1040-5488/14/9112-1474/0 VOL. 91, NO. 12, PP. 1474Y1482 OPTOMETRY AND VISION SCIENCE Copyright * 2014 American Academy of Optometry
ORIGINAL ARTICLE
Corneal Biomechanics, Retinal Nerve Fiber Layer, and Optic Disc in Children Inmaculada Bueno-Gimeno*, Andres Gene-Sampedro†, David P. Pin˜ero-Llorens*, Aitor Lanzagorta-Aresti*, and Enrique Espan˜a-Gregori*
ABSTRACT Purpose. To evaluate the possible associations between corneal biomechanical parameters, optic disc morphology, and retinal nerve fiber layer (RNFL) thickness in healthy white Spanish children. Methods. This cross-sectional study included 100 myopic children and 99 emmetropic children as a control group, ranging in age from 6 to 17 years. The Ocular Response Analyzer was used to measure corneal hysteresis (CH) and corneal resistance factor. The optic disc morphology and RNFL thickness were assessed using posterior segment optical coherence tomography (Cirrus HD-OCT). The axial length was measured using an IOLMaster, whereas the central corneal thickness was measured by anterior segment optical coherence tomography (Visante OCT). Results. The mean (TSD) age and spherical equivalent were 12.11 (T2.76) years and j3.32 (T2.32) diopters for the myopic group and 11.88 (T2.97) years and +0.34 (T0.41) diopters for the emmetropic group. In a multivariable mixed-model analysis in myopic children, the average RNFL thickness and rim area correlated positively with CH (p = 0.007 and p = 0.001, respectively), whereas the average cup-to-disc area ratio correlated negatively with CH (p = 0.01). We did not observe correlation between RNFL thickness and axial length (p = 0.05). Corneal resistance factor was only positively correlated with the rim area (p = 0.001). The central corneal thickness did not correlate with the optic nerve parameters or with RNFL thickness. These associations were not found in the emmetropic group (p 9 0.05 for all). Conclusions. The corneal biomechanics characterized with the Ocular Response Analyzer system are correlated with the optic disc profile and RNFL thickness in myopic children. Low CH values may indicate a reduction in the viscous dampening properties of the cornea and the sclera, especially in myopic children. (Optom Vis Sci 2014;91:1474Y1482) Key Words: corneal biomechanics, myopia, optic disc parameters
M
yopia is among the most common refractive errors and is associated with a greater risk of certain pathological consequences. Higher levels of myopia are closely associated with ocular pathologies such as retinal detachment and chorioretinal degeneration and could increase the risk of developing glaucoma.1 Several studies have investigated the relationship between corneal biomechanical properties (CBPs) and refractive error, reporting a reduced corneal hysteresis (CH) and corneal resistance *PhD † MSc Department of Optics (IB-G, AG-S) and Department of Surgery (EE-G), University of Valencia, Valencia, Spain; Foundation for the Visual Quality (Fundacio´n para la Calidad Visual, FUNCAVIS), Alicante, Spain (DPP-L); Department of Optics, Pharmacology, and Anatomy, University of Alicante, Alicante, Spain (DPP-L); Fisabio Oftalmologı´a Me´dica (FOM), Valencia, Spain (AL-A); and University Hospital La Fe, Valencia, Spain (EE-G).
factor (CRF) in myopic eyes.2,3 These measurements are thought to be related to the viscoelastic properties of the cornea. In a previous study,4 we examined 293 eyes from 293 children with a mean (TSD) age of 10.8 (T3.1) years and a mean (TSD) spherical equivalent (SE) of +0.14 (T3.41) diopters (D) (range, j8.75 to + 8.25 D) and found that CH was associated with axial length (AL) in the high myopia group (SE greater than j6.00 D) and reported that the Ocular Response Analyzer (ORA) CBPs are compromised in myopia from an early age, especially in high myopia. Chang et al.5 reported that lower CH and CRF were associated with longer AL, suggesting an association between CBPs and whole eye biometry in myopic children, aged 12.02 T 3.19 years, and demonstrated the importance of CH as a determinant of ocular biometry in both the anterior and posterior segments. However, Lim et al.6 showed no correlation between CH and AL in 271 right eyes from 271 Singaporean children with a mean (TSD) age of 13.97 (T0.89) years and a mean (TSD) SE of j2.35 (T2.49) D.
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
These divergent results may be attributable to factors such as mixed ethnicity in the populations analyzed, differences in study methodologies, levels of refractive errors, or other unknown factors.4 The relationship between anterior and posterior ocular biomechanical properties has also been studied, reporting a reduced CH in eyes with primary open-angle, normal tension, and congenital glaucoma.7Y9 These associations suggest that a more deformable cornea might be linked to a greater susceptibility of the lamina cribrosa and might help explain why some subjects are more predisposed to optic nerve damage than others.10 Kotecha et al.10 suggested that measurements of corneal biomechanics such as the CH could give an idea of the structural integrity of the optic nerve head (ONH). Information on the changes occurring at the ONH and in the thickness of the retinal nerve fiber layer (RNFL) is essential for the assessment of patients with, or at risk of, optic neuropathy, because RNFL thinning could be an early sign of glaucomatous damage.11,12 Chang and Chang13 evaluated the association between CBPs and optic disc morphology (disc area, rim area, cup area, cup-to-disc [C/D] ratio, and cup volume) and peripapillary retinal nerve fiber layer (pRNFL) thickness in myopic adults, and found a negative relationship between central corneal thickness (CCT) and disc area, rim area, cup area, C/D ratio, and cup volume. Corneal hysteresis correlated negatively with disc area and cup area. Lim et al.,14 in a study with Singaporean schoolchildren, showed negative correlations between CCT and disc area. Both studies13,14 reported that these relationships might be linked to increased glaucoma risk in myopic subjects. The ONH changes that occur in association with myopia in childhood have been analyzed in several studies.15,16 Kim et al.15 suggested that tilted disc, as well as peripapillary atrophy, may be an acquired feature in myopic eyes, arising from scleral stretching in children from 1 to 17 years with a mean (TSD) refractive error of j0.9 (T1.9) D (range, j5.9 to +3.0 D), and Samarawickrama et al.16 found a high prevalence of optic disc tilting and other very early retinal and disc changes including peripapillary atrophy associated with myopia in Singapore Chinese adolescent children, aged 12 to 16 years. Eyes with tilted optic discs were more myopic and astigmatic, had longer ALs, and had smaller optic discs, cups, and C/D ratios than eyes without tilted optic discs. Whereas the distribution of optic disc parameters and RNFL thickness has been measured in children,17 their relationship with CBPs has not been sufficiently investigated. The knowledge of the normal structure of optic disc parameters and their possible associations with corneal biomechanics in children would provide important information about possible changes during the child’s growth and contribute to our understanding of the ONH changes that occur in association with myopia in childhood (and the potential underlying causes of them). Although it is relatively rare to develop glaucoma in children, the data of normal conditions in this population could help us to understand changes in pathological conditions such us glaucoma. To date, there are only a small number of studies that have analyzed the association between CBPs and RNFL in children. Therefore, this study aimed to assess whether corneal biomechanical parameters were related to optic disc morphology and RNFL thickness in healthy white Spanish children. The study also evaluated the association between the AL and RNFL thickness in myopia.
1475
METHODS This cross-sectional study included 199 eyes from 199 children. The samples were selected according to cycloplegic SE refraction, and the subjects were divided into two groups: 99 eyes of 99 emmetropic children (45 boys and 54 girls) were used as a control group, and 100 of 100 myopic children (46 boys and 54 girls), ranging in age from 6 to 17 years, were included as the test group. All children were recruited from the Fisabio Oftalmologı´a Me´dica (FOM) hospital. The exclusion criteria were a corrected distance visual acuity of worse than 20/25 in either eye, a refractive cylinder of more than 2.00 D, and being older than 18 years. Subjects with a previous history of ocular surgery, trauma, pathology, or ocular medication were also excluded from the study. Children with a tilted optic disc, spherical equivalent refraction (SER) anisometropia more than 1.00 D, or strabismus were also excluded from the study. A complete ocular examination was performed in all eyes including a visual acuity measurement, stereopsis assessment, motility examination, cycloplegic refraction, and anterior segment and dilated fundus examination. Cycloplegia was induced with three drops of cyclopentolate 1% separated by 5 minutes, to achieve adequate mydriasis (Q6 mm).17 At least 30 minutes after the last drop, autorefraction was measured with an autorefractometer (Topcon KR-8100P), followed by a subjective refinement. Fifteen days after the ocular examination, to avoid any effect induced by cycloplegia and according to clinical procedures of the institution (FOM), the same experienced examiner (IBG) performed all the measurements in both eyes in a random order; however, only the data from one randomly selected eye were included in the study. These measurements were AL, using optical biometry (IOLMaster; Carl Zeiss Meditec Inc, Dublin, CA), the CBPs (Ocular Response Analyzer, ORA, Reichert), CCT (Visante OCT, Carl Zeiss Meditec), RNFL, and ONH parameters (Cirrus HD-OCT, Carl Zeiss Meditec). All measurements were taken without pupillary dilation. To reduce the effects of diurnal corneal variation, all examinations were performed between 3:00 PM and 6:00 PM.18 Participants were classified according to the cycloplegic SE refraction of both eyes (SER, sphere plus half the negative cylinder) as either emmetropia SER between +0.75 and j0.25 D, low myopia SER between j0.50 and j3.00 D, moderate myopia SER between j3.25 and j6.00 D, or high myopia SER greater than j6.00 D.19 Only one randomly chosen eye was included for analysis and the classification was based on the eye selected. The study adhered to the tenets of the Declaration of Helsinki. Informed written consent was obtained from the parents of the subjects, and assent was given by the children. The study was approved by the FOM Ethics Committee.
