- Email: [email protected]
Evaluation of anterior segment parameters in patients with Turner syndrome using Scheimpflug imaging
Accepted Manuscript Evaluation of anterior segment parameters in patients with Turner syndrome using Scheimpflug imaging Merve Inanc, MD, Kemal Tekin, MD, Erdal Kurnaz, MD, Mehmet Citirik, MD, Gülsah Altas, MD, Zehra Aycan, MD PII:
S1091-8531(17)30369-5
DOI:
10.1016/j.jaapos.2017.10.007
Reference:
YMPA 2734
To appear in:
Journal of AAPOS
Received Date: 13 May 2017 Revised Date:
28 September 2017
Accepted Date: 4 October 2017
Please cite this article as: Inanc M, Tekin K, Kurnaz E, Citirik M, Altas G, Aycan Z, Evaluation of anterior segment parameters in patients with Turner syndrome using Scheimpflug imaging, Journal of AAPOS (2018), doi: 10.1016/j.jaapos.2017.10.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Evaluation of anterior segment parameters in patients with Turner syndrome using Scheimpflug imaging Merve Inanc, MD,a Kemal Tekin, MD,b Erdal Kurnaz, MD,c Mehmet Citirik, MD,a Gülsah Altas, MD,c and Zehra Aycan, MDc
RI PT
Author affiliations: aAnkara Ulucanlar Eye Training and Research Hospital, Ankara, Turkey; b Department of Ophthalmology, Kars State Hospital, Kars, Turkey; cDepartment of Pediatric Endocrinology, Dr. Sami Ulus Children’s Health and Disease Training and Research Hospital, Ankara, Turkey
SC
Submitted May 27, 2017. Revision accepted October 4, 2017.
M AN U
Correspondence: Merve Inanc, MD, Ulucanlar Eye Training and Research Hospital, Ankara, 06240, Turkey (email: [email protected]).
AC C
EP
TE D
Word count: 2,530 Abstract only: 254
ACCEPTED MANUSCRIPT
Abstract Purpose To compare the anterior segment parameters in patients with Turner syndrome (TS) as measured
RI PT
by the Pentacam HR-Scheimpflug imaging system with those of healthy control subjects. Methods
This cross-sectional prospective study included 35 patients with TS and 30 age-matched
SC
controls. Corneal topographic analysis was performed using the Pentacam HR-Scheimpflug imaging system (Oculus, Wetzlar, Germany). The power of the corneal astigmatism, mean
M AN U
keratometry (Km) values for the both front and back surfaces of the cornea, maximum keratometry (Kmax), central corneal thickness (CCT), corneal volume (CoV), white-to-white diameter (WTW), chamber volume (CaV), angle and anterior chamber depth (ACD) values were recorded.
TE D
Results
The mean age of TS subjects was 17.2 ± 6.1 years; of controls, 16.4 ± 5.7 years. All participants were female. There was a significant difference in the mean values of WTW (11.3 ± 0.5 mm vs
EP
12.0 ± 0.4 mm [P < 0.001]), CaV (148.4 ± 33.5 mm3 vs 191.9 ± 27.6 mm3 [P < 0.001]), and ACD (2.8 ± 0.3 mm vs 3.1 ± 0.2 mm [P < 0.001]) between TS versus group and the control
AC C
group. The mean values of the power of the corneal astigmatism, Km values for the both front and back of the corneal surface, Kmax, CCT, CoV, and angle values were similar between groups (P > 0.05 for each one). Conclusions
There was a reduction in CaV, ACD, and WTW measurements in TS patients compared with controls.
ACCEPTED MANUSCRIPT
Turner syndrome (TS) is a chromosomal disorder in which phenotypic women have a missing or abnormal X chromosome. The incidence of TS is approximately 1 in 2500 live female births.1 Although some phenotypic features, such as short stature and reproductive system abnormalities,
RI PT
belong to the most common clinical features of TS, many ocular abnormalities are also
associated with TS, including strabismus, ptosis, epicanthal folds, red-green color deficiency, and nystagmus.2-4 Anterior segment abnormalities such as keratoconus, anterior chamber
SC
dysgenesis and posterior segment abnormalities such as Coats disease, formation of drusen, vascular lesions or retinal detachment have been reported in patients with TS.5-11 The literature
M AN U
concerning ophthalmological problems in patients with TS is limited. Although numerous case reports have suggested associations of ocular features with TS, few studies evaluate larger groups of patients.2-4 The aim of this study was to evaluate the anterior segment parameters in patients with TS by using Pentacam HR-Scheimpflug imaging system (Oculus Optikgerate
TE D
GmbH, Wetzlar, Germany), a reproducible method that measures almost all anterior segment parameters, and to compare those parameters with those in healthy control subjects. Subjects and Methods
EP
This prospective cross-sectional study was carried out from May 2016 to December 2016 at Ankara Ulucanlar Eye Training and Research Hospital, a tertiary referral eye hospital, and at the
AC C
pediatric endocrinology and metabolism clinic of Dr. Sami Ulus Children’s Health and Disease Training and Research Hospital, a children’s health and disease training and research hospital. The study protocol was approved by the Ankara Numune Training and Research Hospital Ethics Committee, and the study was carried out in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from adult patients and the parents or legal guardians of children prior to enrollment. All patients were white.
ACCEPTED MANUSCRIPT
A total of 42 consecutive patients with TS who were referred for ophthalmic assessment during the study period were enrolled; 30 age-matched control subjects were also included. All control subjects were healthy females without any systemic or ocular disease and had presented
RI PT
to the ophthalmology clinic for a routine ocular examinations. Only right eyes of all subjects were analyzed for the study.
Subjects with any of the following conditions were excluded: strabismus, nystagmus, a
SC
history of previous ocular surgery, trauma or uveitis, corneal diseases (such as corneal scarring), fundus abnormalities (such as retinopathy of prematurity or hypertensive/diabetic retinopathy),
M AN U
optic nerve diseases and glaucoma, neurological disease or other diseases of the visual pathways, ocular media opacities, use of topical medication, and high spherical (> −6.0 D or > +6.0 D) or cylindrical (> ± 3.00 D) refractive errors. Subjects who were not able to cooperative for Scheimpflug system examinations were also excluded. Seven of the 42 TS patients were
TE D
excluded because of ocular abnormalities: 2 patients had keratoconus, 2 had lens opacities, 1 had high cylindrical refraction, 1 had strabismus, and 1 had abnormal retinal vein tortuosity compatible with early stages of hypertensive retinopathy.
