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1 From the Department of Ophthalmology and Eye Hospital, Friedrich-Alexander University of Erlangen-Nürnberg, Germany; and 2 Departments of Ophthalmology and Visual Sciences, College of Medicine, University of Iowa, Iowa City.
| Abstract |
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METHODS. Color stereo fundus photographs of 17 normal eyes of 17 rhesus monkeys aged between 13 and 23 years were morphometrically evaluated.
RESULTS. The neuroretinal rim was significantly (P < 0.008) broadest in the inferior disc region followed by the superior disc region, the nasal region, and the temporal region. Retinal nerve fiber layer visibility was significantly highest in the inferior temporal fundus region followed by the superior temporal fundus region, the superior nasal fundus region, and the inferior nasal fundus region. It decreased significantly (P < 0.001) with increasing age. The retinal arterioles were significantly (P < 0.01) wider in the inferior temporal and superior temporal fundus regions than in the superior nasal and inferior nasal fundus regions. The alpha zone of parapapillary atrophy (14/17 or 82.4%) occurred significantly (P < 0.001) more often than the beta zone (2/17 or 11.8%). In 15 eyes (88.2%), the foveola was located inferior to a horizontal line drawn through the center of the optic disc. Neuroretinal rim shape and area and size of alpha and beta zones of parapapillary atrophy were independent of age.
CONCLUSIONS. As in humans, in normal rhesus monkeys the neuroretinal rim has a typical physiologic configuration that spatially correlates with the retinal arteriole diameter, retinal nerve fiber layer visibility, and position of the foveola inferior to the center of the optic disc. Neuroretinal rim shape is independent of age. Retinal nerve fiber layer visibility decreases significantly with increasing age. These findings may be useful for the early detection and differentiation of experimental optic nerve damage in rhesus monkeys.
| Introduction |
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In view of these considerations, the present study had a twofold objective: to evaluate the normal appearance and parameters of the optic disc, parapapillary region, and retinal nerve fiber layer in normal rhesus monkeys eyes, which should enable early detection and follow-up of experimentally induced changes in the optic nerve in monkeys, and to compare the findings in rhesus monkeys with those in humans.
| Materials and Methods |
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The morphometric analysis of the fundus photographs that had been taken at the University of Iowa was performed in Erlangen (Germany). After viewing the pairs of diapositive images stereoscopically, one of the two disc slides of each eye was projected in a scale of 1 to 15. The outlines of the optic cup, optic disc, peripapillary scleral ring, alpha and beta zones of parapapillary atrophy, and the retinal arterioles at the optic disc border in the inferior temporal, superior temporal, superior nasal, and inferior nasal regions were plotted on paper and morphometrically analyzed. The optic cup was defined on the basis of contour and not of pallor. The border of the optic disc was identical with the inner side of the peripapillary scleral ring. The neuroretinal rim width was measured in the inferior, superior, nasal, and temporal disc regions. The parapapillary atrophy was differentiated into a peripheral alpha zone with irregular pigmentation and a central beta zone with visible Bruchs membrane and visible large choroidal vessels (Figs. 1 2) .6 The parapapillary region was divided into four sectors. The temporal horizontal sector covered 64°. The inferior temporal and the superior temporal sectors were right-angled, and their middle lines were tilted 13° temporal to vertical optic disc axis. The nasal sector covered the remaining area of 116°. The method has been described in detail elsewhere.2 Because the magnification of the optic disc photographs varied according to the period of the study and the fundus camera used, and because keratometric readings and refractometry had not been performed for all monkeys included in the study, the optic disc measurements were expressed in relative size units.
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To determine the reproducibility of the semiquantitative assessment of the retinal nerve fiber layer visibility, each of 10 photographs of 10 randomly selected eyes was re-evaluated five times. The coefficient of variation, calculated as the ratio of the mean of the SD divided by the mean of the mean values, was 0.131 for the reassessment of the visibility of the retinal nerve fiber layer. When the study on reproducibility was performed, the photographs were mixed with photographs of monkeys showing optic nerve atrophy in eyes with experimentally elevated intraocular pressure and photographs of monkeys with nonglaucomatous optic nerve damage.
For statistical analysis of the data, Wilcoxons signed rank test was used in the evaluation of differences between fundus regions. Pearsons correlation coefficient was calculated for the evaluation of the relationship between visibility of the retinal nerve fiber layer and age.
| Results |
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Cup-to-Disc Ratios
In agreement with the shape of the neuroretinal rim, the
horizontal cup-to-disc diameter ratio was significantly
(P < 0.001) higher than the vertical cup-to-disc
diameter ratio (Table 1)
. Correspondingly, the quotient of the
horizontal cup-to-disc ratio divided by the vertical cup-to-disc ratio
was higher than 1.0 (Table 1)
. The cup-to-disc diameter ratios and the
quotient of both ratios were independent of age (P >
0.20).
