Comparison of corneal biomechanics in pre and post-refractive surgery andkeratoconic eyes by Ocular Response Analyser

Sunil Shah a,b,c,1,*, Mohammed Laiquzzaman a,1

a Birmingham Heartlands and Solihull NHS Trust, Solihull, UKb Anterior Eye Group, Neurosciences Research Institute, Aston University, Birmingham, UKc Birmingham and Midland Eye Centre, Birmingham, UK

Contact Lens & Anterior Eye 32 (2009) 129–132

A R T I C L E I N F O

Keywords:

Hysteresis

Corneal resistance factor

Keratoconus

LASIK/LASEK

A B S T R A C T

Purpose: To compare biomechanical parameters measured by the Ocular Response Analyser (ORA) in the

form of corneal hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT) in

eyes before and after excimer laser refractive surgery and keratoconic eyes.

Setting: Teaching Hospital and private eye clinic in Solihull, UK.

Methods: Prospective case comparison of 110 eyes selected for refractive surgery and 132 keratoconic

eyes. The CH and CRF of each eye was measured by the ORA. The CCT was measured using ultrasonic

pachymetry.

Results: The mean preoperative (pre-op) CH for the normal refractive surgery eyes was 11.4 � 1.9 mmHg,

CRF 10.0 � 1.6 mmHg and CCT 546.5 � 33.0 mm. Post-operatively CH was 9.2 � 2.1 mmHg, CRF

7.6 � 1.8 mmHg and CCT 483.1 � 40.8 mm. The values for keratoconic eyes were 9.4 � 2.2 mmHg,

7.7 � 2.6 mmHg and 488.1 � 52.6 mm, respectively. The CH, CRF and CCT decreased as the severity of

keratoconic eyes increased. All these parameters showed statistically significant difference between normal

eyes and keratoconic eyes. This was also the case between post-operative eyes.

Conclusion: The biomechanical parameters measured were very similar when comparing keratoconic

and post-refractive surgery eyes.

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1. Introduction

Surgical interventions and diseases of corneal tissue have beenfound to result in substantial changes in corneal tissue structure,which can then also alter the biomechanical properties of thecornea [1–3]. The surgical procedures used to perform cornealrefractive surgery result in changes in the corneal tissue structure,which affect the corneal thickness (CCT) and curvature of thecornea [4,5]. Corneal refractive surgery and corneal diseases thuscan alter corneal biomechanics.

Keratoconus is usually a bilateral [6], non-inflammatorycondition of unknown aetiology affecting the central corneacharacterised by thinning and ectasia of cornea [7]. It may affectvision significantly due to irregular astigmatism and corneal

* Corresponding author at: Heart of England Foundation Trust, Lode Lane,

Solihull, West Midlands, B91 2JL, UK. Tel.: +44 121 424 4456; fax: +44 121 424 5462.

E-mail address: sunilshah@doctors.net.uk (S. Shah).1 Each author states that he has no proprietary interest in the development or

marketing of any instruments used.

1367-0484/$ – see front matter � 2009 British Contact Lens Association. Published by

doi:10.1016/j.clae.2008.12.009

scarring. Keratoconic eyes are also known to have altered cornealbiomechanics (more elastic and less rigid than normal eyes) [8].

A recent instrument for assessing corneal biomechanics, theOcular Response Analyser (ORA) has been introduced by Reichert[Reichert Ophthalmic Instruments, Buffalo, USA]. This is anadaptation of their non-contact tonometer, which allows mea-surement of IOP as well as new measurements called cornealhysteresis (CH) and the corneal resistance factor (CRF). CH and CRFare determined by releasing an air puff from the ORA that causesinward and then outward corneal motion, which in turn providestwo applanation measurements during a single measurementprocess. Reichert suggest that CH may be a measurement, which isthe result of the damping of the cornea because of its visco-elasticproperties and is derived from the difference of the twoapplanation measurements during the applanation process. CRFis dominated by the elastic properties of the cornea and appears tobe an indicator of the overall ‘‘resistance’’ of the cornea’’ [9].

This study was performed to compare three corneal biome-chanical parameters; CH, CRF and CCT in a cohort of eyes beforeand after excimer laser refractive surgery with that of a cohort ofkeratoconic eyes.

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S. Shah, M. Laiquzzaman / Contact Lens & Anterior Eye 32 (2009) 129–132130

2. Materials and methods

110 eyes of patients (72 females and 38 males; age range21.0–62.0 years) attending a private eye clinic for refractivesurgery in Solihull, UK were recruited for this study. All had normaleyes and no history of ocular disease, surgery or trauma. Thesepatients were divided into two groups: those undergoing laser-assisted in situ keratomileusis (LASIK) and laser epithelialkeratomileusis (LASEK). A full assessment for refractive surgeryincluding refraction, full ocular examination, topography, abbero-metry and pachymetry was performed. All the patients underwentLASEK or LASIK by one surgeon (SS).

