|Year : 2013 | Volume
| Issue : 3 | Page : 50-55
Normative macular cirrus spectral domain optical coherence tomography data in Indian pediatric population
Vishal Katiyar, Kumari Mugdha, Sonal Bangwal, Sanjiv Kumar Gupta
Department of Ophthalmology, K.G.M.U., Lucknow, Uttar Pradesh, India
|Date of Web Publication||1-Nov-2014|
Department of Ophthalmology, K.G.M.U., Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Aim: Cirrus spectral-domain optical coherence tomography (SD-OCT) being noninvasive is gaining more popularity in identifying, monitoring, and classifying children with vitreo-retinal disorder. Normal values of cirrus SD-OCT from children are currently available from developed countries, but not from India. Objective: The primary objective of this study is to provide a normative pediatric database for macular thickness in healthy Indian children using the cirrus SD-OCT. Materials and Methods: The prospective observational study on 157 consecutive healthy children seen between January 2013 and January 2014. Included in the study were 157 subjects with no ocular abnormality, normal (20/20) visual acuity and normal fundoscopy. Cirrus HD-OCT (Carl Zeiss, Dublin, California, USA) device was used. Outcome: Study patients have a mean age of 12.59 ± 3.5 years, with 112 male (12.88 ± 3.5 years) and 45 female (11.8612.88 ± 3.5 years) children. In the linear regression analysis, changes in central subfield thickness and field of the outer macula were independently affected by increase in the age (β = −1.17-1.7, P = 0.004-0.022) and male are found to have significantly higher value when compared with the female (the t-test; t = 1.9-4.8, P = 0.00-0.24). Conclusion: This study established normal reference values for macular parameters measured by Cirrus SD-OCT in healthy Indian children 6-17 years of age, which is statistically different from the databases from other countries. It establishes the importance of the fact that age and gender warrants special consideration during cirrus SD-OCT interpretations in children.
Keywords: Cirrus spectral-domain optical coherence tomography, healthy, Indian children, macular thickness
|How to cite this article:|
Katiyar V, Mugdha K, Bangwal S, Gupta SK. Normative macular cirrus spectral domain optical coherence tomography data in Indian pediatric population
. Egypt Retina J 2013;1:50-5
|How to cite this URL:|
Katiyar V, Mugdha K, Bangwal S, Gupta SK. Normative macular cirrus spectral domain optical coherence tomography data in Indian pediatric population
. Egypt Retina J [serial online] 2013 [cited 2022 Jan 20];1:50-5. Available from: https://www.egyptretinaj.com/text.asp?2013/1/3/50/143818
| Introduction|| |
Optical coherence tomography (OCT) is a noninvasive, noncontact, transpupillary imaging method that performs objective high-resolution cross-sectional images of retinal tissue. The spectral-domain OCT (SD-OCT) provides measurements of macula with greatly improved image acquisition speed and image resolution up to 5 μm.  This is particularly helpful during the examination of an unco-operative children. Though the feasibility of OCT in the pediatric population is well-established, ,,,,,,, all OCT devices have an integrated normative database only for adult subjects 18 years of age and older, mostly derived from developed countries. The reported normative values of macular thickness in children using the time-domain OCT (TD-OCT) devices ,,,,,,,, are available, but is very limited using SD-OCT. ,,,,,
Cirrus SD-OCT is gaining more popularity in identifying, monitoring, and classifying children with vitreo- retinal disorder. , However, for the scans to be the most useful for detecting diseases in children, quantitative measures from children should be compared with age-matched normal controls. Normal reference values of macular thickness are needed in the pediatric population as the software in cirrus SD-OCT has no pediatric nomogram for comparison. Normal values of cirrus SD-OCT from children are currently available from developed countries, , but not from India. The primary objective of this study is to provide a normative pediatric database for macular thickness in healthy Indian children using the cirrus SD-OCT. The secondary objectives are to analyze the effect of age and gender on macular thickness assessment using the cirrus SD-OCT.
This was prospective observational study on 157 consecutive healthy children seen between January 2013 and January 2014. Resident doctors and OCT technicians recruited for OCT scanning and data collection were blinded for the study objectives.
It is a northern Indian university hospital-based study.
