the prevalence of keratoconus in a young population in mashhad, iran

The prevalence of keratoconus in a young population inMashhad, IranHassan Hashemi1, Mehdi Khabazkhoob2, Negareh Yazdani3, Hadi Ostadimoghaddam3, RezaNorouzirad4, Kazem Amanzadeh1, Mohammad Miraftab1, Akbar Derakhshan5 and AbbasAli Yekta3

1Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran, 2Department of Epidemiology, Faculty of Public Health, Shahid Beheshti

University of Medical Sciences, Tehran, Iran, 3Department of Optometry, School of Paramedical Sciences, Mashhad University of Medical Sciences,

Mashhad, Iran, 4Dezful University of Medical Sciences, Dezful, Iran, and 5Department of Ophthalmology, Mashhad University of Medical Sciences,

Mashhad, Iran

Citation information: Hashemi H, Khabazkhoob M, Yazdani N, Ostadimoghaddam H, Norouzirad R, Amanzadeh K, Miraftab M, Derakhshan A,

Yekta A. The prevalence of keratoconus in a young population in Mashhad, Iran. Ophthalmic Physiol Opt 2014; 34: 519–527. doi: 10.1111/opo.12147

Keywords: keratoconus, Middle East,

prevalence, risk factors

Correspondence: AbbasAli Yekta

E-mail: [email protected]

Received: 7 January 2014; Accepted: 27 June

2014; Published Online: 11 August 2014

Abstract

Purpose: To determine the prevalence of keratoconus and some associated factors

in the students of Mashhad University of Medical Sciences, Iran.

Method: In this cross sectional study, multistage cluster sampling was used to

select the participants. All participants underwent retinoscopy, slit lamp examina-

tion, topography with the TMS-4 and corneal assessment with the Orbscan II.

The diagnosis of keratoconus was based on both clinical evidence and the results

of corneal imaging.

Results: Of 1280 selected students, 1073 agreed to participate in the study, and of

those who agreed, 1027 fulfilled the inclusion criteria. 42.5% of the study popula-

tion was male with a mean age of 26.1 � 2.3 years. The prevalence of keratoc-

onus was 2.5% (n = 26) (95% confidence interval, CI 1.6–3.5). Eighteen students

(69%) had bilateral keratoconus. Imaging of the cornea revealed that 70% of the

keratoconics had nipple cones and the remaining had asymmetric bow-tie pat-

terns. The prevalence of keratoconus was not significantly associated with age or

gender (p > 0.05). In a multiple logistic regression model, family history

(OR = 11.4, 95% CI: 2.5–51.3) and eye rubbing (OR = 6.3, 95% CI: 1.6–24.3)were significantly correlated with keratoconus.

Conclusions: These results taken together with recent studies in the area suggest

that keratoconus may have a higher prevalence in the Middle East and Asia than

in Western Countries.

Introduction

Keratoconus is a non-inflammatory disorder of the cornea,

with symptoms that include decreased resolution at all dis-

tances, poor vision quality due to changes in aberrations,

seeing haloes around objects and/or lights and decreased

quality of life.1–4 Numerous recent studies have evaluated

the prevalence of keratoconus, and its diagnostic and treat-

ment methods.5–11 Studies on the epidemiology of keratoc-

onus have resulted in a wide range of prevalence

figures.6,7,9,10 For many years, it was believed that keratoc-

onus had a low prevalence of about 1 in every 2000

individuals12 while recent studies using corneal topography

devices have reported higher prevalence rates.6,7,9,10 Ethnic

and environmental factors may also contribute to the wide

range of prevalence figures.6,7,9,10,13–16 Studies on twins and

genetic studies have shown the important role of genetics

in the development of keratoconus,17,18 with keratoconus

following an autosomal dominant mode of inheritance in

some patients,.19,20 Although there are many reports on the

prevalence of keratoconus, some reports are limited as they

do not provide an accurate definition of keratoconus. For

example, some studies did not use topographic devices13–16

and/or did not assess clinical signs6,9,21,22.

