Grand Rounds at the New England Eye Center

Man experiences recurrent bilateral optic neuritis

After the recurrence, visual acuity in the patient's left eye decreased to hand motion.

A 71-year-old man was referred by his usual ophthalmologist to the neuro-ophthalmology clinic at Tufts Medical Center for bilateral decreased vision associated with bilateral optic disc edema.

His medical history was notable for trigeminal neuralgia diagnosed after a negative temporal artery biopsy and currently treated with low-dose steroids. He also had a history of Lyme disease complicated by a cardiac arrhythmia, hypertension and hyperlipidemia. His ocular history included cataracts and presbyopia.

About 1 month before his vision loss, he had an upper respiratory tract infection that developed into pneumonia and was treated with antibiotics. His vision loss in both eyes was acute and associated with photophobia. He was first seen by his local optometrist, who noted mild anterior chamber inflammation and disc edema in both eyes. The patient was started on Durezol (difluprednate, Novartis) three times daily in both eyes and referred to a local ophthalmologist, who found the patient’s best corrected visual acuity to be 20/200 in the right eye and count fingers at 2 feet in the left eye with bilateral mild disc edema. The patient’s oral steroids were increased to 60 mg of prednisone daily, and Durezol was discontinued.

When he presented to our neuro-ophthalmology service, he reported a gradual improvement in his vision with the increased dose of oral steroids. He denied any headache, scalp tenderness, jaw claudication or myalgias. He had no other neurologic symptoms.

Initial Humphrey visual field
Figure 1. Humphrey visual field 30-2 of the left and right eye from initial presentation.

Source: Alison J. Lauter, MD, and Laurel N. Vuong, MD

Figure 2. Optic disc photos from initial presentation demonstrating mild disc edema.
Figure 3. OCT RNFL and GCC from initial presentation.

Examination

On examination, the patient’s BCVA was 20/40 in both eyes, and color vision was normal bilaterally. Humphrey visual field 24-2 showed an inferonasal defect in the right eye and an inferior altitudinal defect in the left eye (Figure 1). Pupils were round and reactive with no evidence of a relative afferent pupillary defect. Extraocular movements were full in both eyes. IOP was 16 mm Hg in the right eye and 17 mm Hg in the left eye. Anterior slit lamp examination was notable for mild nuclear sclerotic cataracts in both eyes. There was no anterior chamber inflammation. Dilated funduscopic exam of both eyes showed mild disc edema (Figure 2). OCT of the retinal nerve fiber layer (RNFL) showed thickening greater in the right eye than left. Measurements of the ganglion cell complex (GCC) were normal in both eyes (Figure 3). Additional workup including blood work for sarcoidosis, Lyme disease and syphilis was negative. An MRI of the brain and orbits with and without contrast and fat saturation was unremarkable.

The patient was seen 1 week later, and his visual acuity was improved to his baseline. Given his negative workup and improvement with steroids, it was thought he had a post-viral optic neuritis in the setting of a recent upper respiratory tract infection. His oral steroids were slowly tapered, and he followed up with his local ophthalmologist.

Six weeks later, after tapering down his prednisone to alternating daily doses of 20 mg and 40 mg, he had a sudden decrease in vision in his left eye. His visual acuities were 20/25 in the right eye and hand motion in the left eye. Pupils were equal and reactive with a relative afferent pupillary defect in the left eye. IOP was 17 mm Hg in both eyes, and anterior slit lamp exam continued to be unremarkable. Funduscopic examination showed a pink optic nerve with sharp margins in the right eye and mild pallor of the left optic nerve. OCT RNFL was full in both eyes with thinning of the GCC, left eye greater than right. The patient was admitted to the hospital for additional evaluation.

What is your diagnosis?

See answer on next page.

Optic neuritis

The differential diagnosis for this patient included lymphoma, chronic relapsing inflammatory optic neuropathy, neuromyelitis optica (NMO) optic neuritis and anti-myelin oligodendrocyte glycoprotein (MOG) optic neuritis.