One hundred and seventy consecutive healthy children presenting to the ophthalmology department of the university hospital between January 2013 and January 2014 were recruited for the study after ethical clearance and written consent from the subject's parents. A total of 170 subjects were recruited out which 13 subjects were excluded due to nonreliable scan (signal strength <6). One hundred and fifty-seven subjects with no ocular abnormality, normal visual acuity (best corrected Snellen visual acuity of 20/20) and normal fundoscopy were included in the study, and detailed demographic data were obtained. Excluded were patients with refractive error more than ± 0.5 D (sphere or cylinder) history of intraocular surgery, strabismus, anisometropia more than 0.50 diopters, amblyopia, retinal pathology, glaucoma, optic nerve cup to disc ratio >0.5 or asymmetry of >0.2 between fellow eyes. Patients with a history of prematurity, neurologic, metabolic or other systemic diseases, or not co-operative for OCT assessment and cases more than or equal to 18 years were also excluded.
All subjects received a comprehensive ophthalmologic examination by a resident ophthalmologist. The visual acuity of each eye was recorded using the Snellen chart; intraocular pressure assessment, motility examination, stereoacuity testing, slit lamp exam, cycloplegic refraction, and dilated fundoscopy were performed.
Spectral domain optical coherence tomography imaging
Cirrus HD-OCT (Carl Zeiss, Dublin, California, USA) device was used to obtain high-definition images. Signal strength of 6 or higher was considered acceptable. Internal fixation was used to ensure proper alignment of the eye. All imaging was performed by an experienced ophthalmic assistant. Multiple measurements were taken, and the best centered one with good signal strength was chosen for analysis.
Optical coherence tomography protocol
512 × 128 B-scans from top to bottom protocol were used for retinal thickness assessment. The software then constructs aretinal map by aligning the B-scans. In addition to creating a retinal thickness map, the SD-OCT software calculates the retinal volume for each map. , Each scan was individually reviewed, and segmentation lines were adjusted to ensure the accuracy in macular thickness measurements. Macular thickness was reported in a modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular map with the central subfield 1 mm in diameter and the inner and outer subfields having diameters of 3 mm and 6 mm, respectively [Figure 1]a-c. The retinal thickness in the inner and outer subfields, the central foveal thickness (CFT), the center point thickness (CPT), and the macular volume were calculated. CPT was defined as the average of 6 radial scans centered at the foveola, whereas the CFT was defined as the average of all points within the central 1 mm diameter circle surrounding fixation [Figure 2]. 
|Figure 1: (a) Macular thickness map using Early Treatment of Diabetic Retinopathy Study (ETDRS) circles of 1 mm, 3 mm, and 6 mm showing the mean thickness in each of the 9 subfields in a subject. (b) Macular thickness map using ETDRS circles of 1 mm, 3 mm, and 6 mm showing the mean thickness in each of the 9 subfields in a subject. (c) Macular thickness map using ETDRS circles of 1 mm, 3 mm, and 6 mm showing the mean thickness in each of the 9 subfields in a subject|
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|Figure 2: The standard Early Treatment of Diabetic Retinopathy Study subfields dividing the macula into central fovea, inner macula, and outer macula. CFT: Central foveal thickness, SIM: Superior inner macula, NIM: Nasal inner macula, IIM: Inferior inner macula, TIM: Temporal inner macula, SOM: Superior outer macula, NOM: Nasal outer macula, IOM: Inferior outer macula, TOM: Temporal outer macula|
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The macular parameters were compared with the published normative data on the healthy pediatric population from other countries. Descriptive statistics included mean ± standard deviation for the normally distributed variables. Linear regression analyzes were done to assess the effects of age on macular parameters measured by SD-OCT. Student's t-test was used to compare the effects of gender on the macular thickness. Welch alternate test was used to assess the difference between the observed data in this group and reported normative data from healthy pediatric population from other countries. Statistical analyzes were performed with commercial software (SPSS version. 20.0, IBM Inc, USA).
| Results|| |
The prospective data of study patients was collected. Study patients have a mean age of 12.59/±3.5 years, with 112 male (mean age 12.88 ± 3.5 years) and 45 female (mean age 11.8612.88 ± 3.5 years) children of north Indian origin as shown in [Table 1].