132 keratoconic eyes (90 males, 42 females; range 15.1–54.1years) were recruited from a specialist corneal clinic in a teachinghospital in Solihull, UK. The diagnosis of keratoconus was made byan experienced corneal specialist (SS) on the basis of the followingdiagnostic criteria (one and or combination of signs); externalsigns such as Munson’s sign (v-shaped conformation of lower lidon down gaze), Rizzuti’s sign (sharply focused beam on nasallimbus produced by illumination temporally); and biomicrosopysigns such as stromal thinning, conical protrusion, Fleischer’s ring,Vogt’s striae, enlarged corneal nerves and an abnormal retinoscopyreflex. Topography was performed by Orbscan II (Bausch & Lomb,Rochester, NY)

In addition to the diagnosis of keratoconus, severity of thekeratoconus was graded according to the criteria reported in one ofour earlier studies (Table 1) [10]. The severity of keratoconic eyeswere graded as mild, moderate and severe on the basis of theOrbscan II (Bausch & Lomb Surgical, Rochester, New York, USA)readings. Five objective measurements were determined (anteriorcorneal curvatures, difference of astigmatisms in each meridians,anterior Best Fit Sphere and posterior Best Fit Sphere). Each eyewas given a score for each of the parameters, e.g. a score 1 foranterior keratometry K1, if K1 was between 45.1 and 46.9. Inaddition an overall subjective assessment of the Orbscan imagewas made and scored from 0 to 3. Each parameter was graded 0–3and a total score was calculated. A total score of 0–2 was graded asnormal, 3–6 as mild, 7–11 as moderate and>12 as severe (Table 1).The grading and was performed by an experienced corneal surgeon(SS).

The ORA measurements (CH and CRF) were taken whilst thepatient was seated. The CCT was measured using a hand heldultrasonic pachymeter (DGH-550, DGH Technology Inc., Exton, PA)

Table 1The criteria for grading of severity of keratoconic eyes.

Grading score Anterior

keratometry K1

Anterior

keratometry K2

Differen

Sim K

0 <45.0 <45.0 0–1.49

1 45.1–46.9 45.1–46.9 1.5–

2 47.0–49.9 47.0–49.9 2.5–

3 >50.0 >50.0 >3.5

Table 2Shows the mean � S.D. and range of CH, CRF and CCT in pre-op, post-op and eyes after L

Number of eyes CH mean � S.D. mmHg (median) [range] CRF m

All pre-op (110 eyes) 11.4 � 1.9 (11.1) [6.4–16.7] 10.0 �

All post-op (110 eyes) 9.2 � 2.1 (9.2) [2.5–13.1] 7.6 �

LASIK (53 eyes)

Pre-op 11.9 � 2.0 (11.9) [8.9–16.7] 10.4 �Post-op 9.8 � 1.9 (10.1) [5.5–13.1] 8.0 �

LASEK (57 eyes)

Pre-op 10.9 � 1.6 (10.8) [6.4–14.6] 9.7 �Post-op 8.7 � 2.1 (8.9) [2.5–12.6] 7.2 �

after instilling a drop of topical anaesthetic Proxymethacaine(Bausch & Lomb, Rochester, New York, USA) in the eye prior toperforming pachymetry. Three readings were taken and the meanvalue was used as the CCT. These measurements were taken beforeand after refractive surgery in the same order to avoid any bias inthe data collection.

Institutional review board approval was obtained from theSolihull Research Ethics Committee.

For the data analysis, several computer packages were used,including Excel (Microsoft1 Inc.) and Medcalc1 (Medcalc Inc.). Thelevel of statistical significance level was chosen at 0.05.

3. Results

3.1. Refractive surgery eyes data analysis

Data for 110 eyes undergoing refractive surgery eyes wereanalysed (one eye of each patient). The pre-op and post-op mean,standard deviation (SD) and range for CH, CRF and CCT values aresummarised in Table 2. All measured biomechanical parameterswere statistically significant when pre and post-operative valueswere compared (p < 0.0001, paired t-test). The difference in CCTbetween the pre-op eyes and post-op eyes ranged from 11 mm to136 mm, for CH the difference ranged from �1.2 mmHg to7.9 mmHg and for CRF it was �0.7 mmHg to 7.6 mmHg.

