Contact Lens & Anterior Eye

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The use of the Ocular Response Analyser to determine corneal hysteresis

in eyes before and after excimer laser refractive surgery

Sunil Shah

a,b,c

, Mohammad Laiquzzaman

a,

*

, Ian Yeung

c

, Xueliang Pan

d

, Cynthia Roberts

e

a

Heart of England Foundation Trust, Solihull, UK

b

Ophthalmic Research Group, Aston University, Birmingham, UK

c

Midland Eye Institute, Birmingham, UK

d

Department of Statistics, The Ohio State University, Columbus, OH, USA

e

Department of Ophthalmology and Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA

1. Introduction

The cornea is a largely transparent tissue that also serves as a

very powerful optical lens [1] accounting for 70% of the total

refractive power of the eye [2]. It forms a mechanically tough

membrane. It is because of its mechanical strength and transpar-ency that the cornea serves both as an efﬁcient protective barrier and as a refractive lens.

Various surgical procedures used for corneal refractive surgery result in substantial changes in corneal tissue structure that affect

the central corneal thickness (CCT) and curvature[3–7]. Corneal

refractive surgery can thus alter corneal biomechanical properties.

There is evidence that the biomechanical properties of the cornea can inﬂuence the diagnosis and hence management of ocular disease(s), but the factors which inﬂuence these properties are not well understood and hence cannot be controlled without the knowledge and ability to measure the biomechanical properties in

vivo[8]. An example is the validity of intraocular pressure (IOP)

after refractive surgery[9]. With the ever increasing popularity of

refractive surgery, the knowledge of the factors that determine the biomechanical properties of the eye and their importance in the management of disease process has gained importance.

So far there has been no easy method reported to determine bio-mechanical corneal properties in vivo other than indirectly through CCT measurements. A recent addition to the armamen-tarium for assessing biomechanics has been the Ocular Response Analyser (ORA) [Reichert Ophthalmic Instruments, Buffalo, USA] which in addition to being a non-contact tonometer, measures new metrics referred to as ‘corneal hysteresis’ (CH) which is said to be a

A R T I C L E I N F O Keywords: CCT CH CRF IOPg IOPcc A B S T R A C T

Purpose: To compare corneal biomechanical parameters and two measures of intraocular pressure (IOP) in eyes before and after excimer laser refractive surgery, with the Ocular Response Analyser (ORA). Materials and methods: Eighty normal eyes of 41 patients undergoing excimer laser refractive surgery in Birmingham, U.K. were recruited into three groups: Laser Assisted-Epithelial Keratomileusis (LASEK) (Myopes), Laser Assisted in Situ Keratomileusis (LASIK) (myopes) and LASIK (hyperopes). The preop and 3 months postop Goldmann correlated IOP (IOPg), corneal compensated IOP (IOPcc), corneal hysteresis (CH), and corneal resistance factor (CRF) were measured by the ORA. Central corneal thickness (CCT) was measured using ultrasonic pachymeter. The differences of the changes in IOPg, IOPcc, CH, CRF and CCT between the three groups were estimated. A General Linear Model was selected to investigate the inﬂuence of gender, age, initial conditions (CH, CRF, CCT, IOPcc and IOPg) and changes in CCT on the measured IOP.

Results: The differences between the mean IOPg, CH and CRF after refractive surgery were statistically significant for all three groups. The hyperopic LASIK group had a significantly smaller change compared to the other groups (which had no statistical significance). The preop IOPg, preop CH and gender were significant predictors of the changes in measured pressure and biomechanical parameters after surgery in the myopic groups only.

Conclusion: CH and CRF were found to decrease after both myopic and hyperopic refractive surgery. CH and CRF measurement may prove important tools to clarify the role of corneal biomechanics for refractive surgery.

* Corresponding author at: Midland Eye Institute, 50 Lode Lane, Solihull, West Midlands B91 2AW, UK. Tel.: +44 121 711 2020; fax: +44 121 711 4040.

