Corneal thickness measured by Scheimpflug imagingin children with Down syndromeLokman Aslan, MD,a Murat Aslankurt, MD,a Erdem Y€uksel, MD,b Murat €Ozdemir, MD,a

Esin Aksakal, PhD,c Yakup G€um€usalan, MD,c and G€okhan €Ozdemir, MDa

PURPOSE To measure corneal thickness via the use of a Scheimpflug imaging system (OCULUS

Author affiliations: aOphthalmolKahramanmaras, Turkey; bOphKahramanmaras; cAnatomy DepSubmitted July 13, 2012.Revision accepted October 23,Published online March 25, 2Correspondence: Lokman Asla

Department of Ophthalmology, 4yahoo.com).Copyright � 2013 by the Am

Strabismus.1091-8531/$36.00http://dx.doi.org/10.1016/j.ja

Journal of AAPOS

Optikger€ate GmbH, Wetzlar, Germany) in children with Down syndrome.

METHODS This prospective, nonrandomized, clinical trial included children with Down syndrome

and age- and sex-matched healthy controls. All subjects received a complete ophthalmo-logic examination. Corneal topography measurements were acquired by means ofScheimpflug imaging. Central corneal thickness (CCT), thinnest point of cornea (TP),and corneal volume (CV) were analyzed.

RESULTS A total of 27 children with Down syndrome and 37 control subjects were included in the

study. In children with Down syndrome, the mean CCT was 494.27 � 47 mm, the meanTP was 487 � 49 mm, and the mean CV was 56.2 � 6. In the controls, the mean CCTwas 539.3 � 40 mm, the mean TP was 538.0 � 40.8 mm, and the mean CV was 61.3 � 4.For all 3 parameters, the difference was statistically significant (P\ 0.001). In the Downsyndrome group, the CCT was \500 mm in 16 subjects (59.2%) and \450 mm in 5(18.5%). In the control group, the CCT was \500 mm in 14 subjects (37.8%) and\450 mm in 2 (5.4%).

CONCLUSIONS In this study, corneal thickness was less in children with Down syndrome than in healthy

control subjects. Decreased corneal thickness may be an early sign of a degenerative cornealdisease such as keratoconus in children with Down syndrome. ( J AAPOS 2013;17:149-152)

Accurate measurement of corneal thickness, includ-ing both central corneal thickness (CCT) and thin-nest point (TP), is important for the assessment of

corneal pathology,1-3 in determining the effectiveness ofmedical and surgical treatment, in determining IOP, andin appraising patients for contact lens wear.4 In previousstudies authors have reported corneal changes to be morecommon in individuals with Down syndrome than in thegeneral population.5-8 Moreover, degenerative cornealdiseases such as keratoconus, which may lead toprogressive thinning of the paracentral cornea, have beenreported as occurring more often in individuals withDown syndrome.5,9,10 The Pentacam Scheimpflugimaging system (OCULUS Optikger€ate GmbH, Wetzlar,Germany) provides accurate measurement of cornealthickness by means of a rotating camera that captures

ogy Department, KSU Faculty of Medicine,thalmology Department, Necip Fazıl State Hospital,artment, KSU Faculty of Medicine

2012.013.n, MD, Sutcu Imam University, Faculty of Medicine, and6050 Kahramanmaras, Turkey (email: lokaslan46@

erican Association for Pediatric Ophthalmology and

apos.2012.10.020

dozens of cross-sections of the anterior segment, illumi-nated by slit-lamps at different meridians, within 2seconds.1-3 The device offers advantages such asautomatic shots, rapid measurement, and a second eyealignment camera. Scheimpflug imaging provides theability to detect subtle changes in the cornea.1 Unlike thesingle-point measurement of ultrasound pachymetry,Scheimpflug imaging measures corneal thickness on theentire cornea from limbus to limbus.3 The purpose of thepresent study was to examine the individual full cornealthickness, including central and paracentral areas, bymeansof a Scheimpflug imaging system, in children with Downsyndrome and to determine the relationship betweenDown syndrome and corneal thickness. We also assessedkeratoconus probability by using customized software forimaging system used in this study.

Subjects and Methods

This study was approved by the Sutcuimam University Ethics

Committee and was conducted in accordance with the Declara-

tion of Helsinki. Informed consent was obtained from the parents

of patients and control subjects.

We prospectively examined with trisomy 21 Down syndrome.