© 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists

Ophthalmic & Physiological Optics 34 (2014) 519–527

519

Ophthalmic & Physiological Optics ISSN 0275-5408

Some reports indicate that the prevalence of keratoconus

is higher in South Asian and Middle-Eastern popula-

tions.7,9,23,24 Two recent studies have evaluated keratoconus

in Iran; the Tehran study21 reported that the prevalence of

keratoconus was 3.3% based on Orbscan II findings, and

the Shahroud study6 reported a prevalence of 0.76% in

individuals aged 40–64 years old based on Pentacam imag-

ing. However, keratoconus was diagnosed based on topo-

graphic findings in these studies and clinical findings were

not considered. Due to the limitations of the previous stud-

ies and the sparse number of studies on keratoconus world-

wide, our objective was to evaluate the prevalence of

keratoconus in a young population in Iran using both cor-

neal imaging and clinical findings. In addition, we assessed

the association between keratoconus and the history of

allergy, family history of keratoconus and history of eye

rubbing.

Materials and methods

Participants were recruited from the student body of the

Mashhad University of Medical Sciences in 2013. Stratified

cluster sampling was used to select the participants. In the

first step, all students from each academic department were

considered as a stratum. In the second step, stratification

was performed-based on the entrance year and finally, pro-

portionate to the number of students in each strata, ran-

dom sampling was performed using the student ID

number. The selected students were then invited to partici-

pate in the study. All examinations were performed in one

location. The students signed informed consent before

entering the study. In the first stage, an interview was con-

ducted with each participant regarding demographic infor-

mation and then examinations were performed. During the

interview, in addition to demographic information, the

family history of keratoconus, history of allergy, and eye

rubbing were also investigated. Participants were excluded

from the study if they had a positive history of refractive

surgery or any ocular surgery or a positive history of using

contact lenses for reasons other than keratoconus.

Examinations

Examinations included refraction, slit lamp examination,

and imaging. Refraction was performed with an auto

refractometer (Topcon RM8800, www.topcon.com.sg/

medical/rm.html) by an experienced optometrist, and

retinoscopy was done with the Heine Beta 200 retinoscope

(http://www.heine.com). Imaging studies included topog-

raphy (TMS-4; www.Tomey.com) and Orbscan II (www.

Bausch.com). Imaging was performed with both the TMS-

4 and Orbscan II on all participants. The major criteria for

keratoconus diagnosis using TMS-4 topography are a

Keratoconus Prediction Index (KPI) of more than 0.23 and

corneal power more than 47.2D.25 Opposite sector index

(OSI), irregular astigmatism index (IAI), differential sector

index (DSI), centre surround index (CSI), surface regular-

ity index (SRI), Surface asymmetry index (SAI), standard

deviation of power (SDP), and Analysed Area (AA) were

also measured.

Orbscan II quad map was used including the anterior

and posterior surface maps, keratometry reading, and cor-

neal thickness. We applied the following criteria for the

diagnosis of keratoconus by Orbscan II25: keratometry

more than 47.2 dioptre, more than 3D difference between

maximum and minimum keratometry in the 3 mm central

cornea, a ratio more than 1.27 in anterior/posterior cor-

neal curvature, posterior BFS power more than 55D, more

than 100 l difference between 7 mm central cornea and

the thinnest point of the cornea, more than 0.9 mm dis-

tance between the apex and thinnest point of the cornea,

and the thinnest point of the cornea <470 micron. The

Orbscan was used to calculate the inferior–superior (I–S)value, the amount of inferior cornea steepening vs the

superior cornea, through subtracting the superior value

from the inferior value. We derived the inferior value via

the average of five data points along the inferior cornea at a

distance of 3.0 mm from the corneal centre at the intervals

of 30� (i.e. at 210, 240, 270, 300, and 330 degrees). Simi-

larly, we calculated the superior value by the average of five

points on the superior cornea at a distance of 3.0 mm from

the corneal centre (i.e. at 30, 60, 90, 120, and 150 degrees).