Clinical course

OCT RNFL and GCC 6 months after
Figure 4. OCT RNFL and GCC 6 months after initial presentation.

The patient had a repeat MRI of the brain and orbits with and without contrast and fat saturation that continued to show no findings. He had a lumber puncture; the cerebrospinal fluid (CSF) profile was normal, and a large volume of CSF sent for cytology and cytometry was normal. The CSF was also tested for NMO and anti-MOG, which were negative. However, serum testing eventually returned positive for anti-MOG. While he was admitted in the hospital, he was treated with intravenous methylprednisolone for 5 days and then transitioned to 60 mg oral prednisone when he was discharged home.

Discussion

Humphrey visual field 6 months after
Figure 5. Humphrey visual field 30-2 of the left and right eye 6 months after initial presentation.

There are multiple causes of optic neuritis, including infectious, demyelinating (such as in multiple sclerosis) and idiopathic. With recent abilities to test for more antibodies, other causes for optic neuritis now include MOG immunoglobulin G and aquaporin-4 immunoglobulin G, which causes NMO.

MOG is a highly immunogenic glycoprotein expressed in the central nervous system on oligodendrocytes and myelin sheaths. If released into the CSF or drained into the periphery, MOG can induce autoimmunity, causing an inflammatory demyelination without astrocytopathy. The inflammatory demyelination can specifically affect the optic nerves, causing an autoimmune optic neuropathy. Features of anti-MOG optic neuritis include bilateral disease, frequent relapses and optic disc edema. Patients with anti-MOG optic neuritis often present with severe vision loss but favorable visual outcomes in contrast to NMO optic neuritis in which vision remains poor. The visual acuity on initial presentation with anti-MOG disease is between count fingers and hand motion. Relapses occur more frequently in anti-MOG optic neuritis than in NMO, seronegative and MS optic neuritis patients. The disc edema can be severe with associated peripapillary hemorrhages. OCT measurements of the RNFL are often overall preserved despite frequent relapses of optic neuritis.

Diagnosis of anti-MOG optic neuritis includes an MRI of the orbits and brain, which will typically reveal perineural optic nerve enhancement proximal to the chiasm. This enhancement can extend to the orbits and does not occur in any other form of optic neuritis. NMO, on the other hand, typically affects the optic chiasm and posterior optic pathways. A lumbar puncture should be performed along with blood work to test for MOG antibodies, which will be positive in patients with disease.

Acute treatment of suspected anti-MOG optic neuritis includes high-dose intravenous methylprednisolone. Early treatment of severe optic neuritis with steroids has been shown to lead to better outcomes. Patients are then transitioned to oral prednisone, which should be tapered as vision improves. Plasmapheresis or intravenous immunoglobulin (IVIG) should be considered in addition to methylprednisolone in patients with recurrent disease during acute attacks. Long-term immunotherapy is recommended in patients with relapsing disease or disease with severe residual deficits after a first attack. The ideal treatment for anti-MOG optic neuritis is unknown, but recent studies demonstrate the disease responds well to rituximab, azathioprine, methotrexate, mycophenolate mofetil and IVIG. Typical therapies for MS are ineffective at preventing relapses in anti-MOG optic neuritis patients. Patients should be followed closely for relapse of disease by a neuro-ophthalmologist and neurologist.

Clinical course continued

While on high-dose oral steroids, the patient’s vision slowly improved to 20/25 in both eyes. He was referred to one of the neurologists at Tufts who started the patient on a long-term immunotherapy, rituximab, in an effort to wean him off steroids and to prevent recurrent optic neuritis. At his 6-month follow-up, OCT (Figure 4) showed significant RNFL thinning in the left eye greater than in the right, with GCC thinning in both eyes (Figure 4). Automated perimetry showed superior and inferior arcuate defects in the left eye (Figure 5). He has remained stable on rituximab while slowly tapering off prednisone. He will continue to have close follow-up with neuro-ophthalmology and neurology.

