To determinate the physiological asymmetry of retinal measurements in the pediatric population with Fourier-domain optical coherence tomography (Cirrus HD-OCT).
Prospective cross-sectional study.
Three hundred and fifty-seven healthy children were recruited. All subjects underwent a comprehensive ophthalmologic examination and an evaluation of the retinal nerve fiber layer (RNFL), optic nerve head, and macula with Cirrus OCT. Differences between right and left eyes were calculated and values were compared by means of a paired t test. Normal ranges of interocular differences were established as the 2.5th and the 97.5th percentiles. The correlations between right and left eyes were assessed by the intraclass correlation coefficients.
Mean best-corrected visual acuity (logMAR) was −0.01. Differences in the average RNFL between right and left eyes were not statistically significant. The RNFL in the right eyes was thicker in the temporal and nasal quadrants, whereas the left eyes showed thicker RNFL in the superior quadrant. The interocular difference tolerance limits for average RNFL and macular thicknesses were 13.00 μm and 23.20 μm, respectively. There was a strong correlation for all the parameters between the right and the left eyes.
The asymmetry of retinal parameters might be more valuable than the absolute values in assessing certain early diseases. The interocular differences in average RNFL and macular thickness of normal individuals should not exceed 13 μm and 23 μm, respectively, if measured with Cirrus HD-OCT.
Organ pairs in the human body are virtually never symmetrical, and this fact has been used as a tool to investigate certain diseases. Asymmetrical parameters in the retina, between the right and left eyes of the same person, are considered to be a hallmark of certain unilateral or asymmetrical diseases, such as glaucoma or optic nerve tumors.
In recent years, several devices that allow an objective and quantitative evaluation of retinal structures have become useful in clinical practice. Traditional assessments by funduscopy or retinography are being improved by digital measurements. Certain tests may be difficult to perform in children and objective tests are required. One of the instruments becoming increasingly popular in pediatric ophthalmology clinics is optical coherence tomography (OCT). OCT has emerged as a useful imaging technique that provides new high-resolution, cross-sectional information about various pathologic features of the retina.
The latest OCT device, Fourier-domain (FD) OCT, offers increased resolution compared to time-domain-based instruments, which range from 5-7 μm for the currently available instruments and 8-10 μm for the earlier instruments.
Normative distribution data on macular and retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters and reproducibility of these values using high-resolution OCT in children have been recently published.
Because OCT is currently included in most clinical protocols for diagnosis and follow-up of pediatric glaucoma and optic nerve diseases (glioma, compressive optic neuropathies, hereditary neuropathies, and macular diseases ), it is important to determine which values of asymmetry should be considered as symptoms of pathology.
The purpose of the present study is to assess physiological asymmetry in the RNFL, ONH, and macular measurements with FD OCT using a community sample of children and to establish the limits beyond which the clinician should suspect the presence of pathology.
Patients and Methods
This study was undertaken in an elementary school, from December 2010 until March 2011, as part of the Environmental Fetal Factors in the Development of the Optic Nerve and the Retina (EFFORT) study. This was a prospective study. The study adhered to the tenets of the Declaration of Helsinki and was approved by the local ethics committee (CEICA; Comité Ético de Investigación Clínica de Aragón).
Of 598 eligible children, 357 (60%) participated in the study and were finally included. Children were prospectively and consecutively recruited from the school. For the children to be enrolled, parents or guardians of the children had to provide written informed consent and complete a questionnaire providing prenatal and postnatal information about the children. Children older than 12 years of age also gave written informed assent to participate in the study. This study conformed to the tenets of the Helsinki Agreement on the use of human subjects in research.
All subjects underwent a comprehensive ophthalmologic examination and an evaluation of the RNFL, ONH, and macula with Cirrus OCT (Carl Zeiss Meditec, Dublin, California, USA). The images from the ONH and the RNFL were acquired using the Optic Disc Cube 200 × 200” seconds of arc scanning protocol and the macular images were obtained using the Macula Cube 200 × 200 protocol. These protocols analyzed a cube 6 mm in width around the optic nerve and 6 mm in width around the macula and generated volume cube images with 200 linear scans performed by A-scans.
The examinations were performed without pupil dilation. Only scans with a signal strength of at least 7 were accepted. Images with artifacts or missing parts were excluded and repeated. Internal fixation was used to suppress ocular movements, because it results in the highest reproducibility.
The parameters collected were mean RNFL thickness (360 degrees), RNFL thickness in the 4 quadrants (inferior, superior, nasal, and temporal), rim area, disc area, cup-to-disc area ratio, central macular thickness, and macular volume. Differences between right and left eyes were calculated and values were compared by means of a paired t test.
The only exclusion criterion was the absence of a signed informed consent. Because we wanted to examine a sample representative of the normal pediatric population, no other exclusion criteria were considered.
Normal ranges of interocular differences were established as the 2.5th and the 97.5th percentiles. The correlations between right and left eyes were assessed by the intraclass correlation coefficients (ICC). Correlation was considered slight if values were 0-0.2, fair if 0.21-0.4, moderate if 0.41-0.6, substantial if 0.61-0.8, and almost perfect if greater than 0.81. The influence of age on interocular asymmetry was also evaluated by a regression model.
Statistical analyses were carried out with the Statistical Package for the Social Sciences software (SPSS 15.0; SPSS Inc, Chicago, Illinois, USA). P values less than .05 were considered statistically significant.
