|Year : 2017 | Volume
| Issue : 1 | Page : 11-14
Analysis of normal retinal nerve fiber layer thickness by age and sex using spectral domain tomography
R Aiswarya1, Hemant Singh Trehan2
1 Graded Specialist, Department of Ophthalmology, Command Hospital, Udhampur, India
2 Senior Advisor Vitreo Retinal Surgery and HOD, Department of Ophthalmology, Army Hospital, Research and Referral, New Delhi, India
|Date of Web Publication||17-Aug-2017|
Maj R Aiswarya
Department of Ophthalmology, Command Hospital, Udhampur - 182 101, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Background: To analyze the nerve fiber layer thickness in a heterogeneous Indian population according to age and sex and to compare this parameter to published normative data on the Caucasian population to better understand the racial differences. Materials and Methods: A total of 400 patients of both gender belonging to various age groups were evaluated using Cirrus HD optical coherence tomography (OCT), Carl Zeiss, Meditec, Dublin. The results were evaluated and compared to determine the normal retinal nerve fiber layer thickness (RNFLT) and its variations with age and sex. Results: Average nerve fiber thickness along the 3.4 mm diameter circle around the optic nerve head was approximately 90.57 ± 11.59 μm. There was no significant difference seen between males and females for mean, quadrant, and clockwise RNFLT. This was the same in all the subgroups of our study. Conclusions: Our results provide the variations of RNFL in Indian population. To the best of our knowledge, this is the first study in our country done with a high sample size in the Cirrus HD-OCT machine.
Keywords: Normative database, retinal nerve fiber layer, types of optical coherence tomography
|How to cite this article:|
Aiswarya R, Trehan HS. Analysis of normal retinal nerve fiber layer thickness by age and sex using spectral domain tomography. J Mar Med Soc 2017;19:11-4
| Introduction|| |
Glaucoma is the second leading cause of blindness in the world. It causes retinal ganglion cell damage. It can cause retinal nerve fiber layer (RNFL) thinning as the ganglion cell axons are nonmyelinated. Optical coherence tomography (OCT) is a noninvasive test which provides precise measurements of RNFL thickness (RNFLT).
OCT provides significant clinical values of RNFLT due to its high diagnostic sensitivity and specificity.,,, Furthermore, the result can be quantified and reproduced. Unlike visual field testing which is a subjective test prone to variability, OCT is objective. In addition, RNFL thinning can predict the location of impending visual field loss.
Since it was described in 1991 by Huang et al., OCT imaging has undergone many significant technological advances. Wojtkowski et al. reported the firstin vivo imaging of the human retina using spectral domain OCT (SD-OCT) technology (also known as Fourier domain OCT). Subsequently, de Boer et al. developed the first SD-OCT device with video-raster imaging capabilities, which allowed for three-dimensional imaging in effective real time for clinical use. Current commercially available SD-OCT systems provide video-raster, ultrahigh-speed images with improved resolution and greater sensitivity compared with older time domain (TD-OCT) devices.
The normal variability of RNFLT values by race, age, sex, refractive error, axial length, and disc area has been extensively studied using TD-OCT technology. More recent studies have evaluated normal variations of RNFLT values using SD-OCT technology. Studies have shown that TD-OCT and SD-OCT results are not interchangeable. The SD-OCT has now replaced TD-OCT in most parts of the world. Several reports also suggest that the RNFLT vary between ethnic groups. Therefore, data documenting normal nerve fiber measurements and variations associated with demographic and ocular variables in healthy Indian controls on SD-OCT are required for clinicians, to make decisions on pathologic changes in this ethnic group.
To interpret the RNFLT generated by SD-OCT machines, each machine has a normative database of values for age-matched normal. The database is not race specific. A better understanding of normal RNFLT in Indians is therefore imperative in clinical settings.
The objective of this study is to analyze the nerve fiber layer thickness in a heterogeneous Indian population according to age and sex and to compare this parameter to published normative data on the Caucasian population to better understand the racial differences.
This study has been aimed at determining effects of age and gender on RNFLT in normal human eye as measured by the Cirrus HD-OCT, Zeiss Machine.
The earlier studies on Indian population were on sample sizes <200. In addition, no study has been done using the latest HD-OCT machine. To the best of our knowledge, this is the first study in our country done with a high sample size in the Cirrus HD-OCT machine.
| Materials and Methods|| |
Our participants were both males and females aged between 20 and 80 years, with a best corrected visual acuity of 6/12 or better.
We excluded patients who had undergone any intraocular surgery and those with corneal scarring, media opacities, retinal disease, anterior segment dysgenesis, and past chronic steroid use, from our study. Those also excluded from the study were patients with ocular hypertension (history of eye pressure readings of 23 mmHg or higher), pigment dispersion syndrome, pseudoexfoliation syndrome and glaucoma.