EP
All subjects underwent a comprehensive ophthalmic examination, including bestcorrected visual acuity tests using the Snellen chart (20 feet), intraocular pressure measurements,
AC C
slit-lamp biomicroscopy, and dilated fundus examination. Refraction measurements were performed by using the same automatic refractor-keratometer device (Canon RF-K2 Full Auto Ref-Keratometer, Japan). Red-green color deficiency was measured by Ishihara cards. Corneal topography was examined using a noncontact, noninvasive rotating Scheimpflug
camera system. Before Pentacam examination, participants had not undergone any contact ocular examination, such as tonometry, gonioscopy, or pupil dilation. Pentacam generates a three-
ACCEPTED MANUSCRIPT
dimensional model of the cornea and anterior segment. Corneal topographic analysis was performed by the same masked experienced clinician using the same Pentacam HR-Scheimpflug imaging system, and all measurements were taken under standard dim-light conditions. Three
RI PT
measurements were made per eye; the one with the best alignment and fixation was selected for data analysis. Distorted images caused by high reflection that were not eligible for evaluation were not included in the analysis. Corneal refractive map indices were evaluated for each subject
SC
in the study. The power of the corneal astigmatism, mean keratometry (Km) values for the both front and back surfaces of the cornea, maximum keratometry (Kmax), central corneal thickness
M AN U
(CCT), corneal volume (CoV), white-to-white diameter (WTW), chamber volume (CaV), and angle and anterior chamber depth (ACD) values were recorded. Statistical Analysis
The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 for
TE D
Windows (SPSS Inc, Chicago, IL). Descriptive statistics were recorded as mean ± standard deviations, frequency distributions, and percentages. Pearson’s χ2 test and one-sample χ2 test were used in the analysis of categorical variables. The normal distribution of the variables was
EP
tested using visual (histogram and probability graphs) and analytical methods (KolmogorovSmirnov/Shapiro-Wilk test). An independent sample t test was used for normally distributed
AC C
data, and a Mann-Whitney U test was used for non-normally distributed data to compare the TS and control groups. The Bonferroni test was used as post hoc test after t test and Mann-Whitney U test. Statistical significance was assumed at P < 0.05; however, for multiple comparisons and correlations among the 11 Pentacam parameters, Bonferroni’s correction was applied with a resultant significance level of P < 0.0045. Results
ACCEPTED MANUSCRIPT
This study included 65 eyes of 65 subjects: 35 subjects in the TS group and 30 in the control group. All participants were female. Genetic analysis of our subjects with TS revealed that 20 of 35 had a 45,X0 karyotype
RI PT
(pure Turner), and the remaining 15 had other karyotypes (5 had having both 45,X/46,XX; 3 had both 45,X/46,X,i(Xq); 2 had 45,X/46,XX/47,XXX; 2 had 46,X,i(Xq); and 2 had 46,X,del(Xq); the remaining patient had 45,X/46,X,r(X) karyotype pattern). All patients with TS were divided
SC
into 2 groups according to karyotype analysis: group 1, 45,X0; group 2, other karyotypes.
Recombinant growth hormone (GH) therapy (GHT) was used in 28 of the 35 subjects in
M AN U
the TS group (the number of patients treated previously or currently continuing treatment), and the remaining 7 patients did not receive recombinant GHT. We also divided the TS group according to use of recombinant GHT. These groups were compared regarding to their karyotypes and the status of use of recombinant GHT.
TE D
The mean age of TS patients was17.2 ± 6.1 years (range, 6-27 years); of controls, 16.4 ± 5.7 years (range, 6-29 years). There was no statistically significant difference in age of study participants between groups (P > 0.05). Although the subjects in the control group had no
EP
systemic disease, some patients in the TS group had systemic disorders: 4 had hypertension without retinopathy, 2 had autoimmune thyroiditis, 2 had hypertension and diabetes mellitus
AC C
without retinopathy, and 1 had celiac disease. Also, there was no statistically significant difference in the best-corrected visual acuity measurements and in spherical equivalence between groups (P > 0.05).
There were significant differences in the mean values of the WTW (11.3 ± 0.5 mm vs
12.0 ± 0.4 mm [P < 0.001]), CaV (148.4 ± 33.5 mm3 vs 191.9 ± 27.6 mm3 [P < 0.001]), and ACD (2.8 ± 0.3 mm vs 3.1 ± 0.2 mm [P < 0.001]) values between the TS and the control groups.
ACCEPTED MANUSCRIPT
However, the mean values of the power of the corneal astigmatism, Km values for the both front and back of the corneal surface, Kmax, CCT, CoV, and angle values were similar between groups (P > 0.05 for each). A comparison of the corneal topographic parameters between the TS
RI PT
and control groups appears in Table 1.
A comparison was performed with regards to the karyotype analysis in the patients with TS. There were significant differences in the mean values of the CaV (134.0 ± 29.9 mm3 vs
SC
166.9 ± 29.2 mm3 [P = 0.004]) and ACD (2.7 ± 0.3 mm vs 3.0 ± 0.2 mm [P = 0.003]) between the 45X0 subgroup and the other karyotypes subgroup. The other corneal topographic parameters
M AN U
were similar between the groups. Results are summarized in Table 2.
The status of recombinant GHT usage among TS patients was also analyzed, but there were no significant differences in the mean values of all corneal topographic parameters(P > 0.05 for each).
TE D
Discussion
Ocular abnormalities are common in TS but are underestimated and often neglected. The recent guidelines for diagnosis and treatment of TS reported common ophthalmologic abnormalities.12
EP
Strabismus and amblyopia are the most common abnormalities, present in more than one-third of patients.3,13 Other abnormalities in TS include hypertelorism, epicanthus, down-slanting
AC C
palpebral fissures, ptosis, hypermetropia, reduced color vision, congenital cataract, congenital glaucoma, uveitis, neovascularization, retinal detachment, and papilledema.3,13,14 The high prevalence of eye abnormalities in TS may be explained by the similar genetic
pathway for ocular and ovarian development. For example, the USP9X gene, which causes gonadal dysgenesis in TS, plays a significant role in the development of the eye and ovary in Drosophila.15 In TS, anomalies were detected in different parts of the eye, which may be due to
ACCEPTED MANUSCRIPT
the defect or abnormal structure of the X chromosome. Although anterior segment dysgenesis is not a common feature in TS, anterior segment abnormalities such as astigmatism and keratoconus have been described in TS. Nucci and colleagues8 reported a case with both TS and
RI PT
keratoconus and hypothesized that corneal thinning in TS is an expression of a mesodermal defect because mesodermal structures are sometimes affected in TS. However, the cornea is not predominantly mesodermal derived. The corneal epithelium is derived from surface ectoderm,
SC
whereas the corneal stroma and endothelium are derived predominantly from neural crest, and the minority population of cells within the corneal stroma and endothelium are derived from the
M AN U
mesoderm.16 We found no evidence of corneal thinning in TS subjects compared with controls. Wikiera and colleagues17 reported that prevalence of astigmatism in TS was approximately three times higher than the reported rate in the general population of Polish children. Our study showed, on the contrary, that the mean values of power of the corneal
TE D
astigmatism, Km values for the both front and back of the corneal surface, and Kmax values were similar between the groups. Because 2 patients with keratoconus and 1 patient with high cylindrical refraction were excluded from the study, no difference could be detected between
EP
groups. Nalcacioglu and colleauges18 found that CCT values are higher in patients with TS than in healthy children by using ultrasound pachymeter. However, in our study, there was no
AC C
difference regarding the CCT values between TS subjects and controls. In Nalcacioglu and colleauges,18 adjustment of the contact system may have been difficult due to the majority of participants being children, and the measurements may had been taken from the peripheral region, where the cornea is thickened, rather than from the central region.18 In our study the noncontact Scheimpflug imaging system was used to minimize these risks. Different results may be due to either measurement error or CCT variability.
