An Ocular Chameleon

Abstract

Patients presenting with transient visual loss is common in emergency departments. Neurologists, ophthalmologists and emergency care physicians may be called upon to evaluate such patients. Monocular visual loss should be differentiated from the binocular involvement as the oetologies, investigations and management of such patients differ considerably. We report a case of monocular visual loss that involved predominantly one eye but affected the other side independently, albeit less frequently. A meticulous history, thorough general, neurological and ophthalmological examinations are necessary in such patients to identify the cause and to treat appropriately. Ocular ischemic syndrome (OIS) is due to chronic hypoperfusion of the structures supplied by ophthalmic artery leading to monocular visual loss. Stenosis of the ipsilateral internal carotid artery from a variety of causes is the main underlying mechanism. The first case of OIS was reported by Hedges in 1963 and the term was coined later by Barry and Magargal. Ocular ischemic syndrome is an important differential diagnosis to consider especially in older people and those with vascular risk factors. An overview of important differential diagnosis, clinical features and treatment of OIC are discussed in this article. A multidisciplinary team is optimal for the management of ocular ischemic syndrome.

Introduction

Monocular visual loss is not an uncommon presenting symptom which needs a meticulous history, full medical and neurological examinations as well as a detailed ophthalmological assessment. It carries a wide differential diagnosis. Amaurosis fugax secondary to embolisation from the ipsilateral carotid arteries, central retinal artery occlusion (CRAO), ocular ischemic syndrome, retinal migraine, acute angle closure glaucoma, retinal detachment, giant cell arteritis/anterior ischaemic optic neuropathy (AION), non-arteritic ischaemic optic neuropathy (NAION), optic neuritis, orbital and pituitary tumours are some of the important causes that may lead to unilateral blindness. The correct diagnosis and treatment can not only save the sight on the affected side but could also foretell life threating disease such as ischaemic strokes. A multi-speciality team may improve the outcome.

Case Report

A 68-year-old ex-serviceman attended the emergency department with a history of recurrent visual symptoms. He had noticed transient coloured lights, 1 year prior to the presentation which subsided without any intervention after a few weeks. The symptoms recurred 6 months later and were described as episodes of bright lights that would last ∼30 minutes followed by “grey pixels” persisting for 5 minutes before settling abruptly. He complained of poor vision during these attacks in the affected eye with full recovery in between. Attacks were more frequent and severe on the right side but could affect both eyes independently. Some of these episodes were associated with discomfort in the right supra-orbital region. He had no nausea, vomiting or phonophobia. Background medical history included migraines in his younger days, hypertension, restless leg syndrome, depression and post-traumatic stress disorder. He is a non-smoker. He was in sinus rhythm with normal blood pressure. Neurological examination was normal. Visualisation of optic fundi through an undilated pupil was interpreted as unremarkable. No carotid or ocular bruits were heard. A provisional diagnosis of retinal migraine was made and he was given calcium channel blocker as a preventive medication. Subsequently, he had trials of pizotifen, propranolol and Topiramate. Amitriptyline was not tried due to potential interaction with moclobomide. ¹

When the patient failed to improve, further investigations were ordered including an MR scan of the brain (Figure 1A) and the cerebral vasculatures as well as carotid Doppler ultrasound scans. The neuroimaging showed an almost completely occluded right internal carotid artery (ICA) and focus of previous infarction in frontal lobe. Carotid Doppler ultrasonography reported 70-80% stenosis of the left ICA and total occlusion of right ICA. Anterograde flow was noted in both vertebral arteries. Ultrasound findings were later confirmed by CT angiogram.