Age and macular thickness
In the linear regression analysis of various SD-OCT parameters of macular thickness, We observed that the changes in central subfield thickness, field of outer macula (superior outer macula [SOM], inferior outer macula [IOM], temporal outer macula [TOM], perifoveal thickness[PIT]) were independently affected by increase in the age of subject (β = −1.17-1.7, P = 0.004-0.022) as shown in [Table 2]. All these areas except SOM had a positive correlation with the age (Pearson co = 0.03-0.35). Macular thickness of parafoveal region (central volume [CV], central average thickness [CAT], superior inner macula [SIM], nasal inner macula [NIM], inferior inner macula [IIM], temporal inner macula [TIM]) does not appear to be affected by changes in the age of the studied children (β = −1.15-1.4, P = 0.09-0.78).
|Table 2: Regression analysis and Pearson co-efficient between age and macular thickness parameters assessed by cirrus SD-OCT in healthy Indian pediatrics population|
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Gender and macular thickness. There was significant statistical difference in the mean values of different OCT parameters of macular thickness among male and female (the t-test; t = 1.9-4.8, P = 0.00-0.24) as shown in [Table 3]. Male are found to have significantly higher value as compared to the female. Difference appears to be most significant for central subfield thickness, CFT and parafoveal region (SIM, NIM, IIM, TIM, parafoveal thickness [PAT]) (P = 0.00).
|Table 3: The difference in the mean values of different macular thickness parameters between male and female children in Indian Pediatrics patients|
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When compared with the normative macular thickness data from other countries, we observed that normative data from Indian pediatric population is statistically different from what has been reported from similar cohorts from white middle eastern and Caucasian population (Welch alternate test P = 0.0001) as shown in [Table 4].
|Table 4: Reported macular thickness measurements by cirrus SD-OCT in normal children from different countries|
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| Discussion|| |
Optical coherence tomography is increasingly being utilized as a diagnostic and monitoring tool in children with visual loss. SD-OCT being noninvasive, is gaining more popularity in identifying, monitoring, and classifying children with genetic retinal diseases such as Leber congenital amaurosis, retinitis pigmentosa, and Stargardt disease, or with abnormal retinal development such as in retinopathy of prematurity.  OCT, SD-OCT, the latest generation of the technology, provides higher resolution and decreased acquisition time, hence is more useful in the pediatric population. Direct comparison of macular parameters between TD-OCT and SD-OCT is not possible due to different scanning algorithms. ,, Studies using the earlier TD-OCT in children have shown good reproducibility. , Altemir et al. showed good reliability and repeatability in children using cirrus SD-OCT.  With Stratus OCT, good quality scans could be obtained in 93% and 96% of children. 1,3 using spectralis SD-OCT, Turk, et al. reported higher feasibility of 99%.  Using cirrus OCT scans Al-Haddad et al.  reported a feasibility of 96% of enrolled children. In our study, we were able to get a good scan (signal strength ≥ 6) in 92.35% enrolled children. Most available literature reporting normative macular thickness OCT values in children either used TD-OCT ,,,,,, or recently, Spectralis in Turkish and North American children , and RTVue-100 OCT in Chinese children. 
For the cirrus SD-OCT scans to be the most useful for detecting diseases in children, quantitative measures from children using cirrus SD-OCT should be compared to age-matched normal controls. Normal values from children using Cirrus SD-OCT are currently available from developed countries , but not from India. We noted two recent reports of similar work using Cirrus SD-OCT, Barrio-Barrio Jet al in Caucasian children Spain,  Al-Haddad et al. study in children from the Middle East  as shown in [Table 4]. The present study establishes a normative pediatric database for macular thickness in healthy Indian children using the cirrus SD-OCT.
Macular parameters show the greatest variability among different OCT devices and algorithms:  Discrepancies have also been noted across different versions of OCT. , Mean of different macular parameters our study was statistically different from the corresponding value reported from children from Middle Eastern and Caucasians from three centers of Spain (Welch alternate test P = 0.0001) as shown in [Table 4]. Confounding variables like ethnicity, the race, gender ratio and the mean age of the studied population could explain the discrepancies noted in recorded normative cirrus SD-OCT values from different countries. In the present study, the mean age of the children was 12.59/±3.5 years that was statistically higher than the comparable Barrio-Barrio et al. (mean age 10.71 ± 3.12 years) and Al-Haddad et al. (10.71 ± 3.12 years) study (P = 0.001). All our subjects were of north Indian origin, Al-Haddad et al. study has white and Middle Eastern subjects while the Barrio-Barrio et al. (Spain) were having Caucasian subjects from a Spanish population. These could explain the observed difference in reported values in the present and compared studies. This study presents a strong case for noncomparability among normative population data generated from different ethnic population groups. Though comparative studies with a similar objective are not available from the pediatrics population from India, Appukuttan et al.  reported a similar difference among normative cirrus SD-OCT values of adult south Indian and adult Caucasian population. Our study is first to provide a detailed reference normative cirrus SD-OCT values of macular thickness for the pediatric population from India.
