Brit. J. Ophthal. (1976) 60, 428

Central retinal artery occlusion (reversible) insickle trait with glaucoma

RONALD L. RADIUS AND DANIEL FINKELSTEINFrom the Wilmer Ophthalmological Institute, The Johns Hopkins Universityand Hospital, Baltimore, Maryland, USA

Retinal vascular occlusions of several types occur

in the various sickle haemoglobin disorders (SS,SA, SC, S-Thal) (Edington and Sarkies, I952;Henry and Chapman, 1954; Goldberg, 197Ia;Kennedy and Cope, I958; Isbey, Clifford, andTanaka, I958; Lieb, Geeraets, and Guerry,I959). Occlusions are primarily of small vesselsin the peripheral retina preceding the developmentof neovascularization (Welch and Goldberg, I966;Goldberg, 197Ia, b). Occlusions of small vesselsin the macula have also been reported in SS andSC haemoglobinopathy (Knapp, I972; Acacioand Goldberg, I973; Ryan, 1974). They are

probably due to intravascular emboli of sickledred blood cells (Welch and Goldberg, I966;Goldberg, I97ia, b). Factors known to enhancesickling of red cells thereby influencing therisk of vascular thrombosis include hypoxia,dehydration, lowered pH, and hyperviscosity(Sherman, I940; Griggs and Harris, 1956; Perillieand Epstein, I962; Charache and Conley, I964).Not surprisingly, therefore, under certain condi-tions occlusion of large vessels such as the centralretinal artery occur (Kabakow, Van Wiemokly, andLyons, I955; Conrad and Penner, I967; Steinand Gay, I970; Michelson and Pfaffenbach,I972). We report a case of central retinal arteryocclusion in SA disease immediately after diureticand hyperosmotic therapy for acute traumaticglaucoma. We believe that this treatment must beused cautiously in the sickle patient whose ocularcirculation is already compromised by acuteglaucoma.

Case report

An i8-year-old black woman presented to the Wilmeremergency room with a traumatic hyphaema 24 hoursafter a blunt ocular injury. Her medical and familyhistory were unremarkable. Uncorrected visual acuitywas light perception right eye, 20/20 left eye. The

Address for reprints: D. Finkelstein, MD, The Wilmer Ophthal-mological Institute, Johns Hopkins University and Hospital,Baltimore, Maryland 21205, USA

anterior chamber contained diffuse haemorrhage witha layered hyphaema of about io per cent. Ocularmotility was normal. Intraocular pressure by applanationwas 55 mmHg. The fundus could not be visualizedthrough the anterior chamber blood. Examination ofthe left eye was normal in all respects.Treatment consisted of atropine cycloplegia, topical

dexamethasone, and I 20 ml glycerol 75 per cent.Emesis followed shortly after osmotic therapy. Intra-ocular pressure remained raised at 55 mmHg. Subse-quent treatment consisted of intravenous acetazolamide500 mg and mannitol I00 g (1-5 g/kg) at an infusionrate of 5 g/minute. One hour later ocular tension was55 mmHg. Vision in the right eye was no light percep-tion when tested with the American optical indirectophthalmoscope at maximum voltage.The clinical impression was that the patient had

suffered a central retinal artery occlusion. An anteriorchamber paracentesis of o-o8 ml was performed. Afterthis vision returned to brisk light perception. Intra-ocular pressure was subsequently controlled with oralacetazolamide. With clearing of the ocular haemorrhagefundus examination showed disc hyperaemia. Fluores-cein angiography was essentially unremarkable. Elec-troretinography could not be performed. Subsequentserum electrophoresis showed sickle-cell trait (SA)haemoglobinopathy with 42 per cent sickle-cell haemo-globin. Visual acuity returned to the 20/30 level.

Discussion

Our patient presented with an intraocular pressureof 55 mmHg and brisk light perception vision.One hour after diuretic and osmotic therapy thepressure remained at 55 mmHg with no lightperception. This time sequence suggests thatincreased intravascular tonicity and altered haemo-dynamics after these medications may have pre-cipitated an occlusion in an already compromisedvascular system. Intravenous infusion of mannitolis known to increase serum osmolarity fromIo-40 mosm/l depending on rate of infusion anddosage (Galin, Davidson, and Pasmanik, I963;Weiss and Wise, I962; Kolker and Hetherington,1970). Increased serum tonicity occurs rapidlythroughout the infusion and returns to equilibrium

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Central retinal artery occlusion (reversible) 429

over a period of from one to two hours (Galin andothers, I963; Weiss and Wise, I962). The effect ofintravenous acetazolamide is difficult to quantify.The susceptibility of patients with sickle-trait

haemoglobinopathy to central retinal artery occlu-sion at moderately raised or even normal ocularpressures has been well documented. Five cases ofcentral retinal artery occlusion have been reported(Kabakow and others, I955; Conrad and Penner,i967; Stein and Gay, 1970; Michelson and Pfaffen-bach, 1972). Bilateral vascular occlusions weredescribed in a 36-year-old patient with activepulmonary tuberculosis, systemic lupus erythe-matosus, and sickle-cell trait (Kabakow andothers, 1955). Conrad and Penner described centralretinal artery occlusion in a 32-year-old pilot withsickle-trait haemoglobinopathy (unassociated withactive flying duties) (Conrad and Penner, I967).No other precipitating ocular or systemic conditionswere found; the proportion of sickle haemoglobinwas 42 per cent. Vision remained at no light per-ception in the affected eye. Stein and Gay reportedbilateral arterial occlusions in a six-month-oldinfant suffering from high fever and markeddehydration (Stein and Gay, 1970). They suggestthat metabolic abnormalities induced by pneumoniaand renal failure in this 'SA infant might well haveproduced intravascular sickling leading to bilateralcentral artery occlusion. Finally, Michelson andPfaffenbach described two sickle-trait youths witharterial occlusions after blunt trauma and ocularhaemorrhage (Michelson and Pfaffenbach, 1972).Both these patients were treated with diuretic andosmotic agents to control raised intraocular pres-sures ranging from 20 to 50 mmHg.

