To assess the symmetry of optic nerve head parameters measured by the Heidelberg Retina Tomograph 3 (HRT 3) between fellow eyes in a normal elderly population.
Cross-sectional population-based study.
Participants of the Blue Mountains Eye Study 10-year follow-up who did not have optic disc disease, including glaucoma, were included. Optic nerve head parameters measured by HRT 3 were compared between fellow eyes. The normal range of interocular asymmetry (larger disc minus smaller disc) was determined by the 2.5th and 97.5th percentiles.
A total of 1276 eligible participants had HRT scans of both eyes. HRT measurements in right eyes differed slightly in rim steepness and rim volume from those in left eyes ( P < .05). The 2.5th and 97.5th percentile of interocular asymmetry limits were −0.41 and 0.45 for cup-to-disc ratio and −0.19 and 0.22 for cup-to-disc area ratio, respectively. The highest interocular correlation was found in disc area and cup area ( r ranged from 0.74-0.76), whereas mean cup depth, cup volume, and retinal nerve fiber layer thickness had the poorest correlation ( r ≤ 0.07). Greater optic disc area asymmetry was associated with a larger interocular difference in the other optic nerve head parameters.
There was minimal interocular difference and substantial interocular correlation in optic nerve head parameters measured by HRT 3. Interocular asymmetry greater than 0.2 for cup-to-disc area ratio was considered outside the normal range.
Interocular asymmetry of the optic disc neuroretinal rim is well recognized as a sign suggesting glaucoma. Understanding the symmetry of optic nerve head (ONH) parameters in healthy eyes is essential in determining the accuracy of such signs. Using high-definition spectral-domain optical coherence tomography (OCT), a recent study reported a marginally significant difference in average peripapillary retinal nerve fiber layer (RNFL) thickness between 2 eyes (0.52 μm, P = .049) in healthy eyes, and suggested that an asymmetry of 9 μm could indicate early glaucoma damage.
The Heidelberg Retina Tomograph (HRT; Heidelberg Engineering GmbH, Heidelberg, Germany) is a confocal scanning laser ophthalmoscope that acquires 3-dimensional topographic images of the ONH and the RNFL with a high degree of discrimination between healthy and glaucomatous eyes. Some studies have reported no significant interocular difference in HRT-measured ONH parameters, whereas others have reported small but significant differences in normal subjects.
The purpose of this study was to evaluate the symmetry of Heidelberg Retina Tomograph 3 (HRT 3)-measured ONH parameters in a large, well-described older normal population, and to determine the limits of the normal amount of interocular symmetry of these ONH parameters in normal eyes.
The study population comprised 1952 participants (75.6% of survivors) of the Blue Mountains Eye Study cohort who were examined at the 10-year follow-up examination (BMES 3). The study population and methods have been described previously. Ethics committee approval was provided by the Western Sydney Area Health Service Human Research Ethics Committee and written informed consent was obtained from each participant. All methods adhered to the tenets of the Declaration of Helsinki guidelines for research in human subjects.
All participants underwent full ophthalmic examinations. Diagnosis of glaucoma was based on typical glaucomatous visual field loss and with matching optic disc appearance on stereophotographs after gonioscopy showed no evidence of angle closure, rubeosis, or secondary glaucoma, other than pseudoexfoliation syndrome, as previously described. Participants with nonglaucomatous visual field loss were excluded from open-angle glaucoma diagnosis, irrespective of the optic disc appearance.
The methodology of ONH imaging with HRT has been described elsewhere. Subjective refraction results were used to set initial scan focus. The HRT cylindrical lenses were adapted for subjects with astigmatism ≥1.0 diopter (D). In brief, a 3-dimensional topographic image was constructed from multiple focal planes arranged axially along the ONH. An average of 3 consecutive scans were obtained and aligned to compose a single mean topography for analysis. The disc margin was defined as the inner edge of the Elschnig ring and an experienced examiner outlined the optic disc contour on the topographic and reflectance images. ONH parameters were analyzed by HRT 3 software automatically.
Eyes with a topography standard deviation (TSD) higher than 50 μm were excluded from analysis because of the unreliability of measurement. Only subjects with eligible HRT scans for both eyes were included in the study. Subjects with glaucoma or other optic disc conditions in either eye were excluded from the study.
We used SAS version 9.2 (SAS Inc, Cary, North Carolina, USA) for statistical analyses. Symmetry in optic disc parameters was evaluated by the difference of the values between the right and left eyes by paired Student t test. Asymmetry measures were calculated by subtracting ONH parameters of smaller-disc eyes from those of larger-disc eyes. RADAAR (rim area–to–disc area asymmetry ratio) was further calculated as described by Harasymowycz and associates, by dividing the rim area–to–disc area ratio of the eye with the larger disc by that of the smaller disc. Pearson correlation coefficients ( r ) were calculated to assess the correlation between eyes. Normal ranges for interocular differences were calculated as the 2.5th and 97.5th percentiles for all parameters. General linear regression models (GLM) were used to assess the influences of optic disc size on interocular difference and interocular correlation for HRT measurements after adjustment for age, sex, height, refraction, intraocular pressure, and TSD. A P value less than .05 was used as the cut-off for statistical significance.