ORA Measurements The ORA (Reichert Ophthalmic Instruments, Depew, NY) device attempts to characterize the viscoelastic properties of the cornea by means of two principal parameters: the CH, which is defined as the difference between the two pressures (P1 and P2) recorded during the described measurement process, and the CRF, which is calculated using a proprietary algorithm (P1 j kP2) and is predominantly related to the elastic properties of the cornea.20,21
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1476 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
The ORA also provides two measures of the intraocular pressure (IOP) (IOPg and IOPcc). The IOPg provides a Goldmanncorrelated IOP, which is a mean of the two IOP applanation pressures P1 and P2.21 The IOPcc is known as the corneal compensated IOP, which is less affected by corneal properties than other methods of tonometry.22 The ORA measurement technique has already been described,15,16 including its high repeatability in both children23 and adults.24 The ORA (Software Version 1.10) was used to obtain four consecutive measurements in each eye from every patient, and the mean of these readings was used in the analysis according to the manufacturer’s instructions. The manufacturer recommends that the quality of the waveform should be assessed by identifying two well-defined peaks that are reasonably symmetrical and higher than the superimposed pressure curve. If the measurements differed by more than 2 mm Hg, an additional measurement was taken, and the two extreme values were excluded from the analysis.25
Optical Coherence Tomography (Cirrus HD-OCT) Measurements Measurements of the RNFL and ONH parameters were obtained using the Cirrus HD-OCT system (Software Version 5.0.0.326) with a scan speed of 27,000 A-scans per second and an axial resolution of 5 Km. An optic disc cube 200 200 protocol was used to obtain the RNFL thickness and ONH measurements. The OCT technique12,17,26 and its reproducibility in children27,28 have already been described in several reports. Cirrus HD-OCT software algorithm automatically detects the center of the optic disc and positions a calculation circle of 3.46 mm diameter evenly around it.27,29 From the 256 A-scans along the circle, the anterior and posterior boundaries of RNFL are delimited and thickness is calculated at each point along this circle. In each series of scans, average RNFL thickness and RNFL thickness in each quadrant (superior, inferior, temporal, and nasal) were analyzed.28,29 For image acquisition, an internal fixation target was used, and the alignment was properly positioned to the ONH in the center of the scan. Average measurements of three sequential circular scans of diameter 3.4 mm on the optic disc were recorded. Scan quality was checked for every OCT image and manual correction of the boundary detection was enabled if segmentation errors are present. If an involuntary saccadic eye movement was detected during the scan, it was discarded and repeated.26Y28 Only the images of satisfactory quality, defined as images properly centered on the optic disc with a signal strength of greater than or equal to 7, were included in the analysis. For calculating the corrected AL-related ocular magnification, we used the Littmann formula (t = pIq Is)29 according to other authors’ suggestion,29Y32 where t is the actual fundus dimension, s is the measurement obtained using the OCT, p is the magnification factor of the imaging system camera, and q is the magnification factor related to the eye.30,31 The ocular magnification factor q of the eye can be determined using the formula q = 0.01306 I(AL j 1.82).30 Factor p is a constant, is instrument dependent, and remains a constant in a telecentric imaging system in both the Stratus OCT and Cirrus HD-OCT. The p of the latter system is known to be 3.382.31,32 Because t = p Iq Is refers to linear
magnification, the equation should be modified to t 2 = p2 Iq 2 Is 2 for the area magnification.
Other Examinations The AL was measured with a noncontact partial coherence interferometer (IOLMaster; Carl Zeiss Meditec Inc, Software Version 5.2.1). Three consecutive AL and corneal curvature readings were taken and averaged. Only the AL measurements with a signal-to-noise ratio greater than 2 were included in the database.33 The CCT was measured by anterior segment optical coherence tomography (Visante OCT; Carl Zeiss Meditec Inc, Software Version 3.0.1.8), which is a noncontact device that provides crosssectional images of the anterior segment of the eye. The scans were centered on the pupil and taken along the horizontal meridian. The scan was optimally aligned when the optically produced corneal reflex was visible as a vertical white line along the center of the cornea.34
Statistical Analysis Statistical analysis was performed with the commercially available statistical package SPSS version 19.0 (SPSS, Chicago, IL). Kolmogorov-Smirnov tests were used to analyze the data for normality and were normally distributed. The Pearson correlation coefficient was used to test for correlations between the variables. A Student t test for unpaired data (two samples) or a one-way analysis of variance (ANOVA) with a Scheffe´ post hoc analysis (more than two samples) was used to compare the parameters among the groups classified by SER. A multiple linear regression model was constructed with RNFL thickness, rim area, disc area, and average C/D ratio as dependent variables to assess their relationship with the ORA measurements (CH, CRF, IOPg, and IOPcc), CCT, age, and AL covariates. To diminish the colinearity problem, the SER was not included in the multivariate model because of its high correlation with AL. A value of p G 0.05 was considered statistically significant.
RESULTS The mean (TSD) age was 12.11 (T2.76) years and 11.88 (T2.97) years for the myopic and emmetropic groups, respectively. There were no statistically significant differences between right and left eyes or between sexes for any of the parameters assessed (p Q 0.05, Student t test). The mean (TSD) values of the AL, age, CH, CRF, CCT, RNFL thickness measurements, and optic disc parameters for the myopic and emmetropic groups and the comparisons among these parameters are summarized in Table 1. Significant differences were found between the myopic and emmetropic groups in CH, CRF, and average RNFL thickness (Student t test, p G 0.001, p = 0.009, and p = 0.001, respectively). In the myopic group, there was a significant positive correlation between the CH and the average RNFL thickness (r = 0.22, p = 0.03) (Fig. 1) and between the CH and the nasal and temporal RNFL thickness (r = 0.22, p = 0.02 and r = 0.23, p = 0.02, respectively); however, we found a negative correlation between the CH and the average C/D ratio (r = j0.35,
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al. TABLE 1.
Values of age, AL, SE, corneal biomechanical parameters, RNFL thickness, and optic disc morphology measurements for myopic and emmetropic groups (mean T SD) Emmetropic group (n = 99) Age, y AL, mm SE, D CCT, Km CH, mm Hg CRF, mm Hg Average RNFL thickness, Km Superior RNFL thickness, Km Inferior RNFL thickness, Km Nasal RNFL thickness, Km Temporal RNFL thickness, Km Rim area, mm2 Disc area, mm2 Average C/D ratio
Myopic group (n = 100)
p (by t test)
11.88 T 2.97 12.11 T 2.76 23.12 T 0.79 24.51 T 1.11 +0.34 T 0.41 j3.32 T 2.32 543.85 T 35.65 543.02 T 45.38 12.56 T 1.68 11.55 T 1.45 12.63 T 1.91 11.93 T 1.85 100.39 T 11.31 95.30 T 9.97
0.34 G0.001* G0.001* 0.88 G0.001* 0.009* 0.001*
123.53 T 23.81 121.85 T 24.03
0.62
130.11 T 21.33 116.81 T 17.81
G0.001*
72.12 T 16.76
65.25 T 12.61
0.001*
74.51 T 17.78
72.64 T 16.47
0.44
1.67 T 0.34 2.09 T 0.44 0.36 T 0.17
1.58 T 0.28 1.85 T 0.34 0.32 T 0.19
0.06 G0.001* 0.08
*Statistically significant.
p G 0.001). The CRF negatively correlated with the average C/D ratio (r = j0.28, p = 0.005) and positively correlated with the RNFL thickness in the temporal quadrant (r = 0.28, p = 0.006),
1477
whereas the CCT only negatively correlated with the average C/D ratio (r = j0.22, p = 0.03). We found a positive correlation between RNFL and AL (r = 0.22, p = 0.03) (Fig. 2); however, no correlation was observed between RNFL and SER in the myopic children (r = 0.06, p = 0.56). Regarding the superior and inferior quadrants, these relationships were not statistically significant. Among the emmetropic group, no significant correlations between the CBPs and optic disc parameters or RNFL thickness were found (p 9 0.05 for all parameters). Table 2 shows the differences in all the measured parameters for the three myopic subgroups and the control group including the comparisons among them using one-way ANOVA. Significant differences in the average RNFL thickness were found between the emmetropic and high myopic groups (Scheffe´ test, p = 0.008) and between the emmetropic and moderate myopic subgroups (p = 0.04). No significant differences were found between the emmetropic and low myopic subgroups (p = 0.88). We also compared the three myopic subgroups, and a significant difference in the average RNFL thickness and the thickness in the inferior quadrant was found between the high and low myopic groups (p = 0.04 and p = 0.03, respectively). Moreover, significantly higher CH values were obtained in the emmetropic group in comparison with the values in the myopic subgroups (p = 0.01, p = 0.03, and p = 0.01 for the high, moderate, and low myopic subgroups, respectively). There were no significant differences in the CH among the three myopic subgroups (p 9 0.70). No significant differences in the CRF were found among the emmetropic and myopic subgroups (p = 0.62, p = 0.46, and p = 0.15 for the high, moderate, and low myopic subgroups, respectively). Although a trend toward a reduction in the CRF with increasing
FIGURE 1. Correlations between CH and average RNFL thickness in myopic children. Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1478 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
FIGURE 2. Correlations between AL and average RNFL thickness in myopic children.
myopia was found, it was not statistically significant (one-way ANOVA test, p = 0.07). In the multivariate mixed-model analysis, for the myopic group (Table 3), the average RNFL thickness and rim area decreased with lower CH (p = 0.004 and p = 0.01, respectively), whereas the average C/D area ratio increased as the CH decreased (p = 0.01). Therefore, with a decrease of 1 mm Hg in the CH, the average RNFL thickness decreased by 6.24 Km; for every 1 mm Hg
decrease in the CH, there was a decrease of 0.1 mm2 in the rim area; and for every 1 mm Hg decrease in the CH, the average C/D ratio increased by 0.06. The CRF only positively correlated with the rim area (p = 0.01); hence, for every 1 mm Hg decrease in the CRF, the rim area decreased by 0.1 mm2. IOPg and IOPcc correlated negatively with disc area (p = 0.008 and p = 0.005, respectively) and positively with C/D ratio (p = 0.007 and p = 0.004, respectively). The relationship between
TABLE 2.
