British Journal of Ophthalmology, 1985, 69, 681-687

Syndrome of ischaemic ocular inflammation: six casesand a reviewN A JACOBS AND A E A RIDGWAY

From Manchester Royal Eye Hospital

SUMMARY Patients with carotid occlusive disease may develop a variety of symptoms and signssecondary to chronic ocular ischaemia. We report six cases affecting nine eyes and review thefindings of teichopsia, anterior segment ischaemia, venous stasis retinopathy, and ocularneovascularisation. The assessment and surgical management of carotid obstruction are.discussed.Some comments on the relevance of coexisting diabetes are made.

Although much attention has been paid to the acuteocular manifestations of carotid arterial disease, thechronic aspects have been less well reported. Retinalischaemia is a more familiar concept than ischaemiaof the eye as a whole.The syndrome of ischaemic ocular inflammation

described by Knox' consists of amaurosis fugax, painwithout photophobia, and marked reduction in visualacuity disproportionate to the degree of inflamma-tion. The pupil is dilated, and the fundus showsmidperipheral haemorrhages and arterial narrowing.We discuss the manifestations of chronic ocular

ischaemia in six patients with underlying carotidocclusive disease. Successful management maydepend on expeditious identification and referral ofthese patients.

Case reports

CASE 1A woman aged 39, a smoker and a hypertensive witha history of right-sided transient ischaemic attacksand angina, presented with a two-year history ofblurred left vision. This followed an episode ofamaurosis fugax. She also complained of pain andpersisting after-images in this eye for two months.Visual acuity (VA) was 6/12, with mild anteriorchamber activity and early formation of peripheralanterior synechiae (PAS). The fundus showedmarked venous stasis with beading, haemorrhages,

Correspondence to Mr N A Jacobs, Dcpartment of Ophthalmology,Charing Cross Hospital, Fulham Palace Road, London W6 8RF.

and microaneurysms (Fig. 1). Fine disc new vesselswere present.We saw her one month after the successful

saphenous by-pass graft for a left common carotidartery occlusion which had been demonstrated onangiography (Fig. 2).

CASE 2A man aged 55, a smoker, presented with a five-dayhistory of a 'fierce pain' over the right eye associatedwith blurred vision. VA was 6/36, with an unreactivedilated pupil, rubeosis of the angle, and an intraocularpressure (IOP) of 30 mmHg. Iris angiography con-firmed ischaemia. There was also venous stasisretinopathy (Fig. 3) associated with cotton-woolspots. On review three months later episcleral injec-tion, uveitis, and new vessels over the disc were alsoobserved.A left carotid bruit was heard. Angiography

revealed occlusion of the right internal carotid arteryand left internal carotid stenosis (Fig. 4). A leftcarotid endarterectomy was performed.One year after the patient's initial presentation the

right VA was perception of light (PL), with forma-tion of a complicated cataract.

CASE 3A man aged 67, a smoker and a hypertensiverecovering from a right hemiparesis, presented with asix-month history of gradually deteriorating leftvision. He also complained of pain over the left eyeand a persisting after-image described as a 'jaggedgold light'. His VA was counting fingers (CF), withepiscleral injection, anterior chamber flare, early

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Fig. 1 Leftfundusfluorescein angiogram (case 1) showingmicroaneurysms and venous beading.

rubeosis iridis, and an unreactive dilated pupil.Fundal examination showed venous stasis retino-pathy and cotton-wool spots.

Carotid auscultation was hindered by an aorticvalve murmur, but intravenous digital subtractionangiography showed arch atheroma with leftcommon carotid artery occlusion.

Fig. 2 Arch aortogram (case 1) showing occluded leftcommon carotid artery (arrow).

Fig. 3 Venous stasis retinopathy (case 2) well marked innasal quadrant.

Eight months after the patient's initial presenta-tion the left VA was PL, with a complicated cataractand rubeotic glaucoma. The IOP was 25 mmHg.

