ORIGINAL PAPER

Corneal thickness and volume in subclinical and clinicalkeratoconus

Seyed Mahdi Ahmadi Hosseini • Norhani Mohidin • Fereshteh Abolbashari •

Bariah Mohd-Ali • Chandramalar T. Santhirathelagan

Received: 8 June 2012 / Accepted: 10 October 2012 / Published online: 9 November 2012

� Springer Science+Business Media Dordrecht 2012

Abstract To evaluate corneal thickness and volume

in subclinical and clinical keratoconus in Asian popu-

lation with the aim of discriminating between normal

and ectatic cornea. Eyes were placed into one of the

following three groups: normal, subclinical, and mild–

moderate keratoconus. Pentacam Scheimpflug imaging

(Oculus Inc., Wetzlar, Germany) was performed for

each participant to record thinnest corneal thickness,

central corneal thickness, corneal volume (CV), periph-

eral corneal thickness (PCT) and percentage thickness

increase (PTI) at 2, 4, 6, and 8 mm. The data were

exported to SPSS for statistical analysis. Subjects

comprised 52 normal, 15 subclinical keratoconus, and

32 mild–moderate clinical keratoconus eyes. Our

results indicated that corneal thickness (CT) distribu-

tion, PTI, and CV in normal eyes were significantly

different compared with subclinical and clinical kera-

toconus (P \ .05). Overall, subclinical group exhibited

lower CT distribution and volume, and higher PTI in

comparison with normal eyes. However, they showed

higher CT distribution and volume, and lower PTI

compared with keratoconus group. In addition, there

was a smaller change in PCT and PTI from the thinnest

point of the cornea to the periphery. The results of the

present study indicate that CT parameters and CV were

significantly different in normal versus subclinical

group and in normal versus keratoconus group. These

findings could help clinicians to better discriminate

between normal and ectatic cornea.

Keywords Pentacam � Keratoconus � Corneal

thickness � Corneal volume

Introduction

Keratoconus is the most common type of corneal

dystrophy, with prevalence of around 5 per 10,000 in

general population [1]. This noninflammatory corneal

ectasia is bilateral [2, 3], asymmetric [4, 5], and

characterized by central and paracentral corneal

stromal thinning and subsequent conical ectasia. It is

believed that tissue loss and decreasing corneal

thickness are related to keratocyte apoptosis around

the cone area [6].

The most common criteria for keratoconus diagno-

sis have been based on slit-lamp biomicroscopy and

corneal topography [1, 7]. Corneal steepening, local-

ized corneal thinning, Fleischer’s ring, Munson’s sign,

S. M. Ahmadi Hosseini � N. Mohidin �F. Abolbashari (&) � B. Mohd-Ali

School of Healthcare Sciences, Faculty of Health

Sciences, Universiti Kebangsaan Malaysia, Jalan Raja

Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

e-mail: f.abolbashari@gmail.com

C. T. Santhirathelagan

Sungai Buloh Hospital, Selangor, Malaysia

123

Int Ophthalmol (2013) 33:139–145

DOI 10.1007/s10792-012-9654-x

and Vogt’s striae are the signs that can be easily

detected in moderate to advanced stage of the disease

[1]. However, the diagnosis is difficult in preclinical or

early stages of keratoconus. The early stage, also

known as forme fruste keratoconus or subclinical

keratoconus, does not have any signs on slit-lamp

biomicroscopic examination but shows subtle changes

in topographic and pachymetry features similar to

those of clinical keratoconus [5].

Differentiating between healthy and ectatic cornea

is a prerequisite for several ophthalmic procedures

such as refractive surgeries and orthokeratology.

Patients with irregular or ectatic cornea may have

poor outcome or develop progressive ectasia after

refractive surgeries [8]. It has been reported that

1–6 % of myopic candidates for corneal refractive

surgeries are suspected to have or have keratoconus or

other forms of corneal ectasia [9, 10].

To date, many studies have been conducted to

determine accurate criteria for detecting early-stage

keratoconus, and many indices such as posterior

corneal elevation [11], corneal thickness (CT) and

corneal volume (CV) [12], and anterior and posterior

corneal aberration [13] have been presented.

Modern instruments such as corneal topographers

provide information concerning both corneal topog-

raphy and pachymetry simultaneously, and therefore

CV can be calculated. This is the case for the rotatory-

slit Scheimpflug camera system, i.e., Pentacam (Ocu-

lus Inc., Wetzlar, Germany), which provides CT and

CV measurements from analysis of multiple corneal

sections. The aforementioned values could help clini-

cians to better follow up the disease and improve

keratoconus staging [12].

Previous studies reported the alteration of CV at

different stages of clinical keratoconus [14]. It has

been proposed that there are some ethnic variations in

the development and distribution of the disease [15].

