Central retinal artery occlusion.: Retinal survival time

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Abstract

Purpose. To investigate the retinal survival time following central retinal artery occlusion (CRAO).

Methods. In 38 elderly, atherosclerotic and hypertensive rhesus monkeys, transient CRAO (varying from 97 to 240 min) was produced by temporarily clamping the CRA at its site of entry into the optic nerve. Stereoscopic color fundus photography, fluorescein fundus angiography, electroretinography (ERG), and visual evoked potential (VEP) recording were performed before and during CRA clamping, after unclamping, and serially thereafter. After unclamping of the CRA, the animals were followed for variable lengths of time (median duration 8·14 weeks). Finally, the eyes and optic nerves were examined histologically. The data on ERG changes were analyzed in the following four time frames: (1) baseline before CRA clamping, (2) during CRA clamping, (3) immediately after unclamping, and (4) at the end of follow-up. Duration of CRAO was divided into four groups: 97, 105–120, 150–165, and ≥180 min.

Results. A ‘negative ERG’ appeared during CRA clamping. With removal of the CRA clamp, there was b-wave recovery, with differential rates of recovery of ERG-eyes with shorter CRAO recovered sooner than those with longer occlusion. On removal of clamp, recovery was seen in scotopic 24 dB b-wave, photopic 0 dB single flash b-wave and 30 Hz flicker, with the b/a ratio of the combined rod and cone response and selective rod response showing statistically significant differences amongst the shorter and longer periods of CRAO. A delayed normalization of the depressed b/a ratio immediately after CRA reperfusion may indicate high-grade ischemic damage. At the final follow-up test session, no clear-cut derangement of any ERG parameter was seen for any group, with subtotal b-wave amplitude recovery for all groups. Longer CRAO produced incomplete VEP recovery.

On histology, in the macular retina, eyes with CRAO for 97 min showed practically no damage, but duration of CRAO was found to be significantly associated with the amount of damage in the ganglion cell layer (p=0·009) and inner nuclear layer (p=0·017). Outer nuclear and plexiform layers and photoreceptors showed no damage at all with CRAO. There was no significant association of the ERG measures and histologic changes with any of the residual retinal circulation variables.

Conclusions. Our electrophysiologic, histopathologic and morphometric studies showed that the retina of old, atherosclerotic, hypertensive rhesus monkeys suffers no detectable damage with CRAO of 97 min but above that level, the longer the CRAO, the more extensive the irreversible damage. The study suggests that CRAO lasting for about 240 min results in massive irreversible retinal damage.

Introduction

Central retinal artery occlusion (CRAO) produces sudden, catastrophic visual loss. It is a true ophthalmic emergency, in that every minute that elapses increases the chances of irreversible retinal damage. In 1980, based on experimental studies in rhesus monkeys, Hayreh and co-workers (Hayreh et al., 1980, Hayreh and Weingeist, 1980a, Hayreh and Weingeist, 1980b) reported that retinal damage following CRAO is reversible if CRAO lasts for 97–98 min, but the retina suffers irreversible damage after ischemia of 105 min. This contradicted the conventional thinking based on findings in the brain, that irreversible ischemic damage in the retina occurred much sooner. Critics felt that the retina survived as long as it did in that study because the monkeys were young, normal and healthy, and that typical CRAO patients, who are generally old, atherosclerotic and hypertensive, would probably have a much shorter retinal ischemic tolerance time. To investigate whether that was the case, we embarked upon the development of a cohort of rhesus monkeys which would mimic typical CRAO patients — by means of experimental atherosclerosis and chronic arterial hypertension, lasting for many years. By the time we undertook the present experimental study on CRAO, the monkeys were indeed old, atherosclerotic and hypertensive.

Section snippets

Material and methods

The study comprised 38 rhesus monkeys (Macaca mulatta) with a mean age of 19·5±2·8 years (mean±s.d.; median: 20 years; range, 13–24 years; human equivalent about 50–90 years). The study design complied with the National Institute of Health's as well as the University of Iowa's Institutional Guidelines for the Care and Use of Laboratory Animals. In these monkeys atherosclerosis was produced experimentally by feeding the animals a special atherogenic diet continuously for many years (Hayreh et

Follow-up duration from CRA unclamping onwards

All animals, except for one (with CRAO for 105 min that died on the day of CRAO), were followed serially by doing various studies mentioned above. The median (25–75th percentile) follow-up duration was: (i) 5·93 (2·00–8·86) weeks for 97 min CRAO, (ii) 8·00 (4·86–11·86) weeks for 105–120 min CRAO, (iii) 9·28 (7·36–10·78) weeks for 150–165 min CRAO, and (iv) 10·72 (7·00–15·86) weeks for ≥180 min CRAO. The duration of follow-up was not significantly different among the four CRAO duration groups (p

Discussion

The primary objective of the present study was to find out from an experimental study in rhesus monkeys how long it takes for CRAO to produce irreversible retinal damage, because of the paramount importance of that fact in the management of patients with CRAO. There is much confusion in the literature about this length of time, based on anecdotal clinical case reports and experimental studies (Hayreh and Weingeist, 1980b).

Acknowledgments

We are grateful to Mrs Donna McAllister and Ms Betty Follmer for their expert assistance with the experimental study, and to Ms Georgiane Perret and Ms Trish Duffel for help with bibliography. Supported in part by grants EY-1576 from the National Institutes of Health, Bethesda, MD, USA, and in part by unrestricted grant from Research to Prevent Blindness, Inc., New York, USA.

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    Dr S.S. Hayreh is a Research to Prevent Blindness Senior Scientific Investigator.

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