CASE 4A man aged 66, a hypertensive recovering from aright hemiparesis, was found to be diabetic on

Fig. 4 Carotid angiography (case2) shows rightinternalcarotid occlusion (black arrow) with left internal carotidstenosis (white arrow).

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Syndrome ofischaemic ocular inflammation: six cases and a review

presentation. He complained of left-sided floatersfollowing an episode of amaurosis fugax. His VA was6/18 right, 6/12 left, with bilateral rubeosis iridis andIOPs of 20 mmHg right, 24 mmHg left. Both fundishowed only mild background diabetic change. Inaddition there was a left vitreous haemorrhageemanating from the disc.Two months later he complained of pain over the

left eye. His VA was CF, with anterior chamber flareand rubeotic glaucoma, with an IOP of 35 mmHg. Afull retinal laser photocoagulation was carried out inthis eye. After a further four months the VA on theright had fallen to 6/36, and a right macular branchvein occlusion was noted. The left fundus showed theappearance of an old central retinal artery occlusionassociated with a pale disc. Rubeosis iridis wasmarked bilaterally.He was experiencing episodes of disorientation.

Bilateral carotid bruits were noted, but intravenousdigital subtraction angiography was not helpful.

Eighteen months after initial presentation his VAwas hand movements right, PL left, with complicatedcataracts and rubeotic glaucoma bilaterally (Fig. 5).

CASE 5A man aged 55, a diabetic with hypertension andangina pectoris, presented with episodes of upperfield amaurosis in his amblyopic right eye. His VAwas 6/60, with an upper macular branch arteryocclusion. Six months later he complained of'coloured lights' affecting central vision, precipitatedby straining. Soon afterwards he returned with a rightvitreous haemorrhage and disc new vessels.Episcleral injection, anterior uveitis with posteriorsynechiae, and early PAS were noted. Despite partialretinal laser photocoagulation, gross proliferative

Fig. 5 End stage ofrubeotic glaucoma with secondarycataract (case 4).

Fig. 6 Gross proliferativeretinopathy (caseS) in diabeticpatient whosefellow eyeshowed minimal change.

retinopathy with traction detachment ensued(Fig. 6). At around this time he suffered two left-sided hemipareses.On review two years after his initial presentation

he gave a history of persisting positive scotomata inthe left eye, particularly on waking. His VA was 6/9,and examination of this previously normal eyeshowed the appearance of venous stasis retinopathy.

Bilateral carotid bruits were detected. Angio-graphy revealed occlusion of the right internalcarotid artery, with tight stenoses of the left internaland external carotid arteries.

CASE 6A man aged 77, a hypertensive and an ex-smoker,presented with episodes of left upper fieldamaurosis fugax and blurring of vision. He alsocomplained of seeing bright flashes of light andpersisting after-images likened to 'a bright map ofAustralia'. His VA was 6/5 and no ocular abnor-mality was found. Fifteen months later he returnedwith a VA of 6/24 in this eye. Fine rubeosis of thepupil margin, gross disc new vessels (Figs. 7A, B) andperipheral blot haemorrhages on the retina wereapparent. A full retinal laser photocoagulationcaused only a temporary regression of the disc newvessels. After a further three months he complainedof blurred right vision, and this eye also showedvenous stasis retinopathy with disc new vessels.A right carotid bruit was heard. Carotid angio-

graphy showed bilateral internal carotid stenoses,more marked on the right, and in addition bilateral

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Fig. 7A Left redfreephotograph showing gross discneovascularisation (case 6).

external carotid stenoses were present, more markedon the right (Fig. 8).The case reports are summarised in Table 1.