The present study was conducted to investigate

changes in corneal parameters in order to differentiate

subclinical and mild–moderate clinical keratoconus

from normal eyes in patients attended the primary eye

clinic in one of the states in Malaysia. Understanding

such differences is important so early intervention can

be provided to improve the quality of life of kerato-

conus patients. To the best of our knowledge, this is

the first study aiming to evaluate CT distribution and

CV in subclinical and clinical keratoconus in Asian

population.

Materials and methods

The subjects who agreed to participate in this study

were given a brief explanation, and consent forms

were obtained for their participation. All study proce-

dures adhered to the tenets of the Declaration of

Helsinki and were approved by the human ethical

committee of University Kebangsaan Malaysia.

Subjects and patient grouping

This study consisted of two types of investigations.

The first part was a retrospective cross-sectional study

for collecting data of subclinical and mild–moderate

keratoconus groups. In these groups, subjects were

chosen from clinical records [general and ocular

history, Pentacam map (Oculus Inc., Wetzlar, Ger-

many)] of keratoconus patients who came to the

ophthalmic clinic of Sungai Buloh Hospital for eye

examination from 2009 to 2011. Files of patients were

assessed, and data were recorded from patients who

met the inclusion criteria. Clinical keratoconus eyes

were diagnosed according to the criteria in Collabo-

rative Longitudinal Evaluation of Keratoconus

(CLEK) [16]. Then, based on keratometry reading

(K-reading) driven from the Pentacam topographic

maps, patients with mean K-reading between 47 D and

52 D were selected as the mild–moderate keratoconus

group (Fig. 1) [17].

Subclinical keratoconus eyes were selected from

the fellow eyes of the clinical keratoconus patients [1].

This group presented normal appearance on slit-lamp

biomicroscopy and retinoscopy examination [16] with

abnormal corneal topography including inferior–supe-

rior localized steepening or asymmetric bowtie pattern

[1]. In this study, subjects presenting with any corneal

scar, history of surgery, or contact lens wearing

1 week before examination or any other ocular

pathology were excluded.

The second part of the study followed a prospective

cross-sectional design using new subjects as the

control group. Data for the control group were

collected from the staff and family members of

patients in the hospital. The inclusion criteria for

normal subjects included absence of any ocular

pathology, no previous history of ocular surgery,

moderate refractive error (–6 D \ sphere \ ?6 D and

astigmatism \ 4.00 D), free from contact lens wearing

1 week prior to examination, and regular corneal

140 Int Ophthalmol (2013) 33:139–145

123

pattern on topography examination. Figure 2 illus-

trates the corneal thickness and total corneal power of

a normal eye. In this study, only the right eyes of the

normal participants were included in the analysis.

Pentacam procedures

For the measurement in the control group, subjects

were asked to sit and fix on the blue fixation target. The

operator then used the joystick to focus and align the

eye. When a clear image was maintained and focused,

the Scheimpflug images were taken automatically.

The instrument took 25 images in 3608 within 2 s. In

this study, only one measurement was performed for

each subject, and if the quality specification was not a

white ‘‘OK’’ reading, the reading was discarded and

the examination was repeated. Mean K-reading,

central corneal thickness (CCT), thinnest corneal

thickness (TCT), CT at 2, 4, 6, and 8 mm, percentage

thickness increase (PTI) at 2, 4, 6, and 8 mm, and

average, minimum, and maximum PTI and CV were

extracted from the Pentacam topographic maps for

statistical analysis.

Statistical analysis

Topographic and pachymetric data were imported to

SPSS software (version 18.0; SPSS, Inc.) for Windows

Fig. 1 Corneal thickness (left) and total corneal refractive power (right) of a subject with keratoconus eye

Fig. 2 Corneal thickness (left) and total corneal refractive power (right) of a subject with normal eye

Int Ophthalmol (2013) 33:139–145 141

123

for statistical analysis. Shapiro–Wilk test was performed

to assess the normality of the data. One-way analysis of

variance test was used to compare the topographic and

pachymetric parameters between groups. P \ .05 was

considered as statistically significant.

Results

This study included 32 mild–moderate keratoconus

eyes of 21 patients, 15 subclinical eyes of 15 patients,

and 52 right eyes of 52 healthy volunteers.

Mean ± SD age was 24.12 ± 6.80 years in mild–

moderate keratoconus group, 22.80 ± 8.06 years in

subclinical, and 25.29 ± 5.37 years in normal volun-

teers. There was no significant difference in age

distribution between the groups (P [ .05). Demo-

graphic data of participants are summarized in Table 1.

