Grand Rounds at the New England Eye Center

Young woman presents with acute-onset unilateral vision loss

The right eye had severe optic nerve head edema with flame hemorrhages and a cecocentral scotoma.

A 27-year-old marketing professional was seen at Tufts Medical Center emergency department with new-onset vision changes in the right eye. She first noted a change in vision approximately 30 hours before while visiting her family in Philadelphia. She described sudden onset of a “dark storm cloud” covering the vision in her right eye. She was seen at a local emergency room and treated for a migraine. When her vision symptoms persisted, she was evaluated by a local ophthalmologist just before her scheduled flight back to Boston. She was urgently referred to the neuro-ophthalmology department at Tufts on landing in Boston.

Her medical history was significant for migraines. Her only medication was birth control (desogestrel and ethinyl estradiol), which she started taking 2 weeks before presentation.

Examination

Initial examination revealed vision of counting fingers in the patient’s right eye and 20/20 in the left eye. The right pupil was sluggishly reactive with a trace afferent pupillary defect. The left pupil was briskly reactive. Color vision, evaluated by Ishihara plates, was full in both eyes. Extraocular movements were full bilaterally. IOPs were within normal limits in both eyes. External and anterior segment evaluation of both eyes was normal. No anterior or posterior cells were seen.

Figure 1. Fundus photographs of the right and left eyes. In the right eye, there is 360° of optic nerve head edema with flame hemorrhages and scattered retinal hemorrhages. The macula was elevated with overlying hemorrhage. The left eye is normal.

Source: Aubrey R. Tirpack, MD, and Thomas R. Hedges III, MD

Figure 2. Humphrey visual fields of the left and right eyes. The right eye demonstrates a cecocentral scotoma. The left eye is normal.
Figure 3. OCT of the right (above) and left (below) eyes. OCT of the right eye shows severe edema of the optic nerve and subretinal hyperreflective material with elevation of the fovea. OCT of the left eye is normal.
Figure 4. Fluorescein angiography (early above, late below) of the right eye demonstrates blockage from peripapillary and retinal hemorrhages with early hyperfluorescence of the disc that does not appear to increase in later frames. No leakage within the macula or retinal vasculitis is seen.

Dilated fundus exam of the right eye demonstrated severe optic nerve head edema with flame hemorrhages as well as focal elevation of the macula with overlying retinal hemorrhage (Figure 1). Posterior examination of the left eye was normal. Automated visual field testing (Figure 2) demonstrated a cecocentral scotoma of the right eye. OCT of the right eye showed severe edema of the optic nerve and subretinal hyperreflective material with elevation of the fovea (Figure 3). Fluorescein angiography of the right eye showed blockage from peripapillary and retinal hemorrhages with early hyperfluorescence of the disc that did not increase in later frames (Figure 4).

What is your diagnosis?

See answer on next page.

Unilateral optic disc edema

The presence of unilateral optic disc edema associated with an afferent pupillary defect and cecocentral scotoma is consistent with a clinical diagnosis of papillitis. The differential diagnosis of papillitis includes infectious, autoimmune and demyelinating etiologies. Infectious causes of papillitis include ocular bartonellosis, syphilis, tuberculosis, Lyme and viral etiologies. Sarcoidosis, an autoimmune inflammatory disease, can also lead to unilateral papillitis. Demyelinating neuritis can present with unilateral disc edema. However, demyelinating neuritis is typically associated with pain with eye movements, which was not present in our patient. Additionally, the extensive peripapillary hemorrhages seen in our patient are not consistent with a demyelinating neuritis. On extensive review of systems, our patient denied any history of recent illness, cat exposure, tick bites or travel outside the United States. She was in a long-term monogamous relationship. She denied any cough, breathing difficulties, rash or joint pain.

Diagnosis and management

The patient was admitted to the neurology service for further workup and management. Complete blood count, angiotensin-converting enzyme (ACE), lysozyme and antinuclear antibodies were all within normal limits. Infectious workup for Lyme, syphilis, Bartonella, tuberculosis and HIV was negative. An MRI of the orbits with and without gadolinium did not demonstrate optic nerve enhancement or the presence of demyelinating lesions. Chest X-ray did show mild prominence of the hila, suggesting hilar lymphadenopathy. Based on these findings, a CT of the chest was ordered, which showed enlarged mediastinal and hilar lymph nodes (Figure 5), suggesting sarcoidosis.