Both of the above mentioned studies address similar objectives as the current study, except that they also assess the effect of refractive error on macular thickness assessment. As the primary objective of the study was to analyze the correlation of age and sex on the macular thickness measurements in children, we excluded the children with refractive errors more than 0.5 D, avoid the confounding effect of refractive error on the macular thickness assessment.
Age group of children was 4-17 years in Barrio-Barrio et al. (Spain) study, 6-17 years in Al-Haddad et al. (Middle Eastern) study and 5-17 years in the present study. These studies reported positive correlation of central macular thickness with age and male gender but regression analysis was not done to identify if age is independently predicating the changes in the macular thickness values. In our study, positive correlation with age was observed with all the OCT parameters except the SOM and TOM which exhibited a negative correlation. Moreover, with the increasing age of children, we observed that the changes are more obvious in central subfield thickness, field of the outer macula (SOM, IOM, TOM, PIT) (β = −1.17-1.7, P = 0.004-0.022) whereas CV, CAT and parafoveal region (SIM, NIM, IIM, TIM) does not appear to be affected by changes in the age (β = −1.15-4, P = 0.09-0.78) as shown in [Table 2]. Other two studies did not do regression analysis of age with macular thickness parameters nor do they recorded macular parameters of 9 subfields using ETDRS circles of 1 mm, 3 mm, and 6 mm. Again we are first to provide a detailed reference normative values of 9 subfields using ETDRS circles of 1 mm, 3 mm, and 6 mm for the pediatric population from India.
Previous reports by Barrio-Barrio et al.  , Huynh et al.  and Al-Haddad et al.  study reported that gender differences applied only in central macular thickness measurements which were significantly increased in males. We observed that male children have significantly higher values for central subfield thickness, CFT and parafoveal region (SIM, NIM, IIM, TIM, PAT) (P = 0.00) but not for perifoveal region. It shows that gender differences may need to be accounted for during OCT interpretations especially for central and parafoveal fields.
Strengths of our study included a large cohort of healthy North Indian children and the use of commonly used cirrus SD-OCT technology with reproducible thickness measurements. The confounding effect of refractive error on the macular thickness assessment was avoided by excluding the children with refractive errors more than 0.5 D. We assessed 14 parameters of macular thickness assessment on cirrus SD-OCT, and observed that the age as an independent factor affecting the macular thickness in children. Similar observations are being made in recent reports for an adult population from India  but none in the previously reported studies in Indian pediatric population. One limitation of our study is that the axial length was not measured; however, axial length has minimal influence on macular thickness assessment. ,
Limitations of this work include the mostly uniform ethnic group (northern Indian only) so the effect of race and ethnicity could not be tested. We also excluded patients with refractive errors; normative data for these groups were not established. In addition, our study was single centric hospital-based and not multi-centric or population-based.
| Conclusions|| |
This study established normal reference values for macular parameters measured by cirrus SD-OCT in healthy Indian children 6-17 years of age which is statistically different from the databases from other countries. This not only adds a detailed database to the available literature on normative values using cirrus SD-OCT, but also and highlights the importance of assessment and analysis of individual macular parameter in facilitating evaluation of OCT measurements in children. The data presented is of north Indian children; hence, other subjects of other regions of India should be studied in future research. The study emphasis the need for the development of a separate database of cirrus SD-OCT for Indian pediatric population for reference. It establishes the importance of the fact that age and gender warrants special consideration during Cirrus SD-OCT interpretations in children.
| References|| |
Leung CK, Cheung CY, Weinreb RN, Qiu Q, Liu S, Li H, et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: A variability and diagnostic performance study. Ophthalmology 2009;116:1257-63,1263.e1.
Altemir I, Pueyo V, Elía N, Polo V, Larrosa JM, Oros D. Reproducibility of optical coherence tomography measurements in children. Am J Ophthalmol 2013;155:171-176.e1.
Salchow DJ, Oleynikov YS, Chiang MF, Kennedy-Salchow SE, Langton K, Tsai JC, et al. Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786-91.
Eriksson U, Holmström G, Alm A, Larsson E. A population-based study of macular thickness in full-term children assessed with Stratus OCT: Normative data and repeatability. Acta Ophthalmol 2009;87:741-5.
El-Dairi MA, Asrani SG, Enyedi LB, Freedman SF. Optical coherence tomography in the eyes of normal children. Arch Ophthalmol 2009;127:50-8.
Leung MM, Huang RY, Lam AK. Retinal nerve fiber layer thickness in normal Hong Kong chinese children measured with optical coherence tomography. J Glaucoma 2010;19:95-9.