Apical thinning was defined as reduction in the thickness

of the cornea to one-third of the thickness in the periphery.

The shape of the corneal cone was determined based on the

power of the corneal map available in both Orbscan II and

TMS 4. We categorized the corneal shape as symmetrical

bow-tie, asymmetrical bow-tie, and nipple shaped.8,26

The presence or absence of a scissors reflex was deter-

mined by retinoscopy. On slit lamp examination, the par-

ticipants were investigated for Fleisher’s ring, Vogt striae,

corneal thinness, and rupture in Bowman’s layer. Finally,

based on the topographic maps and clinical findings, a

diagnosis of keratoconus was made for each patient. In

some cases the topographic indices were within the normal

range, but a diagnosis of keratoconus was made based on

the findings of the topographic maps plus the clinical

indices.

Interview

A history of eye rubbing was defined as rubbing of the eye

for any reason including ocular disease, ocular dryness, or

allergy for a rather long duration of time. A positive history

of allergy was recorded if the subject was ever informed by

a doctor that (s) he was allergic. A family history of



520

Keratoconus and its associated factors H Hashemi et al.

keratoconus was positive if a first degree relative had kera-

toconus.

Statistical analysis

After detecting the cases of keratoconus, its prevalence in

the study population was reported as a percentage with a

95% confidence interval. Logistic regression was used to

investigate the association because our main variable was

binary. Student’s t-tests (2-tailed, Independent Samples

Test) were used to compare quantitative variables between

participants with and without keratoconus and p < 0.05

were considered statistically significant.

Multiple logistic regressions were used to evaluate the

relationship between keratoconus and other variables and

to control for confounding variables. The variables of age,

sex, family history of keratoconus, history of allergy, and

history of eye rubbing were entered into the model and

non-significant variables were removed from the model

using the backward method. In the end, the model in which

all variables were significantly correlated with keratoconus

was presented.

All statistical analyses were performed with STATA

v.11.0 (www.stata.com). A history of allergy, family history,

and history of eye rubbing were entered into the model as

binary variables. In the multiple model, p < 0.05 were con-

sidered statistically significant.

Ethical Issues

The ethics committee of Mashhad University of Medical

Sciences approved the study proposal. Each student signed

a consent form before entering the study and after receiving

information on the objective of the study.

Results

Of the 6745 students attending Mashhad University of

Medical Sciences in 2013, 1280 were invited to participate

in the study, and 1073 responded (response rate = 83.8%).

We excluded 37 students who had a history of refractive

surgery and nine students who wore contact lenses due to

refractive errors. Final analyses were performed on the data

of 1027 students. The mean age of the participants was

26.1 � 2.3 years (ranging from 20 to 34 years). 42.5% of

the participants (n = 437) were male and 68.5% (n = 703)

were female. The mean age of the male and female partici-

pants was 26.1 � 3.3 and 26.0 � 3.3 years, respectively.

Independent sample t-test showed no significant difference

in age between the sexes (t = 0.29, p = 0.77).

Table 1 presents the prevalence of keratoconus according

to age, sex, family history, history of allergy and history of

eye rubbing. The prevalence of keratoconus was 2.5%

(n = 26) (95% CI 1.6–3.5) for the entire cohort. Bilateral

keratoconus was observed in 69% (n = 18) of the kerato-

conic participants. Eleven keratoconic students (42% of the

keratoconus patients) were unaware of their condition,

which was bilateral in each case. The prevalence of keratoc-

onus was not significantly associated with sex (p = 0.11).