The children were referred to the clinic for ophthalmological

examination as a part of health screening from three rehabilita-

tion centers for intellectual disabilities. The control group

149

150 Aslan et al Volume 17 Number 2 / April 2013

included age- and sex-matched healthy children. All of the par-

ticipants were examined clinically by an experienced ophthal-

mologist at the same time of day (9:00-11:00 a.m.) and at the

same constant room temperature. Each subject underwent

a complete ophthalmologic examination, including the measure-

ment of visual acuity, refraction, slit-lamp biomicroscopy,

screening for strabismus, and fundus examination. IOP was

not measured. Children with Down syndrome who had clinical

evidence of corneal disease such as scar, opacity, dystrophies,

previous anterior segment surgery, and contact lens wear were

excluded from the study.

Corneal measurements were acquired by use of the Pentacam.

Measurements were performed until the acceptable quality value

was obtained. Three quantitative parameters, including CCT,

TP, and corneal volume (CV) values were recorded, and only

right eye values of groups were compared (Table 1). SPSS 16.0

(SPSS Inc, Cary, NC) was used for statistical analysis. The un-

paired t test was used to compare groups. All values were stated

as means plus/minus SD unless noted.

Results

A total of 27 children, all white, with Down syndrome(16 boys) and 37 controls (20 boys) were included. Of 31children with Down syndrome, 4 were excluded becauseof poor Scheimpflug imaging results. Mean age in theDown syndrome group was 8.94 � 2.35 years (range,5-12 years); in the control group, it was 8.88 � 2.24 years(range, 6-12 years). The age and sex distribution of bothgroups did not differ significantly (sex, c2 5 1.28,P 5 0.22; age, P 5 0.89).No statistically significant difference between left and

right eyes within groups was found for CCT, TP, andCV (Down syndrome group: P5 0.5, P5 0.6, P5 0.6, re-spectively; control group: P 5 0.9, P 5 0.6, P 5 0.7, re-spectively). Hence only right eye values (see Table 1)were used for statistical analysis. CCT values in childrenwith Down syndrome were \500 mm in 16 subjects(59.2%) and\450 mm in 5 (18.5%); in the control group,CCT values were \500 mm in 14 subjects (37.8%) and\450 mm in 2 (5.4%). In the Down syndrome group, TPvalues were \500 mm in 17 subjects (62.9%) and \450mm in 11 (21.1%); in the control group, TP values were

Table 1. CCT and CV values in groups

Groups n (right eyes) Mean � SD M

CCT values, mmDown syndrome 27 494.2 � 47.82Control group 37 539.3 � 38.02

TP values, mmDown syndrome 27 487.8 � 49.5Control group 37 538.0 � 40.8

CV values, mm3

Down syndrome 27 56.2 � 6.2Control group 37 61.3 � 4.2

CCT, central corneal thickness; CV, corneal volume; TP, thinnest point of coaUnpaired t test.

\500 mm in 16 subjects (43.2%) and \450 mm in 4(10.8%). Corneal thickness was .600 mm in 1 subjectwith Down syndrome.

Mean CCT values in children with Down syndromewere 45 mm less than the corresponding values in the con-trol group. TP in children with DS was 51 mm less in theright eye than in the control group. The difference betweenmean CCT and TP values in the right eyes of Down syn-drome subjects was 6.4 mm and, in control subjects, 1.3mm (P \ 0.001). The mean CV in the Down syndromegroup was 56.2 � 6.2 mm3 compared with and 61.3 � 4.2mm3 in controls (P\ 0.001).

An evaluation to assess the probability of keratoconus inboth eyes, via the use of Pentacam software, revealed earlysubclinical disease in 11 eyes (21.1%) of children withDown syndrome and 1 eye (1.35%) in the control group(P\ 0.001). TPs of children with Down syndrome weremainly localized in the central zone (52%) and inferotem-poral area (38%).

Discussion

In previous studies authors have demonstrated that chil-dren with Down syndrome are at risk for ocular disorderssuch as refractive error, strabismus, cataract, and glau-coma. Glaucoma is less common than other ocular disor-ders, but it has serious visual implications.9-14 Althoughthe prevalence of glaucoma is as low as 1.9%9 in childrenwith Down syndrome, it is 11.5% in an adult Down syn-drome group.10 The correlation between CCT and IOPhas not been clearly revealed in children with Down syn-drome, but it is well known that the Goldman applanationtonometry IOP values in thicker corneas are falselygreater, and in thinner corneas falsely lesser, than in nor-mal population.15,16 The correlation between CCT andIOP in children with Down syndrome requires furtherinvestigation.

