Sumatriptan dose increase-induced acute angle closure glaucoma in chronic migraine sufferer

Abstract

In this case study, we explore a case of bilateral acute angle closure (AAC) attack detected in a 52-year-old female patient with no other ophthalmic background or predisposition to angle closure, following an increase of her regular sumatriptan dose used for migraine relief. Even though the initial presentation was misinterpreted as migraine attack, it nevertheless alerted the treating physicians to immediate cessation of the drug, allowing for the pertinent ocular symptomatology to be unveiled. Drug-induced bilateral AAC is a rare occurrence and can lead to significant ocular morbidity if not detected and treated early. Clinicians of emergency care should be aware of this uncommon association, as prompt ophthalmology input is vital. Interestingly, although it would be anticipated that people prone to angle closure attack after sumatriptan intake would exhibit symptoms after initiation of the drug, our patient suffered an attack while on long-term treatment and following dose increase.

Background

Simultaneous bilateral acute angle closure (AAC) glaucoma is a rare ophthalmic emergency that requires prompt recognition and treatment to prevent permanent optic nerve damage. An attack can often be precipitated by the administration of certain drugs. Previous reports include AAC attacks among patients taking sulfa-based drugs; tricyclic, antipsychotics, benzodiazepines, antiparkinsonians, anticonvulsants (namely, topiramate) and anti-inflammatory agents.¹ It is essential that clinicians are aware of the signs and symptoms of AAC glaucoma and the potential drugs that may precipitate an attack. Although AAC glaucoma is difficult to miss when presenting in its typical form, atypical presentations may pose a significant challenge, and the diagnosis can be missed unless a high index of suspicion guides the emergency physician.²

Case presentation

A 52-year-old female patient presented to our emergency department with a history of severe headache, loss of vision, nausea and vomiting. Her previous medical history included hypertension and migraines for which she would usually take 100 mg of sumatriptan as required for symptomatic relief, with good response. Over the preceding 3 days, she had experienced migraines of increasing severity, urging her to double the regular dose to 200 mg/24 hours to achieve adequate pain control. At presentation in the emergency department, she was alert and orientated, hypertensive with a blood pressure of 185/95 mm Hg, tachycardic at 98 bpm, apyrexial and with a pain score of 10/10. Her pupils were found moderately dilated at 6 mm; the rest of the neurological examination was normal. Sumatriptan was immediately stopped and the patient received intravenous fluids, analgesia and remained under close observation. The following day, her vision remained poor. An urgent ophthalmology review was then requested.

Investigations

Prior ocular history was unremarkable except for mild myopia corrected with spectacles for distance. Ocular examination confirmed bilaterally reduced best corrected visual acuity (right eye (RE) 3/60cc, left eye (LE) 2/60cc) and raised intraocular pressure (IOP: RE 55 mm Hg, LE 58 mm Hg) by applanation tonometry. Slit lamp examination revealed marked bilateral conjunctival hyperaemia, corneal oedema with Descemet’s folds, fixed mid-dilated pupils, a uniformly shallow anterior chamber and early nuclear sclerosis.

Gonioscopy demonstrated bilateral appositional angle closure of 360 degrees. Funduscopy was not feasible due to marked corneal oedema, therefore, B-scan ultrasonography was conducted, showing intact flat retina. The anterior chamber angle closure was also demonstrated on an anterior segment optical coherence tomography scan (figures 1 and 2).

Figure 1.

Anterior segment OCTs of right (A) and left eye (B) acquired on presentation, revealing a markedly shallow anterior chamber, closed AC angles and corneal oedema. AC, angle closure; OCT, optical coherence tomography.

Figure 2.

Anterior segment OCT of right (A) and left (B) eye acquired on presentation, revealing a markedly shallow anterior chamber, closed AC angles and corneal oedema. AC, angle closure; OCT, optical coherence tomography.