ACCEPTED MANUSCRIPT
The Turner phenotype is caused by X-linked genes that escape inactivation. One of these genes is the short-stature-homeobox (SHOX) gene, mutations of which result in characteristic features such as short stature.19,20 Recent studies have revealed that body height is associated
RI PT
with eye parameters that can be correlated with ocular diseases in a multivariate statistical
analysis.21,22 For example, body height appears to correlate with anterior chamber depth.23-25 This is of clinical pathologic importance given the correlation between anterior chamber depth and
SC
primary angle closure glaucoma.23,26-28 This agrees with the finding that patients with chronic angle-closure glaucoma are significantly shorter than patients with chronic open-angle
M AN U
glaucoma.29 Further, this study suggests that short body height may be a potential screening parameter to detect individuals at risk for developing angle closure.29 We found that CaV and ACD values, that are correlated with each other,30 and WTW values were lower in patients with TS than in controls. One reasons could be that patients with TS had a shorter body stature than
TE D
controls. While changes in the anterior eye segment have been related to karyotype mosaicism,6 our analysis did not confirm this. We found that the mean values of the CaV and ACD were lower in the 45X0 group than the other karyotypes. This may correlate with genes on the short
EP
arms of the X and Y chromosomes that are responsible for normal growth and stature. Further, some reports indicate that 45,X/46,XY or 46,X,del(Xq) TS patients are on average taller than
AC C
other TS karyotypes.31 Thus, the lower values in the 45X0 group with TS may be explained by body height differences.
Organic GH deficiency is not a feature of TS, but recombinant human GH has been used
to increase linear growth and final height in these patients.32,33 Although the intrinsic mechanisms of GH actions on eyes are still not fully known, it is well known that the eye represents a target site for GH action. GH and IGF-I are known to be involved in ocular
ACCEPTED MANUSCRIPT
development.34 In addition, the evidence that, acromegalic patients with longer active and uncontrolled disease showed greater CCT values supported the hypothesis that GH may have stimulatory effects on the cornea as well as on other target organs.35 Nalcacioglu and
RI PT
colleauges18 revealed that exposure to recombinant GHT or the duration of GHT were not the main causes of increased corneal thickness. They suggested that the lack of a GHT effect on CCT could be attributed to the restriction of access to ocular tissues due to blood-ocular barrier.
receiving and not receiving recombinant GHT.
SC
Also in our study, there was no difference regarding the CCT values between the groups
M AN U
One of the limitations of the present study is that axial length was not measured; therevore, it has not been determined whether decreased CaV, ACD, and WTW indicate that the overall eye size is less or that the anterior segment is disproportionately smaller in TS. In addition, the number of patients in the group who did not receive GHT was low. Finally, because
TE D
of the cross-sectional nature of the study, the causal relationship between the TS and anterior
AC C
EP
segment changes cannot be inferred.
ACCEPTED MANUSCRIPT
References 1.
Kriksciuniene R, Zilaitiene B, Verkauskiene R. The current management of Turner Syndrome. Minerva Endocrinol 2016;41:105-21. Brunnerová R, Lebl J, Krásný J, Průhová S. Ocular manifestations in Turner’s syndrome.
RI PT
2.
Cesk Slov Oftalmol 2007;63:176-84.
Denniston AK, Butler L. Ophthalmic features of Turner’s syndrome. Eye (Lond) 2004;18:680-84.
4.
Chrousos GA, Ross JL, Chrousos G, et al. Ocular findings in Turner syndrome. A
Austin MW, Patterson A, Bates RA. Conjunctival lymphoedema in Turner’s syndrome. Eye (Lond) 1992;6:335-6.
6.
M AN U
prospective study. Ophthalmology 1984;91:926-8. 5.
SC
3.
Lloyd IC, Haigh PM, Clayton-Smith J, et al. Anterior segment dysgenesis in mosaic
7.
Macsai M, Maguen E, Nucci P. Keratoconus and Turner’s syndrome. Cornea 1997;16:534-6.
Nucci P, Trabucchi G, Brancato R. Keratoconus and Turner’s syndrome: a case report.
EP
8.
TE D
Turner syndrome. Br J Ophthalmol 1997;81:639-43.
Optom Vis Sci 1991;68:407-8. Beatty S, Black G, Rhatigan M, Bishop P. Bilateral subfoveal choroidal
AC C
9.
neovascularization in Turner’s syndrome: coincidence or consequence? Can J Ophthalmol 1999;34:346-8.
10.
Gotoh M, Yamamoto M, Kawasaki T, Shigetoh M, Inomata H. Two cases of unilateral retinal neovascularization in Turner syndrome. Am J Ophthalmol 1998;126:144-6.
11.
Mason JO 3rd, Tasman W. Turner’s syndrome associated with bilateral retinal
ACCEPTED MANUSCRIPT
detachments. Am J Ophthalmol 1996;122:742-3. 12.
Bondy CA; Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab
13.
RI PT
2007;92:10-25.
Adhikary HP. Ocular manifestations of Turner’s syndrome. Trans Ophthalmol Soc UK 1981;101:395-6.
Tsunekawa H, Ohno-Jinno A, Zako M. Uveitis in 2 cases of Turner’s syndrome. Can J
SC
14.
Ophthalmol 2007;42:756-7.
Noma T, Kanai Y, Kanai-Azuma M, et al. Stage- and sex-dependent expressions of
M AN U
15.
Usp9x, an X-linked mouse ortholog of Drosophila Fat facets, during gonadal development and oogenesis in mice. Mech Dev 2002;119 Suppl 1:S91-5. 16.
Gage PJ, Rhoades W, Prucka SK, Hjalt T. Fate maps of neural crest and mesoderm in the
17.
TE D
mammalian eye. Invest Ophthalmol Vis Sci 2005;46:4200-208. Wikiera B, Mulak M, Koltowska-Haggstrom M, Noczynska A. The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype. Clin
18.
EP
Endocrinol (Oxf) 2015;83:842-8.
