Original article
Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: an experimental study in rhesus monkeys

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Abstract

PURPOSE: To evaluate the retinal tolerance time to acute ischemic insult in middle-aged or elderly rhesus monkeys with pre-existing atherosclerosis and arterial hypertension.

METHODS: In 39 eyes of 39 middle-aged and elderly rhesus monkeys with a mean age of 19.5 ± 2.8 years, occlusion of the central retinal artery was produced by temporary clamping of the central retinal artery at its site of entry into the dural sheath of the optic nerve for 97 to 300 minutes. Stereoscopic color fundus photography and fluorescein fundus angiography were performed before central retinal artery occlusion and serially thereafter. Retinal nerve fiber layer damage and optic disk changes were assessed by comparing morphometric evaluation of the color fundus photographs taken before central retinal artery occlusion and color fundus photographs taken at the end of the study.

RESULTS: There was a significant correlation between duration of central retinal artery occlusion and decreased visibility of retinal nerve fiber layer (P = .018) and increasing optic disk pallor (P = .014), and a trend between residual retinal circulation and decreased visibility of retinal nerve fiber layer (P = .085) and optic disk pallor (P = .162). However, there was a marked interindividual variation between the length of central retinal artery occlusion and degree of increased optic disk pallor and decreased visibility of the retinal nerve fiber layer, even among eyes with similar duration of central retinal artery occlusion. Complete or almost total optic nerve atrophy and nerve fiber damage were present in all eyes in which the duration of central retinal artery occlusion was 240 minutes or more.

CONCLUSIONS: The findings of this study, compared with our previous study in young healthy rhesus monkeys, indicate that in middle-aged or elderly atherosclerotic and arterial hypertensive rhesus monkeys, central retinal artery occlusion for less than 100 minutes produced no apparent morphometric evidence of optic nerve damage; however, central retinal artery occlusion of 105 minutes but less than 240 minutes produced a variable degree of damage; central retinal artery occlusion for 240 minutes or more produced total or almost total optic nerve atrophy and nerve fiber damage.

Section snippets

Material and methods

This study was conducted on 39 rhesus monkeys (Macaca mulatta), with a mean age of 19.5 ± 2.8 years (mean ± SD; median, 20 years; range, 13 to 24 years, equivalent to 50 to 90 years in humans). At Iowa City, experimental unilateral central retinal artery occlusion was produced in one eye of each monkey by performing a lateral orbitotomy and clamping the central retinal artery transiently, for a variable length of time, at its site of entry into the dural sheath of the optic nerve; the method is

Results

In this study, as in our previous studies with central retinal artery occlusion,3, 10, 11, 12 fluorescein fundus angiography showed that, despite complete occlusion of the central retinal artery by the clamp at its site of entry into the dural sheath of the optic nerve, the retinal vascular bed still filled very slowly and to a highly variable extent, by means of the various anastomoses established by the central retinal artery distal to the site of occlusion.13 The mechanism of filling of the

Discussion

In the present study, there was a significant correlation between duration of central retinal artery occlusion and decreased visibility of retinal nerve fiber layer (P = .018) and increased optic disk pallor (P = .014; Figure 5, Figure 6; there was also a trend between residual retinal circulation and decreased visibility of retinal nerve fiber layer (P = .085) and increased optic disk pallor (P = .162) Figure 7, Figure 8, Figure 9, Figure 10. It is possible that this was a trend but not a

Clinical implications

The primary objective of our experimental study was to find out how long the retina can survive with central retinal artery occlusion before it undergoes irreversible damage. It is essential to have that information before we can assess the outcome of treatment and the prognosis of central retinal artery occlusion in humans. It is also essential to know how applicable the findings of central retinal artery occlusion in elderly, atherosclerotic, hypertensive rhesus monkeys are to humans. The

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    This work was supported by grant EY-1576 from the U.S. National Institutes of Health, in part by unrestricted grants from Research to Prevent Blindness, Inc, New York, New York, and by Deutsche Forschungsgemeinschaft (SFB 539). Dr. S. S. Hayreh is a Research to Prevent Blindness Senior Scientific Investigator.

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