Various factors affect the severity of the symp-toms in patients with sickle-cell disease. Percentageof abnormal haemoglobin as well as oxygen tension,lowered pH, fever, vascular stasis, hyperkalaemia,raised carbon dioxide level, and serum hyper-tonicity increase the amount of erythrocyte sicklingand subsequent clinical symptoms (Sherman,1940; Griggs and Harris, 1956; Perillie andEpstein, I962; Charache and Conley, I964).Increased serum tonicity after diuretic and osmoticmedications in combination with vascular stasis,presumably coincident with raised intraocularpressures, may have precipitated vascular occlusionin this patient with sickle-cell trait.The possibility that ocular hypotensive medica-

tions may have aggravated the situation calls forre-evaluation of the management of raised oculartension in black patients. We recommend anemergency sickle cell preparation as part of theinitial examination of every black patient withhyphaema. In those with sickle-cell haemoglobinan intraocular pressure over 40 mmHg requirescareful monitoring of vision for the earliest sign

of vascular occlusion. Osmotic agents should begiven with caution and vision must be checkedfrequently thereafter. Only experience with similarcases will show whether such medications mustalways be avoided.

In our case good visual function returned afterretinal blood flow had apparently ceased. Recentreports emphasize that retinal function may returneven when vascular occlusion lasts up to one houror more. Neuronal function may be much moreresistant to absolute ischaemia than previouslyrecognized. After reversible ligation of the centralretinal artery in Squirrel monkeys Kroll (I968)showed that a period of retinal ischaemia limited to15 minutes produced no significant gross or histo-logical damage. Only after one hour of obstructionwas the earliest neuronal damage seen. Reinecke,Kuwabara, Cogan, and Weis (I962) producedretinal ischaemia in cats by increasing intraocularpressure above systolic arterial pressure by externalmassage. In cases in which ischaemia was limitedto less than iI hours only minimal histopathologicalchanges were noted. Lessell and Miller (I975) pro-duced total cerebral as well as retinal ischaemia bycross-clamping the ascending aorta in adult Rhesusmonkeys. When the arterial obstruction was releasedafter periods of 14 to 24 minutes 14 of the 22monkeys had survived this vascular insult, and whenperiods of post-arrest hypotension were avoided,histopathological retinal abnormalities were not seen.These histopathological studies have been corro-

borated by a number of experiments to assess thefunctional resistance of retinal tissue to ischaemia.After reversible occlusion of the retinal vascularsupply in rabbits electroretinograms have returnedto pre-insult levels when anoxia was limited toio minutes (Arden and Greaves, I956). Popp(I955) found that even after 6o to 90 minutes ofischaemia partial recovery was seen in the rabbitERG. Working with Squirrel monkeys, Hamasakiand Kroll (I968) produced reversible retinalartery occlusion by placing a ligature round thesurgically exposed vessel. Remarkably, they showedthat more than two hours of occlusion were re-quired to produce irreversible changes in electricalactivity of the retina and optic nerve. Gourasand Hoff (1970) made similar observations usingan isolated, perfused mammalian eye system.Extending these studies to man, Wegner (1928)produced retinal ischaemia in pre-enucleationspecimens by raising ocular tension well abovesystolic pressures. When the period of retinalischaemia was limited to I5 minutes visual recoverywas full: even after 45 minutes of ischaemia somefunction returned. Under similar experimentalconditions Bock, Bornschein, and Hommer (I963,I964) showed that complete recovery of bothelectrical and physiological retinal activity can be

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430 British Journal of Ophthalmology

obtained even after so long as one hour of absoluteretinal ischaemia. Such investigations suggestthat moderate periods of ischaemia may be expectedto show significant functional recovery if adequateblood supply is restored and maintained.We emphasize that the sickle-cell patient with an

intraocular pressure over 40 mmHg is approachinga precarious situation which may be exacerbatedby osmotic therapy. In our case function returnedfrom no light perception to 20/30 vision. A reviewof the literature on experimental occlusion sug-gests that efforts to restore vision even after one totwo hours of known occlusion should not beconsidered only heroic.

SummaryWe report a case of central retinal artery occlusionin an i8-year-old black woman with sickle-traithaemoglobinopathy and acute glaucoma afterhyphaema. The central retinal artery occlusionoccurred immediately after treatment of the glau-coma with osmotic agents, raising the possibilitythat they played a precipitating role. We suggestthat osmotic agents be used with extreme cautionin sickle patients with glaucoma. The occlusionwas treated by anterior chamber paracentesis witheventual return of good vision. The reversibility ofretinal and optic nerve function after total ischae-mia is discussed.

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