Moreover, no significant changes were observed in the

prevalence of keratoconus with the increase in age

(p = 0.09, univariate logistic regressions). Univariate analy-

sis showed that keratoconus was significantly associated

with a positive history of allergy (odds ratio, OR = 7.7,

95% CI 2.7–21.8, p < 0.001), a positive family history of

keratoconus (OR = 22.6, 95% CI 6.3–80.6, p < 0.001), and

a positive history of eye rubbing (OR = 11.0, 95% CI 4.5–26.8, p < 0.001). A multivariate logistic regression model

(Table 2), indicated that family history of keratoconus and

a history of eye rubbing were significantly associated with

keratoconus, while sex and a history of allergy were not.

Table 3 presents the clinical and topographic findings of

the 26 patients with keratoconus. It should be noted that

the findings of the worse eye were reported in bilateral

cases. Moreover, Figures S1 and S2 show the posterior and

axial maps of the keratoconic eyes whose characteristics are

presented in Table 3, separately. Nipple-shaped keratoc-

onus and asymmetric bow-tie keratoconus were seen in

70% and 30% of the keratoconics, The location of the cone

was superior in one eye and inferior in all the other eyes.

The mean � SE was �4.98 � 5.2D in keratoconic and

�1.14 � 2.0 in non keratoconic participants, which were

significantly different (p < 0.001). The cylinder power was

2.1D worse in keratoconic vs non-keratoconic participants

(p < 0.001). A scissor reflex was observed in all but one of

the students with keratoconus (96%), a Fleischer ring was

observed in 18 (69%), Vogt striae in three (12%) and apical

Table 1. The prevalence of keratoconus amongst 1027 medical stu-

dents, including by risk factors of age, sex and self-report of history of

allergy, family history of keratoconus and eye rubbing

Total Keratoconic

% prevalence

(95% CI)

1027 26 2.5 (1.6–3.5)

Age (year)

20–22 175 6 3.4 (0.7–6.2)

23–25 275 9 3.3 (1.2–5.4)

26–28 239 5 2.1 (0.3–3.9)

>28 338 6 1.8 (0.4–3.2)

Sex

Male 437 12 3.7 (1.6–5.8)

Female 590 14 2.0 (1.0–3.0)

History of allergy 35 5 14 (2–27)

Family history of keratoconus 12 4 33 (2–65)

Self-reported eye rubbing 47 8 17 (6–28)



521

H Hashemi et al. Keratoconus and its associated factors

thinning seen in two (8%). Table 4 shows mean topo-

graphic and some Orbscan II indices in participants with

and without keratoconus. According to Table 4, except for

the corneal and pupil diameter and the anterior chamber

depth, there was a significant difference in all other indices

between the two groups.

Discussion

This study determined the prevalence of keratoconus in a

young Iranian population to be 2.5%. It is one of the few

studies to report the prevalence of keratoconus based on

clinical signs using retinoscopy, slit lamp examination,

topographic evidence, and Orbscan II indices worldwide,6

which should keep the false positive and false negative

rates low. Some other studies have used video keratogra-

phy.21,27–29 Table 5 summarises the results of other

Table 2. Odds ratios (OR) and 95% confidence intervals (CI) for risk

factors for keratoconus from a multiple logistic regression analysis of

data from 1027 students

OR (95%CI) p-value

Age (years)

20–22 1

23–25 0.94 (0.31–2.83) 0.91

26–28 0.61 (0.17–2.17) 0.44

>28 0.49 (0.15–1.62) 0.25

Sex

Male/female 0.48 (0.21–1.12) 0.09

History of Allergy

Yes/no 1.4 (0.3–6.8) 0.68

Family history of keratoconus

Yes/no 11.4 (2.5–51.3) <0.001

History of eye rubbing

Yes/no 6.3 (1.6–24.3) 0.008

Table 3. Quantitative variables in the eye of keratoconics according to Topography TMS-4 and Orbscan II and clinical finding