Figure 1:

(a) T2 weighted axial MRI image showing previous right frontal infarction, (b) Fluorescein angiography showing mid choroidal blockage, (c) Retinal photograph of the right eye showing dot and blot haemorrhage, (d) SPECT image post Diamox showing reduced perfusion in the right frontal lobe. (e) Left common carotid DSA showing severe stenosis at the origin of internal carotid in the neck (arrow), (f) Right common carotid DSA showing severe stenosis at the origin of internal carotid in the neck (arrow), (g) DSA study post carotid endarterectomy showing improved left ICA calibre, (h) DSA study post carotid stent showing improved right ICA calibre.

In view of the above findings, further investigations (Table 1) were ordered and history was revisited. A positive family history of premature atherosclerosis and precipitation of symptoms, initially after strenuous physical exertion and later on during routine activities were obtained.

Table 1.

Investigations Performed in Our Patient.

Investigations
• Routine bloods	• ECG
• ESR	• Transthoracic echocardiogram
• Lupus anticoagulant	• 24-h Holter monitor
• Anticardiolipin antibody	• MRI brain & MRA
• Serum homocysteine	• Doppler carotid ultrasound
• Lipid profile	• CT cerebral angiogram
• Fasting blood sugar	• Fluorescein angiogram
• VDRL	• Diamox SPECT scan
• Vasculitis screen	• DSA of carotid arteries

The diagnosis of this gentleman was changed to bilateral ocular ischemic syndrome after ophthalmological consultation. Visual acuity was recorded as 6/6, N6 on the right and 6/4, N5 on the left. He was bilaterally pseudophakic. Asymmetric lowering of IOP of the right eye was noted. Fluorescein angiography revealed choroidal blockage on the right side (Figure 1B). The right fundus showed mid-peripheral haemorrhages (Figure 1C). Rubeosis was not present. Antiplatelet agents (aspirin and clopidogrel) and statin were added.

Due to the persistent symptoms in spite of medical therapy, the patient underwent left carotid endarterectomy after a digital substraction cerebral angiogram which improved his left eye symptoms and stabilized the progression of the symptoms in the right eye. ² A diamox SPECT study demonstrated the improved perfusion on the left cerebral hemisphere but persistent changes on the right (Figure 1D). The response was a clear indication that augmentation of blood flow to the right hemisphere could potentially help further. Previously noted right carotid occlusion, likely from an arterial dissection at the onset of symptoms demonstrated partial recanalization of the occluded lumen in the follow up imaging. The treatment options in this scenario were either endovascular stenting or extracranial to intracranial (EC-IC) bypass surgery. ³ The concern for EC-IC bypass was damage to the already developed collaterals and the age of the patient. The patient underwent stenting of the cervical portion of the right ICA that was initially complicated by stent blockage needing suction thrombectomy (Figures 1E-1H). Following the procedure, clopidogrel was replaced with ticagrelor. Patient reported complete resolution of his ocular symptoms and had no focal neurological deficits when followed up 3 months after the procedure.

Discussion

The retina, optic nerve head and choroid has a high oxygen requirement and is supplied by two arteries, central retinal (CRA) and short posterior ciliary arteries (SPCA). The blood flow to these tissues are 10-fold higher than to the brain. ⁴ Both CRA and SPCA originates from the ophthalmic artery which is the first intradural branch of ICA. Hence occlusion and critical stenosis of ICA or common carotid arteries (CCA) may cause impaired blood flow to the retina, choroid and optic nerve head. CRA and SPCA are considered as end-arterial systems, however micro-cannulation, perfusion and labelling studies have shown that there is a cross supply of these tissues. ⁵