Nalcacioglu-Yüksekkaya P, Sen E, Onder A, et al. Increased central corneal thickness in
19.
AC C
patients with Turner syndrome. Eur J Ophthalmol 2014;24:309-13.
Rao E, Weiss B, Fukami M, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet 1997;16:54-63.
20.
Clement Jones M, Schiller S, Rao E, et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet 2000;9:695-702.
ACCEPTED MANUSCRIPT
21.
Saw SM, Chua WH, Hong CY, et al. Height and its relationship to refraction and biometry parameters in Singapore Chinese children. Invest Ophthalmol Vis Sci 2002;43:1408-13. Eysteinsson T, Jonasson F, Arnarsson A, Sasaki H, Sasaki K. Relationships between
RI PT
22.
ocular dimensions and adult stature among participants in the Reykjavik Eye Study. Acta Ophthalmol Scand 2005;83:734-8.
Congdon NG, Youlin Q, Quigley H, et al. Biometry and primary angle-closure glaucoma
SC
23.
among Chinese, white, and black populations. Ophthalmology 1997;104:1489-95. Devereux JG, Foster PJ, Baasanhu J, et al. Anterior chamber depth measurement as a
M AN U
24.
screening tool for primary angle-closure glaucoma in an East Asian population. Arch Ophthalmol 2000;118:257-63. 25.
Nolan WP, See JL, Chew PT, et al. Detection of primary angle closure using anterior
26.
TE D
segment optical coherence tomography in Asian eyes. Ophthalmology 2007;114:33-9. George R, Paul PG, Baskaran M, et al. Ocular biometry in occludable angles and angle closure glaucoma: a population based survey. Br J Ophthalmol 2003;87:399-402. Aung T, Nolan WP, Machin D, et al. Anterior chamber depth and the risk of primary
EP
27.
angle closure in 2 East Asian populations. Arch Ophthalmol. 2005;123:527-32. Casson RJ, Marshall D, Newland HS, et al. Risk factors for early angle-closure disease in
AC C
28.
a Burmese population: the Meiktila Eye Study. Eye (Lond) 2009;23:933-9.
29.
Xu L, Li J, Wang Y, Jonas JB. Anthropomorphic differences between angle-closure and open-angle glaucoma: the Beijing Eye Study. Acta Ophthalmol Scand. 2007;85:914-15.
30.
Rabsilber TM, Khoramnia R, Auffarth GU. Anterior chamber measurements using Pentacam rotating Scheimpflug camera. J Cataract Refract Surg. 2006;32:456-9.
ACCEPTED MANUSCRIPT
31.
Ferguson-Smith MA. Genotype-phenotype correlations in the Turner syndrome. In: Hibi I, Takano K, eds. Basic and clinical approach to Turner syndrome. Amsterdam: Elsevier; 1993;17-25. Baxter L, Bryant J, Cave CB, Milne R. Recombinant growth hormone for children and
RI PT
32.
adolescents with Turner syndrome. Cochrane Database Syst Rev 2007;24:CD003887. 33.
Bolar K, Hoffman AR, Maneatis T, Lippe B. Long-term safety of recombinant human
34.
SC
growth hormone in turner syndrome. J Clin Endocrinol Metab 2008;93:344–51.
Cuthbertson RA, Beck F, Senior PV, Haralambidis J, Penschow JD, Coghlan JP. Insulin-
M AN U
like growth factor II may play a local role in the regulation of ocular size. Development 1989;107:123-30.
Ciresi A, Amato MC, Morreale D, Lodato G, Galluzzo A, Giordano C. Cornea in acromegalic patients as a possible target of growth hormone action. J Endocrinol Invest
EP
TE D
2011;34:e30-35.
AC C
35.
ACCEPTED MANUSCRIPT
Table 1. Comparison of corneal topographic parameters between Turner syndrome (TS) and control groups Controls (n = 30) Mean ± SD 1.2 ± 0.3 43.5 ± 1.2 0.3 ± 0.2 −6.5 ± 0.2 44.6 ± 1.5 550.8 ± 31.7 61.3 ± 3.1 12.0 ± 0.4 191.9 ± 27.6 37.7 ± 6.1 3.1 ± 0.2
P value
a
b
0.182 c 0.110 b 0.082 c 0.499 c 0.078 c 0.460 c 0.057 <0.001c c <0.001 c 0.418 c <0.001
RI PT
Astig, front, D Km, front, D Astig, back, D Km, back, D Kmax, D CCT, µm 3 CoV, mm WTW, mm 3 CaV, mm Angle, degree ACD, mm
TS (n = 35) Mean ± SD 0.9 ± 0.3 44.2 ± 1.7 0.3 ± 0.2 −6.5 ± 0.3 45.5 ± 1.9 557.3 ± 33.5 63.2 ± 3.9 11.3 ± 0.5 148.4 ± 33.5 37.6 ± 5.8 2.8 ± 0.3
SC
Topographic feature
M AN U
ACD: anterior chamber depth; Astig, astigmatism; CaV, chamber volume; CCT, central corneal thickness; Cov, cornea volume; D, diopter; K, kerotometry; Km, mean keratometry; Kmax, maximum keratometry; WTW, white-to-white; SD, standard deviation a
P < 0.0045 considered statistically significant. Mann-Whittney U test. c Independent samples t test.
AC C
EP
TE D
b
ACCEPTED MANUSCRIPT
Group 2 a (other karyotypes) P value (n = 15) Mean ± SD b 0.9 ± 0.3 0.988 c 44.6 ± 1.2 0.270 b 0.3 ± 0.1 0.399 c −6.6 ± 0.2 0.324 c 46.0 ± 1.3 0.141 c 550.2 ± 29.0 0.294 c 63.2 ± 3.1 0.965 c 11.4 ± 0.4 0.552 c 166.9 ± 29.2 0.004 c 37.7 ± 5.9 0.116 c 3.0 ± 0.2 0.003
SC
Group 1 (45,X0 karyotype) (n = 20) Mean ± SD Astig, front, D 0.9 ± 0.3 Km, front, D 43.9 ± 1.9 Astig, back, D 0.3 ± 0.2 Km, back, D −6.5 ± 0.4 Kmax, D 45.0 ± 2.2 CCT, µm 562.9 ± 36.4 3 CoV, mm 63.1 ± 4.6 WTW, mm 11.3 ± 0.5 3 CaV, mm 134.0 ± 29.9 Angle, degree 37.6 ± 6.4 ACD, mm 2.7 ± 0.3
RI PT
Table 2. Comparison of corneal topographic parameters in patients with Turner syndrome (TS) according to karyotype
M AN U
ACD: anterior chamber depth; Astig, astigmatism; CaV, chamber volume; CCT, central corneal thickness; Cov, cornea volume; D, diopter; K, kerotometry; Km, mean keratometry; Kmax, maximum keratometry; WTW, white-to-white; SD, standard deviation a
P < 0.0045 considered statistically significant. Mann-Whittney U test. c Independent samples t test.