E-mail address:mohammadlaiquzzaman@hotmail.com(M. Laiquzzaman).

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Contact Lens & Anterior Eye

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c l a e

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measure of the visco-elastic properties of the cornea and corneal resistance factor (CRF) which is said to be a measure of elasticity. CH is the difference between the inward and outward applanation pressure. The air pressure pulse which impinges on the corneal surface is a precisely, metered ramp of air. If purely elastic, it would be expected that the cornea would applanate at the same pressure in both directions i.e. inward and outward; however, due to the visco-elastic properties of the cornea two different applanation pressures are noted. The CH is described as the loss or delay of energy due to resistance of the cornea to the air puff. Reichert believes that CRF derived in this process is dominated by the elastic properties of the cornea and appears to be

an indicator of the overall ‘‘resistance’’ of the cornea[10].

This study focuses on the change in three corneal parameters, CH, CRF, CCT, as well as two measures of IOP, corneal compensated IOP (IOPcc) and Goldmann correlated IOP (IOPg), 3 months following corneal refractive surgery. This is the ﬁrst study to address the differences in biomechanical properties in hyperopic eyes compared to myopic eyes following refractive surgery. 2. Materials and methods

Eighty eyes of 41 patients (25 females and 16 males) were recruited for this study from the Midland Eye Institute, Solihull, U.K. The mean age was 41.2 10.8 SD (age range 21.0–62.0 years). All had normal eyes and no history of ocular disease, surgery or trauma. IRB approval was obtained from the Local Research Ethics Committee. These patients undergoing refractive surgery were divided into three groups: Laser Assisted-Epithelial Keratomileusis (LASEK) (Myopes), Laser Assisted in Situ Keratomileusis (LASIK) (myopes) and LASIK (hyperopes) based on refractive error, corneal thickness and patient and surgeon preference i.e. these were not randomised groups. A full assessment for refractive surgery including refraction, full ocular examination, topography, abberometry and pachymetry was performed.

The ORA measurements were taken while the patient was seated in a standard fashion. The IOPg, IOPcc, CH and CRF were determined by the ORA. The CCT was measured using a hand held ultrasonic pachymeter (SP-2000, Tomey Corp, Japan) after instil-ling a drop of topical anaesthetic Proxymethacaine (Bausch & Lomb, Rochester, New York, USA) in the eye prior to performing pachymetry. The patient was asked to ﬁxate at a target in order to minimise any eye movement, and to avoid damage to the corneal epithelium. The pachymeter probe was gently placed onto the mid-pupillary axis in a perpendicular orientation. Upon contact with the corneal surface, the CCT value was displayed on the monitor attached to the probe. Six readings were taken and the mean value was used as the CCT. These measurements were taken before and after refractive surgery in the same order to avoid any bias in the data collection.

All the patients underwent LASEK or LASIK by one surgeon (SS). All surgery was uncomplicated. For LASEK, the cornea was anaesthetised by topical proxymethacaine. The patient was made

to lie on the couch and asked to focus on a flashing light. A lid speculum was inserted to open the lids. A 9.0 mm alcohol well was applied and was filled with 18% ethanol and left for 30 s. An 8 mm epithelial flap was fashioned, and then laser was applied to the bare corneal stroma. For LASIK, the cornea was anaesthetised and a lid speculum inserted. The cornea was marked with gentian violet to help realign the flap. A suction ring was applied to the limbus and IOP increased to ensure a smooth cut. A NIDEK MK2000 automated microkeratome (Gamagori, Japan) was used to create a corneal stromal flap, and all flaps were cut to a nominal depth plate

of 160

m

m. The hinge was made nasally. Laser was applied to

ablate the corneal stroma. After laser ablation, the stromal ﬂap was replaced.

Data were collected preoperatively and 3 months post-operatively following refractive surgery.