Parapapillary Atrophy
An alpha zone of parapapillary atrophy was present in 14 (82.4%)
of the 17 eyes. It was significantly (P = 0.039) larger in
the temporal horizontal parapapillary region than in the inferior
temporal region, where it was significantly (P = 0.009)
larger than in the superior temporal region, where it was significantly
(P = 0.035) larger than in the nasal region (Table 1)
. The
beta zone of parapapillary atrophy was present in 2 (11.8%) of the 17
eyes. The number of eyes with a beta zone was too small for a
statistical analysis of regional differences in the extent of beta
zone.
In a comparison of alpha zone with beta zone in each of the four sectors, the alpha zone was significantly larger than the beta zone in the temporal horizontal (P = 0.002), the inferior temporal (P = 0.003), and the superior temporal (P = 0.008) regions. In the nasal region, the difference was not significant (P = 0.180; Table 1 ). The alpha zone occurred significantly (P < 0.001) more often than the beta zone (Table 1) . The sizes of the alpha and beta zones of parapapillary atrophy area were independent of age (P > 0.05).
Retinal Vessels
The retinal arterioles were significantly (P <
0.01) wider in the inferior and superior temporal fundus regions than
in the superior and inferior nasal fundus regions (Table 1)
. The
inferior temporal arteriole did not differ significantly
(P = 0.46) in diameter from the superior temporal
arteriole, and the superior nasal arteriole did not vary significantly
(P = 0.19) in diameter from the inferior nasal
arteriole.
Retinal Nerve Fiber Layer
Visibility of the retinal nerve fiber layer was significantly
(P = 0.033) higher in the inferior temporal fundus
region than in the superior temporal fundus region, where it was
significantly (P < 0.001) higher than in the superior
and inferior nasal fundus regions (Table 1)
. In the two latter fundus
regions, which did not differ significantly in visibility of the
retinal nerve fiber layer (P = 0.80), retinal nerve
fiber layer visibility was significantly higher (P <
0.01) than in the temporal horizontal fundus, the superior fundus, and
the inferior fundus regions. The visibility was lowest in the nasal
fundus region (Table 1)
. Retinal nerve fiber layer visibility decreased
significantly (P < 0.001) with increasing age (Fig. 3)
.
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Optic Disc Shape
The shape of the optic disc was quantified by calculating the
vertical-to-horizontal disc diameter ratio, the minimal-to-maximal disc
diameter ratio, the difference of maximal disc diameter minus vertical
disc diameter, and the difference of minimal disc diameter minus
horizontal disc diameter.
The vertical-to-horizontal disc diameter ratio was an average of 1.39 ± 0.09 with a minimum of 1.18 and a maximum of 1.57, which indicates that the vertical disc diameter was an average of 39% longer than the horizontal disc diameter. The ratio of the maximal-to-minimal disc diameter was 1.40 ± 0.09 with a minimum of 1.19 and maximum 1.58, showing that the maximal disc diameter was an average of 40% longer than the minimal disc diameter. With the mean difference of maximal disc diameter minus vertical disc diameter and the difference of minimal disc diameter minus horizontal disc diameter being almost zero (Table 1) , the vertical disc diameter was almost identical with the maximal disc diameter, and the horizontal disc diameter almost equaled the minimal disc diameter (Table 1) .
| Discussion |
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As a consequence of the configuration of the neuroretinal rim with the rim being broader inferiorly than superiorly, the inferior-to-temporal rim width ratio was significantly higher than the superior-to-temporal rim width ratio (Table 1) . Both rim width ratios depended on the shape of the optic disc: the more horizontally elongated the optic disc, the lower the rim width ratios. A similar finding has been reported in normal human eyes.9 In horizontally oval optic discs in humans, the retinal nerve fiber bundles in the inferior and superior disc regions have a longer part of the disc circumference to enter the optic nerve head than they have in vertically oval optic discs. This leads to a narrower neuroretinal rim in the inferior and superior disc regions and, consequently, to a lower inferior-to-temporal rim width ratio and a lower superior-to-temporal rim width ratio in horizontally elongated optic nerve heads than in vertically shaped optic discs. This finding may have diagnostic importance, because the neuroretinal rim width ratios can be taken as quantitative measures of the neuroretinal rim shape in the early detection of glaucomatous optic nerve damage.9
Size and shape of the neuroretinal rim were independent of age, in agreement with findings in human eyes in which neuroretinal rim size and shape do not change with age.3 The findings contrast with the decrease in the visibility of the retinal nerve fiber layer and in optic nerve fiber count with increasing age in monkeys (Fig. 3) as well as in humans.10 11 12 The discrepancy may be explained by the fact that in eyes with a nonglaucomatous reason for optic nerve fiber loss, such as central retinal artery occlusion,13 nonarteritic anterior ischemic optic neuropathy,14 and age, the neuroretinal rim does not decrease in shape and size despite the loss of nerve fibers.
An alpha zone of parapapillary atrophy was present in almost all eyes (in 14 of 17 eyes examined). A beta zone was found in 2 (11.8%) of the 17 eyes. Both zones were largest in the temporal horizontal sector and smallest in the nasal region. Similar data have been reported in normal human eyes.6 As in the human eyes, both zones were independent of age.6 15 The findings suggest that the alpha zone of parapapillary atrophy, but not the beta zone, is a physiologic element in the normal appearance of the optic nerve head. It suggests that, in rhesus monkeys as well as in humans with suspected glaucoma,16 the presence of a beta zone is a qualitative hint for glaucomatous optic nerve damage.