Evereklioglu and colleagues17 compared CCTmeasure-ments by ultrasound pachymetry in children with Downsyndrome and age- and sex-matched healthy controls.CCT values were\500 mm in 19 of 28 children (67.8%)with Down syndrome and\450 mm in 4. They concludedthat children with Down syndrome had a decreased CCT

inimum Maximum Mean difference P valuea

410 651458 622 45.1 \0.001

398 648444 618 50.2 \0.001

46.0 71.857.0 70.7 5.1 \0.001

rnea.

Journal of AAPOS

Volume 17 Number 2 / April 2013 Aslan et al 151

compared with healthy control subjects. Haugen and col-leagues12 evaluated biometric measurements, includingcorneal thickness in adults with Down syndrome, andthey described steeper cornea, decreased corneal thickness,and high frequency of astigmatism.Karadag and colleagues15 reported that CCT values

were significantly greater in those with intellectual disabil-ities, including Down syndrome, for both right and lefteyes than in unaffected individuals. CCT was also assessedby Akıncı and colleagues18 using ultrasound pachymetryin children with intellectual disabilities, including Downsyndrome. They found significantly greater CCT in indi-viduals with Down syndrome (554) than in their idiopathicgroup (539) and nonsignificant difference between patientswith Down syndrome and other intellectual disabilities ofsyndromic etiology (565). In the present study, althoughcorneal thickness was measured at greater than 600 mm in1 subject withDown syndrome, themean corneal thicknessof subjects were found to be lower than in the controlgroup. In contrast to the aforementioned two reports, weshowed that corneal thickness in children with Down syn-drome was less than in the controls, as discussed in thestudies by Haugen and Evereklioglu,12,17 whose reportsmay be related to Down syndrome evaluated with otherintellectual disabilities and/or measurements performedin a single point of the cornea with contact pachymetry.Corneal thinning may be present at any location on the

cornea and may be a sign of degenerative corneal disease.Focal corneal thinning may be a more specific indicatorof keratoconus and does occur more frequently in individ-uals with Down syndrome than in the general popula-tion.4,8,19 Subclinical keratoconus is difficult todistinguish initially from clinically ordinary refractiveerrors, and such cases can be determined by means ofappropriate imaging techniques.4,19,20

Previous studies of corneal thickness in Down syndromemeasured only the central cornea: we obtained measure-ments over a wide corneal area, including both centraland ectatic corneal thickness. This approach could be im-portant in detecting early signs of keratoconus.1,2

Brautaset and colleagues21 have reported that keratoconusshows the greatest change in thickness in the ectatic region,but attenuation is not limited to the ectatic portion and de-creases toward the periphery. In the present study, the dif-ference between mean CCT and TP in Down syndromesubjects was found to be greater than in the control group(P\0.001). This differencemay be a significant clinical ev-idence of degenerative corneal diseases. In addition, whenusing the Pentacam software, we found the rate of earlykeratoconus in Down syndrome to be significantly greaterthan in controls. The corneal localization of TP was foundmainly in the central zone and inferotemporal area.Inferotemporal localization in particular provides valuableinformation for early diagnosis of keratoconus. If earlydiagnosis is made, corneal cross-linking treatment to haltthe progression may be implemented.19 This treatment isan outpatient, minimally invasive, cost-effective treatment

Journal of AAPOS

involving minimal effort for the individual concerned.22 Ithas also performed in patients with Down syndrome in re-cent a few studies.22,23

In conclusion, Scheimpflug imaging is a noncontactmethod that may be used in children to measure a widearea of the cornea. Because the system ensures rapid mea-surement, it is well suited for examinations of individualswith low cooperation.8 The present study showed that chil-dren with Down syndrome had a lower corneal thicknessthan healthy controls and may provide early evidence ofa degenerative corneal disease such as keratoconus in chil-dren with Down syndrome.

Literature Search

PubMed and Google Scholar were searched without daterestriction using the following terms: Down syndrome,cornea, thickness, anterior segment.

References

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2. Quisling S, Sjoberg S, Zimmerman B, Goins K, Sutphin J. Compar-ison of Pentacam and Orbscan IIz on posterior curvature topographymeasurements in keratoconus eyes. Ophthalmology 2006;113:1629-32.

3. Ambr�osio R Jr, Caiado AL, Guerra FP, et al. Novel pachymetricparameters based on corneal tomography for diagnosing keratoconus.J Refract Surg 2011;27:753-8.