For the data analysis, several computer packages were used,

including Excel (Microsoft1

inc.) and MINITAB1

(Minitab Inc.). The changes of IOPg, IOPcc, CH, and CRF after surgery were compared between different groups of patients. ANOVA with post hoc test was performed for statistical analysis. The level of statistical significance level was chosen at 0.05. In addition, the influential predictive variables were identified based on the best subset regression and general linear models from a group of predictor variables, such as age, gender, the initial conditions (preop CCT, preop IOPg and preop CH), and ablation (CCT difference), on the IOP and CH change (IOPg difference, IOPcc difference, CH difference, and CRF difference).

To count for dependence between the two eyes of the same person in this study, we analysed the data based on two models; the simple model assuming the independence of eyes in that same patient and the nested model that counted for the dependence. While the p-values for the tests are slightly different, the conclusions of the signiﬁcance are the same. For simplicity, only the results based on the simple models are reported.

3. Results

The preop conditions of the patients from three different groups

are summarised inTable 1. It is important to note that the three

groups are not comparable (except for CRF) but this is to be expected as the corneal parameters were taken into account when choosing the appropriate procedure for the patients. There was no signiﬁcant difference between the LASIK myopes and LASIK hyperopes (Fig. 1a and b). On average, the myopic LASIK eyes

had 25

m

m greater preop CCT, 0.9 mmHg higher preop CH and

0.5 mmHg higher preop CRF than the myopic LASEK eyes, as well as 0.9 mmHg lower preop IOPg, and 1.7 mmHg lower preop IOPcc.

Fig. 2shows the CCT before and after the surgery for three groups. The IOPg and CH changes after surgery for three groups of patients

are shown inFig. 3a and b. The changes of the CCT, IOPg, IOPcc, CH

and CRF after refractive surgery are summarised inTable 2. The

mean IOPg, CH and CRF after refractive surgery were statistically lower than their initial values for all three groups of patients. The

Table 1

Initial characteristics of patients.

Group n Age** M/F Preop CCT** (mm) Preop IOPg** (mmHg) Preop CH** (mmHg) Preop IOPcc** (mmHg) Preop CRF (mmHg) 1. LASEK (myopes) 35 38.3 11.3 8/27 532.1 37.3 13.3 1.4 11.0 1.6 14.0 1.8 10.4 1.5 2. LASIK (myopes) 26 42.6 6.9 6/20 557.4 36.3 12.4 1.3 11.9 2.3 12.3 1.9 10.9 2.2 3. LASIK (hyperopes) 19 45.3 11.4 15/4 557.5 23.6 12.6 1.7 12.1 1.5 12.2 2.4 11.1 1.2 All 80 41.1 10.5 29/51 546.4 36.1 12.9 1.5 11.5 1.9 13.0 2.1 10.7 1.7

Means SDs; IOPg = (IOP1 + IOP2)/2.

**

The initial value of CCT, IOPg and IOPcc are significantly different between three groups of patients (p-values are 0.006, 0.029, 0.001 respectively), while age and initial value of CH are marginally different (p = 0.06 for both). The preop differences between the LASEK and the LASIK patients are statistically significant for all parameters. The preop differences between the LASIK myopes and LASIK hyperopes are not statistically significant for any parameter.

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mean IOPcc, however, increased after surgery. While the myopic LASEK eyes and the myopic LASIK eyes have similar values in IOPg

difference ( 1.4 1.1 and 1.7 1.8 respectively), CH difference

(2.7 1.4 mmHg and 2.5 1.7 mmHg) and CRF difference (2.7 1.4 mmHg and 2.6 1.3 respectively) after surgery, the hyperopic LASIK eyes have statistically signiﬁcantly smaller values of IOPg difference (0.6 1.2 mmHg), CH difference (1.1 1.7 mmHg) and CRF difference (1.2 1.3) than the previous two myopic groups with p-values of 0.016, 0.002 and 0.001 respectively.