Study design, material, and methods
The study was conducted in the Department of Ophthalmology of a tertiary care hospital setting after taking approval from the hospital ethics committee. It was a cross-sectional study which spread over a timeline of 18 months. We evaluated 400 patients (400 eyes) during this period. A written informed consent was taken from all patients who participated before the evaluation.
The evaluation started with a complete history taking of both ocular and medical conditions. All patients underwent visual acuity measurement by Snellen's chart and auto refractometer Grand Seiko was used followed by a subjective correction. Ocular examination by slit lamp was done including a fundus examination. Intraocular pressure was measured by Applanation tonometer.
Patients underwent OCT with Cirrus HD-OCT, Carl Zeiss, Meditec, Dublin. Only well-centered images with a signal strength of >6 were used for analysis. OCT was performed by the same person on all patients. All the information were recorded in a precoded pro forma.
Procedure of measuring retinal nerve fiber layer thickness
RNFLT was measured around the disc. It was determined as the distance from the inner margin of the internal limiting membrane to the outer margin of the RNFL layer measured by circular B-scans.
| Results|| |
Comparison among age group
The average RNFLT in each decade was calculated separately for males and females [Figure 1] and [Table 1] and [Table 2].
|Figure 1: Comparison of retinal nerve fiber layer thickness (μM) among study groups.|
Click here to view
Average nerve fiber thickness along the 3.4 mm diameter circle around the optic nerve head was approximately 90.57 ± 11.59 μm (P = 0.000). Overall measurements produced a double-hump pattern curve, similar to the one previously reported with OCT and on histopathology.
Effect of age on RNFLT was analyzed by linear regression analysis and Pearson coefficient of correlation. Student's t-test was used to compare RNFLT between genders. The analysis of variance with post hoc test of Tukey was used to compare differences in RNFLT parameters among various age groups.
The average RNFLT showed a trend of decrease with the advancing age. The age had significant negative correlation with average RNFLT. On applying regression equation, average RNFLT showed negative slope of 0.236 μm/year (average RNFLT = 102.05 − 0.236 age, Pearson's correlation coefficient r = −0.343, P = 0.000).
We noticed a significant difference in the average RNFLT between our group and other groups. The comparison and summary of previous reports of RNFLT in normal individuals is provided in [Table 3].
Among the international studies, only Mistlberger et al. reported a similar RNFLT. The studies by Bendschneider et al., Alasil et al. and Kampougeris et al., showed higher values compared with our study. All these studies showed statistically significant decline in the RNFLT according to age in consensus with our study. The rate of decline was also similar to that of our study. Kampougeris et al. did not study the influence of gender on NFL thickness. All other studies showed that gender has no influence on the thickness.
Among the Indian studies, Appukuttan et al. studied 105 patients of South Indian origin between age group 20 and 75 years. They found the mean RNFLT to be 101.43 ± 8.63 μm. It showed significant negative correlation with age. There was no influence of gender on the RNFLT.
The study by Ramakrishnan et al. included 118 eyes and did not find a significant relation to age and gender. Mean peripapillary RNFLT on average was 105 ± 38.79 μm.
Sony et al. studied  146 patients. The average RNFLT in the sample population under study was 104.27 ± 8.51 μm. There was no significant difference seen between males and females for mean, quadrant and clockwise RNFLT. This was the same in all the subgroups of our study. The study, like ours, also concluded that age had significant negative correlation on the thickness.
We could not make a reference database for each decade as it is mandatory to have at least 120 participants in each group as per NCCLS guidelines.
Limitation of this study is that it was based on cross-sectional data and to know the effect of age on RNFLT, it would be ideal to measure RNFLT longitudinally over a period of time. In addition, the disc size of the individuals were not estimated; however, a recent study  on Indian eyes reported that disc size did not influence RNFLT.
High myopes were not included in the normative database. Myopic eyes have thinner RNFL measurements, which can confound comparisons to the normative database. In addition, myopic eyes can have unique distributions of RNFL bundles.
Furthermore, even in normal eyes, split RNFL bundles, both superiorly and inferiorly, have been found on histologic section, thus representing a true normal variant which may appear abnormal on OCT.
The measurements from this study may serve as a reference during glaucoma screening with OCT in Indian population.
For everyday management of patients, ophthalmologists should be more inclined to take a baseline OCT image and then serially follow each patient compared to him or herself. The gold standard should be the baseline OCT of the individual patient. We should use the normative information from large populations keeping in mind the average differences among different demographic groups.
While clinical examination of the optic disc is indispensable in diagnosing glaucoma, RNFLT evaluation is important in confirming the diagnosis and monitoring the progression of the disease.
In addition, we should look at a number of factors, like morphology, on the OCT study, not just thickness.