Discussion

Because the time sequence of events is relativelyshort prompt investigation of patients presentingwith symptoms and signs of chronic ocular ischaemiais desirable, as early intervention may offer hope oftherapeutic effect. For this reason a high index ofsuspicion is necessary.The visual symptom of note was the description of

positive after-images on exposure to bright light,described variously by our patients as 'jagged goldlights', 'coloured lights', and 'a bright map ofAustralia'. Ross-Russell and Page2 have previouslydrawn attention to positive scotomata in patientswith carotid artery obstruction. Furlan et al.3reported five such patients who complained of blur-ring of vision after exposure to sunlight. Brindley,4investigating positive after-images, concluded thatafter the first few seconds these were due to photo-chemical effects. Possibly choroidal vascular in-sufficiency leads to compromise of photoreceptormetabolism.The signs of chronic anterior segment ischaemial

have been well documented in the context of thechanges seen after extensive extraocular musclesurgery.6 Our patients showed episcleral injection,anterior uveitis, and iris atrophy. Iris angiography

Fig. 7B Fluorescein angiogram shows leakage ofdisc newvessels associated with slow irregular choroidalfilling.

confirmed ischaemia (case 2). Of six eyes withinflammatory signs four had rubeotic glaucoma, asign which has not been reported after acute anteriorsegment ischaemia.5 Neovascularisation of the iris,may follow release of vasoproliferative agents,anteriorly from chronically ischaemic iris andposteriorly from ischaemic retina and choroid.7 Theeyes with rubeosis had relatively low TOPs(25-35 mmHg), which we think are explained by lowperfusion pressures' causing reduced ciliary bodyblood flow. Pain in this syndrome'89 is probablyrelated to ischaemia rather than to increase of IOP.Venous stasis retinopathy, described by Kearns

and Hollenhorst9 and consisting of venous dilatation,microaneurysms (Fig. 1), and blossom haemorrhages(Fig. 3), is the commonest ocular sign of chronicischaemia in carotid obstruction, reported in up to20%9 "' of cases.The haemorrhages are larger and darker than

those of diabetic retinopathy, are found in themidperiphery, and may be limited to one quadrant.In addition cotton-wool spots may be seen. Discneovascularisation (Fig. 7) has been described morerecently' as a response to chronic ischaemia of theretina and choroid (Fig. 7B). Diabetic patients pre-sent special diagnostic difficulty, for early stasisretinopathy is difficult to recognise. Important cluesare marked asymmetry of retinopathy8 (Fig. 6) andgross disproportion in the extent of anterior andposterior segment pathology (case 4).

Earlier reports of chronic ocular ischaemia showed

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most patients to have aortic arch disease, with loss ofperipheral pulses'" due to atheroma, Takayashu'spulseless disease,'2" or syphilitic aortitis. In ourpatients the major factor was atheroma affecting thecarotid systems. Four of them had central nervoussystem involvement consistent with carotid arterydisease, three of them having had a completedstroke. Amaurosis fugax is the commonest ocularsymptom of carotid occlusive disease, and was des-cribed by four patients. The manifestations ofchronic ocular ischaemia are far less common, and,although they may coexist, patients presenting withamaurosis fugax are not particularly likely to developchronic ischaemic signs.Many diagnostic techniques are available for

carotid investigation. Ophthalmodynamometry andocular plethysmography assess carotid artery patencyby measurement of the ophthalmic artery pulsepressure. The latter is the more useful test if bilaterallesions are present. 4 The dynamic response tocarotid artery compression may be monitored tono-graphically. '5 Continuous wave Doppler'6 is helpful inestablishing whether a significant stenosis is presentat the carotid bifurcation, and has the advantage ofbeing non-invasive. Real-time ultrasound'6 canreveal the presence of atheromatous plaques even ifthey do not have a significant haemodynamic effect.If no carotid artery lesions are present, or if thepatients have cardiac arrhythmias, cardiacechography'7 should be carried out to exclude emboli

of cardiac origin. Arteriography is the most reliablemethod of demonstrating carotid artery lesions, butthis carries a complication rate of up to 3.7%.'Intravenous digital subtraction angiography is safer,and has been reported in as many as 96% '8of selectedcases to show a lesion at the carotid bifurcation.Our findings were similar to those of Brown et al.'