There are many potential factors that may inﬂuence the IOPg difference, CH difference and CRF difference, such as surgery type (LASEK/LASIK), diagnosis (myopes/hyperopes) the initial conditions (preop IOPg, preop CCT, preop CH and preop CRF), ablation depth (CCT difference), age, and gender. Since the three groups are not comparable in terms of preop CCT, preop IOPg, preop CH and CCT difference (but were comparable for CRF), it is important to evaluate

the inﬂuence of these four factors.Table 3shows the correlation

between these initial conditions that were statistically signiﬁcantly

Fig. 1. (a) Boxplot showing the IOPg before surgery for the three groups of patients. (b) Boxplot showing the IOPcc before surgery for the three groups of patients.

Fig. 2. Boxplot showing the CCT before and after the surgery for three groups.

Table 2

Changes in CCT, IOPg, hysteresis, IOPcc and CRF after surgery.

Group n CCT difference**

IOP difference**

CH difference**

IOPcc difference CRF difference**

1. LASEK (myopes) 35 63 27 1.7 1.4* 2.5 1.7* 1.2 2.7* 2.6 1.3* 2. LASIK (myopes) 26 86 22 1.4 1.1* 2.6 1.4* 1.5 1.5* 2.7 1.4* 3. LASIK (hyperopes) 19 48 33 0.6 1.3 1.1 1.7* 0.7 2.5 1.2 1.3* All 80 67 311 1.3 1.5 2.2 1.7* 1.2 2.3 2.3 1.4* Means SDs.

For IOPg, CH, IOPcc and CRF, the differences are calculated as postop preop, for example, IOPg difference = postop IOP preop IOPg; for CCT, CCT difference = preop CCT postop CCT.

*

Denotes the value is statistically different from zero at 0.05 level.

**

CCT difference, IOPg difference, CH difference, and CRF difference are significantly different among three groups (p = 0.001, 0.045, 0.006, and 0.001 respectively); the differences were significant between myopes and hyperopes and insignificant between LASIK myopes and LASEK myopes, with the exception of CCT difference.

Fig. 3. (a) Boxplot showing the IOPg changes after surgery for three groups of patients. (b) Boxplot showing CH changes after surgery for three groups of patients.

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different and the CCT difference across all three groups. While the preop CH correlated to the preop CCT (r = 0.489), no other pair wise linear relationship was statistically signiﬁcant among them.

Figs.4a, b and5a, b show the inﬂuence of initial IOPg and CH on

the IOPg difference, CH difference, IOPcc difference and CRF difference. For all three groups of patients, the IOPg difference is proportional to the preop IOPg value. The higher the preop IOPg, the larger the IOPg difference (i.e. IOPg decreased more after surgery). The preop CH had a weak inﬂuence on the CH change as

one can see fromFig. 4a and b. Similar relationships can also be

observed between IOPcc difference and preop IOPg and between CRF difference and preop CH (Fig. 5a and b) and CH difference and CCT difference (Fig. 6).

Comparing the two groups of myopic patients, according to the models selected by the best subset regression, the influences of the type of surgery (LASEK and LASIK procedures) on IOPg difference, IOPcc difference, CH difference and CRF difference at the 3 months post-op time point are not statistically significant when other factors were considered. The factors influencing the IOPg difference are preop IOPg and preop CH. The IOPg decreases the most for those with higher preop IOPg and higher preop CH. The factors influencing the IOPcc difference are preop IOPg, preop CH

and gender. The IOPcc decreases the most for females with a higher preop IOPg. The factors influencing the CH difference were preop CH, preop IOPg and gender. The CH decreased the most for males with a higher preop CH and lower preop IOPg. The factors influencing the CRF difference were preop CH and gender. The CRF decreased the most for males with a higher preop CH. Age, ablation (CCT difference) and preop CCT were not influential on IOPg difference, IOPcc difference, CH difference and CRF difference.

Comparing the two groups of patients who had LASIK surgery, the type of diagnosis (myopia/hyperopia) has a significant influence on the IOPg difference, IOPcc difference, CH difference and CRF difference. For IOPg difference, the additional influential

Fig. 4. (a) Scatterplot showing the inﬂuence of initial IOPg on the IOPg difference in three groups of patients. (b) Scatterplot showing the inﬂuence of initial CH on the

CH difference in three groups of patients. Fig. 5. (a) Scatterplot showing the inﬂuence of initial CH on the CRF difference inthree groups of patients. (b) Scatterplot showing the inﬂuence of initial IOPg on the IOPcc difference in three groups of patients.