As expected, mean K-reading in the subclinical

keratoconus group was statistically higher than in

normal group (P = .006). Furthermore, subclinical

eyes exhibited lower values in comparison with

keratoconus group (P = .002). The mean ± SD for

mean K-reading was 43.19 ± 1.31, 45.16 ± 2.36, and

47.45 ± 2.89 diopter for normal, subclinical, and

keratoconus group, respectively (Table 2).

Table 2 summarizes the mean ± SD for all param-

eters in the three studied groups. The results indicated

statistically significant differences in all measured

parameters between the normal and keratoconus group,

including CCT, TCT, CV, peripheral corneal thickness

(PCT) and PTI at 2, 4, 6, and 8 mm (P \ .05). There

were statistically significant differences in all parame-

ters except maximum PTI between the subclinical eyes

and normal eyes. The mean CCT and TCT in subclinical

Table 1 Demographic features of subjects

Group Mild–

moderate

Subclinical Normal

Number of

eyes

32 15 52

Age

(mean ± SD)

24.12 ± 6.80 22.80 ± 8.06 25.29 ± 5.37

Table 2 Mean ± SD of parameters in the three groups of subjects

Parameters Mean ± SD P value*

Normal Subclinical Keratoconus

Km (D) 43.19 ± 1.31 45.16 ± 2.36 47.45 ± 2.89 .000/.000

CCT (lm) 543.51 ± 32.14 510.6 ± 21.78 499.68 ± 39.59 .000/.000

TCT (lm) 539 ± 96 ± 35.08 498.8 ± 24.33 484.21 ± 40.09 .000/.000

CT2 (lm) 551.83 ± 31.27 510.00 ± 21.62 501.63 ± 39.05 .000/.000

CT4 (lm) 574.98 ± 35.39 543.87 ± 18.17 543.28 ± 36.44 .002/.003

CT6 (lm) 627.75 ± 34.72 600.53 ± 16.72 607.28 ± 36.36 .005/.012

CT8 (lm) 703.29 ± 38.18 678.67 ± 17.15 680.44 ± 47.24 .018/.039

PTI2 (%) 1.38 ± .49 2.27 ± 1.16 3.63 ± 1.13 .022/.000

PTI4 (%) 6.50 ± 1.00 9.00 ± 3.02 13.09 ± 3.7 .010/.000

PTI6 (%) 15.87 ± 1.99 20.53 ± 4.38 26.06 ± 5.09 .001/.000

PTI8 (%) 28.88 ± 3.74 36.33 ± 5.31 42.25 ± 7.72 .002/.000

Max PTI (%) 1.17 ± .21 1.68 ± .50 2.35 ± .64 .092/.000

Avg PTI (%) .96 ± .14 1.42 ± .50 1.71 ± .43 .002/.000

Min PTI (%) .71 ± .13 .89 ± .27 1.26 ± .47 .001/.000

CV (mm3) 61.07 ± 3.54 58.43 ± 1.85 58.88 ± 3.57 .007/.007

Avg PTI average percentage thickness increase, CCT central corneal thickness, TCT thinnest corneal thickness, CT2 corneal thickness

at 2 mm, CT4 corneal thickness at 4 mm, CT6 corneal thickness at 6 mm, CT8 corneal thickness at 8 mm, Km mean keratometry,

Max PTI maximum percentage thickness increase, Min PTI minimum percentage thickness increase, PTI2 percentage thickness

increase at 2 mm, PTI4 percentage thickness increase at 4 mm, PTI6 percentage thickness increase at 6 mm, PTI8 percentage

thickness increase at 8 mm

* Subclinical versus normal/keratoconus versus normal

142 Int Ophthalmol (2013) 33:139–145

123

group were 510.6 ± 21.78 and 498.8 ± 24.33 lm,

being statistically lower than in normal group and

higher than in mild–moderate keratoconus (P \ .05).

The mean ± SD for CV in normal, subclinical, and

keratoconus groups was 61.07 ± 3.54, 58.43 ± 1.85,

and 58.88 ± 3.57 mm3, respectively.

Overall, subclinical group showed lower CT dis-

tribution and volume, and higher PTI value compared

with normal. However, this group had higher CT

distribution and volume, and lower PTI compared with

keratoconus group. In addition, the changes in PCT

and PTI were decreased from the thinnest point of the

cornea to the periphery.

Discussion

Previous studies reported higher incidence of kerato-

conus in Asian population compared with Caucasians

[18]. In addition, Asian eyes are more likely to

progress to severe form of keratoconus and need

corneal grafting at younger age [18]. This study was

conducted to record the alteration in CT distribution

and CV of subclinical and clinical keratoconus eyes in

Asian population for better understanding of the

changes and to improve early intervention of this

progressive disorder. Results of the current study

revealed significant differences in CT distribution and

CV between normal versus subclinical and normal

versus keratoconus. However, from the thinnest point

to the periphery, smaller differences were found

between control and ectatic corneas.