AC C
EP
TE D
b
S1091-8531(17)30369-5
DOI:
10.1016/j.jaapos.2017.10.007
Reference:
YMPA 2734
To appear in:
Journal of AAPOS
Received Date: 13 May 2017 Revised Date:
28 September 2017
Accepted Date: 4 October 2017
Please cite this article as: Inanc M, Tekin K, Kurnaz E, Citirik M, Altas G, Aycan Z, Evaluation of anterior segment parameters in patients with Turner syndrome using Scheimpflug imaging, Journal of AAPOS (2018), doi: 10.1016/j.jaapos.2017.10.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Evaluation of anterior segment parameters in patients with Turner syndrome using Scheimpflug imaging Merve Inanc, MD,a Kemal Tekin, MD,b Erdal Kurnaz, MD,c Mehmet Citirik, MD,a Gülsah Altas, MD,c and Zehra Aycan, MDc
RI PT
Author affiliations: aAnkara Ulucanlar Eye Training and Research Hospital, Ankara, Turkey; b Department of Ophthalmology, Kars State Hospital, Kars, Turkey; cDepartment of Pediatric Endocrinology, Dr. Sami Ulus Children’s Health and Disease Training and Research Hospital, Ankara, Turkey
SC
Submitted May 27, 2017. Revision accepted October 4, 2017.
M AN U
Correspondence: Merve Inanc, MD, Ulucanlar Eye Training and Research Hospital, Ankara, 06240, Turkey (email: [email protected]).
AC C
EP
TE D
Word count: 2,530 Abstract only: 254
ACCEPTED MANUSCRIPT
Abstract Purpose To compare the anterior segment parameters in patients with Turner syndrome (TS) as measured
RI PT
by the Pentacam HR-Scheimpflug imaging system with those of healthy control subjects. Methods
This cross-sectional prospective study included 35 patients with TS and 30 age-matched
SC
controls. Corneal topographic analysis was performed using the Pentacam HR-Scheimpflug imaging system (Oculus, Wetzlar, Germany). The power of the corneal astigmatism, mean
M AN U
keratometry (Km) values for the both front and back surfaces of the cornea, maximum keratometry (Kmax), central corneal thickness (CCT), corneal volume (CoV), white-to-white diameter (WTW), chamber volume (CaV), angle and anterior chamber depth (ACD) values were recorded.
TE D
Results
The mean age of TS subjects was 17.2 ± 6.1 years; of controls, 16.4 ± 5.7 years. All participants were female. There was a significant difference in the mean values of WTW (11.3 ± 0.5 mm vs
EP
12.0 ± 0.4 mm [P < 0.001]), CaV (148.4 ± 33.5 mm3 vs 191.9 ± 27.6 mm3 [P < 0.001]), and ACD (2.8 ± 0.3 mm vs 3.1 ± 0.2 mm [P < 0.001]) between TS versus group and the control
AC C
group. The mean values of the power of the corneal astigmatism, Km values for the both front and back of the corneal surface, Kmax, CCT, CoV, and angle values were similar between groups (P > 0.05 for each one). Conclusions
There was a reduction in CaV, ACD, and WTW measurements in TS patients compared with controls.
ACCEPTED MANUSCRIPT
Turner syndrome (TS) is a chromosomal disorder in which phenotypic women have a missing or abnormal X chromosome. The incidence of TS is approximately 1 in 2500 live female births.1 Although some phenotypic features, such as short stature and reproductive system abnormalities,
RI PT
belong to the most common clinical features of TS, many ocular abnormalities are also
associated with TS, including strabismus, ptosis, epicanthal folds, red-green color deficiency, and nystagmus.2-4 Anterior segment abnormalities such as keratoconus, anterior chamber
SC
dysgenesis and posterior segment abnormalities such as Coats disease, formation of drusen, vascular lesions or retinal detachment have been reported in patients with TS.5-11 The literature
M AN U
concerning ophthalmological problems in patients with TS is limited. Although numerous case reports have suggested associations of ocular features with TS, few studies evaluate larger groups of patients.2-4 The aim of this study was to evaluate the anterior segment parameters in patients with TS by using Pentacam HR-Scheimpflug imaging system (Oculus Optikgerate
TE D
GmbH, Wetzlar, Germany), a reproducible method that measures almost all anterior segment parameters, and to compare those parameters with those in healthy control subjects. Subjects and Methods
EP
This prospective cross-sectional study was carried out from May 2016 to December 2016 at Ankara Ulucanlar Eye Training and Research Hospital, a tertiary referral eye hospital, and at the
AC C
pediatric endocrinology and metabolism clinic of Dr. Sami Ulus Children’s Health and Disease Training and Research Hospital, a children’s health and disease training and research hospital. The study protocol was approved by the Ankara Numune Training and Research Hospital Ethics Committee, and the study was carried out in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from adult patients and the parents or legal guardians of children prior to enrollment. All patients were white.
ACCEPTED MANUSCRIPT
A total of 42 consecutive patients with TS who were referred for ophthalmic assessment during the study period were enrolled; 30 age-matched control subjects were also included. All control subjects were healthy females without any systemic or ocular disease and had presented
RI PT
to the ophthalmology clinic for a routine ocular examinations. Only right eyes of all subjects were analyzed for the study.
Subjects with any of the following conditions were excluded: strabismus, nystagmus, a
SC
history of previous ocular surgery, trauma or uveitis, corneal diseases (such as corneal scarring), fundus abnormalities (such as retinopathy of prematurity or hypertensive/diabetic retinopathy),
M AN U
optic nerve diseases and glaucoma, neurological disease or other diseases of the visual pathways, ocular media opacities, use of topical medication, and high spherical (> −6.0 D or > +6.0 D) or cylindrical (> ± 3.00 D) refractive errors. Subjects who were not able to cooperative for Scheimpflug system examinations were also excluded. Seven of the 42 TS patients were
TE D
excluded because of ocular abnormalities: 2 patients had keratoconus, 2 had lens opacities, 1 had high cylindrical refraction, 1 had strabismus, and 1 had abnormal retinal vein tortuosity compatible with early stages of hypertensive retinopathy.