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;113:1583-92.
Huynh SC, Wang XY, Rochtchina E, Mitchell P. Distribution of macular thickness by optical coherence tomography: Findings from a population-based study of 6-year-old children. Invest Ophthalmol Vis Sci 2006;47:2351-7.
Ahn HC, Son HW, Kim JS, Lee JH. Quantitative analysis of retinal nerve fiber layer thickness of normal children and adolescents. Korean J Ophthalmol 2005;19:195-200.
Ecsedy M, Szamosi A, Karkó C, Zubovics L, Varsányi B, Németh J, et al. A comparison of macular structure imaged by optical coherence tomography in preterm and full-term children. Invest Ophthalmol Vis Sci 2007;48:5207-11.
Qian J, Wang W, Zhang X, Wang F, Jiang Y, Wang W, et al.Optical coherence tomography measurements of retinal nerve fiber layer thickness in chinese children and teenagers. J Glaucoma 2011;20:509-13.
Turk A, Ceylan OM, Arici C, Keskin S, Erdurman C, Durukan AH, et al. Evaluation of the nerve fiber layer and macula in the eyes of healthy children using spectral-domain optical coherence tomography. Am J Ophthalmol 2012;153:552-559.e1.
Yanni SE, Wang J, Cheng CS, Locke KI, Wen Y, Birch DG, et al. Normative reference ranges for the retinal nerve fiber layer, macula, and retinal layer thicknesses in children. Am J Ophthalmol 2013;155:354-360.e1.
Tsai DC, Huang N, Hwu JJ, Jueng RN, Chou P. Estimating retinal nerve fiber layer thickness in normal schoolchildren with spectral-domain optical coherence tomography. Jpn J Ophthalmol 2012;56:362-70.
Elía N, Pueyo V, Altemir I, Oros D, Pablo LE. Normal reference ranges of optical coherence tomography parameters in childhood. Br J Ophthalmol 2012;96:665-70.
Hess DB, Asrani SG, Bhide MG, Enyedi LB, Stinnett SS, Freedman SF. Macular and retinal nerve fiber layer analysis of normal and glaucomatous eyes in children using optical coherence tomography. Am J Ophthalmol 2005;139:509-17.
Barrio-Barrio J, Noval S, Galdós M, Ruiz-Canela M, Bonet E, Capote M, et al. Multicenter Spanish study of spectral-domain optical coherence tomography in normal children. Acta Ophthalmol 2013;91:e56-63.
Al-Haddad C, Barikian A, Jaroudi M, Massoud V, Tamim H, Noureddin B. Spectral domain optical coherence tomography in children: Normative data and biometric correlations. BMC Ophthalmol 2014 22;14:53.
Gupta V, Gupta P, Singh R, Dogra MR, Gupta A. Spectral-domain Cirrus high-definition optical coherence tomography is better than time-domain Stratus optical coherence tomography for evaluation of macular pathologic features in uveitis. Am J Ophthalmol 2008;145:1018-1022.
Leung CK, Cheung CY, Weinreb RN, Lee G, Lin D, Pang CP, et al. Comparison of macular thickness measurements between time domain and spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2008;49:4893-7.
Appukuttan B, Giridhar A, Gopalakrishnan M, Sivaprasad S. Normative spectral domain optical coherence tomography data on macular and retinal nerve fiber layer thickness in Indians. Indian J Ophthalmol 2014;62:316-21.
Wang XY, Huynh SC, Burlutsky G, Ip J, Stapleton F, Mitchell P. Reproducibility of and effect of magnification on optical coherence tomography measurements in children. Am J Ophthalmol 2007;143:484-8.
Geitzenauer W, Kiss CG, Durbin MK, Abunto MT, Callan TM, Stetson PF, et al. Comparing retinal thickness measurements from Cirrus spectral domain- and Stratus time domain-optical coherence tomography. Retina 2010;30:596-606.
Kanamori A, Nakamura M, Tomioka M, Kawaka Y, Yamada Y, Negi A. Agreement among three types of spectral-domain optical coherent tomography instruments in measuring parapapillary retinal nerve fibre layer thickness. Br J Ophthalmol 2012;96:832-7.
Pierre-Kahn V, Tadayoni R, Haouchine B, Massin P, Gaudric A. Comparison of optical coherence tomography models OCT1 and Stratus OCT for macular retinal thickness measurement. Br J Ophthalmol 2005;89:1581-5.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]