A 71-year-old man was referred by his usual ophthalmologist to the neuro-ophthalmology clinic at Tufts Medical Center for bilateral decreased vision associated with bilateral optic disc edema.

His medical history was notable for trigeminal neuralgia diagnosed after a negative temporal artery biopsy and currently treated with low-dose steroids. He also had a history of Lyme disease complicated by a cardiac arrhythmia, hypertension and hyperlipidemia. His ocular history included cataracts and presbyopia.

About 1 month before his vision loss, he had an upper respiratory tract infection that developed into pneumonia and was treated with antibiotics. His vision loss in both eyes was acute and associated with photophobia. He was first seen by his local optometrist, who noted mild anterior chamber inflammation and disc edema in both eyes. The patient was started on Durezol (difluprednate, Novartis) three times daily in both eyes and referred to a local ophthalmologist, who found the patient’s best corrected visual acuity to be 20/200 in the right eye and count fingers at 2 feet in the left eye with bilateral mild disc edema. The patient’s oral steroids were increased to 60 mg of prednisone daily, and Durezol was discontinued.

When he presented to our neuro-ophthalmology service, he reported a gradual improvement in his vision with the increased dose of oral steroids. He denied any headache, scalp tenderness, jaw claudication or myalgias. He had no other neurologic symptoms.

Initial Humphrey visual field
Figure 1. Humphrey visual field 30-2 of the left and right eye from initial presentation.

Source: Alison J. Lauter, MD, and Laurel N. Vuong, MD

Figure 2. Optic disc photos from initial presentation demonstrating mild disc edema.
Figure 3. OCT RNFL and GCC from initial presentation.

Examination

On examination, the patient’s BCVA was 20/40 in both eyes, and color vision was normal bilaterally. Humphrey visual field 24-2 showed an inferonasal defect in the right eye and an inferior altitudinal defect in the left eye (Figure 1). Pupils were round and reactive with no evidence of a relative afferent pupillary defect. Extraocular movements were full in both eyes. IOP was 16 mm Hg in the right eye and 17 mm Hg in the left eye. Anterior slit lamp examination was notable for mild nuclear sclerotic cataracts in both eyes. There was no anterior chamber inflammation. Dilated funduscopic exam of both eyes showed mild disc edema (Figure 2). OCT of the retinal nerve fiber layer (RNFL) showed thickening greater in the right eye than left. Measurements of the ganglion cell complex (GCC) were normal in both eyes (Figure 3). Additional workup including blood work for sarcoidosis, Lyme disease and syphilis was negative. An MRI of the brain and orbits with and without contrast and fat saturation was unremarkable.

The patient was seen 1 week later, and his visual acuity was improved to his baseline. Given his negative workup and improvement with steroids, it was thought he had a post-viral optic neuritis in the setting of a recent upper respiratory tract infection. His oral steroids were slowly tapered, and he followed up with his local ophthalmologist.

Six weeks later, after tapering down his prednisone to alternating daily doses of 20 mg and 40 mg, he had a sudden decrease in vision in his left eye. His visual acuities were 20/25 in the right eye and hand motion in the left eye. Pupils were equal and reactive with a relative afferent pupillary defect in the left eye. IOP was 17 mm Hg in both eyes, and anterior slit lamp exam continued to be unremarkable. Funduscopic examination showed a pink optic nerve with sharp margins in the right eye and mild pallor of the left optic nerve. OCT RNFL was full in both eyes with thinning of the GCC, left eye greater than right. The patient was admitted to the hospital for additional evaluation.

What is your diagnosis?

See answer on next page.

PAGE BREAK

Optic neuritis

The differential diagnosis for this patient included lymphoma, chronic relapsing inflammatory optic neuropathy, neuromyelitis optica (NMO) optic neuritis and anti-myelin oligodendrocyte glycoprotein (MOG) optic neuritis.

