A case of immunoglobulin G4-related ophthalmic disease with unilateral visual field deficiency
A 76-year-old man receiving maintenance therapy with oral steroids for immunoglobulin G4 (IgG4)-related disease presented to our hospital with the chief complaint of visual disturbances. His best corrected visual acuities in the right eye and the left eye were 1.2 and 0.7 respectively. Humphrey’s visual field test revealed lower atriotemporal blindness of a quarter of the left eye. After a detailed history of IgG4-related disease, clinical diagnosis based on imaging revealed marked enlargement of the pituitary/pituitary stalk with associated compression of the optic chiasm. Based on the history and the results of the initial evaluation, a diagnosis of IgG4-related ophthalmic disease was made. Intensified corticosteroid therapy was performed, which led to the resolution of symptoms. 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 organic disorders 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. In ophthalmology, the orbit is most often disturbed . 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 envelopment of the optic nerve by enlarged tissue in the orbit and compression of the optic chiasm by the enlarged pituitary gland. In the first case, compression or coating of the optic nerve by the hypertrophied extraocular muscle or localized or diffuse tissue proliferation in the orbit has been reported. . The latter is a condition that can develop into any disease that causes pituitary enlargement; however, few studies have reported such cases [5,6] and there are no case reports of visual impairment alone.
Presentation of the case
A 76-year-old man visited his family physician in late April 2021 for a visual disturbance in his left eye and was referred to our service on May 27, 2021. Ophthalmologic 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. A detailed history revealed that the patient had received treatment for an IgG4-related disease (retroperitoneal fibrosis; maintenance dose of prednisolone 2.5 mg/day) by his treating physician.
At the initial visit on May 27, 2021, there was no conjunctival hyperemia in either conjunctiva and occasional anterior chamber cells in the left eye. Pupillary reflexes were not disturbed and no relative afferent pupillary defect (RAPD) was noted in the left eye. The left optic nerve papilla was mildly erythematous and swollen. Best corrected visual acuities were 1.2 in the right eye and 0.7 in the left eye, and intraocular pressures were 18 mmHg in the right eye and 16 mmHg in the left eye. Critical flicker frequency (CFF) decreased in the left eye (right ↑ 38 Hz ↓ 41 Hz, left ↑ 36 Hz ↓ 36 Hz) and Humphrey’s visual field test revealed inferior arcuate quadrantanopia in the eye left (Picture 1).
Brain magnetic resonance imaging (MRI) showed no abnormal signals in the intraorbital optic nerve; however, a marked enlargement of the pituitary/pituitary stalk with associated compression of the optic chiasm was observed (Figure 2).
Based on the history and initial evaluation findings, a diagnosis of left optic neuropathy associated with pituitary/pituitary stalk enlargement caused by IgG4-related disease was made. He was presented to the internal medicine expert at the Endocrinology and Metabolism Hospital and diagnosed with panhypopituitarism due to inflammation of the pituitary funnel. Then the prednisolone dose was increased to 20 mg/day. On June 10, visual acuity and visual field defects improved (Figure 3).
On examination on July 7, the size of the pituitary gland and pituitary stalk decreased (Figure 4).
CFF decreased (right ↑42Hz↓43Hz, left ↑37Hz↓43Hz) (39 Hz). The steroid dose was gradually reduced and maintenance treatment with 2.5 mg of prednisolone per day was resumed on August 11.
In this case, no optic nerve swelling or signal change was evident on imaging, but fundus examination revealed mild erythema of the optic nerve papilla. Although this finding could be attributed to the production of inflammatory cytokines in the eye by iritis, the optic neuritis was probably caused by an autoimmune mechanism in an IgG4-related disease. However, the visual field findings did not match those commonly seen in optic papillitis or pituitary hypertrophy. Additionally, brain MRI findings suggest compression of the optic chiasm due to pituitary hypertrophy. However, judging from our MRI data, the relationship between the optic chiasm and the pituitary was unclear and remained to be elucidated. The patient’s visual acuity and visual field defects improved after steroid treatment, suggesting that pituitary gland and pituitary stalk enlargement was the primary pathophysiology for vision loss and visual field defects. .
The ophthalmologic clinical hallmark of IgG4-related eye disease is bilateral lacrimal gland enlargement with three features: infraorbital nerve enlargement proptosis and compressive optic neuropathy . IgG4-related optic neuropathy is usually caused by compression of the optic nerve by 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 seen with pituitary enlargement, the present case showed inferior arcuate quadrantanopsia only in the left eye. The exact mechanism of this visual field impairment remains unclear, as described above. A previous study  found visual field defects in only one eye in two of 10 patients with symmetrical pituitary enlargement. Since the present case also showed compression of the optic chiasm due to an enlargement of the pituitary gland, it is possible that it caused an atypical visual field defect and associated impaired visual acuity.
Alternatively, as other studies have shown infiltration of IgG4-positive plasma cells around the trigeminal nerve in the same disease a deep infiltrative or inflammatory mechanism may be involved in this case of optic neuropathy.
IgG4-related disease, an autoimmune disease of unknown etiology, causes vision loss and visual field defects. Compression or envelopment of the optic nerve by an enlarged tissue in the orbit would be the main cause of visual disturbances. However, the possibility of compression of the optic chiasm by the enlarged pituitary should be kept in mind.