Clinical findings Orbscan II

Topography

TMS-4

ID AT VS SR TC K_max K_min Sim_k TP CT I-S KPI A.A

1 n y y n 43.8 41.8 �2.1 401 467 5.8 0.29 70

2 n n y n 49.2 42.6 �6.6 447 464 2.8 0.26 99

3 n n n a 51.4 44.5 �6.9 434 469 6.2 0.38 81

4 n n y n 46.0 44.0 �2.0 461 486 5.6 0.39 91

5 n n y n 53.8 48.6 �5.2 467 489 5.9 0.48 95

6 n n y n 54.1 46.7 �7.4 460 495 6.4 0.42 90

7 n y y n 56.1 47.2 �8.8 374 404 3.6 0.37 88

8 y n y n 45.2 41.4 �3.8 488 522 5.0 0.34 87

9 n n y n 50.3 47.2 �3.1 370 417 5.9 0.42 88

10 n n y a 46.6 43.7 �2.8 295 418 3.9 0.33 81

11 n n y n 49.1 44.9 �4.2 458 479 3.7 0.34 88

12 n n y n 51.2 49.2 �1.9 452 474 4.1 0.4 87

13 n n y a 51.0 46.3 �4.7 430 459 1.6 0.37 85

14 n n y n 48.3 45.0 �3.3 456 481 3.6 0.25 80

15 n n y n 49.1 45.8 �3.3 477 497 5.1 0.32 83

16 n y y n 64.7 58.0 �6.7 368 398 a 0.35 51

17 n n y n 50.8 47.6 �3.1 535 544 2.2 0.34 90

18 n n y n 55.7 50.9 �4.8 478 509 6.1 0.43 77

19 n n y n 52.4 46.1 �6.4 425 466 4.0 0.36 83

20 n n y n 54.2 49.7 �4.5 393 418 3.6 0.34 83

21 n n y n 54.5 47.9 �6.6 479 491 8.1 0.54 99

22 n n y a 51.0 49.0 �2.0 353 380 �0.2b 0.35 85

23 n n y a 49.7 46.3 �3.4 306 344 1.7 0.26 83

24 n n y a 50.6 44.9 �5.7 435 493 5.5 0.39 81

25 n n y n 45.7 43.4 �2.3 466 487 3.8 0.29 91

26 n n y a 52.6 44.5 �8.1 562 587 c 0.35 98

AT, Apical thinning; VS, Vogt strea; SR, Scissor reflex; TC, type of cone (asymmetric bow-tie: a; nipple: n); TP, thickness in thinnest point; CT, Corneal

thickness; I-S, inferior– superior index; KPI, Keratoconus Prediction Index; AA, Area analyzed.aIn this case (no = 16), due to the severity of keratoconus, it was not possible to calculate I-S.bThe type of cone in this patient (no = 22) was superior; therefore, a negative I-S value was obtained. The power of the cornea in this patient in the

three zones of 3, 5, and 7 was more in the superior than the inferior steepening.cThe topographic data of the patient number 26 was not available.



522


keratoconic prevalence studies for comparison, and indi-

cates a range in prevalence from 0.0002% in Russia-

Urals15 to 3.33% in Lebanon24. The prevalence of keratoc-

onus found in this study is similar to that reported in at

India7, Israel9, Lebanon24 and other parts of Iran21.

The relatively high prevalence of keratoconus in this

study may be due to different diagnostic methods or ethnic

and genetic differences. Older studies used keratometry or

the retinoscopic reflex to diagnose keratoconus because

topographic maps were not available; as a result, some

cases, especially mild ones, may have been missed and the

prevalence would have likely been underreported. In addi-

tion, a number of studies have investigated the role of eth-

nicity in the prevalence of keratoconus,30,31 with studies

from Lebanon24, Israel9, and Saudi Arabia23 as well as the

present study suggesting that the prevalence of keratoconus

is relatively high in Middle-East countries while its preva-

lence is lower in reports from European countries.10,14,32

The prevalence of keratoconus was also found to be high in

India,7 and the higher prevalence in people from the Mid-

dle-East and Asia is supported by studies from England that

show that the prevalence is higher in Asians than in Cauca-

sians.32

About 70% of our patients had bilateral keratoconus. This

is lower than previous studies including y Ljubic22, Weed et

al33, Schmitt-Bernard et al18 and Rabinowitz12,18. We cannot

offer an explanation for this and more prospective studies

are required to explain this difference in findings.