A total of 357 subjects were recruited for the study: 182 male (51.11%) and 175 female (48.89%). Only 1 subject was excluded because the signal strength in 1 eye was below 7.
Most subjects were white (96%) and 4% belonged to other races. The mean age of subjects was 9 years (standard deviation [SD] 1.7 years; range 6.11-13.58 years). Children were divided into 6 groups according to their ages: younger than 7 years of age (n = 47), 7-8 years (n = 63), 8-9 years (n = 54), 9-10 years (n = 69), 10-11 years (n = 60), and older than 11 years (n = 64).
Mean best-corrected visual acuity (BCVA, logMAR) was -0.01 (20/20 for Snellen charts), with a range from 0.01 to −0.2. Mean stereoacuity was 75.71 ± 67.30 seconds of arc. The refractive errors ranged from −3.00 diopters to +4.50 of spherical equivalent. Strabismus was found in 11 children and another 1 subject presented with congenital nystagmus.
Table 1 shows the mean differences of OCT parameters between right and left eyes. Differences in the average RNFL between right and left eyes were not statistically significant. The RNFL in the right eyes was thicker in the temporal and nasal quadrants, whereas the left eyes showed thicker RNFL in the superior quadrant. These differences were statistically significant for the superior, temporal, and nasal quadrants ( P < .05). None of the macular or optic disc parameters showed statistically significant differences between both eyes.
|Right Eye||Left Eye||Difference||Standard Deviation||95% Confidence Interval||P Value|
|Average RNFL, μm||98.50||97.76||0.74||7.93||−0.09||1.56||.079|
|Superior RNFL, μm||123.61||125.88||−2.26||21.08||−4.46||−0.06||.044|
|Temporal RNFL, μm||69.32||65.73||3.59||7.74||2.79||4.40||<.0005|
|Inferior RNFL, μm||130.42||131.24||−0.82||13.62||−2.24||0.59||.254|
|Nasal RNFL, μm||71.25||68.66||2.59||14.28||1.10||4.07||.001|
|Rim area, mm 2||1.59||1.57||0.02||0.34||−0.02||0.06||.281|
|Disc area, mm 2||2.06||2.03||0.03||0.39||−0.02||0.07||.221|
|C/D area ratio||0.43||0.43||0.00||0.12||−0.01||0.01||.765|
|Macular thickness, μm||282.61||282.31||0.31||10.46||−0.79||1.41||.582|
|Macular volume, mm 3||10.18||10.17||0.01||0.37||−0.03||0.05||.644|
The percentile distributions of the interocular asymmetry in peripapillary RNFL and macular thicknesses and optic nerve parameters are shown in Table 2 . The 2.5th and 97.5th percentiles of interocular difference tolerance limits for average RNFL thicknesses were −12.10 μm and 13.00 μm, respectively, depending on whether the RNFL was thicker in the left or right eye. Cut-off points for quadrants using the 2.5th and 97.5th percentiles were higher than those of average RNFL thicknesses, ranging from −37.20 to 34.60. The 2.5th and 97.5th percentiles of interocular difference tolerance limits for central macular thickness were −17.60 μm and 23.20 μm, respectively.
|Average RNFL, μm||−12.10||−9.00||−6.00||−2.00||1.00||4.00||6.20||9.00||13.00|
|Superior RNFL, μm||−37.20||−27.40||−20.00||−10.00||−2.00||7.00||13.00||22.40||34.60|
|Temporal RNFL, μm||−10.00||−7.00||−4.00||0.00||3.00||7.00||11.00||14.10||21.10|
|Inferior RNFL, μm||−31.10||−25.00||−18.20||−9.00||0.00||8.00||15.00||18.10||24.00|
|Nasal RNFL, μm||−29.10||−16.00||−10.00||−2.00||3.00||8.00||16.00||19.10||28.10|
|Macular thickness, μm||−17.60||−11.00||−6.00||−3.00||0.00||3.00||6.00||13.00||23.20|
|Macular volume, mm 3||−0.62||−0.40||−0.20||−0.10||0.00||0.10||0.20||0.40||0.64|
|Rim area, mm 2||−0.67||−0.53||−0.37||−0.16||0.03||0.17||0.41||0.61||0.78|
|Disc area, mm 2||−0.91||−0.62||−0.39||−0.15||0.02||0.23||0.47||0.68||0.81|
|C/D area ratio||−0.31||−0.21||−0.15||−0.06||0.00||0.07||0.15||0.20||0.25|
Interocular correlations between right and left eyes were significant for all the parameters, as shown in Table 3 . ICC was higher than 0.6 (substantial correlation) for all the measurements except for the nasal quadrant, and higher than 0.8 (almost-perfect correlation) for most of the parameters.
|ICC||95% CI||P Value|
|Average RNFL, μm||0.845||0.809-0.874||<.0005|
|Superior RNFL, μm||0.621||0.533-0.692||<.0005|
|Temporal RNFL, μm||0.846||0.810-0.875||<.0005|
|Inferior RNFL, μm||0.826||0.785-0.858||<.0005|
|Nasal RNFL, μm||0.597||0.504-0.673||<.0005|
|Rim area, mm 2||0.634||0.550-0.703||<.0005|
|Disc area, mm 2||0.627||0.541-0.698||<.0005|
|C/D area ratio||0.848||0.813-0.877||<.0005|
|Macular thickness, μm||0.804||0.758-0.841||<.0005|
|Macular volume, mm 3||0.812||0.768-0.847||<.0005|