4. Steele TM, Fabinyi DC, Couper TA, Loughnan MS. Prevalence ofOrbscan II corneal abnormalities in relatives of patients with kerato-conus. Clin Experiment Ophthalmol 2008;36:824-30.

5. Cunha RP, Moreira JB. Ocular findings in Down’s syndrome. Am JOphthalmol 1996;122:236-44.

6. Creavin AL, Bruwn RD. Ophthalmic abnormalities in children withDown syndrome. J Pediatr Ophthalmol Strabismus 2009;46:76-82.

7. Yanovitch T, Wallance DK, Freedman SF, et al. The accuracy ofphoto screening at detecting treatable ocular conditions in childrenwith Down syndrome. J AAPOS 2010;14:472-7.

8. Vincent AL, Weiser BA, Cupryn M, Stein RM, Abdolell M,Levin AV. Computerized corneal topography in a pediatric popula-tion with Down syndrome. Clin Exp Ophtalmol 2005;33:47-52.

9. Karlica D, Skelin S, Culic V, et al. The ophthalmic anomalies in chil-dren with Down syndrome in Split-Dalmatian County. Coll Antropol2011;35:1115-18.

10. JYokoyama T, Tamura H, Tsukamoto H, Yamane K, Mishima HK.Prevalence of glaucoma in adults with Down’s syndrome. Jpn J Oph-thalmol 2006;50:274-6.

11. Motley WW, Saltarelli DP. Ophthalmic manifestations of mosaicDown syndrome. J AAPOS 2011;15:362-6.

12. Haugen OH, Hovding G, Eide GE. Biometric measurements of theeye in teenagers and young adults withDown syndrome. Acta Ophtal-mol Scand 2001;79:616-25.

13. Little JA, Woodhouse JM, Saunders KJ. Corneal power and astigma-tism in Down syndrome. Optom Vis Sci 2009;86:748-54.

14. Yahalom C, Mechoulam H, Cohen E, Anteby I. Strabismus surgeryoutcome among children and young adults with Down syndrome.J AAPOS 2010;14:117-19.

15. Karadag R, Erdurmus M, Yagci R, Keskin UC, Hepsen _IF,Durmus M. Central corneal thickness in individuals with intellectualdisability. Cornea 2007;26:421-3.

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16. Muir KW, Jin J, Freedman SF. Central corneal thickness and its rela-tionship to intraocular pressure in children. Ophthalmology 2004;111:2220-23.

17. Evereklioglu C, YilmazK, BekirNA.Decreased central corneal thick-ness in children with Down syndrome. J Pediatr Ophthalmol Strabis-mus 2002;39:274-7.

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An Eye on the Arts

Abd al-Karim didn’t remember how he lost his leye, to seeing everything, without ever feeling teye bled when he was forty days old. The motheye. His aunt took him to Sheikh Ibrahim, the vture into his eye, but it never got better. It becaShe took him to a Bedouin who was known foshould be cauterized and so he heated a nail, ca“I’ve sent my whole life with only my right ey

to that, and it’s all right. I don’t know why Godbut as for me, it’s all right this way.”

Elias Khoury, The Journey of Little Gandhi, tr2009), 88.

Contributed by Alex V. Levin, MD, MHSc

20. Wollensak G. Crosslinking treatment of progressive keratoconus.Ophthalmology 2006;17:356-60.

21. Brautaset RL, Nilsson M, Miller WL, Leach NE, Tukler JH,Bergmanson JP. Central and peripheral corneal thinning in keratoco-nus. Cornea 2013;32:257-61.

22. Koppen C, Leysen I, TassignonMJ. Riboflavin/UVA crosslinking forkeratoconus in Down syndrome. J Refract Surg 2010;26:623-4.

23. Faschinger C, Kleinert R, Wedrich A. [Corneal melting in both eyesafter simultaneous corneal crosslinking in a patient with keratoconusand Down syndrome]. Ophthalmologe 2010;107:951-2.

eft eye. He got used to living with only onehat his left eye was blind. His aunt said hiser died, and blood gushed from the baby’sillage doctor who squeezed an herbal mix-me inflamed and covered with black spots.r treating incurable cases. He said the eyeuterized it, and blinded it.e. I see everything from the right. I’m usedcreated two eyes, it must be His wisdom,

ans. Paula Haydar (New York: Picador,

Journal of AAPOS