Eleven keratoconus patients were unaware of their con-

dition. The reason for this may be that the visual acuity of

these patients was not yet severely affected because they

were in the primary stages of keratoconus. Alternatively,

they may have complained of visual problems, but the con-

dition was not diagnosed. This finding is very important

from a public health perspective as it suggests that keratoc-

onus is under diagnosed. Collagen cross-linking is a new

technique that stops the progression of keratoconus, but

does not improve vision34. Therefore, it is essential to iden-

tify these patients in the early stages of the disease and sug-

gests the need for national screening policies.

Our findings did not suggest a significant correlation

between age and the prevalence of keratoconus while the

prevalence of keratoconus increased with ageing in the

Tehran study21 and decreased with ageing in the Shahroud

study6. It seems that one of the main reasons for this dif-

ference is the age range of the study populations in these

three studies. The widest age range was seen in the Tehran

study21 (14–90 years of age); therefore, it is possible that

the increase in the prevalence of keratoconus with ageing

was mainly due to the age cohort effect. In the the Shah-

roud study6, since the age range of the participants was

40–64 years old, natural cross linking that occurs with the

increase in age may be the reason for the decreased preva-

lence of keratoconus in older ages.

Many studies have reported a higher prevalence of kera-

toconus in men16,32. Owens et al35 from New Zealand,

Table 4. The topography and Orbscan II indices in keratoconus and non- keratoconus

Non-keratoconus Keratoconus

Mean � SD Range Mean � SD Range

Topography TMS-4

Surface asymmetry index 0.33 � 0.2 0 to 2 1.91 � 0.64 0.8 to 3.78 <0.001

Differential sector index 2.63 � 1.07 0.14 to 9.5 8.71 � 3.44 2.31 to 16.81 <0.001

Surface regularity index 0.19 � 0.19 0 to 1.31 0.92 � 0.42 0.27 to 2.28 <0.001

Opposite sector index 0.80 � 0.67 0 to 8.07 6.55 � 3.37 0.75 to 14.56 <0.001

Centre surround index 0.28 � 0.21 �2.14 to 2.82 2.13 � 1.58 �0.05 to 7.13 <0.001

Standard deviation of power 0.82 � 0.35 0.00 to 3.35 3.59 � 1.22 1.31 to 6.54 <0.001

Irregular astigmatism index 0.34 � 0.06 0.17 to 0.92 0.44 � 0.07 0.32 to 0.66 <0.001

Keratoconus Prediction Index 0.20 � 0.02 0.10 to 0.37 0.35 � 0.06 0.25 to 0.54 <0.001

Area analyzed 89 � 7 45 to 100 85 � 9 51 to 99 <0.001

Orbscan II

Maximum Keratometry (dioptre) 44.5 � 1.7 39.3 to 53.6 50.4 � 3.8 43.8 to 64.7 <0.001

Minimum Keratometry (dioptre) 43.1 � 1.7 31.0 to 52.1 46.1 � 2.9 41.4 to 58.0 <0.001

Corneal astigmatism (dioptre) �1.4 � 1.0 �6.0 to 0.8 �4.3 � 2.3 �11.4 to �1.0 <0.001

Anterior diff (mm) 0.01 � 0 �0.03 to 0.05 0.04 � 0.02 0.01 to 0.11 <0.001

Posterior diff (mm) 0.02 � 0.01 0 to 0.09 0.09 � 0.04 0.04 to 0.23 <0.001

White to White (mm) 11.7 � 0.4 10.2 to 13.6 11.8 � 0.3 11 to 12.4 0.24

Pupil diameter (mm) 4.4 � 0.9 2.0 to 9.4 4.3 � 1.0 2.9 to 8.0 0.68

Thinnest point of corneal thickness (micron) 544 � 35 396 to 657 442 � 62 295 to 581 <0.001

