Migrainous infarction of the eye: Two cases of monocular ischemic complications associated with retinal migraine

Abstract

Background

Retinal migraine is defined by fully reversible monocular visual phenomena. We present two cases that were complicated by permanent monocular vision deficits.

Cases

A 57-year-old man with history of retinal migraine experienced persistent monocular vision loss after one stereotypical retinal migraine, progressing to finger-count vision over 4 days. He developed paracentral acute middle maculopathy that progressed to central retinal artery occlusion. A 27-year-old man with history of retinal migraine presented with persistent right eye superotemporal scotoma after a retinal migraine. Relative afferent pupillary defect and superotemporal visual field defect were noted, consistent with ischemic optic neuropathy.

Conclusion

Retinal migraine can complicate with permanent monocular visual loss, suggesting potential migrainous infarction of the retina or optic nerve. A thorough cerebrovascular evaluation must be completed, which was unrevealing in our cases. Acute and preventive migraine therapy may be considered in retinal migraine patients, to mitigate rare but potentially permanent visual loss.

Introduction

Retinal migraine is defined by The International Classification of Headache Disorders (ICHD) as an aura consisting of fully reversible monocular visual phenomena with at least two of the following characteristics: Spreading gradually over ≥5 min, symptoms lasting 5–60 min, accompanied, or followed within 60 min, by headache (1). The scientific literature reports a large spectrum of ocular complications from retinal migraine (2,3). Whereas the incidence of permanent loss of visual acuity or visual field from retinal migraine is not known, it may be underreported and underestimated (4). We report two patients with retinal migraine with persistent monocular phenomena lasting beyond 60 min that were complicated by permanent visual loss. These presentations suggest migrainous infarction of the retina and optic nerve and raise into question the most appropriate acute and preventive treatment approach in this patient population.

Case 1: A 57-year-old man with a 35-year history of self-reported retinal migraine (described as monocular scintillating scotomas in the right eye temporal hemifield that build over 20 min, lasting a maximum of 60 min, without accompanying headache, occurring on average every other month since age 18, with the patient being able to draw a monocular field defect), hypertriglyceridemia, hypertension, and hypertrophic cardiomyopathy, presented with persistent, painless monocular visual loss in his right eye. His visual symptoms began with a semiology reminiscent of his prior retinal migraine episodes. However, they progressed to permanent right eye visual loss. At 48 h, his visual symptoms were mild right-eye blurry vision, and he was diagnosed with right eye paracentral acute middle maculopathy (PAMM) on fluorescein angiography. He was admitted for acute migraine therapy and vascular work-up. Brain MRI showed mild and chronic non-specific white matter hyperintensities. MR angiogram of the head and neck showed mild right middle cerebral artery atherosclerotic stenosis. Grade 1 aortic arch atherosclerosis and absent right-to-left shunt were noted on transesophageal echocardiogram. ESR and CRP were normal. Temporal artery biopsy and 14-day cardiac monitoring was unrevealing. Comprehensive thrombophilia profile was negative for genetic or acquired coagulopathies, other than mild hyperhomocysteinemia (20.7 nmol/mL, normal 6.9–15.9 nmol/mL), with a heterozygous methylenetetrahydrofolate reductase C677T gene mutation. He was evaluated by Hematology, and this mutation was not felt to be related to his presentation. Digital subtraction angiogram performed at 96 h after visual loss showed normal choroidal blush and no evidence of ophthalmic artery occlusion or vasospasm. Due to progression of visual loss to finger-counting 4 days after the initial symptoms, repeat fluorescein angiography was performed and showed right central retinal artery occlusion (CRAO). For secondary migraine and stroke prevention, he was prescribed daily aspirin, atorvastatin, nortriptyline, and magnesium. He was already taking verapamil for hypertension, which was continued as it is sometimes also used for migraine prevention. For acute therapy in the event of future visual symptoms in the fellow eye, sublingual nitroglycerin and oral lasmiditan and naproxen were prescribed. At 12-month follow-up, he had no further visual episodes, but did have persistent right monocular vision loss with visual acuity of 20/200.

Case 2: A 27-year-old male with self-reported history of one prior retinal migraine and few migraines without aura, presented with a 36-h persistent right eye superior temporal scotoma. His visual symptoms began with right monocular scintillating scotoma lasting 25 min followed by a holocephalic aching headache associated with photophobia and phonophobia, reminiscent of his previous self-reported retinal migraine episode, which was also confined to one eye. The patient had attempted to take a nap and when he awoke 4 h later, he noticed a monocular right eye superotemporal scotoma, in the same location as his scintillating scotoma that preceded his headache. His initial ophthalmologic evaluation showed normal visual acuity, color vision and dilated fundoscopic exam. The patient presented to the ED and was evaluated by our team 36 h after symptom onset, when he continued to experience a monocular right eye superotemporal scotoma, without improvement or progression. Patient was given aspirin 325 mg and intravenous acute migraine therapies, without improvement in the visual defect. A right relative afferent pupillary defect was noted, despite normal visual acuity and normal optic disc and retinal exam. No color desaturation was noted. A thorough vascular work-up was conducted. MRI brain and orbits, MRA head and neck, and thrombophilia profile were unremarkable. Transthoracic echocardiogram was normal and unrevealing for a right-to-left shunt. Formal visual field testing (Zeiss Central 30-2 SITA Humphrey) revealed a small supertemporal scotoma in the right eye with a mean deviation of −0.97. Retinal imaging, including fluorescein angiography, was normal. Given absent optic disc edema, the most likely diagnosis was posterior ischemic optic neuropathy (ION). Migraine preventative therapy with magnesium citrate 500 mg daily and melatonin 5 mg daily was started. For acute therapy, the patient was instructed to take naproxen 500 mg and aspirin 325 mg at the start of his aura. At 1 month follow-up, he continued to have the same monocular visual scotoma, and remained migraine and aura free.