Values of age, AL, SE, corneal biomechanical parameters, RNFL thickness, and optic disc morphology measured for the three myopic groups and the control group (mean T SD)
Age, y AL, mm SE, D CCT, Km CH, mm Hg CRF, mm Hg IOPg, mm Hg IOPcc, mm Hg Average RNFL thickness, Km Superior RNFL thickness, Km Inferior RNFL thickness, Km Nasal RNFL thickness, Km Temporal RNFL thickness, Km Rim area, mm2 Disc area, mm2 Average C/D ratio
Emmetropic (n = 99)
Low myopia (n = 59)
Moderate myopia (n = 24)
High myopia (n = 17)
p (by one-way ANOVA)
11.88 T 2.97 23.12 T 0.79 +0.34 T 0.41 543.85 T 35.65 12.56 T 1.68 12.63 T 1.91 16.74 T 3.40 14.71 T 3.22 100.39 T 11.31 123.53 T 23.81 130.11 T 21.33 72.12 T 16.76 74.51 T 17.78 1.67 T 0.34 2.09 T 0.44 0.36 T 0.17
11.76 T 2.57 23.91 T 0.84 j1.67 T 0.77 535.76 T 40.48 11.68 T 1.45 11.91 T 1.76 16.33 T 3.04 15.18 T 2.95 98.44 T 9.89 121.93 T 23.53 120.79 T 21.15 70.47 T 16.94 76.89 T 22.94 1.57 T 0.26 1.86 T 0.34 0.31 T 0.20
13.74 T 2.60 25.38 T 1.04 j4.56 T 0.78 536.25 T 35.70 11.51 T 1.34 11.94 T 1.64 17.05 T 3.96 15.95 T 3.95 95.32 T 10.05 125.40 T 25.48 118.06 T 16.62 64.17 T 10.14 71.06 T 14.27 1.59 T 0.32 1.85 T 0.34 0.32 T 0.19
11.01 T 2.81 25.37 T 0.46 j7.34 T 0.71 577.76 T 58.50 11.17 T 1.61 11.97 T 2.44 17.99 T 4.97 17.40 T 4.28 90.66 T 8.34 109.41 T 14.54 106.83 T 14.90 61.62 T 11.82 72.10 T 12.10 1.55 T 0.18 1.83 T 0.37 0.37 T 0.08
0.04* G0.001* G0.001* 0.002* G0.001* 0.07 0.37 0.01* 0.001* 0.10 G0.001* 0.002* 0.46 0.27 G0.001* 0.21
*Statistically significant. Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
1479
TABLE 3.
Results of multivariate mixed-model analysis of the association between ORA measurements (CH, CRF, IOPg, and IOPcc), RNFL thickness, optic disc morphology, AL, and age RNFL thickness, Km Regression coefficient Age, y AL, mm CH, mm Hg CRF, mm Hg IOPg, mm Hg IOPcc, mm Hg CCT, Km
0.30 2.00 6.24 j1.03 j2.84 3.27 0.02
SE 0.43 1.00 2.13 2.80 2.70 2.33 0.03
Disc area, mm2 p
Regression coefficient
0.50 0.02 0.05 0.04 0.004* 0.15 0.70 0.10 0.30 j0.25 0.16 j0.23 0.58 0.001
SE 0.01 0.03 0.07 0.10 0.10 0.08 0.001
Rim area, mm2 p
Regression coefficient
0.15 j0.01 0.20 0.06 0.08 0.10 0.30 0.11 0.008* 0.02 0.005* j0.02 0.21 0.001
SE 0.12 0.03 0.05 0.08 0.08 0.07 0.001
Average C/D ratio p
Regression coefficient
0.44 0.01 0.04* 0.01 0.01* j0.06 0.01* 0.10 0.77 0.13 0.78 0.12 0.12 0.01
SE
p
0.008 0.02 0.20 0.05 0.05 0.04 0.01
0.08 0.98 0.01* 0.05 0.007* 0.004* 0.36
*Statistically significant.
average RNFL thickness and AL was not statistically significant (p = 0.05).
DISCUSSION The important role of corneal morphology in the biomechanical properties of the cornea is well known; therefore, it has been thought that the ORA parameters (CH and CRF) may also provide an assessment of the mechanical characteristics of the whole globe.35 Both the sclera and cornea form the connective tissue coat of the globe and therefore are interrelated. The transition of the cornea into the sclera gradually occurs, with a transition zone (limbus) that is thicker than the cornea and sclera. This connective tissue coat of the ocular globe is an integrated fibrous system, which maintains the oval shape of the globe owing to the circular location of fibers at different angles to each other.36 Therefore, as has been demonstrated, the alteration of the mechanical properties of one structure is in relation with an alteration in the properties of the integrated tissue coat.37Y39 For this reason, CBPs are used to estimate indirectly potential abnormalities of the biomechanical properties of the sclera and ocular globe. However, this relationship is complex and unknown when the ORA system is used for evaluating the biomechanical status of the cornea. More studies focused on the analysis of this relationship are still needed in the future. Our study only reports evidence of the correlation between ORA CBPs and ocular globe changes. The CBPs provided by the ORA and their associations with AL and refractive errors have been described in children,2,4Y6 showing reduced CH and CRF in myopic children2,4,5; nevertheless, Lim et al.6 in a large number of children observed that CBPs were associated with IOP but not with AL. Other studies13,14 have evaluated the relationships among CBPs and optic disc parameters and RNFL thickness in myopic adults13 and children.14 The relationship between RNFL thickness and AL or refractive error in children has also been examined,15Y17 as well as the associations between CH and CRF and glaucoma risk.9,40 Congdon et al.8 stated that a low CH value was a predictor of progressive visual field loss. However, there are only a few reports in the literature referring to the relationship between CBPs and optic disc morphology, especially in children.
In our study with healthy children, we evaluated the influence of the CBPs on RNFL thickness and ONH parameters; we also compared these parameters between myopic and emmetropic children. Our results revealed that lower CH values were significantly associated with a thinner RNFL, smaller rim area, and larger average C/D ratios, and the CRF was significantly positively associated with the rim area in a multiple linear regression analysis. We included IOP in the multivariate analysis and found a strong correlation between CH and RNFL. This seems coherent considering that CH has a moderate correlation with IOP and CCT7 and RNFL also correlates with these two parameters.41 However, we did not find associations between RNFL and IOP (IOPg and IOPcc) in the multivariate analysis. Intraocular pressure (IOPg and IOPcc) correlated negatively with disc area and positively with C/D ratio. We consider that these associations are clinically insignificant because all children included in the study were healthy. Chang and Chang13 assessed the association between the CBPs, optic disc morphology, and pRNFL thickness in 100 eyes from 50 adult patients, aged 33.48 T 8.32 years, reporting that CCT and CH varied with optic disc morphology, but not with pRNFL, and Lim et al.14 evaluated 102 children, aged 12.01 T 0.57 years, finding a significant correlation between CCT and tilted disc. The results of both reports suggested that these types of associations are a risk factor for glaucoma in myopic subjects. We evaluated emmetropic and myopic children from 6 to 17 years and all of them were healthy without tilted optic disc or peripapillary atrophy. We found a significant association between CH and RNFL; therefore, our findings are consistent with the assertions made by Chang and Chang.13 From our point of view, we believe that the assessment of the CBP in myopic children should be considered as a relevant clinical test to understand the development of myopia owing to the changes that occur during a child’s growth. Additionally, knowledge of these parameters (CH and CRF) can provide us with additional indirect information about the resistance of the eyeball to deformation, which may be considered risk factors for the development of visual defects, especially myopia. In a previous study, the CCT seemed to be a significant factor for CH, with thinner corneas showing reduced CH values.42 The relationship between the CCT and ONH measurements has also been reported in both ocular hypertensive and normal patients. Lim et al.14 did not find associations between the CCT and RNFL
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1480 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
thickness and the ONH measurements; however, they found an inverse correlation between the CCT and optic disc area in children with a myopic tilted disc. In regard to these assertions, Pakravan et al.43 found an inverse correlation between the CCT and optic disc area in those patients with primary open-angle glaucoma. They related that thinner corneas might have larger and more deformable optic discs and found that the average optic disc area was smaller in whites than in African Americans or people of other races. The findings of the current study indicate that the CCT did not correlate with RNFL thickness and that only a negative correlation was found between the CCT and the average C/D ratio. These divergent results could be explained by differences in the study protocol and methods used. It should be noted that our subjects were healthy children younger than 18 years, and the age range of our sample was small; therefore, they were not influenced by age-related changes in the ONH parameters and RNFL thickness in the narrow age group of 6 to 17 years. Studies conducted in children44Y46 found that AL45 and refractive error44,45 influence both RNFL thickness and ONH parameters. Salchow et al.,44 in a study of 92 normal children, reported that refraction had an effect on RNFL thickness and Huynh et al.45 described RNFL thinning being associated with increasing AL and less positive refractions in a cohort of 1765 children, whereas Tong et al.46 found that optic nerve parameters and RNFL thickness were affected by optic disc tilt but not refractive errors in 316 Singaporean children. In our study, among the myopic children, average RNFL thickness was positively associated with AL and no correlation between average RNFL thickness and SER was found. The average RNFL thickness and the thickness in the inferior quadrant were thinner in the high myopic subgroup (p = 0.04 and p = 0.03, respectively). These findings may be attributed to a potential redistribution of the RNFL occurring as a consequence of the AL growth in the myopic eyes.12 It should be noted that the quantification of peripapillary atrophy was beyond the scope of this study. Because all the children were healthy (without signs of pathological myopia), and only a small number of high myopes were examined, the prevalence of peripapillary atrophy in our sample was less frequent than in previous studies.15,46 In our study, tilted optic disc was one of the exclusion criteria; thus, peripapillary atrophy is expected to be less frequent. On the other hand, we applied the Littmann formula to correct ALrelated ocular magnification29 so that might explain the discrepancies with other studies in children15,44Y46 and the different races studied. Our findings have shown a significant relationship among the CH and RNFL thickness and the ONH parameters, showing that thinner RNFL thickness, smaller rim area, and larger C/D ratio were associated with lower CH values in white Spanish myopic children. The CH decreased with increasing AL and the level of myopia. It has also been reported that high levels of myopia could be related to glaucomatous changes that could be attributed to the increased stress levels induced across the ONH, regardless of the IOP.47 However, lower CH values may indicate an increased predisposition to myopic growth, suggesting that myopic subjects could have a more vulnerable ocular globe.11 According to these assertions, we think that the corneal biomechanical status may be
related to changes in the posterior segment. This speculation lends support to the hypothesis that a low CH may indicate a reduction in the viscous dampening properties of the cornea as well as increased deformability of the ONH and thinning of the RNFL, as was shown in this study. More studies are needed to confirm our initial observations. It should be noted that the sample size may be a potential limitation for the consistency of the results of the study. Future studies are required to confirm the scientific evidence provided by our study. In any case, it should be considered that the population with high myopia is very reduced, especially in white children and therefore less population is required to have a relevant sample. In conclusion, the corneal biomechanics characterized with the ORA system are related to the optic disc profile and RNFL thickness. Low CH values may indicate a reduction in the viscous dampening properties of both the cornea and the sclera, especially in myopic children. This could help us with our understanding of the optic nerve changes that occur in association with myopia. Received February 19, 2014; accepted June 10, 2014.
