of 76 patients with 42 male<br />

(55.3%), 34 female (44.7%), with a mean age of<br />

10.21 ± 3.2 years (range of 4 – 16 years) were<br />

exam<strong>in</strong>ed.<br />

The mean CH was 10.71 ± 1.44 mm of Hg, mean<br />

CRF was 10.80 ± 1.94 mm of Hg, and the mean ±<br />

SD of the various parameters for the entire group<br />

is shown <strong>in</strong> table 1.<br />

None of the parameters showed any significant<br />

difference with age or sex with the student t test<br />

(table 2).<br />

IOPcc showed positive correlation with IOPg (r<br />

= 0.88), CRF(r = 0.4), CCT(r = 0.28) and negative<br />

correlation with CH(r = -0.25) and SE(r = -0.23).<br />

IOPg showed a positive correlation with CRF (r =<br />

0.7), CH (r = 0.2) and CCT(r = 0.5). CRF showed


CORNEA SESSION - III<br />

Table-1: Mean and Range of the various<br />

parameters of the entire sample<br />

Variables Mean ±Std. Range<br />

N= 150 Deviation (SD)<br />

IOPcc ( mm of Hg) 15.83 ± 3.30 6.7 - 24.0<br />

IOPg ( mm of Hg) 15.70 ± 3.79 8.5 - 26.8<br />

CH ( mm of Hg) 10.71 ± 1.44 6.6 - 14.3<br />

CRF ( mm of Hg) 10.80 ± 1.94 5.6 - 18.4<br />

CCT(µm)<br />

Spherical<br />

549.93 ± 33.97 474- 650<br />

equivalent (DS) 0.50 ± 3.40 -13.50 - 10.75<br />

mm of Hg: millimeter of mercury,<br />

DS: Diopter sphere.<br />

µm: micro meter,<br />

Table-2: Correlation of the various biomechanical<br />

parameters with age and sex<br />

(student t test, unpaired).<br />

Biomechanical Age Sex<br />

parameters (P value) (P value)<br />

IOPcc 0.43 0.17<br />

IOPg 0.45 0.11<br />

CH 0.97 0.68<br />

CRF 0.50 0.40<br />

CCT 0.29 0.83<br />

Spherical Equivalent 0.10 0.91<br />

a positive correlation with both CH (r = 0.64), and<br />

CCT(r = 0.64). CH showed a positive correlation<br />

with CCT(r = 0.5).<br />

The distributions of the parameters <strong>in</strong> the 3<br />

subgroup population, consist<strong>in</strong>g of myopic,<br />

emmetropic and hypermetropic children are<br />

shown <strong>in</strong> table 3.<br />

In one way ANOVA a significant difference was<br />

seen between the 3 subgroups among various<br />

parameters (table 4) except CH (P = 0.05). Post<br />

hoc test showed significant difference between<br />

emmetropic and hypermetropic groups for CRF<br />

(P = 0.02), CH (P = 0.01) and CCT (P = .007) and<br />

between myopic and hypermetropic groups for<br />

IOPcc (P = 0.006) and IOPg (P= 0.04) (table 5).<br />

Graphs 1 and 2 represent the CH (r2 = 0.022) and<br />

Table-3: Biomechanical parameters <strong>in</strong> Myopia, Emmetropia and Hypermetropia (±SD)<br />

Subgroups (DS) IOPcc IOPg CH CRF CCT<br />

(mm of Hg) (mm of Hg) (mm of Hg) (mm of Hg) (µm)<br />

> -0.5 (n = 42) 16.90 ± 3.28 16.95 ± 4.25 10.72 ± 1.27 11.11 ± 2.03 554.02 ±35.46<br />

-0.5 - 1.99 (n = 77) 15.67 ± 3.09 15.25 ± 3.74 10.49 ± 1.27 10.41 ± 1.77 542.81 ± 33.58<br />

≥+2.00 (n = 31) 14.75 ± 3.48 15.12 ± 2.86 11.23 ± 1.87 11.33 ± 2.05 562.10 ± 29.14<br />