EP
All subjects underwent a comprehensive ophthalmic examination, including bestcorrected visual acuity tests using the Snellen chart (20 feet), intraocular pressure measurements,
AC C
slit-lamp biomicroscopy, and dilated fundus examination. Refraction measurements were performed by using the same automatic refractor-keratometer device (Canon RF-K2 Full Auto Ref-Keratometer, Japan). Red-green color deficiency was measured by Ishihara cards. Corneal topography was examined using a noncontact, noninvasive rotating Scheimpflug
camera system. Before Pentacam examination, participants had not undergone any contact ocular examination, such as tonometry, gonioscopy, or pupil dilation. Pentacam generates a three-
ACCEPTED MANUSCRIPT
dimensional model of the cornea and anterior segment. Corneal topographic analysis was performed by the same masked experienced clinician using the same Pentacam HR-Scheimpflug imaging system, and all measurements were taken under standard dim-light conditions. Three
RI PT
measurements were made per eye; the one with the best alignment and fixation was selected for data analysis. Distorted images caused by high reflection that were not eligible for evaluation were not included in the analysis. Corneal refractive map indices were evaluated for each subject
SC
in the study. The power of the corneal astigmatism, mean keratometry (Km) values for the both front and back surfaces of the cornea, maximum keratometry (Kmax), central corneal thickness
M AN U
(CCT), corneal volume (CoV), white-to-white diameter (WTW), chamber volume (CaV), and angle and anterior chamber depth (ACD) values were recorded. Statistical Analysis
The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 for
TE D
Windows (SPSS Inc, Chicago, IL). Descriptive statistics were recorded as mean ± standard deviations, frequency distributions, and percentages. Pearson’s χ2 test and one-sample χ2 test were used in the analysis of categorical variables. The normal distribution of the variables was
EP
tested using visual (histogram and probability graphs) and analytical methods (KolmogorovSmirnov/Shapiro-Wilk test). An independent sample t test was used for normally distributed
AC C
data, and a Mann-Whitney U test was used for non-normally distributed data to compare the TS and control groups. The Bonferroni test was used as post hoc test after t test and Mann-Whitney U test. Statistical significance was assumed at P < 0.05; however, for multiple comparisons and correlations among the 11 Pentacam parameters, Bonferroni’s correction was applied with a resultant significance level of P < 0.0045. Results
ACCEPTED MANUSCRIPT
This study included 65 eyes of 65 subjects: 35 subjects in the TS group and 30 in the control group. All participants were female. Genetic analysis of our subjects with TS revealed that 20 of 35 had a 45,X0 karyotype
RI PT
(pure Turner), and the remaining 15 had other karyotypes (5 had having both 45,X/46,XX; 3 had both 45,X/46,X,i(Xq); 2 had 45,X/46,XX/47,XXX; 2 had 46,X,i(Xq); and 2 had 46,X,del(Xq); the remaining patient had 45,X/46,X,r(X) karyotype pattern). All patients with TS were divided
SC
into 2 groups according to karyotype analysis: group 1, 45,X0; group 2, other karyotypes.
Recombinant growth hormone (GH) therapy (GHT) was used in 28 of the 35 subjects in
M AN U
the TS group (the number of patients treated previously or currently continuing treatment), and the remaining 7 patients did not receive recombinant GHT. We also divided the TS group according to use of recombinant GHT. These groups were compared regarding to their karyotypes and the status of use of recombinant GHT.
TE D
The mean age of TS patients was17.2 ± 6.1 years (range, 6-27 years); of controls, 16.4 ± 5.7 years (range, 6-29 years). There was no statistically significant difference in age of study participants between groups (P > 0.05). Although the subjects in the control group had no
EP
systemic disease, some patients in the TS group had systemic disorders: 4 had hypertension without retinopathy, 2 had autoimmune thyroiditis, 2 had hypertension and diabetes mellitus
AC C
without retinopathy, and 1 had celiac disease. Also, there was no statistically significant difference in the best-corrected visual acuity measurements and in spherical equivalence between groups (P > 0.05).
There were significant differences in the mean values of the WTW (11.3 ± 0.5 mm vs
12.0 ± 0.4 mm [P < 0.001]), CaV (148.4 ± 33.5 mm3 vs 191.9 ± 27.6 mm3 [P < 0.001]), and ACD (2.8 ± 0.3 mm vs 3.1 ± 0.2 mm [P < 0.001]) values between the TS and the control groups.
ACCEPTED MANUSCRIPT
However, the mean values of the power of the corneal astigmatism, Km values for the both front and back of the corneal surface, Kmax, CCT, CoV, and angle values were similar between groups (P > 0.05 for each). A comparison of the corneal topographic parameters between the TS
RI PT
and control groups appears in Table 1.
A comparison was performed with regards to the karyotype analysis in the patients with TS. There were significant differences in the mean values of the CaV (134.0 ± 29.9 mm3 vs
SC
166.9 ± 29.2 mm3 [P = 0.004]) and ACD (2.7 ± 0.3 mm vs 3.0 ± 0.2 mm [P = 0.003]) between the 45X0 subgroup and the other karyotypes subgroup. The other corneal topographic parameters
M AN U
were similar between the groups. Results are summarized in Table 2.
The status of recombinant GHT usage among TS patients was also analyzed, but there were no significant differences in the mean values of all corneal topographic parameters(P > 0.05 for each).
TE D
Discussion
Ocular abnormalities are common in TS but are underestimated and often neglected. The recent guidelines for diagnosis and treatment of TS reported common ophthalmologic abnormalities.12
EP
Strabismus and amblyopia are the most common abnormalities, present in more than one-third of patients.3,13 Other abnormalities in TS include hypertelorism, epicanthus, down-slanting
AC C
palpebral fissures, ptosis, hypermetropia, reduced color vision, congenital cataract, congenital glaucoma, uveitis, neovascularization, retinal detachment, and papilledema.3,13,14 The high prevalence of eye abnormalities in TS may be explained by the similar genetic
pathway for ocular and ovarian development. For example, the USP9X gene, which causes gonadal dysgenesis in TS, plays a significant role in the development of the eye and ovary in Drosophila.15 In TS, anomalies were detected in different parts of the eye, which may be due to
ACCEPTED MANUSCRIPT
the defect or abnormal structure of the X chromosome. Although anterior segment dysgenesis is not a common feature in TS, anterior segment abnormalities such as astigmatism and keratoconus have been described in TS. Nucci and colleagues8 reported a case with both TS and
RI PT
keratoconus and hypothesized that corneal thinning in TS is an expression of a mesodermal defect because mesodermal structures are sometimes affected in TS. However, the cornea is not predominantly mesodermal derived. The corneal epithelium is derived from surface ectoderm,
SC
whereas the corneal stroma and endothelium are derived predominantly from neural crest, and the minority population of cells within the corneal stroma and endothelium are derived from the
M AN U
mesoderm.16 We found no evidence of corneal thinning in TS subjects compared with controls. Wikiera and colleagues17 reported that prevalence of astigmatism in TS was approximately three times higher than the reported rate in the general population of Polish children. Our study showed, on the contrary, that the mean values of power of the corneal
TE D
astigmatism, Km values for the both front and back of the corneal surface, and Kmax values were similar between the groups. Because 2 patients with keratoconus and 1 patient with high cylindrical refraction were excluded from the study, no difference could be detected between
EP
groups. Nalcacioglu and colleauges18 found that CCT values are higher in patients with TS than in healthy children by using ultrasound pachymeter. However, in our study, there was no
AC C
difference regarding the CCT values between TS subjects and controls. In Nalcacioglu and colleauges,18 adjustment of the contact system may have been difficult due to the majority of participants being children, and the measurements may had been taken from the peripheral region, where the cornea is thickened, rather than from the central region.18 In our study the noncontact Scheimpflug imaging system was used to minimize these risks. Different results may be due to either measurement error or CCT variability.