Accurate measurement of CT is a key factor in

keratoconus detection and monitoring of the disease

[19]. It is also considered as an important parameter in

screening and follow-up of candidates for refractive

surgeries [8]. Previous studies indicated that early

stages of clinical keratoconus as well as the preclinical

stages might lead to ectatic progression after refractive

surgeries [20, 21]. Although many patients in prestag-

es of clinical keratoconus progress to the clinical stage

[22, 23], early detection might be helpful in early

management of the disease and improve their quality

of life.

In order to better discriminate between early stages

of keratoconus and healthy eyes, several indices with

high sensitivity and specificity were presented in

previous studies. Corneal pachymetry [13], CV [12],

anterior and posterior shape [11], and anterior and

posterior surface aberrations [13] proved to be accu-

rate parameters in keratoconus detection.

This study showed lower values of CCT and TCT in

keratoconus eyes compared with normal and subclin-

ical eyes, broadly in agreement with the Pinero et al.

study [11]. These researchers stated that the mean

CCT and TCT in subclinical group were significantly

lower than in normal eyes and higher than their

moderate keratoconus group.

As detection of the early stage of keratoconus is

very important in keratoconus management and the

outcome of refractive surgeries, we included subclin-

ical eyes in this study. Ambrosio et al. [9] introduced

analysis of corneal thickness spatial profiles using

Pentacam for diagnosis of keratoconus eyes [24]. They

reported statistically significant differences in PCT

and PTI between mild–moderate keratoconus and

normal eyes. Although their method was novel in

corneal tomography, they did not include eyes with

subclinical keratoconus. Both studies indicated statis-

tically significant differences in CT parameters

between mild–moderate keratoconus and the control

group; however, the values in their keratoconus group

were lower compared with our results. This difference

might be related to the different severity of the

keratoconus in the subjects participating in the two

aforementioned studies.

There are few studies available for PCT and PTI

assessment in subclinical and early stages of kerato-

conus. Our statistical analysis for PCT and PTI

showed that normal eyes had more homogeneous

values from the thinnest point to the periphery

compared with keratoconus eyes. These results are

in agreement with the study of Saad and Gatinel, who

used Orbscan II to compare the CT profiles of normal,

forme fruste, and clinical keratoconus eyes [25]. Their

results indicated that normal eyes had significantly

higher thickness values with 1-mm step centered on

the thinnest point compared with forme fruste and

clinical keratoconus.

Results of the present study showed significantly

lower values of CT from the thinnest point to the

periphery. These findings support pervious literature

stating that, in preclinical or early stages of the

disease, corneal thinning in peripheral area occurs

with no tissue loss, only being accompanied by minor

alteration in keratocyte orientation [26].

Although a significant difference in CV was found

between normal and other groups in this study, Pinero

Int Ophthalmol (2013) 33:139–145 143

123

et al. did not find this [11]. They reported values of

60.83 ± 3.27, 58.91 ± 4.87, 60.00 ± 2.84, and

57.98 ± 2.65 mm3 for normal, subclinical, mild, and

moderate, respectively. They believed that, in the

early stages of the disease, redistribution of CV

happened with no tissue loss. This is probably true

according to the changes in keratocyte redistribution

and orientation in keratoconic cornea [27]. However,

it is possible that the changes in CV are directly

associated with PCT. Based on our results and those of

Ambrosio et al. [9], subclinical and clinical keratoco-

nus had lower PCT values compared with normal.

In this study, Pentacam Scheimpflug HR, which is

one of the fairly advanced instruments in corneal

imaging technology, was used. In 2008, Sanctis et al.

suggested use of Pentacam rotating Scheimpflug

camera for recording central pachymetry, disease

staging, and follow-up of keratoconus [28]. Further-

more, other studies reported high repeatability and

reproducibility of this instrument in corneal thickness

measurement [29].

To the best of our knowledge, this is the first study

that recorded the CT distribution and CV profile in

subclinical and clinical keratoconus in Asian popula-

tion. In summary, detection of preclinical and early

stage of keratoconus is of paramount importance in

preoperative examination for refractive surgeries. To

date, most of the criteria for detection and grouping of

keratoconus have been based on anterior corneal

curvature. Our study indicated significant differences

in CT distribution and CV between normal, subclin-

ical, and early stage of keratoconus. The findings

showed that these new parameters obtained from the

Pentacam Scheimpflug machine could be helpful in

better discriminating between normal and ectatic

cornea.

Acknowledgment The authors have no financial or proprietary

interest in a product, method, or material described here.

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