These eyes were then divided into LASIK and LASEK groupsaccording to the type of surgery performed on these eyes and theirdata analysed separately (Table 2).

On average the LASIK eyes had 17 mm greater initial CCT,1.0 mmHg higher initial CH and 0.7 mmHg higher pre-op CRF thanthe LASEK eyes. The difference in all the three parameters betweenpre-op LASIK and LASEK groups were statistically significant(p < 0.0001; unpaired t-test), i.e. they are not comparable groups.

The pre-op CCT in the pre-op LASIK eyes showed a higher meanvalue than pre-op LASEK eyes (Table 2), the difference beingstatistically significant (p < 0.0001) but post-operatively thisdifference became negligible (6.3 mm), and was not statisticallysignificant (p > 0.4).

3.2. Keratoconic eyes data analysis

The analysis of the keratoconic eyes data with that of the pre-oprefractive surgery eyes (regarded as normal in this study for the

ce of Anterior best

fit sphere

Posterior best

fit sphere

Orbscan image

grading

0–41.9 0–50.0 0

2.49 42.1–44.0 50.1–52.0 1

3.45 44.1–46.0 52.1–56.0 2

>46.1 >56.1 3

ASIK and LASEK surgery.

ean � S.D. mmHg (median) [range] CCT mean � S.D. mm (median) [range]

1.6 (9.9) [6.6–14.9] 546.5 � 33.0 (547.0) [467.0–640.0]

1.8 (7.5) [3.6–10.9] 483.1 � 40.8 (485.0) [400.0–588.0]

1.8 (10.1) [7.0–14.9] 555.2 � 29.4 (548.0) [507.0–640.0]

1.9 (8.2) [4.3–10.9] 488.0 � 43.2 (487.0) [412.0–588.0]

1.5 (9.7) [6.6–13.1] 538.5 � 34.4 (542.0) [467.0–598.0]

1.8 (7.2) [3.6–10.9] 481.7 � 40.0 (483.0) [400.0–582.0]

Table 3Shows mean � S.D. and range of CH, CRF and CCT of keratoconic eyes and after division according to severity.

Number of eyes CH mean � S.D. mmHg (range) CRF mean � S.D. mmHg (range) CCT mean � S.D. mm (range)

Keratoconus (all) (132 eyes) 9.4 � 2.2 (4.6–16.7) 7.7 � 2.6 (2.3–15.8) 488.1 � 52.6 (341–611)

Mild (46 eyes) 9.7 � 2.2 (4.6–16.7) 8.7 � 2.6 (4.8–15.8) 517.9 � 48.1 (419–611)

Moderate (27 eyes) 9.5 � 2.0 (5.1–13.5) 7.6 � 2.3 (3.0–12.3) 480.7 � 42.8 (417–599)

Severe (56 eyes) 8.9 � 2.2 (5.0–14.3) 6.8 � 2.3 (2.3–12.2) 466.3 � 49.1 (341–607)

S. Shah, M. Laiquzzaman / Contact Lens & Anterior Eye 32 (2009) 129–132 131

purpose of comparison between normal and keratoconic eyes)determined that the mean CH, CRF and CCT of the normal eyes washigher than that of the overall keratoconic eyes (see Tables 2 and 3)and the difference between the two groups were statisticallysignificant between all the three biomechanical parameters(p < 0.0001, unpaired t-test).

The box and whiskers graph (Fig. 1) shows the median andinterquantile range of CCT for the pre-op, post-op refractivesurgery eyes and keratoconic eyes. Figs. 2 and 3 (box and whiskersplots) show the median and interquartile range of CH and CRF in allthe fore mentioned groups of the eyes.

The keratoconus eyes were divided into three groups on thebasis of severity; mild, moderate and severe. The data wasreanalysed according to severity. The result of the analysis showedthat as the severity of the disease advanced, the mean values of allthe parameters measured decreased. Table 3 summarises the

Fig. 1. Box and whiskers plot of central corneal thickness in pre-op, post-op and

keratoconic eyes.

Fig. 2. Box and whiskers plot of corneal hysteresis (CH) in pre-op, post-op and

keratoconic eyes.

mean, SD and range of all the three parameters in keratoconic eyesand according to the severity of the disease.

The data further analysed on the basis of severity in these eyesshowed that difference in CCT was statistically significant betweenmild and moderate and mild and severe groups (p < 0.001 andp < 0.0001) but not between moderate and severe groups (p > 0.1).However, CH was not found to be statistically significant betweenany of the three groups, i.e. mild versus moderate, mild versussevere or moderate versus severe. CRF was statically significantbetween mild and severe groups (p < 0.0002) but not between theother two groups. Table 4 summarises the p values of relationshipbetween these parameters.