Clinical course

OCT RNFL and GCC 6 months after
Figure 4. OCT RNFL and GCC 6 months after initial presentation.

The patient had a repeat MRI of the brain and orbits with and without contrast and fat saturation that continued to show no findings. He had a lumber puncture; the cerebrospinal fluid (CSF) profile was normal, and a large volume of CSF sent for cytology and cytometry was normal. The CSF was also tested for NMO and anti-MOG, which were negative. However, serum testing eventually returned positive for anti-MOG. While he was admitted in the hospital, he was treated with intravenous methylprednisolone for 5 days and then transitioned to 60 mg oral prednisone when he was discharged home.

Discussion

Humphrey visual field 6 months after
Figure 5. Humphrey visual field 30-2 of the left and right eye 6 months after initial presentation.

There are multiple causes of optic neuritis, including infectious, demyelinating (such as in multiple sclerosis) and idiopathic. With recent abilities to test for more antibodies, other causes for optic neuritis now include MOG immunoglobulin G and aquaporin-4 immunoglobulin G, which causes NMO.

MOG is a highly immunogenic glycoprotein expressed in the central nervous system on oligodendrocytes and myelin sheaths. If released into the CSF or drained into the periphery, MOG can induce autoimmunity, causing an inflammatory demyelination without astrocytopathy. The inflammatory demyelination can specifically affect the optic nerves, causing an autoimmune optic neuropathy. Features of anti-MOG optic neuritis include bilateral disease, frequent relapses and optic disc edema. Patients with anti-MOG optic neuritis often present with severe vision loss but favorable visual outcomes in contrast to NMO optic neuritis in which vision remains poor. The visual acuity on initial presentation with anti-MOG disease is between count fingers and hand motion. Relapses occur more frequently in anti-MOG optic neuritis than in NMO, seronegative and MS optic neuritis patients. The disc edema can be severe with associated peripapillary hemorrhages. OCT measurements of the RNFL are often overall preserved despite frequent relapses of optic neuritis.

Diagnosis of anti-MOG optic neuritis includes an MRI of the orbits and brain, which will typically reveal perineural optic nerve enhancement proximal to the chiasm. This enhancement can extend to the orbits and does not occur in any other form of optic neuritis. NMO, on the other hand, typically affects the optic chiasm and posterior optic pathways. A lumbar puncture should be performed along with blood work to test for MOG antibodies, which will be positive in patients with disease.

Acute treatment of suspected anti-MOG optic neuritis includes high-dose intravenous methylprednisolone. Early treatment of severe optic neuritis with steroids has been shown to lead to better outcomes. Patients are then transitioned to oral prednisone, which should be tapered as vision improves. Plasmapheresis or intravenous immunoglobulin (IVIG) should be considered in addition to methylprednisolone in patients with recurrent disease during acute attacks. Long-term immunotherapy is recommended in patients with relapsing disease or disease with severe residual deficits after a first attack. The ideal treatment for anti-MOG optic neuritis is unknown, but recent studies demonstrate the disease responds well to rituximab, azathioprine, methotrexate, mycophenolate mofetil and IVIG. Typical therapies for MS are ineffective at preventing relapses in anti-MOG optic neuritis patients. Patients should be followed closely for relapse of disease by a neuro-ophthalmologist and neurologist.

PAGE BREAK

Clinical course continued

While on high-dose oral steroids, the patient’s vision slowly improved to 20/25 in both eyes. He was referred to one of the neurologists at Tufts who started the patient on a long-term immunotherapy, rituximab, in an effort to wean him off steroids and to prevent recurrent optic neuritis. At his 6-month follow-up, OCT (Figure 4) showed significant RNFL thinning in the left eye greater than in the right, with GCC thinning in both eyes (Figure 4). Automated perimetry showed superior and inferior arcuate defects in the left eye (Figure 5). He has remained stable on rituximab while slowly tapering off prednisone. He will continue to have close follow-up with neuro-ophthalmology and neurology.