REFERENCES 1. Flitcroft DI. The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res 2012;31:622Y60. 2. Song Y, Congdon N, Li L, Zhou Z, Choi K, Lam DS, Pang CP, Xie Z, Liu X, Sharma A, Chen W, Zhang M. Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4. Am J Ophthalmol 2008;145:819Y26. 3. Shen M, Fan F, Xue A, Wang J, Zhou X, Lu F. Biomechanical properties of the cornea in high myopia. Vision Res 2008;48:2167Y71. 4. Bueno-Gimeno I, Espana-Gregori E, Gene-Sampedro A, LanzagortaAresti A, Pinero-Llorens DP. Relationship among corneal biomechanics, refractive error, and axial length. Optom Vis Sci 2014;91: 507Y13. 5. Chang PY, Chang SW, Wang JY. Assessment of corneal biomechanical properties and intraocular pressure with the Ocular Response Analyzer in childhood myopia. Br J Ophthalmol 2010; 94:877Y81. 6. Lim L, Gazzard G, Chan YH, Fong A, Kotecha A, Sim EL, Tan D, Tong L, Saw SM. Cornea biomechanical characteristics and their correlates with refractive error in Singaporean children. Invest Ophthalmol Vis Sci 2008;49:3852Y7. 7. Touboul D, Roberts C, Kerautret J, Garra C, Maurice-Tison S, Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008;34:616Y22. 8. Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006;141: 868Y75. 9. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intraocular pressure measurement in children using the Reichert Ocular Response Analyzer. Am J Ophthalmol 2006;142:990Y2. 10. Kotecha A, Elsheikh A, Roberts CR, Zhu H, Garway-Heath DF. Corneal thickness and age-related biomechanical properties of the cornea measured with the Ocular Response Analyzer. Invest Ophthalmol Vis Sci 2006;47:5337Y47.
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al. 11. Strouthidis NG, Yang H, Reynaud JF, Grimm JL, Gardiner SK, Fortune B, Burgoyne CF. Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy. Invest Ophthalmol Vis Sci 2009;50:4709Y18. 12. Wang G, Qiu KL, Lu XH, Sun LX, Liao XJ, Chen HL, Zhang MZ. The effect of myopia on retinal nerve fibre layer measurement: a comparative study of spectral-domain optical coherence tomography and scanning laser polarimetry. Br J Ophthalmol 2011;95: 255Y60. 13. Chang PY, Chang SW. Corneal biomechanics, optic disc morphology, and macular ganglion cell complex in myopia. J Glaucoma 2013;22:358Y62. 14. Lim L, Gazzard G, Chan YH,Fong A, Kotecha A, Sim EL, Tan D, Tong L, Saw SM. Corneal biomechanics, thickness and optic disc morphology in children with optic disc tilt. Br J Ophthalmol 2008;92:1461Y6. 15. Kim TW, Kim M, Weinreb RN, Woo SJ, Park KH, Hwang JM. Optic disc change with incipient myopia of childhood. Ophthalmology 2012;119:21Y6. 16. Samarawickrama C, Mitchell P, Tong L, Gazzard G, Lim L, Wong TY, Saw SM. Myopia-related optic disc and retinal changes in adolescent children from Singapore. Ophthalmology 2011;118: 2050Y7. 17. Huynh SC, Wang XY, Rochtchina E, Crowston JG, Mitchell P. Distribution of optic disc parameters measured by OCT: findings from a population-based study of 6-year-old Australian children. Invest Ophthalmol Vis Sci 2006;47:3276Y85. 18. Gonza´lez-Me´ijome JM, Queiros A, Jorge J, Diaz-Rey A, Parafita MA. Intraoffice variability of corneal biomechanical parameters and intraocular pressure (IOP). Optom Vis Sci 2008;85:457Y62. 19. Zadnik K, Mutti DO. Incidence and distribution of refractive anomalies. In: Benjamin WJ, ed. Borish’s Clinical Refraction, 2nd ed. Philadelphia, PA: W.B. Saunders Co; 2006:35Y55. 20. Kotecha A. What biomechanical properties of the cornea are relevant for the clinician? Surv Ophthalmol 2007;52:S109Y14. 21. Ortiz D, Pinero D, Shabayek MH, Arnalich-Montiel F, Alio´ JL. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg 2007; 33:1371Y5. 22. Medeiros FA, Weinreb RN. Evaluation of the influence of corneal biomechanical properties on intraocular pressure measurements using the ocular response analyzer. J Glaucoma 2006;15:364Y70. 23. Hon Y, Cheung SW, Cho P, Lam AK. Repeatability of corneal biomechanical measurements in children wearing spectacles and orthokeratology lenses. Ophthalmic Physiol Opt 2012;32:349Y54. 24. Moreno-Montan˜e´s J, Maldonado MJ, Garcı´a N, Mendiluce L, Garcı´a-Go´mez PJ, Seguı´-Go´mez M. Reproducibility and clinical relevance of the Ocular Response Analyzer in nonoperated eyes: corneal biomechanical and tonometric implications. Invest Ophthalmol Vis Sci 2008;49:968Y74. 25. Prata TS, Lima VC, Guedes LM, Biteli LG, Teixeira SH, de Moraes CG, Ritch R, Paranhos A, Jr. Association between corneal biomechanical properties and optic nerve head morphology in newly diagnosed glaucoma patients. Clin Experiment Ophthalmol 2012;40:682Y8. 26. Vizzeri G, Weinreb RN, Gonzalez-Garcia AO, Bowd C, Medeiros FA, Sample PA, Zangwill LM. Agreement between spectral-domain and time-domain OCT for measuring RNFL thickness. Br J Ophthalmol 2009;93:775Y81. 27. Prakalapakorn SG, Freedman SF, Lokhnygina Y, Gandhi NG, Holgado S, Chen BB, El-Dairi MA. Longitudinal reproducibility of
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38. 39. 40.
41.
42.
43.
44.
1481
optical coherence tomography measurements in children. J AAPOS 2012;16:523Y8. Altemir I, Pueyo V, Elia N, Polo V, Larrosa JM, Oros D. Reproducibility of optical coherence tomography measurements in children. Am J Ophthalmol 2013;155:171Y6. Savini G, Barboni P, Parisi V, Carbonelli M. The influence of axial length on retinal nerve fibre layer thickness and optic-disc size measurements by spectral-domain OCT. Br J Ophthalmol 2012; 96:57Y61. Kang SH, Hong SW, Im SK, Lee SH, Ahn MD. Effect of myopia on the thickness of the retinal nerve fiber layer measured by Cirrus HD optical coherence tomography. Invest Ophthalmol Vis Sci 2010; 51:4075Y83. Leung CK, Cheng AC, Chong KK, Leung KS, Mohamed S, Lau CS, Cheung CY, Chu GC, Lai RY, Pang CC, Lam DS. Optic disc measurements in myopia with optical coherence tomography and confocal scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 2007;48:3178Y83. Hwang YH, Kim YY. Correlation between optic nerve head parameters and retinal nerve fiber layer thickness measured by spectral-domain optical coherence tomography in myopic eyes. Clin Experiment Ophthalmol 2012;40:713Y20. Santodomingo-Rubido J, Mallen EA, Gilmartin B, Wolffsohn JS. A new non-contact optical device for ocular biometry. Br J Ophthalmol 2002;86:458Y62. Baikoff G, Lutun E, Ferraz C, Wei J. Static and dynamic analysis of the anterior segment with optical coherence tomography. J Cataract Refract Surg 2004;30:1843Y50. Kucumen RB, Yenerel NM, Gorgun E, Kulacoglu DN, Oncel B, Kohen MC, Alimgil ML. Corneal biomechanical properties and intraocular pressure changes after phacoemulsification and intraocular lens implantation. J Cataract Refract Surg 2008;34: 2096Y8. Omelyanenko N, Slutsky L, Mironov S. Connective Tissue: Histophysiology, Biochemistry, Molecular Biology, Boca Raton, FL: CRC Press; 2014:80Y189. Asejczyk-Widlicka M, uro´ dka W, Schachar RA, Piervcionek BK. Material properties of the cornea and sclera: a modelling approach to test experimental analysis. J Biomech 2011; 44:543Y6. Asejczyk-Widlicka M, Pierscionek BK. The elasticity and rigidity of the outer coats of the eye. Br J Ophthalmol 2008;92:1415Y8. Edmund C. Corneal elasticity and ocular rigidity in normal and keratoconic eyes. Acta Ophthalmol (Copenh) 1988;66:134Y40. Insull E, Nicholas S, Ang GS, Poostchi A, Chan K, Wells A. Optic disc area and correlation with central corneal thickness, corneal hysteresis and ocular pulse amplitude in glaucoma patients and controls. Clin Experiment Ophthalmol 2010;38:839Y44. Chang M, Yoo C, Kim SW, Kim YY. Retinal vessel diameter, retinal nerve fiber layer thickness, and intraocular pressure in Korean patients with normal-tension glaucoma. Am J Ophthalmol 2011;151: 100Y5. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol 2008;246:1491Y4. Pakravan M, Parsa A, Sanagou M, Parsa CF. Central corneal thickness and correlation to optic disc size: a potential link for susceptibility to glaucoma. Br J Ophthalmol 2007;91:26Y8. Salchow DJ, Oleynikov YS, Chiang MF, Kennedy-Salchow SE, Langton K, Tsai JC, Al-Aswad LA. Retinal nerve fiber layer thickness
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1482 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al. in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786Y91. 45. Huynh SC, Wang XY, Rochtchina E, Mitchell P. Peripapillary retinal nerve fiber layer thickness in a population of 6-year-old children: findings by optical coherence tomography. Ophthalmology 2006;113:1583Y92. 46. Tong L, Chan YH, Gazzard G, Loon SC, Fong A, Selvaraj P, Healey PR, Tan D, Wong TY, Saw SM. Heidelberg retinal tomography of optic disc and nerve fiber layer in Singapore children: variations with disc tilt and refractive error. Invest Ophthalmol Vis Sci 2007;48:4939Y44.
47. Kaushik S, Pandav SS, Banger A, Aggarwal K, Gupta A. Relationship between corneal biomechanical properties, central corneal thickness, and intraocular pressure across the spectrum of glaucoma. Am J Ophthalmol 2012;153:840Y9.