ACCEPTED MANUSCRIPT
The Turner phenotype is caused by X-linked genes that escape inactivation. One of these genes is the short-stature-homeobox (SHOX) gene, mutations of which result in characteristic features such as short stature.19,20 Recent studies have revealed that body height is associated
RI PT
with eye parameters that can be correlated with ocular diseases in a multivariate statistical
analysis.21,22 For example, body height appears to correlate with anterior chamber depth.23-25 This is of clinical pathologic importance given the correlation between anterior chamber depth and
SC
primary angle closure glaucoma.23,26-28 This agrees with the finding that patients with chronic angle-closure glaucoma are significantly shorter than patients with chronic open-angle
M AN U
glaucoma.29 Further, this study suggests that short body height may be a potential screening parameter to detect individuals at risk for developing angle closure.29 We found that CaV and ACD values, that are correlated with each other,30 and WTW values were lower in patients with TS than in controls. One reasons could be that patients with TS had a shorter body stature than
TE D
controls. While changes in the anterior eye segment have been related to karyotype mosaicism,6 our analysis did not confirm this. We found that the mean values of the CaV and ACD were lower in the 45X0 group than the other karyotypes. This may correlate with genes on the short
EP
arms of the X and Y chromosomes that are responsible for normal growth and stature. Further, some reports indicate that 45,X/46,XY or 46,X,del(Xq) TS patients are on average taller than
AC C
other TS karyotypes.31 Thus, the lower values in the 45X0 group with TS may be explained by body height differences.
Organic GH deficiency is not a feature of TS, but recombinant human GH has been used
to increase linear growth and final height in these patients.32,33 Although the intrinsic mechanisms of GH actions on eyes are still not fully known, it is well known that the eye represents a target site for GH action. GH and IGF-I are known to be involved in ocular
ACCEPTED MANUSCRIPT
development.34 In addition, the evidence that, acromegalic patients with longer active and uncontrolled disease showed greater CCT values supported the hypothesis that GH may have stimulatory effects on the cornea as well as on other target organs.35 Nalcacioglu and
RI PT
colleauges18 revealed that exposure to recombinant GHT or the duration of GHT were not the main causes of increased corneal thickness. They suggested that the lack of a GHT effect on CCT could be attributed to the restriction of access to ocular tissues due to blood-ocular barrier.
receiving and not receiving recombinant GHT.
SC
Also in our study, there was no difference regarding the CCT values between the groups
M AN U
One of the limitations of the present study is that axial length was not measured; therevore, it has not been determined whether decreased CaV, ACD, and WTW indicate that the overall eye size is less or that the anterior segment is disproportionately smaller in TS. In addition, the number of patients in the group who did not receive GHT was low. Finally, because
TE D
of the cross-sectional nature of the study, the causal relationship between the TS and anterior
AC C
EP
segment changes cannot be inferred.
ACCEPTED MANUSCRIPT
References 1.
Kriksciuniene R, Zilaitiene B, Verkauskiene R. The current management of Turner Syndrome. Minerva Endocrinol 2016;41:105-21. Brunnerová R, Lebl J, Krásný J, Průhová S. Ocular manifestations in Turner’s syndrome.
RI PT
2.
Cesk Slov Oftalmol 2007;63:176-84.
Denniston AK, Butler L. Ophthalmic features of Turner’s syndrome. Eye (Lond) 2004;18:680-84.
4.
Chrousos GA, Ross JL, Chrousos G, et al. Ocular findings in Turner syndrome. A
Austin MW, Patterson A, Bates RA. Conjunctival lymphoedema in Turner’s syndrome. Eye (Lond) 1992;6:335-6.
6.
M AN U
prospective study. Ophthalmology 1984;91:926-8. 5.
SC
3.
Lloyd IC, Haigh PM, Clayton-Smith J, et al. Anterior segment dysgenesis in mosaic
7.
Macsai M, Maguen E, Nucci P. Keratoconus and Turner’s syndrome. Cornea 1997;16:534-6.
Nucci P, Trabucchi G, Brancato R. Keratoconus and Turner’s syndrome: a case report.
EP
8.
TE D
Turner syndrome. Br J Ophthalmol 1997;81:639-43.
Optom Vis Sci 1991;68:407-8. Beatty S, Black G, Rhatigan M, Bishop P. Bilateral subfoveal choroidal
AC C
9.
neovascularization in Turner’s syndrome: coincidence or consequence? Can J Ophthalmol 1999;34:346-8.
10.
Gotoh M, Yamamoto M, Kawasaki T, Shigetoh M, Inomata H. Two cases of unilateral retinal neovascularization in Turner syndrome. Am J Ophthalmol 1998;126:144-6.
11.
Mason JO 3rd, Tasman W. Turner’s syndrome associated with bilateral retinal
ACCEPTED MANUSCRIPT
detachments. Am J Ophthalmol 1996;122:742-3. 12.
Bondy CA; Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab
13.
RI PT
2007;92:10-25.
Adhikary HP. Ocular manifestations of Turner’s syndrome. Trans Ophthalmol Soc UK 1981;101:395-6.
Tsunekawa H, Ohno-Jinno A, Zako M. Uveitis in 2 cases of Turner’s syndrome. Can J
SC
14.
Ophthalmol 2007;42:756-7.
Noma T, Kanai Y, Kanai-Azuma M, et al. Stage- and sex-dependent expressions of
M AN U
15.
Usp9x, an X-linked mouse ortholog of Drosophila Fat facets, during gonadal development and oogenesis in mice. Mech Dev 2002;119 Suppl 1:S91-5. 16.
Gage PJ, Rhoades W, Prucka SK, Hjalt T. Fate maps of neural crest and mesoderm in the
17.
TE D
mammalian eye. Invest Ophthalmol Vis Sci 2005;46:4200-208. Wikiera B, Mulak M, Koltowska-Haggstrom M, Noczynska A. The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype. Clin
18.
EP
Endocrinol (Oxf) 2015;83:842-8.
Nalcacioglu-Yüksekkaya P, Sen E, Onder A, et al. Increased central corneal thickness in
19.
AC C
patients with Turner syndrome. Eur J Ophthalmol 2014;24:309-13.