Differential diagnosis

The presenting symptoms of severe headache, nausea and vomiting and restlessness combined with hypertension following a step-up in the regular sumatriptan dose in a young patient with migraine led to initial uncertainty regarding diagnosis. Thanks to immediate discontinuation of the drug and administration of analgesia; ocular symptoms became more apparent the following day, prompting ophthalmic assessment and diagnosis of simultaneous bilateral secondary AAC. The bilaterality could point more towards a drug-induced reaction.

Treatment

Following ophthalmology assessment, the patient was given morphine and ketamine. In addition, the patient was treated with intravenous acetazolamide 500 mg, along with topical apraclonidine drops three times a day, timolol drops two times a day, pilocarpine drops three times a day and dexamethasone drops six times in both eyes. This achieved a reduction in intraocular pressure to 30 mm Hg in the right eye and 32 mm Hg in the left eye 6 hours after initiation of treatment, thereby allowing a clearer view of the anterior chamber to perform therapeutic bilateral peripheral iridotomies. It was following this drop in pressure that the patient reported an improvement in her pain.

Outcome and follow-up

On further follow-up, the patient’s visual acuity improved to 6/6 in both eyes, and intraocular pressure was normalised to 18 mm Hg in the right and 16 mm Hg in the left eye, with a deep anterior chamber bilaterally. She was initially noted to have some photophobia and a misshapen pupil in the right eye. On further assessment of the initial CT scan, which was initially thought to be normal by the emergency department, changes suggestive of glaucoma were noted by the ophthalmology team. The patient experienced no further episodes of AAC thereafter. She was gradually weaned off all topical hypertensive agents, with no complications or further side effects. Serial visual fields on subsequent visits confirmed no evidence of optic neuropathy. The patient remained symptom free and no long -term visual consequences ensued (figures 3 and 4). She did, however, undergo cataract surgery, which improved her vision notably.

Figure 3.

Anterior segment OCT of right (A) and left (B) eye acquired 7 days post initial presentation and treatment, showing deepening of the anterior chamber and reduction of corneal oedema. OCT, optical coherence tomography.

Figure 4.

Visual fields 1 year post initial presentation/treatment showing no permanent damage.

Discussion

AAC is an ophthalmic emergency requiring early detection and treatment in order to prevent irreversible optic nerve damage. It is characterised by apposition of the peripheral iris against the trabecular meshwork, resulting in obstruction of aqueous outflow. The peripheral iris may be ‘pulled’ (anterior mechanisms) or ‘pushed’ (posterior mechanisms) into the iridocorneal angle. In the anterior mechanisms, an abnormal tissue bridges the anterior chamber angle, subsequently undergoing contraction and pulling the peripheral iris into this position. In the posterior mechanisms, pressure behind the iris, lens or vitreous pushes the iris forward—this may occur with or without pupillary block.³ Pupillary block is caused by increased resistance to flow of aqueous humour between the pupillary portion of the iris and the anterior lens surface. An AAC attack involves a rapid increase in intraocular pressure above 21 mm Hg, along with conjunctival injection, iris bombe (when pupillary block is the underlying mechanism), corneal epithelial oedema, a mid-dilated unreactive pupil and a shallow anterior chamber. Patients commonly report ocular pain, nausea, vomiting, blurred vision or the presence of visual haloes. The diagnosis of AAC can be confirmed by gonioscopy, with visualisation of an occluded angle in the affected eye. Drug-induced bilateral AAC has been reported to result from a wide spectrum of drugs, although the underlying mechanism remains poorly understood.⁴ This phenomenon is usually considered an idiosyncratic reaction to the offending agent and can occur in eyes with no apparent predisposition to angle closure.⁵

Sumatriptan is a selective 5-HT1B/1D receptor agonist and first-line treatment for moderate to severe acute migraine attacks.⁶ Triptans target various mechanisms involved in the pathophysiology of migraines, including inhibition of nociceptor neurotransmitters, blood vessel constriction and inhibition of vasoactive neuropeptide release by the trigeminal ganglion.⁷ Although serotonergic receptors can be found in the basilar artery and vasculature within the dura mater, they are also present within the iris and ciliary body. As a result, cross-stimulation of these receptors with the use of serotonergic agonists such as sumatriptan can induce an undesirable rise in aqueous humour production and intraocular pressure.

