|Year : 2004 | Volume
| Issue : 3 | Page : 215-20
Retinal nerve fiber layer measurements in indian eyes using the scanning laser polarimeter, GDx.
L Vijaya, M Varma, R Krishna Kumar, AS Saraniya, G Babu, S Subash, B Sukumar
Department of Glaucoma and Optometry Vision Research Foundation, Medical Research Foundation, Chennai, India
|Date of Submission||23-May-2002|
|Date of Acceptance||23-Feb-2004|
Department of Glaucoma and Optometry Vision Research Foundation, Medical Research Foundation, Chennai
Source of Support: None, Conflict of Interest: None
PURPOSE: To obtain retinal nerve fiber layer (RNFL) measurements in normal Indian subjects of different age groups; and to determine the differences between the right and the left eye of a subject and variations between male and female gender using the scanning laser polarimeter GDx. MATERIALS AND METHODS: Prospective cross-sectional study of 180 eyes of 94 subjects. The RNFL values were obtained with the nerve fiber analyser GDx using default quadrant positions supplied by the manufacturer. Fourteen parameters were studied. Of these 6 were average-based parameters (average thickness, superior maximum, inferior maximum, ellipse average, superior average, inferior average), 4 ratio-based parameters (symmetry, superior ratio, inferior ratio, superior/nasal), 4 "other" parameters (maximum modulation, number, ellipse modulation, superior integral). The main outcome measures were effect of age on RNFL values, comparison of males and females and the right and the left eye of a subject. RESULTS: There was a negative linear correlation with age. Three ratio-based parameters showed a statistically significant negative correlation with age. "Number" increased with age. Superior maximum, superior average, superior integral, symmetry and superior ratio were higher for the left eye. 'Number' was higher for the right eye. Superior ratio and maximum modulation were more in females than males, no difference was noted with other parameters. CONCLUSION: There was a gradual decrease of RNFL values with increasing age - the superior quadrant values were higher for the left eye than the right eye, suggesting asymmetry. No significant differences were detected between males and females.
Keywords: Scanning laser polarimeter, retinal nerve fiber layer, GDx
|How to cite this article:|
Vijaya L, Varma M, Krishna Kumar R, Saraniya A S, Babu G, Subash S, Sukumar B. Retinal nerve fiber layer measurements in indian eyes using the scanning laser polarimeter, GDx. Indian J Ophthalmol 2004;52:215
GDx is a newer version of the scanning laser polarimeter (Laser Diagnostic Technologies Ltd., San Diego, CA, USA Model GDx version 1.0.16). It is a clinical device used for the quantitative assessment of retinal nerve fiber layer (RNFL) thickness. Its working principle depends on the birefringence property of RNFL. When a polarised light beam passes through the microtubules in the RNFL, a phase shift occurs. This phase shift is called retardation and correlates linearly with the thickness of the RNFL. Decrease in retinal nerve fiber layer measurements seem to be related to both age and ethnicity. ,,,, In the present study we aimed to obtain the normal RNFL measurements in normal Indian subjects of different age groups using the scanning laser polarimeter, GDx. We also looked at any differences between right and left eyes and variations between males and females.
| Materials and Methods|| |
There were 180 eyes of 94 subjects enrolled in this prospective cross-sectional study. The study period was from December 1997 to December 1999. These subjects were recruited from the staff of our hospital, students, volunteers and friends and relatives of hospital personnel. The subjects were divided into six groups according to age: 10-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60 years and above. The inclusion criteria were age above 10 years, best corrected visual acuity of 6/9 or better, normal intraocular pressure (less than 21mm of Hg with Goldmann applanation tonometer), healthy optic nerve (a cup disc ratio of less than 0.6, no peripapillary atrophy or optic nerve head abnormality on clinical evaluation), normal visual fields (with less than 30% false responses and fixation losses and not fulfilling Anderson's minimum criteria for an abnormal field). The exclusion criteria were refractive errors beyond -5.00 or +5.00 diopters and astigmatic correction above 2 diopters, family history of glaucoma, history of any ocular surgery, optic nerve head abnormality, medullated nerve fibers, any ocular pathology, amblyopia, diabetes mellitus and systemic hypertension. Eligible subjects received a detailed ophthalmic evaluation after obtaining informed consent. Examination included Snellen best corrected visual acuity, intraocular pressure measurement with Goldmann applanation tonometer, gonioscopy, detailed retinal evaluation with indirect ophthalmoscopy, optic nerve head evaluation with +90 diopter lens and visual field examination with Humphrey field analyser (Humphrey systems, Dublin, CA, USA) using the 30-2 Sita standard programme. If both eyes fulfilled the inclusion criteria, both were included.