Rao E, Weiss B, Fukami M, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet 1997;16:54-63.
20.
Clement Jones M, Schiller S, Rao E, et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet 2000;9:695-702.
ACCEPTED MANUSCRIPT
21.
Saw SM, Chua WH, Hong CY, et al. Height and its relationship to refraction and biometry parameters in Singapore Chinese children. Invest Ophthalmol Vis Sci 2002;43:1408-13. Eysteinsson T, Jonasson F, Arnarsson A, Sasaki H, Sasaki K. Relationships between
RI PT
22.
ocular dimensions and adult stature among participants in the Reykjavik Eye Study. Acta Ophthalmol Scand 2005;83:734-8.
Congdon NG, Youlin Q, Quigley H, et al. Biometry and primary angle-closure glaucoma
SC
23.
among Chinese, white, and black populations. Ophthalmology 1997;104:1489-95. Devereux JG, Foster PJ, Baasanhu J, et al. Anterior chamber depth measurement as a
M AN U
24.
screening tool for primary angle-closure glaucoma in an East Asian population. Arch Ophthalmol 2000;118:257-63. 25.
Nolan WP, See JL, Chew PT, et al. Detection of primary angle closure using anterior
26.
TE D
segment optical coherence tomography in Asian eyes. Ophthalmology 2007;114:33-9. George R, Paul PG, Baskaran M, et al. Ocular biometry in occludable angles and angle closure glaucoma: a population based survey. Br J Ophthalmol 2003;87:399-402. Aung T, Nolan WP, Machin D, et al. Anterior chamber depth and the risk of primary
EP
27.
angle closure in 2 East Asian populations. Arch Ophthalmol. 2005;123:527-32. Casson RJ, Marshall D, Newland HS, et al. Risk factors for early angle-closure disease in
AC C
28.
a Burmese population: the Meiktila Eye Study. Eye (Lond) 2009;23:933-9.
29.
Xu L, Li J, Wang Y, Jonas JB. Anthropomorphic differences between angle-closure and open-angle glaucoma: the Beijing Eye Study. Acta Ophthalmol Scand. 2007;85:914-15.
30.
Rabsilber TM, Khoramnia R, Auffarth GU. Anterior chamber measurements using Pentacam rotating Scheimpflug camera. J Cataract Refract Surg. 2006;32:456-9.
ACCEPTED MANUSCRIPT
31.
Ferguson-Smith MA. Genotype-phenotype correlations in the Turner syndrome. In: Hibi I, Takano K, eds. Basic and clinical approach to Turner syndrome. Amsterdam: Elsevier; 1993;17-25. Baxter L, Bryant J, Cave CB, Milne R. Recombinant growth hormone for children and
RI PT
32.
adolescents with Turner syndrome. Cochrane Database Syst Rev 2007;24:CD003887. 33.
Bolar K, Hoffman AR, Maneatis T, Lippe B. Long-term safety of recombinant human
34.
SC
growth hormone in turner syndrome. J Clin Endocrinol Metab 2008;93:344–51.
Cuthbertson RA, Beck F, Senior PV, Haralambidis J, Penschow JD, Coghlan JP. Insulin-
M AN U
like growth factor II may play a local role in the regulation of ocular size. Development 1989;107:123-30.
Ciresi A, Amato MC, Morreale D, Lodato G, Galluzzo A, Giordano C. Cornea in acromegalic patients as a possible target of growth hormone action. J Endocrinol Invest
EP
TE D
2011;34:e30-35.
AC C
35.
ACCEPTED MANUSCRIPT
Table 1. Comparison of corneal topographic parameters between Turner syndrome (TS) and control groups Controls (n = 30) Mean ± SD 1.2 ± 0.3 43.5 ± 1.2 0.3 ± 0.2 −6.5 ± 0.2 44.6 ± 1.5 550.8 ± 31.7 61.3 ± 3.1 12.0 ± 0.4 191.9 ± 27.6 37.7 ± 6.1 3.1 ± 0.2
P value
a
b
0.182 c 0.110 b 0.082 c 0.499 c 0.078 c 0.460 c 0.057 <0.001c c <0.001 c 0.418 c <0.001
RI PT
Astig, front, D Km, front, D Astig, back, D Km, back, D Kmax, D CCT, µm 3 CoV, mm WTW, mm 3 CaV, mm Angle, degree ACD, mm
TS (n = 35) Mean ± SD 0.9 ± 0.3 44.2 ± 1.7 0.3 ± 0.2 −6.5 ± 0.3 45.5 ± 1.9 557.3 ± 33.5 63.2 ± 3.9 11.3 ± 0.5 148.4 ± 33.5 37.6 ± 5.8 2.8 ± 0.3
SC
Topographic feature
M AN U
ACD: anterior chamber depth; Astig, astigmatism; CaV, chamber volume; CCT, central corneal thickness; Cov, cornea volume; D, diopter; K, kerotometry; Km, mean keratometry; Kmax, maximum keratometry; WTW, white-to-white; SD, standard deviation a
P < 0.0045 considered statistically significant. Mann-Whittney U test. c Independent samples t test.
AC C
EP
TE D
b
ACCEPTED MANUSCRIPT
Group 2 a (other karyotypes) P value (n = 15) Mean ± SD b 0.9 ± 0.3 0.988 c 44.6 ± 1.2 0.270 b 0.3 ± 0.1 0.399 c −6.6 ± 0.2 0.324 c 46.0 ± 1.3 0.141 c 550.2 ± 29.0 0.294 c 63.2 ± 3.1 0.965 c 11.4 ± 0.4 0.552 c 166.9 ± 29.2 0.004 c 37.7 ± 5.9 0.116 c 3.0 ± 0.2 0.003
SC
Group 1 (45,X0 karyotype) (n = 20) Mean ± SD Astig, front, D 0.9 ± 0.3 Km, front, D 43.9 ± 1.9 Astig, back, D 0.3 ± 0.2 Km, back, D −6.5 ± 0.4 Kmax, D 45.0 ± 2.2 CCT, µm 562.9 ± 36.4 3 CoV, mm 63.1 ± 4.6 WTW, mm 11.3 ± 0.5 3 CaV, mm 134.0 ± 29.9 Angle, degree 37.6 ± 6.4 ACD, mm 2.7 ± 0.3
RI PT
Table 2. Comparison of corneal topographic parameters in patients with Turner syndrome (TS) according to karyotype
M AN U
ACD: anterior chamber depth; Astig, astigmatism; CaV, chamber volume; CCT, central corneal thickness; Cov, cornea volume; D, diopter; K, kerotometry; Km, mean keratometry; Kmax, maximum keratometry; WTW, white-to-white; SD, standard deviation a
P < 0.0045 considered statistically significant. Mann-Whittney U test. c Independent samples t test.
AC C
EP
TE D
b