Anterior chamber depth (mm) 3.66 � 0.28 2.06 to 4.53 3.73 � 0.24 3.37 to 4.2 0.083

Central corneal thickness (micron) 551 � 35 410 to 662 472 � 55 344 to 604 <0.001



523


Millodot et al9 from Israel, Pearson et al32 from the UK,

and Gorskova and Sevost’ianov15 from Russia, all reported

a higher prevalence of keratoconus in men. Although,

Table 1 indicates that the prevalence of keratoconus in men

was almost twice its prevalence in women (3.7% vs 1.8%),

the multiple logistic regression model suggested that the

prevalence of keratoconus was not different between men

and women (p = 0.09), However, the difference in preva-

lence found plus the borderline p-value in the model sug-

gests that the power of the study in detecting a statistical

relationship was low.

A positive history of allergy (OR = 7.7), and eye rubbing

(OR = 10.1) showed a strong relationship with the preva-

lence of keratoconus in our study in the simple model of

logistic regression.

Of course, as mentioned earlier, the history of allergy was

not significantly correlated with keratoconus in the multi-

ple model after adjusting other variables and only the his-

tory of eye rubbing and the family history of keratoconus

remained in the model. We believe that it is because of the

relationship between the history of allergy and the family

history of keratoconus as these two variables have a strong

association (OR = 10.2, p < 0.001) and due to colinearity,

only the family history of keratoconus remained in the

multiple regression model. These two risk factors have also

been reported in previous studies.30 The odds ratio of kera-

Table 5. Prevalence of keratoconus in studies around the world

Region

Age

range

Prevalence

(per 100 000) Defined keratoconus

Method used to detect

keratoconus

Finland16 – 30 Clinical exam by ophthalmologist Slit lamp

USA14 – 54 Scissors movement on retinoscopy and keratometry Clinical examination

Russia-Urals15 – 0.2 Not available Not available

UK32 10–44 57 (Whites) Clinical exam by ophthalmologist Patients referred for contact lenses

or directly for corneal graft in

whom a clinical diagnosis of

keratoconus had been made by an

ophthalmologist.

229 (Asians) Clinical exam by ophthalmologist

Japan48 15–44 12.4 (Males) Claims of patient Questionnaires

6.7 (Females)

Saudi Arabia23 8–28 – Visual acuity, family history, corneal curvature, scissors reflex Keratometry and refraction

Denmark10 – 86 Keratoconus Prediction Index, KISA index (based on K, I-S, AST

and SRAX values) and Keratoconus Severity Index (KSI) index

Videokeratography, pachymetry,

slit lamp

India7 30+ 2300 Corneal power >48 diopter Keratometry

USA49 65+ 17.5 A beneficiary having one or more claims with keratoconus

within the calendar year

Claims of patients

Jerusalem, Israel9 18–54 2340 Cone apex ≥50D, inferior-superior dioptric difference ≥3.5diopters, positive results from the software indices KISA, KCI

and KSI

Videokeratography

Lebanon24 21–26 3333 Questionnaire and an anterior topography Placido disk Tomey(�) Topographic

Modeling System TMS-4

Indianapolis,

USA50

1–79 600 Not available Placido disk

Muroran, Japan13 10–60 9 Not available Not available

France51 18–22 1190 KC index Refraction and TMS-4

Macedonia22 – 6.8 Group early stage of keratoconus (keratometric values K1 and

K2 (KM < 48D); Group mid stage of Keratoconus (KM =

48–54D); and Group late stage of keratoconus (KM > 54D).