The retinal arterioles were significantly wider in the inferior and superior temporal vascular arcades than in the superior and inferior nasal fundus regions. Similar findings have been reported for normal human eyes.7 This goes along with the regional distribution of the visibility of the retinal nerve fiber layer, which was significantly more detectable in the inferior temporal fundus region followed by the superior temporal fundus region, the superior nasal region, and the inferior nasal region (Table 1) . As in humans, this suggests an anatomic relationship between the caliber of the retinal arterioles and the amount of retinal nerve fibers. In humans, a similar relationship has been demonstrated in eyes with optic nerve damage, in which the reduction in the visibility of the retinal nerve fiber layer was correlated in space and extent with a decrease in the diameter of the retinal arterioles.17 18 The regional distribution of visibility of the retinal nerve fiber layer, which has already been studied using Fourier ellipsometry measurements,19 in correlation with the regional variation in the diameter of the retinal arterioles and the width of the neuroretinal rim, may be explained by the location of the foveola inferior to a horizontal line drawn through the center of the optic disc. As in humans,10 more retinal ganglion cells, and thus more retinal nerve fibers, may be located inferior to this line compared with the region superior to the horizontal line, requiring more supply by the retinal arterioles and leading to a broader neuroretinal rim in the inferior disc region than in the superior disc region.
The regional variability in the retinal nerve fiber layer visibility may be important for the early detection of glaucomatous optic nerve damage. In monkeys20 as well as in humans,21 nerve fiber layer loss in early glaucoma takes place predominantly in the inferior temporal region, followed by the superior temporal region and can lead to a change in the sequence of sectors concerning the best visibility of the retinal nerve fiber layer.
In the monkey eyes in the present study, the visibility of the retinal nerve fiber layer decreased significantly with increasing age (Fig. 3) . Assuming a mostly linear relationship, the average loss per year of monkey life was 0.93/53.98 or 1.72%. Taking into account the difference in the normal life expectancy of monkeys versus humans, a comparable figure of 0.45% of annual loss in the retinal nerve fiber layer visibility has been reported in humans.10 In parallel, the optic nerve fiber count decreases by approximately 0.3% in humans per year of age.12 This shows that in monkeys, as in humans,10 22 age has to be taken into account in the assessment of the retinal nerve fiber layer visibility. If the retinal nerve fiber layer visibility is the same in a young monkey as in an old monkey (and if no other reasons such as an opacity in the optic media or a different pigmentation of the background of the eye can be held responsible), the young monkey may have optic nerve damage, whereas the old monkey may have a normal optic nerve for his age.
The shape of the optic disc was more vertically elongated in the monkeys of the present study compared with the optic disc of humans.3 This was indicated by a relatively high vertical-to horizontal disc diameter ratio in the monkey eyes compared with human eyes3 (Table 1) . The difference in the shape of the optic disc may influence the shape of the neuroretinal rim because the inferior-to-temporal rim width ratio and the superior-to-temporal rim width ratio depend on the shape of the optic disc.
There are limitations in the present study. The findings concerning the location of the fovea in relation to the optic disc may have been influenced by changes in the setup of the monkeys in front of the camerai.e., it could have been caused by head torsion. When the photographs were taken, however, the emphasis was on the orientation of the fundus camera in relation to the head of the monkey. Furthermore, the effects of an oblique angle of photography of the optic nerve head may have partially canceled each other if the torsion of the image was randomly distributed. In humans, the location of the fovea beneath a horizontal line drawn through the center of the optic disc has already been demonstrated.10 For the statistical analysis of the correlation between retinal nerve fiber layer visibility and age (Fig. 3) , the values of the old monkeys were important. A look at the scattergram (Fig. 3) shows that the possibility cannot be excluded that, besides a linear relationship, a curvilinear relationship may exist with almost no changes occurring up to the monkey age of 18 years and then a relatively steep loss occurring beyond this age. Further studies on a larger number of monkeys may reveal whether, as has already been reported in humans, in monkeys the relationship between retinal nerve fiber layer visibility and age is also mostly linear.
In conclusion, the appearance of the normal optic nerve head in healthy rhesus monkeys markedly resembles the morphology of the normal optic nerve head in human subjects, so that findings of studies on the optic nerve head in rhesus monkeys may be applicable in humans. Knowledge of the normal appearance of the optic nerve head and retinal nerve fiber layer may be useful for the detection of early changes in the morphology of the optic nerve due to a pathologic loss of optic nerve fibers.
| Footnotes |
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Submitted for publication December 13, 1999; revised February 23, 2000; accepted March 15, 2000.
Commercial relationships policy: N.
Corresponding author: Sohan Singh Hayreh, Department of Ophthalmology and Visual Sciences, University Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa 52242-1091. sohan-hayreh{at}uiowa.edu
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