Reduced blood flow to the eyes secondary to carotid stenosis can lead to ocular ischemic syndrome (OIS). It is generally seen in the older age groups; males are affected more than females. If undetected, it can lead to permanent visual impairment. Carotid occlusive disease, the underlying pathology for OIS, reflects systemic atherosclerotic process than can lead to ischaemic strokes and cardiovascular events. ⁶ OCI is bilateral in ∼20% of cases and is generally seen when the stenosis is >70% of the ipsilateral ICA or CCA. The variable clinical manifestations could be attributed to the state of collateral circulation with ECA. The clinical features of OIS include amaurosis fugax, prolonged visual recovery on exposure to bright light, photophobia, floaters, metamorphopsia, phosphenes, diplopia, ocular/periorbital pain and progressive visual loss. ⁷ Examination may reveal typical mid-peripheral retinal haemorrhage and lowered intraocular pressure. Neovascular complications may develop with rubeosis iridis leading to neovascular glaucoma and optic neuropathy. Fluorescein angiogram, electroretinogram and indocyanine green angiography may be useful for evaluating choroidal-retinal vasculature. Since ocular features alone can be unreliable predictor of carotid disease, additional signs such as carotid bruit should be sought and patient referred for carotid Doppler ultrasound that has sensitivity of 89% and 96% and specificity of 84% and 100% respectively for detecting stenosis and occlusion. ⁸

OIS carries a wide differential diagnosis such as retinal migraine (ICHD-3; 1.2.4). ⁹ Most common cause for the monocular transient visual loss is amaurosis fugax secondary to an embolus from the carotid arterial system or from the heart. ¹⁰ Retinal migraine (RM) on the other hand is a subcategory of migraine with aura. Generally ocular symptoms last 5-60 minutes and manifest as photopsia or/and scotomas followed by transient blindness (Table 2). Patient develops a dull ache behind the ipsilateral eye within an hour after the onset of visual symptoms. In most cases, RM starts in the second decade and peaks in the 3rd or 4th decades. It is more common in females. The pathophysiology of this condition remains controversial with both vasospasm as well as spreading depression of the retinal neurons suggested as putative mechanisms. It has a prevalence of 1 in 200 in migraineurs. ¹¹ Visual symptoms precipitated by bending over and strenuous exercises has been described. It is important to confirm the monocular, reversible involvement either by examining the patient during an attack or asking the patient to draw the visual field after giving proper instructions.

Table 2.

Salient Features Differentiating OIS From Retinal Migraines.

Clinical features	Ocular ischaemic syndrome	Retinal migraine
Age	Older (typically 60+)	Younger (20-40)
Sex	M>F	F>M
Duration minutes	Minutes to progressive visual loss	Full recovery within 5-60
Signs	Ocular ischemia+/−carotid bruit	Normal between the episodes
Associated features	Vascular risk factors	History of migraines

Other monocular causes that need to be considered are CRAO, acute angle closure glaucoma, giant cell arteritis/AION, NAION, optic neuritis, retinal detachment, orbital and pituitary tumours. NAION typically presents with acute unilateral painless vision loss accompanied by optic disc oedema, ¹² whereas patients with AION often have history suggestive of GSA. ¹³ Guideline exists for the management of CRAO. ¹⁴ Associated clinical features of these diagnosis should be sought in the history, during examination and while ordering investigations. Bilateral transient visual loss results most often from visual aura of migraine with or without headache (ICHD-3; 1.2.1.1/1.2.1.2). Vertebrobasilar ishaemia, and orthostatic hypotension are some of the important aetiologies.

This case highlights a number of valuable lessons in the evaluation of patients with monocular visual loss. First of all, the importance of an accurate history and re-evaluation of the diagnosis when the expected outcomes are not met. Secondly, the visualisation of optic fundi through a fully dilated pupil by an experienced clinician is mandatory and a multispecialty team input is desirable and often necessary. Thirdly, past history of migraine has led to the introduction of bias in the initial assessment of our patient. Hill et al reviewed 142 cases of retinal migraine and found that only 5 have met the international headache society’s criteria at the time. ¹⁵ It is worth remembering that, transient monocular visual loss is ischaemic until proven otherwise especially in older age groups and investigations to look for the vascular causes should be included in the initial evaluation, paying attention to the red flags.

“When you change the way you look at things, the things you look at change.”

- MAX PLANCK

ORCID iD

Mohamed Shaffi https://orcid.org/0000-0001-6935-813X