Fig. 6. Scatterplot showing the change in CCT versus change in CH in three groups of patients.

Table 3

The Pearson correlation between preop CCT, preop IOPg, preop CH and CCT difference. .

Preop IOPg Preop CH Preop CCT

Preop CH 0.125

Preop CCT 0.189 0.489a

CCT difference 0.167 0.06 0.193

a

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factors are gender and preop IOPg. For IOPcc difference, the additional influential factors are preop CH and preop IOPg. For CH difference, the additional influential factors are preop CH and preop IOPg. For CRF difference, the additional influential factor is preop CH. Age, ablation (CCT difference), and preop CCT are not influential on IOPg difference, IOPcc difference, CH difference and CRF difference.

4. Discussion

The corneal stroma constitutes 90% of the corneal thickness and is a highly specialised tissue which is responsible for the

mechanical and refractive properties of cornea[11]. The speciﬁc

architecture of the most anterior part of the corneal stroma (100–

120

m

m) has been suggested to be responsible for the stability of

the corneal shape[12,13]. The exact mechanism which maintains

the corneal shape is not known but this may be due to a passive distension of corneal tissue by IOP. This is maintained due to corneal mass, the elastic properties of the corneal tissue and the

mechanical force acting on this tissue[14].

Corneal properties are different in different individuals and this is related to the structure of the corneal tissue. CCT is only one of

the factors governing the corneal biomechanics[15]. To perform

refractive surgery more accurately, it has been proposed that the biomechanical properties of the cornea should be taken into

account[4].

Several studies have reported that when the structure of corneal tissues is altered, for example either by excimer laser

ablation[3]or due to disease process such as keratoconus[16–18]

corneal tissue rigidity (or elasticity) decreases. Reduced post refractive surgery IOP readings (measured IOP rather than true IOP) have also been cited as indirect evidence of a change in the

biomechanical properties of the cornea[4].

Various investigators have conducted studies to measure ocular

rigidity[14,16–19]but these studies used techniques that are not

practical for ophthalmologists in busy clinical settings.

The ORA is a new device developed by Reichert Ophthalmic Instruments which is a non-contact tonometer that measures the IOP as well as new metrics: CH (which is said to represent the

visco-elastic response of the cornea)[10]and CRF represents the

elastic properties of the cornea and appears to be an indicator of the overall ‘‘resistance’’ of the cornea. The ORA been reported to provide reproducible corneal biomechanical and IOP

measure-ments in non-operated eyes[20].

This study was performed to assess CH and CRF pre and post refractive surgery to see if there was a change in these properties. The results show that both CH and CRF values were signiﬁcantly lower after refractive surgery (p < 0.0001, paired t-test). This is consistent with previous reports in the literature following myopic

refractive surgery[9,21].Table 2shows the distribution of CH and

CRF and indicates these values to be lower after both myopic and hyperopic refractive surgery. This is the ﬁrst paper to report on a comparison of hyperopes and myopes.

The difference between the CCT values before and after refractive surgery was also statistically signiﬁcant (p < 0.0001,

paired t-test).Fig. 2shows the distribution of CCT indicating lower

CCT readings after the refractive surgery for all three groups as one would expect. The scatter plot (Fig. 6) shows the change in CCT versus change in CH. It shows a small, but insigniﬁcant correlation between these two (r = 0.155, p = 0.170). This indicates changing the CCT does not have a predictable effect on the change in CH.

Although no differences were found in the change of biomecha-nical properties between the myopic LASIK and myopic LASEK groups in the current study, it is important to recognize that the two groups were distinct preoperatively from a biomechanical perspec-tive. The LASEK eyes were thinner, had higher IOP, and lower CH and

CRF than the LASIK eyes, conﬁrming a preoperative bias of the surgeon.