The mean values of all the three parameters in keratoconic eyesand post-op eye were almost identical CH 9.4 mmHg and9.2 mmHg, CRF 7.7 mmHg and 7.6 mmHg and CCT 488.1 mmand 483.1 mm, respectively. The difference was not statisticallysignificant between these two groups.

4. Discussion

The ORA allows a measurement in vivo of the visco-elastic andcorneal resistance properties referred to as CH and CRF in additionto intraocular pressure. CH is felt by Reichert to represent ocularresistance due to the combined effect of corneal thickness, ocularrigidity and its visco-elastic properties. CRF is dominated by theelastic properties of the cornea and appears to be an indicator ofthe overall ‘‘resistance’’ of the cornea [9].

The ORA is based on dynamic bidirectional applanation. Itreleases a precisely metered air pulse causing the cornea to move

Fig. 3. Box and whiskers plot of corneal resistance factor (CRF) in pre-op, post-op

and keratoconic eyes.

Table 4Shows p values in keratoconus eyes according to severity.

Severity CH CRF CCT

Mild vs. moderate >0.7 >0.07 <0.001

Mild vs. severe >0.07 <0.0002 <0.0001

Moderate vs. severe >0.2 >0.1 >0.1

S. Shah, M. Laiquzzaman / Contact Lens & Anterior Eye 32 (2009) 129–132132

inwards (inward applanation), and then to the past applanationphase where it becomes slightly concave. Milliseconds after the airpuff shuts off, resulting in a pressure decrease. During this phase,when the cornea is trying to regain its normal shape, it passesthrough an applanation phase (outward applanation). Theoreti-cally, these two pressures should be the same, but are actuallydifferent. This difference is described as the dynamic cornealresponse, which is said to be the resistance to applanationmanifested by the corneal tissue due to its visco-elastic properties.The difference between the outward and inward pressures istermed corneal hysteresis (measured in mmHg).

The results of this study confirmed a statistically significantreduction in CH, CRF and CCT in eyes undergoing refractive surgery(p < 0.0001, paired t-test) as has been shown previously [1].

There are many potential factors that may influence the CH, CRFand CCT such as surgery type (LASEK/LASIK), diagnosis (Myopes/Hyperopes), ablation depth (changes in CCT) corneal profile etc,however a general reduction in biomechanical parameters isconfirmed.

It is worth noting that the pre-op CCT in the pre-op LASIK eyesshowed a higher mean value than pre-op LASEK eyes, thedifference being statistically significant but post-operatively itwas not statistically significant (p > 0.4). The reason for findingsimilar post-op CCT readings in both LASIK and LASIK eyes maybe because of the fact the LASIK is performed in eyes with ahigher refractive error than LASEK (by this surgeon) and greaterdepth of the corneal stroma is ablated. The eyes were also notrandomised into having LASIK or LASEK, so there was surgeonbias based on biomechanical parameters as to what procedurewas chosen.

Comparison of all three biomechanical parameters wasperformed between keratoconic eyes and normal eyes (pre-oprefractive surgery eyes were regarded as normal in this study forthe purposes of comparison).

The analysis showed that the mean CH, CRF and CCT of thenormal eyes was higher than that of the keratoconic eyes and thedifference for all the parameters was statistically significant.

Further analysis of the keratoconic eyes performed on the basisof grading the keratoconus revealed decreasing mean CH, CRF andCCT values with the severity of the disease. CH was not found to bestatistically significant between any of the three groups whereasCRF was statically significant between mild and severe groups butnot between the other two groups whereas for CCT the differencewas statistically significant between mild and moderate groupsand mild and severe groups but not between moderate and severegroups.

It is interesting to note that the mean values of all the threeparameters in keratoconic eyes and post-op eye were almostidentical and which were not statistically significant.

It is known that ulcers and incisions in the cornea mean that thecornea may never restore the original tensile strength of thecorneal tissue [11–13]. The mean higher CH and CRF in the normaleyes may be related to an intact cornea whilst in the surgicallyaltered eyes and also keratoconic eyes the lower CH and CRF arethe result of the relative weakness of the cornea.

5. Conclusion

In summary these results demonstrate that post-refractivesurgery corneas show the same biomechanical characteristics askeratoconic eyes as measured by the ORA. Whilst this is aninteresting observation, this does not explain why some post-operative refractive surgery corneas progressively thin and becomefrankly ecstatic whilst the majority do not. Further work needs to beperformed to establish the features in so called normal eyes thatpredispose to ectasia in the future if they undergo refractive surgery.

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