Inmaculada Bueno-Gimeno Faculty Physics Department of Optics University of Valencia c/ Dr Moliner 50 46100 Burjassot (Valencia) Spain e-mail: [email protected]
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
ORIGINAL ARTICLE
Corneal Biomechanics, Retinal Nerve Fiber Layer, and Optic Disc in Children Inmaculada Bueno-Gimeno*, Andres Gene-Sampedro†, David P. Pin˜ero-Llorens*, Aitor Lanzagorta-Aresti*, and Enrique Espan˜a-Gregori*
ABSTRACT Purpose. To evaluate the possible associations between corneal biomechanical parameters, optic disc morphology, and retinal nerve fiber layer (RNFL) thickness in healthy white Spanish children. Methods. This cross-sectional study included 100 myopic children and 99 emmetropic children as a control group, ranging in age from 6 to 17 years. The Ocular Response Analyzer was used to measure corneal hysteresis (CH) and corneal resistance factor. The optic disc morphology and RNFL thickness were assessed using posterior segment optical coherence tomography (Cirrus HD-OCT). The axial length was measured using an IOLMaster, whereas the central corneal thickness was measured by anterior segment optical coherence tomography (Visante OCT). Results. The mean (TSD) age and spherical equivalent were 12.11 (T2.76) years and j3.32 (T2.32) diopters for the myopic group and 11.88 (T2.97) years and +0.34 (T0.41) diopters for the emmetropic group. In a multivariable mixed-model analysis in myopic children, the average RNFL thickness and rim area correlated positively with CH (p = 0.007 and p = 0.001, respectively), whereas the average cup-to-disc area ratio correlated negatively with CH (p = 0.01). We did not observe correlation between RNFL thickness and axial length (p = 0.05). Corneal resistance factor was only positively correlated with the rim area (p = 0.001). The central corneal thickness did not correlate with the optic nerve parameters or with RNFL thickness. These associations were not found in the emmetropic group (p 9 0.05 for all). Conclusions. The corneal biomechanics characterized with the Ocular Response Analyzer system are correlated with the optic disc profile and RNFL thickness in myopic children. Low CH values may indicate a reduction in the viscous dampening properties of the cornea and the sclera, especially in myopic children. (Optom Vis Sci 2014;91:1474Y1482) Key Words: corneal biomechanics, myopia, optic disc parameters
M
yopia is among the most common refractive errors and is associated with a greater risk of certain pathological consequences. Higher levels of myopia are closely associated with ocular pathologies such as retinal detachment and chorioretinal degeneration and could increase the risk of developing glaucoma.1 Several studies have investigated the relationship between corneal biomechanical properties (CBPs) and refractive error, reporting a reduced corneal hysteresis (CH) and corneal resistance *PhD † MSc Department of Optics (IB-G, AG-S) and Department of Surgery (EE-G), University of Valencia, Valencia, Spain; Foundation for the Visual Quality (Fundacio´n para la Calidad Visual, FUNCAVIS), Alicante, Spain (DPP-L); Department of Optics, Pharmacology, and Anatomy, University of Alicante, Alicante, Spain (DPP-L); Fisabio Oftalmologı´a Me´dica (FOM), Valencia, Spain (AL-A); and University Hospital La Fe, Valencia, Spain (EE-G).
factor (CRF) in myopic eyes.2,3 These measurements are thought to be related to the viscoelastic properties of the cornea. In a previous study,4 we examined 293 eyes from 293 children with a mean (TSD) age of 10.8 (T3.1) years and a mean (TSD) spherical equivalent (SE) of +0.14 (T3.41) diopters (D) (range, j8.75 to + 8.25 D) and found that CH was associated with axial length (AL) in the high myopia group (SE greater than j6.00 D) and reported that the Ocular Response Analyzer (ORA) CBPs are compromised in myopia from an early age, especially in high myopia. Chang et al.5 reported that lower CH and CRF were associated with longer AL, suggesting an association between CBPs and whole eye biometry in myopic children, aged 12.02 T 3.19 years, and demonstrated the importance of CH as a determinant of ocular biometry in both the anterior and posterior segments. However, Lim et al.6 showed no correlation between CH and AL in 271 right eyes from 271 Singaporean children with a mean (TSD) age of 13.97 (T0.89) years and a mean (TSD) SE of j2.35 (T2.49) D.
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
These divergent results may be attributable to factors such as mixed ethnicity in the populations analyzed, differences in study methodologies, levels of refractive errors, or other unknown factors.4 The relationship between anterior and posterior ocular biomechanical properties has also been studied, reporting a reduced CH in eyes with primary open-angle, normal tension, and congenital glaucoma.7Y9 These associations suggest that a more deformable cornea might be linked to a greater susceptibility of the lamina cribrosa and might help explain why some subjects are more predisposed to optic nerve damage than others.10 Kotecha et al.10 suggested that measurements of corneal biomechanics such as the CH could give an idea of the structural integrity of the optic nerve head (ONH). Information on the changes occurring at the ONH and in the thickness of the retinal nerve fiber layer (RNFL) is essential for the assessment of patients with, or at risk of, optic neuropathy, because RNFL thinning could be an early sign of glaucomatous damage.11,12 Chang and Chang13 evaluated the association between CBPs and optic disc morphology (disc area, rim area, cup area, cup-to-disc [C/D] ratio, and cup volume) and peripapillary retinal nerve fiber layer (pRNFL) thickness in myopic adults, and found a negative relationship between central corneal thickness (CCT) and disc area, rim area, cup area, C/D ratio, and cup volume. Corneal hysteresis correlated negatively with disc area and cup area. Lim et al.,14 in a study with Singaporean schoolchildren, showed negative correlations between CCT and disc area. Both studies13,14 reported that these relationships might be linked to increased glaucoma risk in myopic subjects. The ONH changes that occur in association with myopia in childhood have been analyzed in several studies.15,16 Kim et al.15 suggested that tilted disc, as well as peripapillary atrophy, may be an acquired feature in myopic eyes, arising from scleral stretching in children from 1 to 17 years with a mean (TSD) refractive error of j0.9 (T1.9) D (range, j5.9 to +3.0 D), and Samarawickrama et al.16 found a high prevalence of optic disc tilting and other very early retinal and disc changes including peripapillary atrophy associated with myopia in Singapore Chinese adolescent children, aged 12 to 16 years. Eyes with tilted optic discs were more myopic and astigmatic, had longer ALs, and had smaller optic discs, cups, and C/D ratios than eyes without tilted optic discs. Whereas the distribution of optic disc parameters and RNFL thickness has been measured in children,17 their relationship with CBPs has not been sufficiently investigated. The knowledge of the normal structure of optic disc parameters and their possible associations with corneal biomechanics in children would provide important information about possible changes during the child’s growth and contribute to our understanding of the ONH changes that occur in association with myopia in childhood (and the potential underlying causes of them). Although it is relatively rare to develop glaucoma in children, the data of normal conditions in this population could help us to understand changes in pathological conditions such us glaucoma. To date, there are only a small number of studies that have analyzed the association between CBPs and RNFL in children. Therefore, this study aimed to assess whether corneal biomechanical parameters were related to optic disc morphology and RNFL thickness in healthy white Spanish children. The study also evaluated the association between the AL and RNFL thickness in myopia.
1475
METHODS This cross-sectional study included 199 eyes from 199 children. The samples were selected according to cycloplegic SE refraction, and the subjects were divided into two groups: 99 eyes of 99 emmetropic children (45 boys and 54 girls) were used as a control group, and 100 of 100 myopic children (46 boys and 54 girls), ranging in age from 6 to 17 years, were included as the test group. All children were recruited from the Fisabio Oftalmologı´a Me´dica (FOM) hospital. The exclusion criteria were a corrected distance visual acuity of worse than 20/25 in either eye, a refractive cylinder of more than 2.00 D, and being older than 18 years. Subjects with a previous history of ocular surgery, trauma, pathology, or ocular medication were also excluded from the study. Children with a tilted optic disc, spherical equivalent refraction (SER) anisometropia more than 1.00 D, or strabismus were also excluded from the study. A complete ocular examination was performed in all eyes including a visual acuity measurement, stereopsis assessment, motility examination, cycloplegic refraction, and anterior segment and dilated fundus examination. Cycloplegia was induced with three drops of cyclopentolate 1% separated by 5 minutes, to achieve adequate mydriasis (Q6 mm).17 At least 30 minutes after the last drop, autorefraction was measured with an autorefractometer (Topcon KR-8100P), followed by a subjective refinement. Fifteen days after the ocular examination, to avoid any effect induced by cycloplegia and according to clinical procedures of the institution (FOM), the same experienced examiner (IBG) performed all the measurements in both eyes in a random order; however, only the data from one randomly selected eye were included in the study. These measurements were AL, using optical biometry (IOLMaster; Carl Zeiss Meditec Inc, Dublin, CA), the CBPs (Ocular Response Analyzer, ORA, Reichert), CCT (Visante OCT, Carl Zeiss Meditec), RNFL, and ONH parameters (Cirrus HD-OCT, Carl Zeiss Meditec). All measurements were taken without pupillary dilation. To reduce the effects of diurnal corneal variation, all examinations were performed between 3:00 PM and 6:00 PM.18 Participants were classified according to the cycloplegic SE refraction of both eyes (SER, sphere plus half the negative cylinder) as either emmetropia SER between +0.75 and j0.25 D, low myopia SER between j0.50 and j3.00 D, moderate myopia SER between j3.25 and j6.00 D, or high myopia SER greater than j6.00 D.19 Only one randomly chosen eye was included for analysis and the classification was based on the eye selected. The study adhered to the tenets of the Declaration of Helsinki. Informed written consent was obtained from the parents of the subjects, and assent was given by the children. The study was approved by the FOM Ethics Committee.