While this side effect is likely related to cross-stimulation of serotonergical receptors, alternative theories have been suggested. These include the hapten hypothesis, involving an immune-mediated reaction within the choroid causing increased intraocular pressures, ciliary body swelling and zonular relaxation leading to forward displacement of the lens-iris diaphragm (myopic shift) and trabecular meshwork blockage and alteration of vascular permeability.

Withdrawal of the offending agent and controlling the intraocular pressure with topical and/or systemic medication are keys in managing drug-induced AAC. Topical miotics constrict the pupil and pull the iris away from trabecular meshwork, and topical steroids are also important reducing the inflammation. Laser iridotomy is beneficial in these cases as well, easing the flow of aqueous humour to the anterior chamber.⁸

In our case, a total score of 5 was calculated using the Naranjo algorithm determining it is probable the bilateral AAC was actually due to the increased dose of sumatriptan and not the result of other factors.⁹ The Naranjo algorithm was developed in 1991 to help standardise the assessment of a causal relationship between an adverse clinical event and a drug. It provides an adverse drug reaction probability scale with total scores ranging from −4 to +13; the reaction is considered definite for a score of 9 and above, probable for score 5–8, possible for 1–4 and doubtful for 0 or less.¹⁰

Only two previous case reports have been published discussing the potential role of triptan drugs in the development of iatrogenic AAC. A case report by Hsu et al¹ explored a case involving a 26-year-old female patient who had developed AAC following ingestion of a single dose of sumatriptan 1 week prior to symptom development. Following treatment with mannitol, systemic acetazolamide and dorzolamide-timolol eye drops, her intraocular pressures were reduced and symptoms improved within a few days. A second case report by Lee et al¹¹ highlighted a case involving a 42-year-old female patient who had recently increased her regular zolmitriptan dose a few days prior to development of symptoms of AAC. She was treated with topical brimonidine and brinzolamide, which led to reduction in intraocular pressures and resolution of symptoms within 2 weeks. A laser trabeculoplasty was ultimately performed for this case, due to symptom recurrence following topical treatment cessation.

In our patient’s case, the onset of symptoms closely coincided with the increase in her regular sumatriptan prescription. Even though it would be expected for this rare adverse effect of sumatriptan to manifest in a predisposed patient after commencement of the medication, it seems that it can also occur in patients under chronic treatment who increase their regular dose.

It is particularly important for clinicians to be aware of the potential involvement of certain drugs in exacerbating attacks of AAC glaucoma, especially when drug history indicates recent intake or change in frequency or dosage. The bilaterality of signs and symptoms should also raise suspicion. In such cases, immediate withdrawal of the offending agent is critical in order to prevent further symptom development and vision loss.

Learning points.

• It should be highlighted that presenting signs and symptoms of an acute angle closure attack can be misinterpreted, particularly in cases such as this one, where a dose increase of a potentially causative drug rather than the initiation of a new medication precipitated the development of symptoms.

• A thorough history, examination and timely ophthalmology review remain crucial in order to ensure correct diagnosis and effective management of this small group of patients.

• A comprehensive list of potential offending agents could be useful in the acute emergency setting to enable an increase in recognition of the implicated drugs.

• Physicians and ophthalmologists should be encouraged to officially report such adverse reactions. Of note, acute angle closure is not reported as a possible side effect of sumatriptan on the British National Fprmulary (BNF).

• By increasing awareness among patients and treating physicians regarding the signs and symptoms, as well as the potentially causative drugs, early diagnosis can be made and avoidance of irreversible consequences as a result of late detection and treatment.