Sir,

Ocular ischaemic syndrome (OIS) is caused by chronic ocular hypoperfusion, usually secondary to severe carotid artery obstruction.1 Iris neovascularization is the most common anterior segment finding at diagnosis and typical fundus signs include retinal arteriole narrowing, retinal venous dilatation without tortuosity, midperipheral retinal haemorrhages and microaneurysms, and peripheral vascular closure.2,3,4 We report a case of bilateral OIS presenting in the absence of carotid artery obstruction and discuss possible aetiological factors, including elevated plasma homocysteine.

Case report

A 45-year-old man was referred to the eye department with gradual, painless loss of vision in the right eye. He had been a heavy smoker from 13 years of age (30–40 self-rolled cigarettes per day) and had previously consumed significant amounts of alcohol (up to 20 units per day). He had no symptoms of coronary, cerebral or peripheral vascular disease, but reported Raynaud’s phenomenon in his hands and feet.

Initial ocular examination revealed best corrected Snellen visual acuity of right eye 6/36, and left eye 6/9. The right eye showed iris neovascularization, a relative afferent pupil defect, intraocular pressure of 22 mmHg, and mid peripheral retinal dot and blot haemorrhages. Left ocular examination was normal. Fluorescein angiography demonstrated signs of OIS with a leading edge of dye within the retinal arterioles, and midperipheral haemorrhages, microaneurysms and vascular closure.2 Panretinal photocoagulation was applied to the right eye (argon green laser, 5000 burns at 200 μm diameter with the Volk SuperQuad 160 contact lens—magnification factor of 2.0), but over the next 3 years progressive neovascular glaucoma and cataract reduced vision to no light perception.

Seven years after initial presentation, fine iris neovascularization developed in the left eye and the intraocular pressure began to rise progressively. Left fundoscopy showed narrowed retinal arterioles and scattered dot and blot haemorrhages and microaneurysms in the midperiphery with a few extending to the posterior pole. Fluorescein angiography was again typical of OIS with a delayed arm to retina circulation time, a leading edge of dye within narrowed retinal arterioles, prolonged arteriovenous transit time (28 s) and midperipheral haemorrhages and microaneurysms (Figure 1a–f). Panretinal photocoagulation (argon green laser, 8000 burns at 200 μm diameter with the Volk SuperQuad 160 contact lens) supplemented by peripheral retinal cryotherapy caused regression of the iris new vessels, but the intraocular pressure remained elevated despite medical treatment. Following mitomycin trabeculectomy the left intraocular pressure was well controlled without medication. Eighteen months after development of iris neovascularization in the left eye, corrected acuity remained at 6/9.

Figure 1
figure 1

Left eye. Fluorescein angiogram. The times indicate the interval following injection of fluorescein. (a) 69 s. Arrow points to leading edge of fluorescein in arteriole. (b) 72 s. (c) 78 s. Arrow points to arteriole now filled with fluorescein. (d) 83 s. Note delayed venous filling temporal to fovea. (e) 97 s. Note venous filling now complete. (f) 163 s. Inferior mid periphery showing microaneurysms and blot haemorrhages.

Full size image

Systemic investigations showed normal blood pressure (130/80) and sinus rhythm. Carotid doppler ultrasound showed normal flow in the common, external and internal carotid arteries on both sides. Ophthalmic doppler ultrasound showed normal flow in the ophthalmic arteries, the central retinal arteries and veins, and the posterior ciliary vessels of both eyes. The following blood tests were all normal: U&E, LFT, glucose, FBC, ESR, lipids, coagulation, plasma viscosity, serum immunoglobulins, serum electrophoresis, antithrombin III, protein C and S, ANA, rheumatoid factor, VDRL. Plasma vitamin B-12 was 192 ng/l (normal range 155–1100) and folate was 3.0 ng/ml (normal range 2.8–12.4). Plasma homocysteine was elevated at 20.8 μmol/l (normal range 5–15). He was treated systemically with low dose aspirin and folic acid, and was advised to stop smoking.

Comment

Our patient presented with classical signs of OIS but without carotid artery obstruction. Ocular hypoperfusion in OIS is usually secondary to severe carotid artery obstruction but a recent large prospective study found that 26% of eyes with OIS had mild or no ipsilateral carotid artery stenosis.3 The authors of that study suggested vascular occlusive disease of the aortic arch, ophthalmic, central retinal or ciliary arteries as the cause for OIS in such patients. Doppler ultrasound studies showed normal flow in our patient’s carotid, ophthalmic, central retinal and ciliary arteries. He also had no symptoms of macrovascular disease (angina, claudication or transient ischaemic attacks). We presume that widespread microvascular disease and undetected macrovascular disease (without areas of focal stenosis) had cumulatively impaired ocular blood flow.

Cigarette smoking is a well-known risk factor for vascular disease: our patient was counselled to stop smoking and low dose aspirin prescribed. As he presented at a comparatively young age, we screened for haematological risk factors for vascular occlusive disease. The only abnormality detected was a significantly elevated plasma homocysteine level. Elevated plasma homocysteine is considered an independent graded risk factor for arteriosclerotic vascular diseases,5 and modestly elevated plasma homocysteine levels are known to cause vascular endothelial dysfunction.6 Hyperhomocysteinaemia has recently been reported as a possible risk factor for retinal vascular disease,7 and we now suggest that it may be an independent risk factor for ocular ischaemic syndrome.

Daily folic acid and vitamin B-12 supplementation has been shown to reduce blood homocysteine concentrations by about a quarter to a third, with the majority of the effect attributable to folic acid.8 Although there seem to have been no large-scale trials examining the effect on vascular morbidity of lowering plasma homocysteine levels, we prescribed daily low dose folic acid for our patient as his plasma folate was in the lower end of the normal range and he had a high risk of progressive visual loss.

Panretinal photocoagulation (PRP) in OIS has been shown to cause regression of iris new vessels in 36% of eyes.9 Moderate PRP alone was unsuccessful in stabilizing our patient’s right eye. However, more extensive PRP and retinal cryotherapy followed by mitomycin trabeculectomy has currently stabilised his left eye. Through the above surgical treatments and risk factor modifications we hope this patient will preserve useful sight in his left eye.