Total (n=150) 15.83 ± 3.30 15.70 ± 3.79 10.71 ± 1.43 10.80 ± 1.93 549.93 ± 33.97<br />

237<br />

Figure-1: Shows a scatter plot of the corneal hysteresis<br />

(CH) <strong>in</strong> mm of Hg along the y-axis and the refractive<br />

error (spherical equivalent <strong>in</strong> DS) along the x- axis.<br />

Statistical analysis <strong>in</strong>dicates a weak positive correlation<br />

of CH with the refractive error, <strong>in</strong>dicat<strong>in</strong>g possibly that<br />

as the refractive error moves towards hyperopia the CH<br />

also <strong>in</strong>creases.<br />

Figure-2: Shows a scatter plot of the corneal resistance<br />

factor (CRF) <strong>in</strong> mm of Hg along the y-axis and<br />

the refractive error (spherical equivalent <strong>in</strong> DS) along<br />

the x- axis. Statistical analysis <strong>in</strong>dicates a weak positive<br />

correlation of CH with the refractive error, <strong>in</strong>dicat<strong>in</strong>g<br />

possibly that as the refractive error moves towards<br />

hyperopia the CRF also <strong>in</strong>creases.<br />

CRF (r2 = 0.002) plotted aga<strong>in</strong>st the refractive<br />

error. As the refractive error moves towards<br />

hyperopia, the biomechanical parameters also<br />

<strong>in</strong>crease, <strong>in</strong>dicat<strong>in</strong>g a weak positive correlation.


