Increased intraocular pressure as the first presenting sign of Miller Fisher syndrome

Abstract

Background

Miller Fisher syndrome (MFS) is a rare triad of ophthalmoplegia, ataxia, and areflexia. There have been few reports of acute angle-closure glaucoma induced by MFS in the literature. However, acute elevation of intraocular pressure in open angle glaucoma induced by MFS has not been reported.

Case presentation

A 55-year-old male patient with open-angle glaucoma was admitted to the ophthalmology department due to ocular pain, moderate dilation of the pupils, and an acute increase in intraocular pressure. During diagnosis and treatment, neurofunctional deficits such as ophthalmoplegia, ataxia, and areflexia were presented. The blood ganglioside antibody panel was positive for anti-GQ1b IgG, and Miller Fisher syndrome was diagnosed. The symptoms gradually improved after intravenous immunoglobulin treatment. After 3 months of follow-up, ophthalmoplegia, ataxia and areflexia completely resolved, the patient’s intraocular pressure stabilized at baseline, and his pupils returned to normal bilaterally.

Conclusion

This is the first case report of open-angle glaucoma with acute IOP elevation as the first symptom of Miller Fisher syndrome. The mechanism may be due to damage to the trabecular meshwork or maintenance of intraocular pressure, which results in acute intraocular pressure elevation in patients with preexisting open-angle glaucoma when the pupil dilates. Clinicians should be aware of the autonomic dysfunction caused by MFS, dilated pupils, and sudden increases in intraocular pressure, regardless of angle status.

Background

Guillain–Barré syndrome (GBS) is an autoimmune-mediated acute inflammatory demyelinating polyradiculoneuropathy. Miller Fisher syndrome (MFS) is a rare variant of GBS that is typically characterized by the triad of ophthalmoplegia, ataxia, and areflexia. Its pathogenesis is linked to anti-GQ1b IgG antibodies targeting cranial nerves and peripheral ganglia through molecular mimicry. Here, we present a case of anti-GQ1b antibody-positive MFS with increased intraocular pressure as the initial clinical manifestation, which has not been previously reported in the literature.

Case presentation

Medical history

A 55-year-old male presented with a 5-day history of dizziness, headache and bilateral eye pain, followed by 4 days of bilateral blurred vision, bilateral ptosis, and difficulty moving the eyes. He denied any other neurological symptoms. Seventeen days prior, the patient experienced a 2-day episode of cough and joint pain that resolved without treatment. His medical history included hypertension, which was managed with nifedipine and valsartan. The patient denied any history of glaucoma or prior intraocular pressure abnormalities.

Physical examination

The patient was alert but exhibited slurred speech, ataxia, and an unsteady gait. He also had inaccurate finger-to-nose test, a positive Romberg’s sign, and the absence of deep tendon reflexes bilaterally. Otherwise, the neurological examination revealed symmetrical nasolabial folds, a centered tongue, an intact gag reflex, an intact sensation of pain, and normal muscle strength and tone in the upper and lower extremities. Meningeal irritation signs and Babinski’s sign were negative.

Ophthalmological examination revealed best-corrected visual acuity (BCVA) of 20/30 in the right eye (OD) and 20/100 in the left eye (OS). The patient’s intraocular pressure (IOP) was elevated at 35 mmHg OD and 46 mmHg OS. Moderate ptosis (MRD1 1 mm OU, Fig. 1) and fixed globes were observed bilaterally. The pupils were moderately dilated (approximately 4.5 mm in diameter OU, Fig. 1) with sluggish light reflexes. The conjunctiva and cornea were normal bilaterally. Gonioscopy revealed predominantly wide-open angles (Scheie classification: grade I temporally OD and grade I nasally OS; Spaeth classification: D28r OD, D26r OS). The lens cortex exhibited mild opacity with clear vitreous bilaterally. The optic disc margins were sharp, with a cup-to-disc ratio (C/D) of 0.8 OD and 0.9 OS. No retinal hemorrhages, exudates, or macular abnormalities were noted.

Fig. 1

Moderate ptosis and dilated pupil OU

Ancillary tests

Auxiliary examination revealed that the axial length was 24.55 mm OD and 24.31 mm OS. The patient was also found to have anterior chamber depths of 3.713 mm OD and 3.431 mm OS, with thin corneas bilaterally (484 μm OD, 480 μm OS). Optical coherence tomography (OCT) of the anterior chamber revealed a wide open angle OU (Fig. 2). OCT of the optic nerve demonstrated extensive thinning of the retinal nerve fiber layer (Fig. 3), which was consistent with diffuse visual field loss (Fig. 4),.

Fig. 2

Anterior segment OCT image showing wide open anterior chamber angles in both eyes

Fig. 3

Top panel: OCT-NFL image showing severe thinning of the retinal nerve fiber layer (OD 43 μm, OS 37 μm). Bottom panel: OCT image showing large optic cups OU

Fig. 4

The visual fields of both eyes showed moderate-to-severe defects, more pronounced in the left eye (OS)

Initial laboratory investigations revealed a white blood cell count of 9.27 × 10⁹/L, with 71.2% neutrophils and an antinuclear antibody (ANA) titer of 1:100 (cytoplasmic granules). Other routine blood and urine tests, including infectious disease screening, were unremarkable. However, the blood ganglioside antibody panel was positive for anti-GQ1b IgG, anti-GT1a IgG, and anti-GD2 IgG antibodies.