ORA Measurements The ORA (Reichert Ophthalmic Instruments, Depew, NY) device attempts to characterize the viscoelastic properties of the cornea by means of two principal parameters: the CH, which is defined as the difference between the two pressures (P1 and P2) recorded during the described measurement process, and the CRF, which is calculated using a proprietary algorithm (P1 j kP2) and is predominantly related to the elastic properties of the cornea.20,21
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1476 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
The ORA also provides two measures of the intraocular pressure (IOP) (IOPg and IOPcc). The IOPg provides a Goldmanncorrelated IOP, which is a mean of the two IOP applanation pressures P1 and P2.21 The IOPcc is known as the corneal compensated IOP, which is less affected by corneal properties than other methods of tonometry.22 The ORA measurement technique has already been described,15,16 including its high repeatability in both children23 and adults.24 The ORA (Software Version 1.10) was used to obtain four consecutive measurements in each eye from every patient, and the mean of these readings was used in the analysis according to the manufacturer’s instructions. The manufacturer recommends that the quality of the waveform should be assessed by identifying two well-defined peaks that are reasonably symmetrical and higher than the superimposed pressure curve. If the measurements differed by more than 2 mm Hg, an additional measurement was taken, and the two extreme values were excluded from the analysis.25
Optical Coherence Tomography (Cirrus HD-OCT) Measurements Measurements of the RNFL and ONH parameters were obtained using the Cirrus HD-OCT system (Software Version 5.0.0.326) with a scan speed of 27,000 A-scans per second and an axial resolution of 5 Km. An optic disc cube 200 200 protocol was used to obtain the RNFL thickness and ONH measurements. The OCT technique12,17,26 and its reproducibility in children27,28 have already been described in several reports. Cirrus HD-OCT software algorithm automatically detects the center of the optic disc and positions a calculation circle of 3.46 mm diameter evenly around it.27,29 From the 256 A-scans along the circle, the anterior and posterior boundaries of RNFL are delimited and thickness is calculated at each point along this circle. In each series of scans, average RNFL thickness and RNFL thickness in each quadrant (superior, inferior, temporal, and nasal) were analyzed.28,29 For image acquisition, an internal fixation target was used, and the alignment was properly positioned to the ONH in the center of the scan. Average measurements of three sequential circular scans of diameter 3.4 mm on the optic disc were recorded. Scan quality was checked for every OCT image and manual correction of the boundary detection was enabled if segmentation errors are present. If an involuntary saccadic eye movement was detected during the scan, it was discarded and repeated.26Y28 Only the images of satisfactory quality, defined as images properly centered on the optic disc with a signal strength of greater than or equal to 7, were included in the analysis. For calculating the corrected AL-related ocular magnification, we used the Littmann formula (t = pIq Is)29 according to other authors’ suggestion,29Y32 where t is the actual fundus dimension, s is the measurement obtained using the OCT, p is the magnification factor of the imaging system camera, and q is the magnification factor related to the eye.30,31 The ocular magnification factor q of the eye can be determined using the formula q = 0.01306 I(AL j 1.82).30 Factor p is a constant, is instrument dependent, and remains a constant in a telecentric imaging system in both the Stratus OCT and Cirrus HD-OCT. The p of the latter system is known to be 3.382.31,32 Because t = p Iq Is refers to linear
magnification, the equation should be modified to t 2 = p2 Iq 2 Is 2 for the area magnification.
Other Examinations The AL was measured with a noncontact partial coherence interferometer (IOLMaster; Carl Zeiss Meditec Inc, Software Version 5.2.1). Three consecutive AL and corneal curvature readings were taken and averaged. Only the AL measurements with a signal-to-noise ratio greater than 2 were included in the database.33 The CCT was measured by anterior segment optical coherence tomography (Visante OCT; Carl Zeiss Meditec Inc, Software Version 3.0.1.8), which is a noncontact device that provides crosssectional images of the anterior segment of the eye. The scans were centered on the pupil and taken along the horizontal meridian. The scan was optimally aligned when the optically produced corneal reflex was visible as a vertical white line along the center of the cornea.34
Statistical Analysis Statistical analysis was performed with the commercially available statistical package SPSS version 19.0 (SPSS, Chicago, IL). Kolmogorov-Smirnov tests were used to analyze the data for normality and were normally distributed. The Pearson correlation coefficient was used to test for correlations between the variables. A Student t test for unpaired data (two samples) or a one-way analysis of variance (ANOVA) with a Scheffe´ post hoc analysis (more than two samples) was used to compare the parameters among the groups classified by SER. A multiple linear regression model was constructed with RNFL thickness, rim area, disc area, and average C/D ratio as dependent variables to assess their relationship with the ORA measurements (CH, CRF, IOPg, and IOPcc), CCT, age, and AL covariates. To diminish the colinearity problem, the SER was not included in the multivariate model because of its high correlation with AL. A value of p G 0.05 was considered statistically significant.
RESULTS The mean (TSD) age was 12.11 (T2.76) years and 11.88 (T2.97) years for the myopic and emmetropic groups, respectively. There were no statistically significant differences between right and left eyes or between sexes for any of the parameters assessed (p Q 0.05, Student t test). The mean (TSD) values of the AL, age, CH, CRF, CCT, RNFL thickness measurements, and optic disc parameters for the myopic and emmetropic groups and the comparisons among these parameters are summarized in Table 1. Significant differences were found between the myopic and emmetropic groups in CH, CRF, and average RNFL thickness (Student t test, p G 0.001, p = 0.009, and p = 0.001, respectively). In the myopic group, there was a significant positive correlation between the CH and the average RNFL thickness (r = 0.22, p = 0.03) (Fig. 1) and between the CH and the nasal and temporal RNFL thickness (r = 0.22, p = 0.02 and r = 0.23, p = 0.02, respectively); however, we found a negative correlation between the CH and the average C/D ratio (r = j0.35,
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al. TABLE 1.
Values of age, AL, SE, corneal biomechanical parameters, RNFL thickness, and optic disc morphology measurements for myopic and emmetropic groups (mean T SD) Emmetropic group (n = 99) Age, y AL, mm SE, D CCT, Km CH, mm Hg CRF, mm Hg Average RNFL thickness, Km Superior RNFL thickness, Km Inferior RNFL thickness, Km Nasal RNFL thickness, Km Temporal RNFL thickness, Km Rim area, mm2 Disc area, mm2 Average C/D ratio
Myopic group (n = 100)
p (by t test)
11.88 T 2.97 12.11 T 2.76 23.12 T 0.79 24.51 T 1.11 +0.34 T 0.41 j3.32 T 2.32 543.85 T 35.65 543.02 T 45.38 12.56 T 1.68 11.55 T 1.45 12.63 T 1.91 11.93 T 1.85 100.39 T 11.31 95.30 T 9.97
0.34 G0.001* G0.001* 0.88 G0.001* 0.009* 0.001*
123.53 T 23.81 121.85 T 24.03
0.62
130.11 T 21.33 116.81 T 17.81
G0.001*
72.12 T 16.76
65.25 T 12.61
0.001*
74.51 T 17.78
72.64 T 16.47
0.44
1.67 T 0.34 2.09 T 0.44 0.36 T 0.17
1.58 T 0.28 1.85 T 0.34 0.32 T 0.19
0.06 G0.001* 0.08
*Statistically significant.
p G 0.001). The CRF negatively correlated with the average C/D ratio (r = j0.28, p = 0.005) and positively correlated with the RNFL thickness in the temporal quadrant (r = 0.28, p = 0.006),
1477
whereas the CCT only negatively correlated with the average C/D ratio (r = j0.22, p = 0.03). We found a positive correlation between RNFL and AL (r = 0.22, p = 0.03) (Fig. 2); however, no correlation was observed between RNFL and SER in the myopic children (r = 0.06, p = 0.56). Regarding the superior and inferior quadrants, these relationships were not statistically significant. Among the emmetropic group, no significant correlations between the CBPs and optic disc parameters or RNFL thickness were found (p 9 0.05 for all parameters). Table 2 shows the differences in all the measured parameters for the three myopic subgroups and the control group including the comparisons among them using one-way ANOVA. Significant differences in the average RNFL thickness were found between the emmetropic and high myopic groups (Scheffe´ test, p = 0.008) and between the emmetropic and moderate myopic subgroups (p = 0.04). No significant differences were found between the emmetropic and low myopic subgroups (p = 0.88). We also compared the three myopic subgroups, and a significant difference in the average RNFL thickness and the thickness in the inferior quadrant was found between the high and low myopic groups (p = 0.04 and p = 0.03, respectively). Moreover, significantly higher CH values were obtained in the emmetropic group in comparison with the values in the myopic subgroups (p = 0.01, p = 0.03, and p = 0.01 for the high, moderate, and low myopic subgroups, respectively). There were no significant differences in the CH among the three myopic subgroups (p 9 0.70). No significant differences in the CRF were found among the emmetropic and myopic subgroups (p = 0.62, p = 0.46, and p = 0.15 for the high, moderate, and low myopic subgroups, respectively). Although a trend toward a reduction in the CRF with increasing
FIGURE 1. Correlations between CH and average RNFL thickness in myopic children. Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1478 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
FIGURE 2. Correlations between AL and average RNFL thickness in myopic children.
myopia was found, it was not statistically significant (one-way ANOVA test, p = 0.07). In the multivariate mixed-model analysis, for the myopic group (Table 3), the average RNFL thickness and rim area decreased with lower CH (p = 0.004 and p = 0.01, respectively), whereas the average C/D area ratio increased as the CH decreased (p = 0.01). Therefore, with a decrease of 1 mm Hg in the CH, the average RNFL thickness decreased by 6.24 Km; for every 1 mm Hg
decrease in the CH, there was a decrease of 0.1 mm2 in the rim area; and for every 1 mm Hg decrease in the CH, the average C/D ratio increased by 0.06. The CRF only positively correlated with the rim area (p = 0.01); hence, for every 1 mm Hg decrease in the CRF, the rim area decreased by 0.1 mm2. IOPg and IOPcc correlated negatively with disc area (p = 0.008 and p = 0.005, respectively) and positively with C/D ratio (p = 0.007 and p = 0.004, respectively). The relationship between
TABLE 2.