238 AIOC 2010 PROCEEDINGS<br />

Table-4: Correlation of the various biomechanical<br />

parameters with<strong>in</strong> the subgroups (student t<br />

test, unpaired)<br />

Biomechanical Significance<br />

parameter (P value)<br />

IOPcc 0.02<br />

IOPg 0.04<br />

CH 0.05<br />

CRF 0.03<br />

CCT 0.02<br />

Table-5: Comparison of corneal biomechanical<br />

parameters among refractive error subgroups<br />

Para- Sub groups Significance<br />

meters (P value)<br />

IOPcc Myopia with Emmetropia .05<br />

Myopia with Hypermetropia .006<br />

Emmetropia with Hypermetropia .18<br />

IOPg Myopia with Emmetropia .02<br />

Myopia with Hypermetropia .04<br />

Emmetropia with Hypermetropia .87<br />

CH Myopia with Emmetropia .39<br />

Myopia with Hypermetropia .13<br />

Emmetropia with Hypermetropia .02<br />

CRF Myopia with Emmetropia .06<br />

Myopia with Hypermetropia .63<br />

Emmetropia with Hypermetropia .03<br />

CCT Myopia with Emmetropia .08<br />

Myopia with Hypermetropia .31<br />

Emmetropia with Hypermetropia .007<br />

Where: Myopia (spherical equivalent > - 0.5 DS)<br />

Emmetropia (spherical equivalent between - 0.5 DS and<br />

+ 2.00 DS)<br />

Hypermetropia (spherical equivalent > + 2.00 DS)<br />

Table-6: Comparison of mean CH with other<br />

reported studies<br />

Variable Kirwan Song Indian<br />

(mean) et al10 et al11 children<br />

(our data)<br />

Age(years)<br />

CH with SD<br />

11.2(0.8) 14.7(3.2) 10.3(3.2)<br />

(mm of Hg) 12.3(1.3) 10.7(1.5) 10.70(1.3)<br />

Discussion<br />

Corneal hysteresis is thought to represent the<br />

cumulative effects of corneal thickness,<br />

hydration, rigidity, and other as yet<br />

undeterm<strong>in</strong>ed factors14. The mean CH and CRF<br />

were 10.71 ± 1.45 mm of Hg and 10.80 ± 1.90 mm<br />

of Hg respectively. In this study there was no<br />

statistically significant relationship with the<br />

student t test for both CH and CRF with age (P =<br />

0.97), (P = 0.5) or sex (P = 0.68), (P = 0.4). Earlier<br />

reported literature does mention of an <strong>in</strong>verse<br />

relationship between age and corneal<br />

biomechanics. 15,16,17 The corneal thickness <strong>in</strong><br />

children reaches adult dimensions by 5-9 years of<br />

age. 18 Physiological changes do cont<strong>in</strong>ue<br />

throughout their life. In this study the CH was<br />

similar to that reported on adults1, the authors<br />

could not f<strong>in</strong>d an <strong>in</strong>verse relationship with age<br />

possibly due to the fact that the range of age<br />

groups among whom this study was conducted<br />

was too small to establish a significant change.<br />

The results of our children were similar to those<br />

found <strong>in</strong> Asian Ch<strong>in</strong>ese children11 (Table 6), but<br />

were lesser than what was reported on Caucasian<br />

children. 10<br />

As reported by others <strong>in</strong> adults14, CRF showed a<br />

positive correlation with both CH (r = 0.67), and<br />

CCT(r = 0.64) 19, so also did CH with CCT(r =<br />

0.54) 19. This suggests that the corneal thickness<br />

is an important factor <strong>in</strong> determ<strong>in</strong><strong>in</strong>g<br />

biomechanical properties of the eye.<br />

CRF (P = 0.03) and CCT (P = 0.02) showed<br />

significant difference between the refractive error<br />

subgroups. A post hoc test revealed CH (P = 0.02)<br />

and CRF (P = 0.03) to be significantly higher <strong>in</strong><br />

hypermetropes than emmetropes. This could<br />

possibly be due to a significantly higher CCT (P<br />

= 0.007) <strong>in</strong> the hyperopes <strong>in</strong> our sample, although<br />

it is generally accepted that CCT is <strong>in</strong>dependent<br />

of the refractive error status. 20 Reported literature<br />

does <strong>in</strong>dicate that CH does not vary <strong>in</strong> myopia,<br />

or its progression. 19,21 In this study there was no<br />

significant difference <strong>in</strong> the value of CH (P = 0.13)<br />

between the myopic and hyperopic groups,<br />

though a significant difference <strong>in</strong> the value of CH<br />

was seen between emmetropic and hyperopic<br />

groups (P = 0.02). None of the reported studies<br />

had hyperopic group as a control to identify any<br />

significant association between refractive error<br />

groups.<br />

In our study there was no correlation between<br />

IOPcc and IOPg with age (P = 0.4), (P = 0.5) or sex<br />

(P = 0.2), (P = 0.1). On analyz<strong>in</strong>g the parameters<br />

across various subgroups, IOPcc and IOPg<br />

<strong>in</strong>creased <strong>in</strong> the same proportion with refractive<br />