Keratometry

Current study 20–34 2530 Topography, Orbscan, clinical exam by ophthalmologist Orbscan II

Iran (Tehran)21 14–81 3.3 Keratometry >47.2 diopter, ratio of anterior/posterior corneal

curvature >1.27, thinnest point of cornea <470 micron and

posterior best fit sphere >52 diopter

Orbscan II

Iran (Shahroud)6 40–64 0.78 Apex of the cone is not centered at the 6-o’clock semimeridian;

the cone should appear round on the tangential map;

keratometry >45.00 diopters (D); corneal thickness at the apex

of the cone is approximately 30 mm thinner than the

corresponding distance above the pupil center; and

topographic patterns are not symmetric.

Pentacam



524


toconus and eye rubbing were reported to be 6.3, 3.8, 2.3

and 1.6 in studies conducted by Bawazeer et al36, Kim and

Joo37, McMonnies and Boneham38, Millodot et al9 and Ra-

binowitz39, respectively. Some studies have reported no

relationship between eye rubbing and keratoconus.30,40,41

There is controversy regarding the relationship of allergy

or atopy and keratoconus.30 Since our method of evaluat-

ing these variables was by self-report, their findings were

very subjective and prone to recall bias. Therefore, it may

be better to more objectively assess variables like the history

of allergy and eye rubbing in future studies.

Similar to many other reports, we also found that family

history was a strong risk factor of keratoconus.9,30,35,42 This

relationship has also been shown in a number of case-con-

trol studies.36 Genetic investigations and studies on mono-

zygotic twins have confirmed the relationship between

genetics and the family history of keratoconus although it

should be noted that a positive family history may result

from a common residence, nutrition, etc. rather than

genetic factors.18,43,44 However, family history should be

regarded as an important risk factor for keratoconus. In

this respect, it should be noted that a recent report by

Gordon-Shaag et al45 showed that consanguinity was a risk

factor for keratoconus. In 2004, Saadat et al46 reported that

there were many consanguineous marriages in Iran, which

may be one of the reasons for the high prevalence of kera-

toconus found in this study.

Table 4 shows some Orbscan II and topographic findings

in participants with and without keratoconus. As expected,

there are significant differences between the groups, since

these indices served as part of the criteria for the diagnosis

of keratoconus. However, it is interesting to note that the

range of these indices in individuals with and without kera-

toconus overlap. For example, the cornea was very thin in

some non-keratoconic individuals and the cornea was very

thick in one keratoconic patient. Regarding keratometry,

we observed high values of maximum keratometry in nor-

mal individuals with normal corneas. This finding high-

lights the importance of slit lamp examination and

retinoscopy in the diagnosis of keratoconus and shows that

topographic criteria and imaging may result in false posi-

tive and false negative results.

As mentioned above, the analysed area was significantly

less in keratoconus patients based on TMS-4. In keratoc-

onus patients, since the cornea becomes cone-shaped and

the centre of the cornea becomes protruded, the mires are

projected on a small area of the cornea in topography with

the TMS-4; therefore, the mires are closer and a smaller

area is evaluated. This parameter is regarded as AA in

TMS-4 and a smaller area indicates more severe keratoc-

onus. In comparison with normal individuals, this area is

smaller in keratoconus patients, similar to what we found

in our patients.47

Conclusion

These results taken together with recent studies in the area

suggest that keratoconus may have a higher prevalence in

the Middle East and Asia than in Western Countries.

Among the evaluated risk factors, eye rubbing and family

history of keratoconus were significantly associated with

keratoconus.

Acknowledgements

This research was supported by the Deputy of Research of

Mashhad University of Medical Sciences, the Iran (grant

code: 910521).

Disclosure

The authors report no conflicts of interest. The authors

alone are responsible for the content and writing of the

paper.

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Supporting Information

Additional Supporting Information may be found in the

online version of this article:

Figure S1. Axial power maps of the worse eye of kerato-

conic cases.

Figure S2. Posterior elevation maps of the worse eye of

keratoconic cases. (The topographic data of the patient

number 26 was not available.)



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the prevalence of keratoconus in a young population in mashhad, iran

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