A 76-year-old male receiving maintenance therapy with oral steroids for immunoglobulin G4 (IgG4)-related disease presented to our hospital with the primary complaint of visual disturbance. His best corrected visual acuity in the right and left eyes was 1.2 and 0.7, respectively. Humphrey visual field test revealed inferior auriculotemporal one-quarter blindness in the left eye. After a detailed history of IgG4-related disease, clinical diagnosis based on imaging revealed marked enlargement of the pituitary/pituitary stem with associated compression of the optic chiasm. The diagnosis of IgG4-related eye disease was made based on the history and findings of the initial evaluation. Intensive steroid therapy was carried out, which led to symptom resolution. IgG4-related diseases are considered in the differential diagnosis when bilateral hemianopsia is observed. When unilateral visual acuity and visual field defects are present, IgG4-related diseases and other organ conditions should be considered.
Immunoglobulin G4 (IgG4) related disease is an autoimmune disease of unknown etiology in which IgG4-positive plasma cells infiltrate body organs and cause swelling, nodules and hypertrophic lesions in target organs . IgG4-related disease can occur in any organ. When it comes to ophthalmology, the job is disrupted the most . Approximately 20% and 5% of patients have vision loss and visual field defects, respectively .
Two major pathological conditions can cause optic neuropathy in this disease: compression or sheathing of the optic nerve by an enlarged tissue in the orbit and compression of the optic chiasm by the enlarged pituitary gland. In the former, compression or sheathing of the optic nerve by the enlarged extraocular muscle or localized or diffuse tissue proliferation in the orbit has been reported . The latter is a condition that can develop with any disease that causes pituitary gland enlargement; however, few studies have reported such cases [5,6] and there are no reports of visual impairment only.
A 76-year-old man visited his GP at the end of April 2021 due to a visual disturbance in the left eye and was referred to our department on May 27, 2021. Ophthalmic history included bilateral cataract surgery, left ptosis (both in 2017), intrascleral fixation of left intraocular lens dislocation (in 2020), Irvine-Gass syndrome, and ocular hypertension. Detailed history showed that the patient was being treated by his general practitioner for IgG4-related disease (retroperitoneal fibrosis; maintenance dose of prednisolone 2.5 mg/day).
At the first visit on May 27, 2021, there was no conjunctival hyperemia in either conjunctiva and there were occasional anterior chamber cells in the left eye. The pupillary reflexes were not disturbed and no relative afferent pupillary defect (RAPD) was noted in the left eye. The left optic nerve papilla was slightly erythematous and swollen. The best corrected visual acuity was 1.2 in the right eye and 0.7 in the left eye, and the intraocular pressure was 18 mmHg in the right eye and 16 mmHg in the left eye. The critical flicker frequency (CFF) was decreased in the left eye (right 38Hz-41Hz, left ↑36Hz-36Hz), and the Humphrey visual field test revealed inferior arcuate quadrantanopia in the left eye (Figure 1).
Brain magnetic resonance imaging (MRI) showed no abnormal signal in the intraorbital optic nerve; however, a marked enlargement of the pituitary/pituitary peduncle with associated compression of the optic chiasm was observed (Figure: 2).
Based on the history and findings of the initial evaluation, a diagnosis was made of left optic neuropathy associated with pituitary/pituitary stem enlargement caused by IgG4-related disease. He was introduced to the hospital of endocrinology and metabolism internal medicine expert and was diagnosed with panhypopituitarism due to inflammation of the pituitary funnel. Thereafter, the dose of prednisolone was increased to 20 mg/day. On June 10, visual acuity and visual field defects improved (Figure 3).
When examined on July 7, the size of the pituitary gland and pituitary stalk decreased (Figure .) 4).
The CFF decreased (right 42Hz-43Hz, left ↑37Hz-43Hz) (39Hz). The steroid dose was gradually withdrawn and maintenance therapy with 2.5 mg prednisolone per day was resumed on 11 August.
In this case, there were no optic nerve swellings or signal changes on imaging, but fundus examination revealed mild erythema of the optic nerve papilla. While this finding can be attributed to inflammatory cytokine production in the eye from iritis, optic neuritis was likely caused by an autoimmune mechanism in IgG4-related disease. However, the visual field findings were not consistent with those commonly seen in optic papillitis or pituitary enlargement. In addition, brain MRI findings suggested compression of the optic chiasm due to pituitary enlargement. However, judging by our MRI data, the relationship of the optic chiasm to the pituitary gland was unclear and had yet to be elucidated. The patient’s visual acuity and visual field defects improved after steroid treatment, suggesting that pituitary and pituitary stalk enlargement was the major pathophysiology of vision loss and visual field defects.
The ophthalmic clinical feature of IgG4-related eye disease is bilateral lacrimal gland enlargement with three features: suborbital nerve enlargement exophthalmos and compressive optic neuropathy . IgG4-related optic neuropathy is often caused by compression of the optic nerve due to enlargement of the lacrimal glands or other intraorbital tissues [4,8-11]. Few studies have reported on optic neuropathy caused by compression of the optic chiasm by an enlarged pituitary gland, as in the present case [5,10,11]. Although bitemporal hemianopsia is more commonly observed with pituitary enlargement, the present case only showed inferior arcuate quadrantanopia in the left eye. The exact mechanism of this visual field disorder remains unclear, as described above. A previous study  found visual field defects in only one eye in two out of 10 patients with symmetrical pituitary enlargement. Since the present case also showed compression of the chiasm on the eye due to pituitary enlargement, it is possible that it caused an atypical visual field defect and associated visual acuity disturbance.
Alternatively, as other studies have shown that infiltration of IgG4-positive plasma cells around the trigeminal nerve in the same disease In this case of optic neuropathy, a deep infiltrative or inflammatory mechanism may play a role.
IgG4-related disease, an autoimmune disease of unknown etiology, leads to vision loss and visual field defects. Compression or sheathing of the optic nerve by an enlarged tissue in the orbit is said to be the leading cause of visual disturbances. However, be aware of the possibility of compression of the optic chiasm by the enlarged pituitary gland.