There was either common carotid occlusion on theaffected side (Fig. 2) or bilateral internal carotidobstruction (Fig. 4). The patients with bilateralocular involvement showed a combination of internaland external carotid stenoses (Fig. 8). The pattern ofcarotid disease seems to be aetiologically importantin the development of chronic ocular ischaemia.Huckman and Haas'9 have reported two cases inwhich there was reversal of flow in the ophthalmicartery, and have suggested there may be a 'steal'syndrome. However, this reversal of flow is acommon finding in internal carotid obstruction, andone of our patients (case 6) has orthograde flow in theleft and retrograde flow in the right ophthalmicartery, yet shows bilateral ocular ischaemia.

Stenosis of the origin of the internal carotid arterycan be relieved by endarterectomy. However,internal carotid occlusion cannot be dealt with in thisway, as retrograde thrombosis up to the level of theophthalmic artery occurs. By taking advantage of theexternal carotid supply it may instead be by-passedwith an anastomosis of the superficial temporal arteryto a carotid branch of the middle cerebral artery."

Table 1 Summary ofthe case reports

Case General CNS Angio- Eye Amaurosis Ischaemic Episcleral Rubeotic Ischaemic Venous Discno. bealth involvement graphy visual injection glaucoma pain stasis' new

Age results symptoms and/or Low IOP vesselsanteriorchamberactivity

1 Hypertension, Transient LCC LE + + + - + + +angina, smoker, ischaemic occluded39 yr attacks, R side

2 Smoker, Light-headed, R IC occluded RE - - + + + + +55 yr unwell L IC stenosed

3 Hypertension, RCVA LCC LE - + + + + +smoker, occluded67 yr

4 Hypertension, RCVA, LE + - + + + - +diabetes, episodes of66 yr confusion RE + - + +

5 Hypertension, LCVAx2 R IC RE + + + - + - +angina, occludeddiabetes, L IC + EC55 yr stenosed LE - + - - - +

6* Hypertension, Nil Bilateral LE + + - - - + +ex-smoker, IC + EC77 yr stenosed RE - + - - - + +

*This patient's lcft eye showcd fine rubeosis of the pupil margin. CNS=central nervous system. CVA=cerebrovascular accident.CC=common carotid artery. IC=internal carotid artery. EC=external carotid artery.

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Fig. 8 Subtraction angiogram (case 6) showing rightinternal (straight arrow) and external carotid stenoses(curved arrow).

This may not be feasible if the external carotid arteryitself is also severely affected. Several case reports ofsuccessful by-pass surgery for the relief of ocularischaemia have been published. ""-23

Laser retinal photocoagulation was ineffective inthe treatment of disc neovascularisation in our

patients. The possibility exists that in establishedrubeosis, given that ischaemia can be relieved surgic-ally, trabeculectomy may control ocular hyperten-sion, as can occur in the management of diabeticneovascular glaucoma.24 By the end stage of thissyndrome with rubeotic glaucoma, secondarycataract (Fig. 5) and probably occult central retinalartery occlusion,8 nothing can be done except for therelief of ischaemic pain,"' Recorded attempts at lensextraction'2 show this to be unsuccessful.The syndrome of ocular inflammation secondary to

chronic ischaemia is uncommon, and neitherophthalmologists nor other specialists dealing withpatients with carotid artery disease have muchexperience of the condition. Its diagnosis is made

more difficult because it causes a plethora of signsand has to be differentiated from other causes ofdecreased visual acuity, ocular pain, teichopsia,anterior uveitis, rubeotic glaucoma, retinal venousdilatation with haemorrhages, and disc new vesselformation. Early recognition of the syndrome ofchronic ocular ischaemia is important because thereis now hope of useful improvement by reconstructivevascular surgery in the initial stages, while treatmentlater on fails to halt progression of the disease.

We extend our thanks to Lynn Griffin for her secretarial assistance,to the Department of Retinal Photography at Manchester Royal EyeHospital, and to the Department of Medical Illustration atManchester Royal Infirmary.

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