The signiﬁcant predictors of post-operative changes in mea-sured IOP and biomechanical parameters were found to be the preoperative magnitudes of CH and IOPg, as well as gender. Therefore, any differences that might exist in the response based on type of surgery, whether LASIK or LASEK, may be hidden by the preoperative biomechanical distinctions between the populations. In fact, it is interesting that the myopic LASIK group had signiﬁcantly larger ablations than the myopic LASEK group, but experienced similar changes in properties and measured IOP. The hyperopic group experienced the smallest changes in biomecha-nical properties and IOP post-operatively, demonstrating that this procedure is bio-mechanically distinct from a myopic procedure. The caveat in the current study is that the ablation depths were also much lower in the hyperopic group.

The mean measured IOPg in this study was signiﬁcantly lower (p < 0.0001, paired t-test) after refractive surgery. The mean difference between the IOPg pre and post refractive surgery was 1.3 mmHg. This result is in agreement with earlier studies who also reported mean IOP readings to be lower after refractive surgery [3,4,7,22–25].

IOPcc is a corneal compensated IOP value, where the difference in the two pressure readings is calculated which is termed CH and is used to calculate the IOPcc. IOPcc is an IOP that has been claimed to be less affected by corneal biomechanical properties than other methods of measurements. It is believed to compensate for the biomechanical properties of the cornea by adjusting for hysteresis and not just the corneal thickness. Correction of IOP measurements using CCT only may result in signiﬁcant errors in the adjusted IOP values if the other biomechanical properties are ignored.

The results of this study revealed that the mean IOPcc was higher in post-op eyes in all the three groups. If one suggests that the true IOP should be the same following refractive surgery, then it would appear that the difference in IOPcc calculation should be zero.

Refractive surgery has been shown to inﬂuence corneal biomechanics in a manner that differs from the change in CCT, however, the magnitude of effect is subject to much individual variation. Theoretically a LASIK cut of collagen ﬁbres would induce biomechanical changes and weaken the cornea. However, sub-sequent healing may modify this effect. There are no available publications that the authors are aware of that have measured corneal biomechanics after a lamellar cut with no other loss of

tissue. Chihara et al. [7]suggested that ablation of the collagen

ﬁbres of the cornea may lead to reduced corneal rigidity as the cut collagen ﬁbres do have tensile force hence ablation depth per se may not be principal cause of underestimation of IOP post excimer laser refractive surgery. The biomechanical properties of the cornea are variable in different individuals and may have an

inﬂuence on the treatment outcome [8]. It was shown in the

current study that the preoperative properties and measured pressure are the strongest predictors of post-operative change in biomechanical properties and measured IOP. Thus, greater under-standing of the biomechanical properties of cornea in terms of CH and CRF may assist in improving outcomes. Future studies of bio-mechanically matched populations with matched ablation depths will be important to investigate the biomechanical differences in induced response between surface ablation and LASIK.

Each author states that he or his family members have no proprietary interest in the development or marketing of any instruments used.

References

[1] Holly FJ, Lemp MA. Tear physiology and dry eyes. Surv Ophthalmol 1977;22:69–87.

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[2] Hjortdal JO, Jensen PK. In vitro measurement of corneal strain, thickness and curvature using digital imaging processing. Acta Ophthalmol 1995;73: 5–113.

[3] Kaufmann C, Bachmann LM, Thiel MA. Intraocular pressure measurement using dynamic contour tonometry after laser in situ keratomileusis. Invest Ophthalmol Vis Sci 2003;44:3790–4.

[4] Munger R, Dohadwala AA, Hodge WG, Jackson WB, Mintsioulis G, Damji KF. Changes in measured intraocular pressure after hyperopic photorefractive keratectomy. J Cataract Refract Surg 2001;27:1254–62.

[5] Mardelli PG, Piebenga LW, Whitacre MM, Siegmund KD. The effect of excimer laser photorefractive keratectomy on intraocular pressure measurements using the Goldmann applanation tonometer. Ophthalmology 1997;104: 945–9.