The patient was started on 1 g daily of intravenous methylprednisolone for treatment of her papillitis. Four days after her initial presentation and after receiving three doses of intravenous steroid, her vision improved to 20/100 in the right eye. She was discharged from the hospital on 60 mg of prednisone daily with plan for slow taper. As an outpatient, she underwent endobronchial ultrasound-guided biopsy of her enlarged lymph nodes. Pathology revealed granulomas, confirming the diagnosis of sarcoidosis. At 4-month follow-up, the prednisone had been decreased to 17.5 mg daily. Her vision in the right eye had improved to 20/25, and resolution of her optic nerve edema was noted.

Chest x-ray
Figure 5. Chest X-ray (left) demonstrating mild hilar prominence. CT of the chest (right) with enlarged mediastinal and hilar lymph nodes.

Discussion

Sarcoidosis is a multisystem autoimmune disease that leads to granulomatous inflammation. The reported incidence of ophthalmic manifestations of sarcoidosis ranges from 10% to 50% in the literature. Ocular sarcoidosis can have varied presentations, with inflammation affecting nearly every part of the eye. Manifestations include eyelid and conjunctival granulomas, lacrimal gland infiltration, granulomatous anterior uveitis, iris nodules, vitreous opacities, retinal periphlebitis and chorioretinal lesions. Ocular involvement is typically seen in a bimodal age distribution, with peak incidences at 20 to 30 years old and 50 to 60 years old. African-American patients with sarcoidosis are more likely to have ocular involvement and tend to have an earlier age of onset. Interestingly, ocular involvement is the presenting sign of sarcoidosis in 20% to 30% of patients.

Optic nerve involvement of sarcoidosis is a known, but less described, manifestation of the disease. In a large prospective cohort study, 52 patients with sarcoid-associated optic neuropathy were followed over 20 years. The mean age at diagnosis was 42.5 years, and 61% of patients were female. The majority of patients presented with a subacute optic neuropathy, resembling an optic neuritis. MRI showed evidence of optic nerve involvement in 75% of cases, which was not a finding seen on our patient’s neuroimaging. ACE levels were normal in 43% of patients followed in this series. The majority of patients were treated with systemic corticosteroids, with a reported substantial improvement in vision after treatment. Patients with widespread neurologic involvement tended to have a poorer prognosis and visual outcome.

A retrospective case series from the University of Iowa described 20 patients with biopsy-proven sarcoidosis with neuro-ophthalmic manifestations. Optic nerve involvement was the most common neuro-ophthalmic manifestation reported, with 14 patients in the series presenting with an optic neuropathy. Eight patients presented with optic disc edema, five with optic disc pallor and one with an optic disc granuloma. Additional neuro-ophthalmic findings included cranial neuropathies, Horner’s syndrome, tonic pupil and optic tract involvement. Similar to the previously described study, MRI showed contrast enhancement of the optic nerve in the majority of patients. ACE levels were normal in 67% of patients who subsequently went on to have biopsy-proven sarcoidosis. Chest imaging was abnormal in 67% of patients. All patients were treated with systemic corticosteroids, with five patients requiring additional immunosuppressive therapy to control their disease.

Sarcoidosis is a known cause of optic neuropathy and must be considered in the diagnosis of a unilateral papillitis. Optic nerve involvement can be the presenting symptom of sarcoidosis, emphasizing the importance of ophthalmologists in the detection and diagnosis of this multisystemic disease. Serum ACE levels are not sufficient to rule out this disease because levels can be normal despite active inflammation. Chest imaging has shown improved detection, but ultimately tissue diagnosis is required in cases in which suspicion is high. Corticosteroids remain the mainstay of treatment, with consideration of additional immunosuppressive therapy for those with a relapsing or chronic disease course.

A 27-year-old marketing professional was seen at Tufts Medical Center emergency department with new-onset vision changes in the right eye. She first noted a change in vision approximately 30 hours before while visiting her family in Philadelphia. She described sudden onset of a “dark storm cloud” covering the vision in her right eye. She was seen at a local emergency room and treated for a migraine. When her vision symptoms persisted, she was evaluated by a local ophthalmologist just before her scheduled flight back to Boston. She was urgently referred to the neuro-ophthalmology department at Tufts on landing in Boston.

Her medical history was significant for migraines. Her only medication was birth control (desogestrel and ethinyl estradiol), which she started taking 2 weeks before presentation.

Examination

Initial examination revealed vision of counting fingers in the patient’s right eye and 20/20 in the left eye. The right pupil was sluggishly reactive with a trace afferent pupillary defect. The left pupil was briskly reactive. Color vision, evaluated by Ishihara plates, was full in both eyes. Extraocular movements were full bilaterally. IOPs were within normal limits in both eyes. External and anterior segment evaluation of both eyes was normal. No anterior or posterior cells were seen.

Figure 1. Fundus photographs of the right and left eyes. In the right eye, there is 360° of optic nerve head edema with flame hemorrhages and scattered retinal hemorrhages. The macula was elevated with overlying hemorrhage. The left eye is normal.