Of 1952 BMES participants, 1276 had eligible HRT scans for both eyes and were included. The mean age was 71.9 ± 7.0 years, and 545 participants (42.7%) were male. There was no significant difference in image quality (TSD) between fellow eyes (right minus left: 0.46 ± 8.83, P = .064). Table 1 shows the mean ± SD of ONH parameters for right and left eyes and summarizes the correlations between eyes for ONH parameters. There was no statistically significant difference between right and left eyes in any HRT parameter except rim steepness (right minus left: −0.05 ± 0.50, P = .003) and rim volume (right minus left: 0.01 ± 0.16 mm 3 , P = .005). The distributions of interocular difference (right minus left) in optic disc area, rim area, cup area, mean RNFL thickness, vertical cup-to-disc ratio, and cup-to-disc area ratio are shown in the Figure .
|Parameter||Mean ± SD||Interocular Correlation|
|Right Eyes||Left Eyes||P a||Asymmetry b||r||P|
|Disc area (mm 2 )||1.91 ± 0.40||1.92 ± 0.41||.372||0.21 ± 0.20||0.737||<.0001|
|TSD (μm)||22.2 ± 8.6||21.7 ± 8.8||.064||0.30 ± 8.83||0.486||<.0001|
|Vertical cup-to-disc ratio||0.34 ± 0.24||0.34 ± 0.24||.387||0.02 ± 0.19||0.665||<.0001|
|cup-to-disc area ratio||0.23 ± 0.14||0.23 ± 0.15||.487||0.02 ± 0.10||0.735||<.0001|
|Rim-to–disc area ratio||0.77 ± 0.14||0.77 ± 0.15||.649||−0.02 ± 0.10||0.645||<.0001|
|Cup area (mm 2 )||0.46 ± 0.33||0.47 ± 0.35||.232||0.08 ± 0.22||0.763||<.0001|
|Mean cup depth (mm)||0.19 ± 0.09||0.20 ± 0.63||.539||0.01 ± 0.06||0.066||.018|
|Cup volume (mm 3 )||0.09 ± 0.10||0.12 ± 0.91||.355||0.02 ± 0.07||0.060||.031|
|Rim area (mm 2 )||1.45 ± 0.33||1.45 ± 0.33||.919||0.13 ± 0.24||0.641||<.0001|
|Rim steepness||−0.13 ± 0.60||−0.09 ± 0.59||.003||−0.05 ± 0.50||0.533||<.0001|
|Rim volume (mm 3 )||0.38 ± 0.16||0.37 ± 0.16||.005||0.03 ± 0.15||0.633||<.0001|
|Mean RNFL thickness (mm)||0.23 ± 0.07||0.22 ± 0.08||.212||−0.01 ± 0.08||0.026||.362|
|Cup shape measurement||−0.17 ± 0.07||−0.17 ± 0.07||.380||0.00 ± 0.07||0.397||<.0001|
As cup area increases to a larger degree than rim area with increases in disc size, we also examined asymmetry by comparing eyes on the basis of disc size. Table 2 shows the percentiles of the asymmetry measure (larger disc minus smaller disc) in these ONH parameters. None of the asymmetry in ONH parameters was associated with asymmetry in intraocular pressure (IOP) levels in this healthy population (all P > .05).
|Disc area (mm 2 )||0.00||0.01||0.01||0.16||0.55||0.68||0.88|
|Vertical cup-to-disc ratio||−0.49||−0.41||−0.34||0.00||0.37||0.45||0.52|
|cup-to-disc area ratio||−0.23||−0.19||−0.13||0.01||0.18||0.22||0.28|
|Rim-to–disc area ratio||−0.28||−0.22||−0.18||−0.01||0.13||0.19||0.23|
|Cup area (mm 2 )||−0.44||−0.31||−0.22||0.06||0.43||0.56||0.80|
|Mean cup depth (mm)||−0.13||−0.10||−0.08||0.01||0.1||0.12||0.17|
|Cup volume (mm 3 )||−0.14||−0.10||−0.07||0.01||0.14||0.19||0.27|
|Rim area (mm 2 )||−0.41||−0.30||−0.19||0.12||0.52||0.64||0.84|
|Rim volume (mm 3 )||−0.32||−0.22||−0.18||0.02||0.27||0.34||0.43|
|Mean RNFL thickness (mm)||−0.18||−0.15||−0.12||0.00||0.11||0.13||0.17|
|Cup shape measurement||−0.16||−0.14||−0.11||0.00||0.11||0.14||0.16|