[6] Yamaguchi T, Kaufman HE, Fukushima A, Saﬁr A, Asbell PA. Histologic and electron microscopic assessment of endothelial damage in the monkey cornea. Am J Ophthalmol 1981;92:313–27.

[7] Chihara E, Takahashi H, Okazaki K, Park M, Tanito M. The preopera-tive intraocular pressure level predicts the amount of underestimated intraocular pressure after LASIK for myopia. Br J Ophthalmol 2005;89: 160–4.

[8] Roberts C. Biomechanical customization: the next generation of laser refrac-tive surgery. J Cataract Refract Surg 2005;31:2–5.

[9] Liu J, Roberts C. Inﬂuence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Sur 2005;31: 146–55.

[10] Luce DA. Determining in-vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Ref Surg 2005;31:156–62.

[11] Tripathi RC, Tripathi BJ. Anatomy of the human eye and adenexa. In: Davson H, editor. The eye. Vegetative physiology and biochemistry. Florida, USA: Aca-demic Press; 1984. p. 1–102.

[12] Muller LJ, Pels E, Vrensen GF. The speciﬁc architecture of the anterior stroma accounts for maintenance of corneal curvature. Br J Ophthalmol 2001;85: 437–43.

[13] Boote C, Dennis S, Newton RH, Puri H, Meek KM. Collagen ﬁbrils appear more closely packed in the prepupillary cornea: optical and biomechanical implica-tions. Invest Ophthalmol Vis Sci 2003;44:2941–8.

[14] Edmund C. Assessment of an elastic model in the pathogenesis of keratoconus. Acta Ophthalmol 1987;65:545–50.

[15] Brubaker RF. Tonometry and corneal thickness. Arch Ophthalmol 1999;117:104–5.

[16] Hartstein J, Becker B. Research into the pathogenesis of keratoconus. A new syndrome: low ocular rigidity, contact lenses and keratoconus. Arch Ophthal-mol 1970;84:728–9.

[17] Edmund C. Corneal elasticity and ocular rigidity in normal and keratoconic eyes. Acta Ophthalmol 1988;66:134–40.

[18] Foster CS, Yamamoto GK. Ocular rigidity in keratoconus. Am J Ophthalmol 1978;86:802–6.

[19] Pallikaris IG, Kymionis GD, Ginis HS, Kounis GA, Tsilimbaris MK. Ocular rigidity in living human eyes. Invest Ophthalmol Vis Sci 2005;46:409–14. [20] Moreno-Montanes J, Maldonado MJ, Gracia N, Mendiluce L, Gracia-Gomez PJ,

Sequi-Gomez. Reproducibility and clinical relevance of the ocular response analyzer in non-operated eyes: corneal biomechanical and tonometric impli-cations. Invest Ophthalmol Vis Sci 2008;49:968–74.

[21] Pepose JS, Geigenbaum SK, Qazi MA, Sanderson JP, Roberts CJ. Changes in corneal biomechancis and intraocular pressure pre- and post-LASIK using static, dynamic and non-contact tonometry. Am J Ophthalmol 2007;143:39–47. [22] Montes-Mico R, Charman WN. Intraocular pressure after excimer laser myopic

refractive surgery. Ophthalmic Physiol Opt 2001:21;228–35.

[23] Chatterjee A, Shah S, Bessant DA, Naroo SA, Doyle SJ. Reduction in intraocular pressure after excimer laser photorefractive keratectomy; correlation with pre-treatment myopia. Ophthalmology 1997;104:355–9.

[24] Faucher A, Gregoire J, Blondeau P. Accuracy of Goldmann tonometry after refractive surgery. J Cataract Refract Surg 1997;23:832–8.

[25] Lee GA, Khaw PT, Ficker LA, Shah P. The corneal thickness and intraocular pressure story: where are we now? Clin Exp Ophthalmol 2002;30:334–7.