Values of age, AL, SE, corneal biomechanical parameters, RNFL thickness, and optic disc morphology measured for the three myopic groups and the control group (mean T SD)
Age, y AL, mm SE, D CCT, Km CH, mm Hg CRF, mm Hg IOPg, mm Hg IOPcc, mm Hg Average RNFL thickness, Km Superior RNFL thickness, Km Inferior RNFL thickness, Km Nasal RNFL thickness, Km Temporal RNFL thickness, Km Rim area, mm2 Disc area, mm2 Average C/D ratio
Emmetropic (n = 99)
Low myopia (n = 59)
Moderate myopia (n = 24)
High myopia (n = 17)
p (by one-way ANOVA)
11.88 T 2.97 23.12 T 0.79 +0.34 T 0.41 543.85 T 35.65 12.56 T 1.68 12.63 T 1.91 16.74 T 3.40 14.71 T 3.22 100.39 T 11.31 123.53 T 23.81 130.11 T 21.33 72.12 T 16.76 74.51 T 17.78 1.67 T 0.34 2.09 T 0.44 0.36 T 0.17
11.76 T 2.57 23.91 T 0.84 j1.67 T 0.77 535.76 T 40.48 11.68 T 1.45 11.91 T 1.76 16.33 T 3.04 15.18 T 2.95 98.44 T 9.89 121.93 T 23.53 120.79 T 21.15 70.47 T 16.94 76.89 T 22.94 1.57 T 0.26 1.86 T 0.34 0.31 T 0.20
13.74 T 2.60 25.38 T 1.04 j4.56 T 0.78 536.25 T 35.70 11.51 T 1.34 11.94 T 1.64 17.05 T 3.96 15.95 T 3.95 95.32 T 10.05 125.40 T 25.48 118.06 T 16.62 64.17 T 10.14 71.06 T 14.27 1.59 T 0.32 1.85 T 0.34 0.32 T 0.19
11.01 T 2.81 25.37 T 0.46 j7.34 T 0.71 577.76 T 58.50 11.17 T 1.61 11.97 T 2.44 17.99 T 4.97 17.40 T 4.28 90.66 T 8.34 109.41 T 14.54 106.83 T 14.90 61.62 T 11.82 72.10 T 12.10 1.55 T 0.18 1.83 T 0.37 0.37 T 0.08
0.04* G0.001* G0.001* 0.002* G0.001* 0.07 0.37 0.01* 0.001* 0.10 G0.001* 0.002* 0.46 0.27 G0.001* 0.21
*Statistically significant. Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
1479
TABLE 3.
Results of multivariate mixed-model analysis of the association between ORA measurements (CH, CRF, IOPg, and IOPcc), RNFL thickness, optic disc morphology, AL, and age RNFL thickness, Km Regression coefficient Age, y AL, mm CH, mm Hg CRF, mm Hg IOPg, mm Hg IOPcc, mm Hg CCT, Km
0.30 2.00 6.24 j1.03 j2.84 3.27 0.02
SE 0.43 1.00 2.13 2.80 2.70 2.33 0.03
Disc area, mm2 p
Regression coefficient
0.50 0.02 0.05 0.04 0.004* 0.15 0.70 0.10 0.30 j0.25 0.16 j0.23 0.58 0.001
SE 0.01 0.03 0.07 0.10 0.10 0.08 0.001
Rim area, mm2 p
Regression coefficient
0.15 j0.01 0.20 0.06 0.08 0.10 0.30 0.11 0.008* 0.02 0.005* j0.02 0.21 0.001
SE 0.12 0.03 0.05 0.08 0.08 0.07 0.001
Average C/D ratio p
Regression coefficient
0.44 0.01 0.04* 0.01 0.01* j0.06 0.01* 0.10 0.77 0.13 0.78 0.12 0.12 0.01
SE
p
0.008 0.02 0.20 0.05 0.05 0.04 0.01
0.08 0.98 0.01* 0.05 0.007* 0.004* 0.36
*Statistically significant.
average RNFL thickness and AL was not statistically significant (p = 0.05).
DISCUSSION The important role of corneal morphology in the biomechanical properties of the cornea is well known; therefore, it has been thought that the ORA parameters (CH and CRF) may also provide an assessment of the mechanical characteristics of the whole globe.35 Both the sclera and cornea form the connective tissue coat of the globe and therefore are interrelated. The transition of the cornea into the sclera gradually occurs, with a transition zone (limbus) that is thicker than the cornea and sclera. This connective tissue coat of the ocular globe is an integrated fibrous system, which maintains the oval shape of the globe owing to the circular location of fibers at different angles to each other.36 Therefore, as has been demonstrated, the alteration of the mechanical properties of one structure is in relation with an alteration in the properties of the integrated tissue coat.37Y39 For this reason, CBPs are used to estimate indirectly potential abnormalities of the biomechanical properties of the sclera and ocular globe. However, this relationship is complex and unknown when the ORA system is used for evaluating the biomechanical status of the cornea. More studies focused on the analysis of this relationship are still needed in the future. Our study only reports evidence of the correlation between ORA CBPs and ocular globe changes. The CBPs provided by the ORA and their associations with AL and refractive errors have been described in children,2,4Y6 showing reduced CH and CRF in myopic children2,4,5; nevertheless, Lim et al.6 in a large number of children observed that CBPs were associated with IOP but not with AL. Other studies13,14 have evaluated the relationships among CBPs and optic disc parameters and RNFL thickness in myopic adults13 and children.14 The relationship between RNFL thickness and AL or refractive error in children has also been examined,15Y17 as well as the associations between CH and CRF and glaucoma risk.9,40 Congdon et al.8 stated that a low CH value was a predictor of progressive visual field loss. However, there are only a few reports in the literature referring to the relationship between CBPs and optic disc morphology, especially in children.
In our study with healthy children, we evaluated the influence of the CBPs on RNFL thickness and ONH parameters; we also compared these parameters between myopic and emmetropic children. Our results revealed that lower CH values were significantly associated with a thinner RNFL, smaller rim area, and larger average C/D ratios, and the CRF was significantly positively associated with the rim area in a multiple linear regression analysis. We included IOP in the multivariate analysis and found a strong correlation between CH and RNFL. This seems coherent considering that CH has a moderate correlation with IOP and CCT7 and RNFL also correlates with these two parameters.41 However, we did not find associations between RNFL and IOP (IOPg and IOPcc) in the multivariate analysis. Intraocular pressure (IOPg and IOPcc) correlated negatively with disc area and positively with C/D ratio. We consider that these associations are clinically insignificant because all children included in the study were healthy. Chang and Chang13 assessed the association between the CBPs, optic disc morphology, and pRNFL thickness in 100 eyes from 50 adult patients, aged 33.48 T 8.32 years, reporting that CCT and CH varied with optic disc morphology, but not with pRNFL, and Lim et al.14 evaluated 102 children, aged 12.01 T 0.57 years, finding a significant correlation between CCT and tilted disc. The results of both reports suggested that these types of associations are a risk factor for glaucoma in myopic subjects. We evaluated emmetropic and myopic children from 6 to 17 years and all of them were healthy without tilted optic disc or peripapillary atrophy. We found a significant association between CH and RNFL; therefore, our findings are consistent with the assertions made by Chang and Chang.13 From our point of view, we believe that the assessment of the CBP in myopic children should be considered as a relevant clinical test to understand the development of myopia owing to the changes that occur during a child’s growth. Additionally, knowledge of these parameters (CH and CRF) can provide us with additional indirect information about the resistance of the eyeball to deformation, which may be considered risk factors for the development of visual defects, especially myopia. In a previous study, the CCT seemed to be a significant factor for CH, with thinner corneas showing reduced CH values.42 The relationship between the CCT and ONH measurements has also been reported in both ocular hypertensive and normal patients. Lim et al.14 did not find associations between the CCT and RNFL
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1480 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al.
thickness and the ONH measurements; however, they found an inverse correlation between the CCT and optic disc area in children with a myopic tilted disc. In regard to these assertions, Pakravan et al.43 found an inverse correlation between the CCT and optic disc area in those patients with primary open-angle glaucoma. They related that thinner corneas might have larger and more deformable optic discs and found that the average optic disc area was smaller in whites than in African Americans or people of other races. The findings of the current study indicate that the CCT did not correlate with RNFL thickness and that only a negative correlation was found between the CCT and the average C/D ratio. These divergent results could be explained by differences in the study protocol and methods used. It should be noted that our subjects were healthy children younger than 18 years, and the age range of our sample was small; therefore, they were not influenced by age-related changes in the ONH parameters and RNFL thickness in the narrow age group of 6 to 17 years. Studies conducted in children44Y46 found that AL45 and refractive error44,45 influence both RNFL thickness and ONH parameters. Salchow et al.,44 in a study of 92 normal children, reported that refraction had an effect on RNFL thickness and Huynh et al.45 described RNFL thinning being associated with increasing AL and less positive refractions in a cohort of 1765 children, whereas Tong et al.46 found that optic nerve parameters and RNFL thickness were affected by optic disc tilt but not refractive errors in 316 Singaporean children. In our study, among the myopic children, average RNFL thickness was positively associated with AL and no correlation between average RNFL thickness and SER was found. The average RNFL thickness and the thickness in the inferior quadrant were thinner in the high myopic subgroup (p = 0.04 and p = 0.03, respectively). These findings may be attributed to a potential redistribution of the RNFL occurring as a consequence of the AL growth in the myopic eyes.12 It should be noted that the quantification of peripapillary atrophy was beyond the scope of this study. Because all the children were healthy (without signs of pathological myopia), and only a small number of high myopes were examined, the prevalence of peripapillary atrophy in our sample was less frequent than in previous studies.15,46 In our study, tilted optic disc was one of the exclusion criteria; thus, peripapillary atrophy is expected to be less frequent. On the other hand, we applied the Littmann formula to correct ALrelated ocular magnification29 so that might explain the discrepancies with other studies in children15,44Y46 and the different races studied. Our findings have shown a significant relationship among the CH and RNFL thickness and the ONH parameters, showing that thinner RNFL thickness, smaller rim area, and larger C/D ratio were associated with lower CH values in white Spanish myopic children. The CH decreased with increasing AL and the level of myopia. It has also been reported that high levels of myopia could be related to glaucomatous changes that could be attributed to the increased stress levels induced across the ONH, regardless of the IOP.47 However, lower CH values may indicate an increased predisposition to myopic growth, suggesting that myopic subjects could have a more vulnerable ocular globe.11 According to these assertions, we think that the corneal biomechanical status may be
related to changes in the posterior segment. This speculation lends support to the hypothesis that a low CH may indicate a reduction in the viscous dampening properties of the cornea as well as increased deformability of the ONH and thinning of the RNFL, as was shown in this study. More studies are needed to confirm our initial observations. It should be noted that the sample size may be a potential limitation for the consistency of the results of the study. Future studies are required to confirm the scientific evidence provided by our study. In any case, it should be considered that the population with high myopia is very reduced, especially in white children and therefore less population is required to have a relevant sample. In conclusion, the corneal biomechanics characterized with the ORA system are related to the optic disc profile and RNFL thickness. Low CH values may indicate a reduction in the viscous dampening properties of both the cornea and the sclera, especially in myopic children. This could help us with our understanding of the optic nerve changes that occur in association with myopia. Received February 19, 2014; accepted June 10, 2014.