Discussion

We describe two patients with a self-reported history of retinal migraine that developed persistent monocular vision loss, either disabling monocular visual acuity loss or a monocular visual field defect, following a typical attack of retinal migraine. The patients differ in age, vascular risk factors, migraine semiology and ocular symptomatology. Neither were smokers or using illicit drugs, and thorough cerebrovascular and thrombophilia evaluations were unrevealing in bot.

Although ICHD-3 diagnostic criteria for retinal migraine requires vision loss that is reversible, these cases suggest that irreversible vision loss is part of the retinal migraine spectrum of complications (4). In fact, the clinical course of our cases resembles monocular migrainous infarction, though restricted to the retina and optic nerve. This indicates that aura of the retina can be complicated with infarcts of the retina and optic nerve. Migrainous infarction is defined by the ICHD-3 as “a migraine attack occurring in a patient with migraine with aura and typical of previous attacks except that one or more aura symptoms persists for >60 minutes, and that neuroimaging demonstrates ischemic infarction in a relevant area” (1). We propose that the definition of retinal migraine and migrainous infarction could potentially be expanded to include ocular forms of migrainous infarction, highlighting that visual aura can be associated with permanent monocular visual deficits with ischemic infarction demonstrated on ophthalmologic evaluation.

CRAO and ION have been previously described in association with retinal migraine (2,5). The pathophysiology of CRAO and ION involves damage to blood vessels that supply either the retina or the optic nerve, and therefore theories that attempt to explain these complications include migraine-associated vasospasm of the retinal or ciliary vasculature, occlusive thrombosis as a result of endothelial dysfunction, abnormal platelet aggregability or plasma hypercoagulability (6–8). In support of this proposed mechanism, retinal migraine has been documented photographically with fundoscopic examination in real time during an attack, demonstrating multiple areas of vasoconstriction involving the branch retinal arteries and veins (7). Another proposed mechanism is neuronal spreading depression involving the retina, which has been demonstrated in an animal model (9).

Our cases also highlight the importance of safe preventive and acute medications for patients with retinal migraine, to avert the rare but potentially disabling complication of permanent vision loss. To prevent future ischemic events, we prescribed both preventive and acute migraine therapy. Our first patient was given acute therapy in the form of sublingual nitroglycerin, a vasodilator, thus employing a medication that may counteract the vasoconstriction that has been described in this disorder. Aspirin 500 mg should also be considered in these patients. We also had suggested lasmiditan should the above approach fail, as it is a 5-HT_1F receptor agonist that does not cause vasoconstriction. Triptans would be contraindicated given the potential for vasoconstriction and gepants may not be an optimal choice because of their blockade of CGRP, a potent vasodilator that may be important for the compensatory dilation of retinal arteries. Recall, CRAO is acute ischemic stroke of the retina and these patients need long term anti-platelet therapy for secondary stroke prevention. The second patient was instructed to take naproxen 500 mg and aspirin 325 mg as soon as he began experiencing aura to reduce platelet aggregation and inflammation, which may be contributing to acute ION. Preventive therapy for patients with retinal migraine may be trialled to prevent disabling visual loss in the fellow eye, even if patients have only infrequent attacks, especially if patients have monocular vision at baseline. Therapies used for the prevention of migraine with aura, including magnesium, lamotrigine, topiramate, and aspirin, could be considered given the potential to inhibit glutamate-mediated spreading depression (10,11). Although Al-Moujahed et al. demonstrated improvement in retinal ischemia in vaso-occlusive retinal vasculitis with use of nicotinic acid and infliximab; the benefit of nicotinic acid with retinal migraine patients has yet to be determined, however is appealing given its vasodilatory mechanism (12).

In summary, retinal migraine can be associated with ischemic monocular complications causing permanent visual loss, with a clinical course resembling migrainous infarction of the retina and optic nerve. We recommend considering preventive and acute migraine therapy to prevent vision loss, especially in patients with baseline monocular vision. We propose that the ICHD-3 criteria of retinal migraine and migrainous infarction could potentially be expanded to include these unusual ischemic complications. Further studies are warranted to evaluate the utility of prophylaxis in retinal migraine to prevent disabling vision loss.

Clinical implications

Retinal migraine can be complicated by ischemic insults of the retina or optic nerve, with permanent and disabling visual loss.

Migraine preventive and readily available acute therapy should be considered to help prevent vision loss in patients with retinal migraine, especially in cases with monocular vision.