Lumbar puncture performed on day 7 after presentation revealed a cerebrospinal fluid (CSF) pressure of 145 mm H₂O without white blood cells, a negative Pandy test, a total protein concentration of 465 mg/L (normal), and a chloride concentration of 118 mmol/L (low).

A neostigmine test was negative. Electrocardiography, chest CT, and brain MRI with and without contrast agent were normal.

Diagnosis, treatment, and Follow-up

The patient was initially treated with carteolol hydrochloride and brinzolamide eye drops, which reduced IOP to 20 mmHg OD and 23 mmHg OS within 2 days. Owing to the presence of acute binocular ophthalmoplegia, ataxia, and areflexia, a neurology consultation was obtained, and the patient was transferred to the neurology ward with a suspected diagnosis of MFS.

On day 4 after admission, intravenous immunoglobulin (IVIG) 25 g/day was given for 5 days, along with methylprednisolone 500 mg/day for 5 days. This was followed by oral prednisone 60 mg/day with a tapering dose, methylcobalamin, vitamin B1, and vitamin B6. Brinzolamide and tafluprost eye drops were prescribed for long-term IOP control.

At discharge after 22 days of hospitalization, the patient’s deep tendon reflexes had recovered. During the 3-month follow-up, his ophthalmoplegia and ataxia completely resolved. It is noteworthy that when the patient was discharged from hospital, the intraocular pressure (IOP) was 11 mmHg OD and 14 mmHg OS respectively. After discharge, the patient discontinued the use of IOP-lowering medications on his own initiative. However, during the 3-month follow-up visit, the IOP remained normal, being 16 mmHg OD and 18 mmHg OS. His pupils were 3 mm in diameter bilaterally with a normal light reflex.

Discussion and conclusions

MFS, a rare variant of GBS, is characterized by ophthalmoplegia, ataxia, and areflexia [1]. The incidence of GBS is greater in Asia (15–25% of GBS cases) than in Western countries (1–7%) [2]. The pathogenesis is thought to involve molecular mimicry triggered by an infection, most commonly Campylobacter jejuni Haemophilus influenzae [3]. The lipooligosaccharide on the pathogen’s surface mimics gangliosides on Schwann cells, leading to the production of anti-GQ1b IgG antibodies [4]. These antibodies target GQ1b antigens, which are highly expressed in the oculomotor, trochlear, and abducens nerves; dorsal root ganglia; and muscle spindles, thus explaining the classic triad of MFS [5].

Pupillary dilation is a common feature of ophthalmoplegia in MFS patients, likely due to the presence of GQ1b antigens in the ciliary ganglion [6], affecting iris sphincter and ciliary muscle function. This can also disrupt the balance of aqueous humor formation and outflow, which is essential for IOP regulation.

While acute angle-closure glaucoma has been previously reported in MFS patients [7,8,9,10,11], our patient presented with an IOP spike with an open angle as the first manifestation. The patient had multiple risk factors and clinical features of primary open-angle glaucoma (POAG), including thin corneas, myopia, and hypertension. The presence of a deeply cupped optic disc, a significantly increased C/D ratio, severe thinning of the retinal nerve fiber layer, and diffuse visual field defects suggest that POAG is likely present before the onset of MFS.

Autonomic dysfunction may explain the development of an IOP spike in this context. MFS can cause autonomic nervous system dysfunction, leading to pupillary dilation, which can affect IOP and ocular blood flow, potentially increasing IOP. This may be related to decreased aqueous humor outflow due to reduced traction on the trabecular meshwork secondary to ciliary muscle paralysis [12]. Shaw and Lewis reported that significant IOP elevation occurred in 32% of open angle glaucoma patients (2% of normal individuals) [13] following pupil dilation, with marked pressure elevation (> 10 mmHg) in 12% of patients [14]. Lee reported a pressure increase of up to 27 mmHg in select patients with open angle glaucoma after dilation [15], likely due to impaired trabecular meshwork or dysfunction of IOP maintenance. A similar mechanism may play a role in MFS because of damage to the parasympathetic ciliary ganglia caused by anti-GQ1b antibodies.

The observed IOP elevation in this case was likely directly attributable to autonomic dysfunction secondary to MFS. Notably, IOP returned to baseline after successful treatment for MFS, even without the patient continuing the topical IOP-lowering medications.

This case highlights the importance of considering MFS in patients with the classic triad of ophthalmoplegia, ataxia, and areflexia. Additionally, clinicians should be vigilant for autonomic nervous system disorders, such as pupillary dilation, with sudden increases in IOP, regardless of angle status. Early and accurate diagnosis of MFS facilitates prompt treatment, potentially preventing disease progression and reducing the risk of systemic and ocular complications.