Three experienced operators took retinal nerve fibre layer measurements with GDx. All images were taken without dilatation. A set of 6 images was taken and the best three were chosen for the study and analysis. A good image was defined as one that had even illumination in all segments, showed sharp and well defined edges of blood vessels, and lacked red saturation. The operator placed the measuring ring around the inner margin of the peripapillary scleral rim. Measuring circle or ellipse was then generated by the instrument at 1.75 disc diameters concentric with the margin of the optic disc. Default quadrant positions supplied by the manufacturer were applied and retardation was measured in 4 quadrants viz. superior 120°, inferior 120°, temporal 50°, and nasal 70°.
Inter-observer variability was measured for the operators. The intraclass correlation coefficient (ICC) for reproducibility was more than 0.75 for most parameters suggesting good reproducibility. It was 0.78 to 0.90 for average-based parameters, 0.63 to 0.91 for ratio-based parameters and 0.63 to 0.90 for other parameters.
Fourteen parameters were automatically calculated using GDx software.
Average thickness : The average thickness of all pixels in the image using all 65,536 points.
Superior maximum : The average of the 1500 thickest pixels in the superior quadrant was used to calculate all ratios involving the superior quadrant.
Inferior maximum : The average of the 1500 thickest pixels in the inferior quadrant was used to calculate all ratios involving the inferior quadrant.
Ellipse average : Average thickness of the nerve fiber layer beneath the ellipse surrounding the optic nerve.
Superior average : The average thickness of the nerve fiber layer beneath the superior portion of the ellipse.
Inferior average : The average thickness of the nerve fiber layer beneath the inferior portion of the ellipse.
Symmetry : Ratio of the average of the 1500 thickest pixels in the superior quadrant over the average of the 1500 thickest pixels in the inferior quadrant.
Superior ratio : Ratio of the average of the 1500 thickest pixels in the superior quadrant over the average of the 1500 median pixels in the temporal quadrant.
Inferior ratio : Ratio of the average of the 1500 thickest pixels in the inferior quadrant over the average of the 1500 median pixels in the temporal quadrant.
Superior / nasal : Ratio of the average of the 1500 thickest pixels in the superior quadrant over the average of the 1500 median pixels in the nasal quadrant.
Maximum modulation: First, the average was calculated for the 1500 thickest points in the superior and inferior quadrants. Next, the 1500 median points in the nasal and temporal quadrants were calculated. The lowest of these 4 values was subtracted from the highest, then divided by the lowest value. This gave the difference between the thickest and the thinnest parts of nerve fiber layer.
'Number' : A trained neural network assesses all pixels and assigns to an eye a number from 0 to 100 (0 indicates normal and 100 advanced glaucoma). This parameter could be evaluated only for subjects aged 18 years or more because the normative database of GDx software includes only healthy subjects above 18 years of age.
Ellipse modulation : This was calculated by taking the thickest pixel within the elliptical band, subtracting the thinnest pixel within the band and dividing the total by the value of thinnest pixel.
Superior integral : This was calculated as the total area under the curve and within the superior portion of the elliptical band.
Linear regression analysis and Pearson's correlation co-efficient were calculated to determine the effect of age on the RNFL parameters. The Student's t test was used for the correlation between males and females and the paired t-test was used for right and left eye.
| Results|| |
Subjects included 49 males and 45 females. In 86 subjects both eyes were included in the study but by randomisation one eye of each subject was considered for analysis. In 8 subjects only one eye was eligible, accounting for a total of 94 eyes that were studied. The mean age of the male subjects was 36.79 ± 15.61 years, and the female subjects was 33.68 ± 16.37 years - there was no statistically significant difference between the two groups. The refractive error ranged from - 3.5 to + 3.5 diopters (mean 0.08 ± 0.99 D). The number of patients in the subgroups is given in [Table - 1].
Age vs RNFL: Using regression analysis, we found a negative linear correlation of RNFL parameters with age. None of the average-based parameters showed statistically significant correlation, while 3 ratio-based parameters, superior ratio (y = 3.045 - 0.011x), inferior ratio (y = 3.025 - 0.010x) , superior/nasal (y = 2.447 - 0.007x) showed statistically significant negative correlation with age. Similarly maximum modulation (y = 2.235 -0.012x) and ellipse modulation (y = 3.511 - 0.016x) showed a negative correlation with age. As far as the parameter "number" was concerned, only 79 eyes could be evaluated due to the age restriction mentioned above. The "number" (y = 7.816 + 0.147x) showed a statistically significant increase with age [Table - 2].