REFERENCES 1. Flitcroft DI. The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res 2012;31:622Y60. 2. Song Y, Congdon N, Li L, Zhou Z, Choi K, Lam DS, Pang CP, Xie Z, Liu X, Sharma A, Chen W, Zhang M. Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4. Am J Ophthalmol 2008;145:819Y26. 3. Shen M, Fan F, Xue A, Wang J, Zhou X, Lu F. Biomechanical properties of the cornea in high myopia. Vision Res 2008;48:2167Y71. 4. Bueno-Gimeno I, Espana-Gregori E, Gene-Sampedro A, LanzagortaAresti A, Pinero-Llorens DP. Relationship among corneal biomechanics, refractive error, and axial length. Optom Vis Sci 2014;91: 507Y13. 5. Chang PY, Chang SW, Wang JY. Assessment of corneal biomechanical properties and intraocular pressure with the Ocular Response Analyzer in childhood myopia. Br J Ophthalmol 2010; 94:877Y81. 6. Lim L, Gazzard G, Chan YH, Fong A, Kotecha A, Sim EL, Tan D, Tong L, Saw SM. Cornea biomechanical characteristics and their correlates with refractive error in Singaporean children. Invest Ophthalmol Vis Sci 2008;49:3852Y7. 7. Touboul D, Roberts C, Kerautret J, Garra C, Maurice-Tison S, Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008;34:616Y22. 8. Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006;141: 868Y75. 9. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intraocular pressure measurement in children using the Reichert Ocular Response Analyzer. Am J Ophthalmol 2006;142:990Y2. 10. Kotecha A, Elsheikh A, Roberts CR, Zhu H, Garway-Heath DF. Corneal thickness and age-related biomechanical properties of the cornea measured with the Ocular Response Analyzer. Invest Ophthalmol Vis Sci 2006;47:5337Y47.
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al. 11. Strouthidis NG, Yang H, Reynaud JF, Grimm JL, Gardiner SK, Fortune B, Burgoyne CF. Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy. Invest Ophthalmol Vis Sci 2009;50:4709Y18. 12. Wang G, Qiu KL, Lu XH, Sun LX, Liao XJ, Chen HL, Zhang MZ. The effect of myopia on retinal nerve fibre layer measurement: a comparative study of spectral-domain optical coherence tomography and scanning laser polarimetry. Br J Ophthalmol 2011;95: 255Y60. 13. Chang PY, Chang SW. Corneal biomechanics, optic disc morphology, and macular ganglion cell complex in myopia. J Glaucoma 2013;22:358Y62. 14. Lim L, Gazzard G, Chan YH,Fong A, Kotecha A, Sim EL, Tan D, Tong L, Saw SM. Corneal biomechanics, thickness and optic disc morphology in children with optic disc tilt. Br J Ophthalmol 2008;92:1461Y6. 15. Kim TW, Kim M, Weinreb RN, Woo SJ, Park KH, Hwang JM. Optic disc change with incipient myopia of childhood. Ophthalmology 2012;119:21Y6. 16. Samarawickrama C, Mitchell P, Tong L, Gazzard G, Lim L, Wong TY, Saw SM. Myopia-related optic disc and retinal changes in adolescent children from Singapore. Ophthalmology 2011;118: 2050Y7. 17. Huynh SC, Wang XY, Rochtchina E, Crowston JG, Mitchell P. Distribution of optic disc parameters measured by OCT: findings from a population-based study of 6-year-old Australian children. Invest Ophthalmol Vis Sci 2006;47:3276Y85. 18. Gonza´lez-Me´ijome JM, Queiros A, Jorge J, Diaz-Rey A, Parafita MA. Intraoffice variability of corneal biomechanical parameters and intraocular pressure (IOP). Optom Vis Sci 2008;85:457Y62. 19. Zadnik K, Mutti DO. Incidence and distribution of refractive anomalies. In: Benjamin WJ, ed. Borish’s Clinical Refraction, 2nd ed. Philadelphia, PA: W.B. Saunders Co; 2006:35Y55. 20. Kotecha A. What biomechanical properties of the cornea are relevant for the clinician? Surv Ophthalmol 2007;52:S109Y14. 21. Ortiz D, Pinero D, Shabayek MH, Arnalich-Montiel F, Alio´ JL. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg 2007; 33:1371Y5. 22. Medeiros FA, Weinreb RN. Evaluation of the influence of corneal biomechanical properties on intraocular pressure measurements using the ocular response analyzer. J Glaucoma 2006;15:364Y70. 23. Hon Y, Cheung SW, Cho P, Lam AK. Repeatability of corneal biomechanical measurements in children wearing spectacles and orthokeratology lenses. Ophthalmic Physiol Opt 2012;32:349Y54. 24. Moreno-Montan˜e´s J, Maldonado MJ, Garcı´a N, Mendiluce L, Garcı´a-Go´mez PJ, Seguı´-Go´mez M. Reproducibility and clinical relevance of the Ocular Response Analyzer in nonoperated eyes: corneal biomechanical and tonometric implications. Invest Ophthalmol Vis Sci 2008;49:968Y74. 25. Prata TS, Lima VC, Guedes LM, Biteli LG, Teixeira SH, de Moraes CG, Ritch R, Paranhos A, Jr. Association between corneal biomechanical properties and optic nerve head morphology in newly diagnosed glaucoma patients. Clin Experiment Ophthalmol 2012;40:682Y8. 26. Vizzeri G, Weinreb RN, Gonzalez-Garcia AO, Bowd C, Medeiros FA, Sample PA, Zangwill LM. Agreement between spectral-domain and time-domain OCT for measuring RNFL thickness. Br J Ophthalmol 2009;93:775Y81. 27. Prakalapakorn SG, Freedman SF, Lokhnygina Y, Gandhi NG, Holgado S, Chen BB, El-Dairi MA. Longitudinal reproducibility of
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38. 39. 40.
41.
42.
43.
44.
1481
optical coherence tomography measurements in children. J AAPOS 2012;16:523Y8. Altemir I, Pueyo V, Elia N, Polo V, Larrosa JM, Oros D. Reproducibility of optical coherence tomography measurements in children. Am J Ophthalmol 2013;155:171Y6. Savini G, Barboni P, Parisi V, Carbonelli M. The influence of axial length on retinal nerve fibre layer thickness and optic-disc size measurements by spectral-domain OCT. Br J Ophthalmol 2012; 96:57Y61. Kang SH, Hong SW, Im SK, Lee SH, Ahn MD. Effect of myopia on the thickness of the retinal nerve fiber layer measured by Cirrus HD optical coherence tomography. Invest Ophthalmol Vis Sci 2010; 51:4075Y83. Leung CK, Cheng AC, Chong KK, Leung KS, Mohamed S, Lau CS, Cheung CY, Chu GC, Lai RY, Pang CC, Lam DS. Optic disc measurements in myopia with optical coherence tomography and confocal scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 2007;48:3178Y83. Hwang YH, Kim YY. Correlation between optic nerve head parameters and retinal nerve fiber layer thickness measured by spectral-domain optical coherence tomography in myopic eyes. Clin Experiment Ophthalmol 2012;40:713Y20. Santodomingo-Rubido J, Mallen EA, Gilmartin B, Wolffsohn JS. A new non-contact optical device for ocular biometry. Br J Ophthalmol 2002;86:458Y62. Baikoff G, Lutun E, Ferraz C, Wei J. Static and dynamic analysis of the anterior segment with optical coherence tomography. J Cataract Refract Surg 2004;30:1843Y50. Kucumen RB, Yenerel NM, Gorgun E, Kulacoglu DN, Oncel B, Kohen MC, Alimgil ML. Corneal biomechanical properties and intraocular pressure changes after phacoemulsification and intraocular lens implantation. J Cataract Refract Surg 2008;34: 2096Y8. Omelyanenko N, Slutsky L, Mironov S. Connective Tissue: Histophysiology, Biochemistry, Molecular Biology, Boca Raton, FL: CRC Press; 2014:80Y189. Asejczyk-Widlicka M, uro´ dka W, Schachar RA, Piervcionek BK. Material properties of the cornea and sclera: a modelling approach to test experimental analysis. J Biomech 2011; 44:543Y6. Asejczyk-Widlicka M, Pierscionek BK. The elasticity and rigidity of the outer coats of the eye. Br J Ophthalmol 2008;92:1415Y8. Edmund C. Corneal elasticity and ocular rigidity in normal and keratoconic eyes. Acta Ophthalmol (Copenh) 1988;66:134Y40. Insull E, Nicholas S, Ang GS, Poostchi A, Chan K, Wells A. Optic disc area and correlation with central corneal thickness, corneal hysteresis and ocular pulse amplitude in glaucoma patients and controls. Clin Experiment Ophthalmol 2010;38:839Y44. Chang M, Yoo C, Kim SW, Kim YY. Retinal vessel diameter, retinal nerve fiber layer thickness, and intraocular pressure in Korean patients with normal-tension glaucoma. Am J Ophthalmol 2011;151: 100Y5. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol 2008;246:1491Y4. Pakravan M, Parsa A, Sanagou M, Parsa CF. Central corneal thickness and correlation to optic disc size: a potential link for susceptibility to glaucoma. Br J Ophthalmol 2007;91:26Y8. Salchow DJ, Oleynikov YS, Chiang MF, Kennedy-Salchow SE, Langton K, Tsai JC, Al-Aswad LA. Retinal nerve fiber layer thickness
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
1482 Ocular Biometry and Myopia in ChildrenVBueno-Gimeno et al. in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786Y91. 45. Huynh SC, Wang XY, Rochtchina E, Mitchell P. Peripapillary retinal nerve fiber layer thickness in a population of 6-year-old children: findings by optical coherence tomography. Ophthalmology 2006;113:1583Y92. 46. Tong L, Chan YH, Gazzard G, Loon SC, Fong A, Selvaraj P, Healey PR, Tan D, Wong TY, Saw SM. Heidelberg retinal tomography of optic disc and nerve fiber layer in Singapore children: variations with disc tilt and refractive error. Invest Ophthalmol Vis Sci 2007;48:4939Y44.
47. Kaushik S, Pandav SS, Banger A, Aggarwal K, Gupta A. Relationship between corneal biomechanical properties, central corneal thickness, and intraocular pressure across the spectrum of glaucoma. Am J Ophthalmol 2012;153:840Y9.
Inmaculada Bueno-Gimeno Faculty Physics Department of Optics University of Valencia c/ Dr Moliner 50 46100 Burjassot (Valencia) Spain e-mail: [email protected]
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