Due to the relatively small normative database and wide variation of distribution of RNFL, many results obtained by SD-OCT may be flagged as abnormal statistically in patients who are not represented in the database and thus not necessarily representing real disease. Clinicians should exercise caution to avoid over treating in such situations.
Future studies on different ethnicities with repeated measurements in the same patients are needed to compare reproducibility and variability of measurements done with different devices.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
. Bulletin of the World Health Organization Past issues. Bull World Health Organ 2004;82:811-90.
Lin S, Singh K, Jampel H, Hodapp E, Smith S, Francis B, et al
. Optic nerve head and retinal nerve fiber layer analysis. Ophthalmology 2007;114:1937-49.
Zangwill LM, Bowd C. Retinal nerve fiber layer analysis in the diagnosis of glaucoma. Curr Opin Ophthalmol 2006;17:120-31.
Budenz DL, Michael A, Chang RT, McSoley J, Katz J. Sensitivity and specificity of the StratusOCT for perimetric glaucoma. Ophthalmology 2005;112:3-9.
Leung CK, Chan WM, Yung WH, Ng AC, Woo J, Tsang MK, et al.
Comparison of macular and peripapillary measurements for the detection of glaucoma: An optical coherence tomography study. Ophthalmology 2005;112:391-400.
Miki A, Medeiros FA, Weinreb RN, Jain S, He F, Sharpsten L, et al.
Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes. Ophthalmology 2014;121:1350-8.
Huang D, Swanson E, Lin C, Schuman J, Stinson W, Chang W, et al
. Optical coherence tomography. Science 1991;254:1178-81.
Wojtkowski M, Srinivasan V, Fujimoto JG, Ko T, Schuman JS, Kowalczyk A, et al.
Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 2005;112:1734-46.
de Boer JF, Cense B, Park BH, Pierce MC, Tearney GJ, Bouma BE. Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography. Opt Lett 2003;28:2067-9.
Han IC, Jaffe GJ. Comparison of spectral-and time-domain optical coherence tomography for retinal thickness measurements in healthy and diseased eyes. Am J Ophthalmol 2009;147:847-58, 858.e1.
Knight OJ, Girkin CA, Budenz DL, Durbin MK, Feuer WJ; Cirrus OCT Normative Database Study Group. Effect of race, age, and axial length on optic nerve head parameters and retinal nerve fiber layer thickness measured by Cirrus HD-OCT. Arch Ophthalmol 2012;130:312-8.
Mistlberger A, Liebmann JM, Greenfield DS, Pons ME, Hoh ST, Ishikawa H, et al.
Heidelberg retina tomography and optical coherence tomography in normal, ocular-hypertensive, and glaucomatous eyes. Ophthalmology 1999;106:2027-32.
Bendschneider D, Tornow RP, Horn FK, Laemmer R, Roessler CW, Juenemann AG, et al.
Retinal nerve fiber layer thickness in normals measured by spectral domain OCT. J Glaucoma 2010;19:475-82.
Alasil T, Wang K, Keane PA, Lee H, Baniasadi N, de Boer JF, et al.
Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography. J Glaucoma 2013;22:532-41.
Kampougeris G, Spyropoulos D, Mitropoulou A, Zografou A, Kosmides P. Peripapillary retinal nerve fibre layer thickness measurement with SD-OCT in normal and glaucomatous eyes: Distribution and correlation with age. Int J Ophthalmol 2013;6:662-5.
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.
] [Full text]
Ramakrishnan R, Mittal S, Ambatkar S, Kader MA. Retinal nerve fibre layer thickness measurements in normal Indian population by optical coherence tomography. Indian J Ophthalmol 2006;54:11-5.
] [Full text]
Sony P, Sihota R, Tewari HK, Venkatesh P, Singh R. Quantification of the retinal nerve fibre layer thickness in normal Indian eyes with optical coherence tomography. Indian J Ophthalmol 2004;52:303-9.
] [Full text]
How to Define and Determine Reference Intervals in the Clinical Laboratory; Approved Guideline—Second Edition. NCCLS document C28-A2 (ISBN 1-56238-406-6):13.
Rao HL, Kumar AU, Babu JG, Kumar A, Senthil S, Garudadri CS. Predictors of normal optic nerve head, retinal nerve fiber layer, and macular parameters measured by spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52:1103-10.
Leung CK, Yu M, Weinreb RN, Mak HK, Lai G, Ye C, et al.
Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: Interpreting the RNFL maps in healthy myopic eyes. Invest Ophthalmol Vis Sci 2012;53:7194-200.
Kaliner E, Cohen MJ, Miron H, Kogan M, Blumenthal EZ. Retinal nerve fiber layer split bundles are true anatomic variants. Ophthalmology 2007;114:2259-64.
Chong GT, Lee RK. Glaucoma versus red disease: Imaging and glaucoma diagnosis. Curr Opin Ophthalmol 2012;23:79-88.
[Table 1], [Table 2], [Table 3]
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