Laterality of the eye vs RNFL : [Table - 3] shows a comparison of the two eyes of 86 subjects (46 males; 40 females) in whom bilateral evaluation was done. The superior maximum was more for the left eye, resulting in a statistically significant difference in symmetry and superior ratio. The superior average and superior integral were also found to be more in the left eye. The 'number' was calculated for 74 subjects and was found to be higher for the right eye. There was no difference between the two eyes for the other parameters.
Gender vs RNFL : One ratio-based parameter, namely, superior ratio showed significant higher values in females; similarly, maximum modulation was greater in females. There was no significant difference between males and females in regard to rest of the parameters [Table - 4].
| Discussion|| |
The effect of age on the optic nerve axonal counts in normal individuals has been the subject of various histological studies.,,, Some of these studies showed a negative association with age,,, while others have shown no statistically significant association. Balazsi et al quantified the effect of aging on the optic nerve axonal counts and reported a mean loss of 5,637 axons per year, corresponding to a total loss of about 35% of optic nerve axons in an individual's life span. As the optic nerve axonal count decreases with age, variations in the RNFL thickness measurements may also be expected. Jonas et al semi-quantitatively assessed visibility of RNFL on red free photographs of a large number of normal subjects, and described reducing visibility of the RNFL with increasing age. As the visibility of the RNFL depends on its thickness, this optical variation may be related to loss of retinal nerve fibers. The nerve fiber analyser, which is a scanning laser polarimeter was developed to measure RNFL thickness in vivo . Studies have been done using the nerve fiber layer analyser on normal individuals in different ethnic groups. These reports showed that retinal nerve fiber layer thickness decreases with age in normal healthy eyes. ,,,,
However, there have been no such studies in the Indian ethnic group. In this cross-sectional study we determined the RNFL thickness as measured by nerve fibre layer GDx in normal Indian subjects. Consistent with previous studies, our study also showed a general decrease in RNFL values with increasing age. Even though there was a gradual decrease, in average-based parameters, none showed a statistically significant decrease. Three out of four ratio-based parameters showed a significant difference with age. Symmetry, which is a ratio between superior maximum and inferior maximum, did not show any correlation. Superior ratio, inferior ratio (compared with temporal quadrant) and superior/nasal showed a statistically significant negative correlation with age. This is possibly due to asymmetrical decrease of RNFL mostly affecting temporal and nasal quadrants. Maximum modulation and ellipse modulation are parameters that provide an indication of the difference between the thickest and the thinnest parts of the nerve fiber layer and these parameters showed lower values with age, indicating a reduced difference between thickest and thinnest fibers due to non-uniform loss of RNFL. "Number" showed increase with age denoting an overall decrease in thickness of RNFL with age. Hence our study seems to indicate that there is a gradual decrease of RNFL with age and these changes are not uniform across the four quadrants. In contrast, Chi et al reported that nasal and inferior RNFL thickness decreased with age in the Japanese population, while Lee et al showed uniform decrease in RNFL values in four quadrants in the Hong Kong Chinese population. This variation in the age-related changes noted could be due to the different ethnic groups studied. Hence it may be important to have a separate database for each ethnic group in the GDx software.
Asymmetry between the right and left optic discs of the same individual is considered to be a common feature. Jonas et al found a difference of 1mm less of disc area and neural rim area in at least 95% of 138 pairs of eyes. Similar observations were reported by Varma et al. The right eye was compared with the left eye in 86 subjects. We noticed that the superior quadrant values were higher for the left eye than the right, suggesting asymmetry between the two eyes at least where the superior quadrant was involved. Since the optic disc sizes were not measured in this study, the possibility that the asymmetry is due to this confounding factor cannot be excluded.
Varma et al reported that on an average, male subjects had discs that were 2-3% larger than those of female subjects. Similarly Quigley et al have shown in histological studies that the disc diameter is smaller in females, particularly the horizontal disc diameter. In our study we found no statistically significant difference between males and females except for two isolated parameters.
In conclusion, studies of the RNFL thickness as determined by scanning laser polarimeter (GDx) in healthy Indian people reveals a gradual decrease with increasing age. There appears to be a significant asymmetry between the two eyes and there is no significant difference between males and females.
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[Table - 1], [Table - 2], [Table - 3], [Table - 4]
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