error. In each group, measured IOP values were<br />

strongly and positively correlated with each (r =<br />

0.9, r = 0.9, r = 0.8; among myopic, emmetropic


CORNEA SESSION - III<br />

and hyperopic groups respectively). This is a<br />

little surpris<strong>in</strong>g as the IOPcc values are supposed<br />

to be <strong>in</strong>dependent of corneal parameters like<br />

CCT and corneal biomechanics, and one would<br />

ideally expect varied correlation of IOPcc with<br />

IOPg. As the IOPcc takes <strong>in</strong>to consideration the<br />

viscoelastic nature of the cornea to evaluate the<br />

‘‘corneal-compensated IOP,’’ we can expect to<br />

f<strong>in</strong>d a significant difference between IOPcc and<br />

IOPg when tissue viscous damp<strong>in</strong>g is abnormal. 22<br />

The normal range of the biomechanical<br />

parameters would probably expla<strong>in</strong> the positive<br />

correlation between the IOP values <strong>in</strong> our<br />

subgroups.<br />

IOPcc (P = 0.006) and IOPg (P = 0.04) was found<br />

to be more <strong>in</strong> myopic than hyperopic eyes (table<br />

5), although the CCT between the 2 groups <strong>in</strong> our<br />

study was not significant (P = 0.31). S<strong>in</strong>ce myopes<br />

are known to have a higher IOP23 than nonmyopes<br />

and myopia is a def<strong>in</strong>ite risk factor for<br />

the development of glaucoma23, 24, 25 the same<br />

pattern may exists <strong>in</strong> children too.<br />

CH is likely to be a useful additional<br />

measurement to assess the progression of<br />

diseases of the cornea, as it may change before<br />

topographic or cl<strong>in</strong>ical changes becomes<br />

apparent. 1,2 S<strong>in</strong>ce the CCT <strong>in</strong> Asian Indian<br />

population is known to be lesser than that found<br />

<strong>in</strong> other parts of the world, 26 and also keratoconus<br />

that is known to present itself at an earlier age<br />

1. David A. Luce. Determ<strong>in</strong><strong>in</strong>g <strong>in</strong> vivo biomechanical<br />

properties of the cornea with an ocular response<br />

analyzer. J Cataract Refract Surg 2005;31:156–62.<br />

2. Dolores Ortiz, David P<strong>in</strong>˜ ero, Mohamed H.<br />

Shabayek. Corneal biomechanical properties <strong>in</strong><br />

normal, post-laser <strong>in</strong> situ keratomileusis, and<br />

keratoconic eyes. J Cataract Refract Surg<br />

2007;33:1371–5 .<br />

3. Jun Liu, Cynthia J. Roberts. Influence of corneal<br />

biomechanical properties on <strong>in</strong>traocular pressure<br />

measurement. J Cataract Refract Surg 2005;31:146–55.<br />

4. Doughty MJ, Zaman ML. Human corneal thickness<br />

and its impact on <strong>in</strong>traocular pressure measures: a<br />

review and meta-analysis approach. Surv<br />

Ophthalmol 2000;44:367–408.<br />

5. Jay S. Pepose, Susan K. Feigenbaum, Mujtaba A.<br />

Quazi, Jeffrey P. Sanderson, and Cynthia J. Roberts.<br />

Changes <strong>in</strong> Corneal Biomechanics and Intraocular<br />

Pressure Follow<strong>in</strong>g LASIK us<strong>in</strong>g Static, Dynamic,<br />

and Noncontact Tonometry. Am J Ophthalmol<br />

2007;143:39–47.<br />

References<br />

239<br />

among Indians, 27 plann<strong>in</strong>g refractive surgery <strong>in</strong><br />

adults should <strong>in</strong>corporate CH and CRF<br />

measurements. This could also be applied to the<br />

controversial pediatric LASIK whose <strong>in</strong>dications<br />

are now be<strong>in</strong>g more clearly def<strong>in</strong>ed. 28 Keep<strong>in</strong>g<br />

these factors <strong>in</strong> m<strong>in</strong>d record<strong>in</strong>g the<br />

biomechanical parameters and monitor<strong>in</strong>g it over<br />

time would prove useful.<br />

Though the ORA is able to measure corneal<br />

biomechanical parameters; the exact area of<br />

applanation on the cornea is not well def<strong>in</strong>ed.<br />

Know<strong>in</strong>g the applanation surface may provide<br />

additional <strong>in</strong>formation about corneal behavior<br />

and corneal properties. S<strong>in</strong>ce it requires<br />

cooperation of the children, the authors found it<br />

difficult to perform ORA on children less than 5<br />

years of age.<br />

The authors found that the CH <strong>in</strong> a sample of<br />

Asian Indian children is similar to those from<br />

children and adults <strong>in</strong> other parts of the world.<br />

The corneal biomechanical parameters of CH and<br />

CRF varied with the refractive status of a child. It<br />

was higher <strong>in</strong> hyperopes. The IOPg and IOPcc<br />

correlated strongly with each other and myopes<br />

had a higher pressure when compared to the<br />

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