Source: Aubrey R. Tirpack, MD, and Thomas R. Hedges III, MD

Figure 2. Humphrey visual fields of the left and right eyes. The right eye demonstrates a cecocentral scotoma. The left eye is normal.
Figure 3. OCT of the right (above) and left (below) eyes. OCT of the right eye shows severe edema of the optic nerve and subretinal hyperreflective material with elevation of the fovea. OCT of the left eye is normal.
Figure 4. Fluorescein angiography (early above, late below) of the right eye demonstrates blockage from peripapillary and retinal hemorrhages with early hyperfluorescence of the disc that does not appear to increase in later frames. No leakage within the macula or retinal vasculitis is seen.

Dilated fundus exam of the right eye demonstrated severe optic nerve head edema with flame hemorrhages as well as focal elevation of the macula with overlying retinal hemorrhage (Figure 1). Posterior examination of the left eye was normal. Automated visual field testing (Figure 2) demonstrated a cecocentral scotoma of the right eye. OCT of the right eye showed severe edema of the optic nerve and subretinal hyperreflective material with elevation of the fovea (Figure 3). Fluorescein angiography of the right eye showed blockage from peripapillary and retinal hemorrhages with early hyperfluorescence of the disc that did not increase in later frames (Figure 4).

What is your diagnosis?

See answer on next page.

PAGE BREAK

Unilateral optic disc edema

The presence of unilateral optic disc edema associated with an afferent pupillary defect and cecocentral scotoma is consistent with a clinical diagnosis of papillitis. The differential diagnosis of papillitis includes infectious, autoimmune and demyelinating etiologies. Infectious causes of papillitis include ocular bartonellosis, syphilis, tuberculosis, Lyme and viral etiologies. Sarcoidosis, an autoimmune inflammatory disease, can also lead to unilateral papillitis. Demyelinating neuritis can present with unilateral disc edema. However, demyelinating neuritis is typically associated with pain with eye movements, which was not present in our patient. Additionally, the extensive peripapillary hemorrhages seen in our patient are not consistent with a demyelinating neuritis. On extensive review of systems, our patient denied any history of recent illness, cat exposure, tick bites or travel outside the United States. She was in a long-term monogamous relationship. She denied any cough, breathing difficulties, rash or joint pain.

Diagnosis and management

The patient was admitted to the neurology service for further workup and management. Complete blood count, angiotensin-converting enzyme (ACE), lysozyme and antinuclear antibodies were all within normal limits. Infectious workup for Lyme, syphilis, Bartonella, tuberculosis and HIV was negative. An MRI of the orbits with and without gadolinium did not demonstrate optic nerve enhancement or the presence of demyelinating lesions. Chest X-ray did show mild prominence of the hila, suggesting hilar lymphadenopathy. Based on these findings, a CT of the chest was ordered, which showed enlarged mediastinal and hilar lymph nodes (Figure 5), suggesting sarcoidosis.

The patient was started on 1 g daily of intravenous methylprednisolone for treatment of her papillitis. Four days after her initial presentation and after receiving three doses of intravenous steroid, her vision improved to 20/100 in the right eye. She was discharged from the hospital on 60 mg of prednisone daily with plan for slow taper. As an outpatient, she underwent endobronchial ultrasound-guided biopsy of her enlarged lymph nodes. Pathology revealed granulomas, confirming the diagnosis of sarcoidosis. At 4-month follow-up, the prednisone had been decreased to 17.5 mg daily. Her vision in the right eye had improved to 20/25, and resolution of her optic nerve edema was noted.

Chest x-ray
Figure 5. Chest X-ray (left) demonstrating mild hilar prominence. CT of the chest (right) with enlarged mediastinal and hilar lymph nodes.

Discussion

Sarcoidosis is a multisystem autoimmune disease that leads to granulomatous inflammation. The reported incidence of ophthalmic manifestations of sarcoidosis ranges from 10% to 50% in the literature. Ocular sarcoidosis can have varied presentations, with inflammation affecting nearly every part of the eye. Manifestations include eyelid and conjunctival granulomas, lacrimal gland infiltration, granulomatous anterior uveitis, iris nodules, vitreous opacities, retinal periphlebitis and chorioretinal lesions. Ocular involvement is typically seen in a bimodal age distribution, with peak incidences at 20 to 30 years old and 50 to 60 years old. African-American patients with sarcoidosis are more likely to have ocular involvement and tend to have an earlier age of onset. Interestingly, ocular involvement is the presenting sign of sarcoidosis in 20% to 30% of patients.

PAGE BREAK

Optic nerve involvement of sarcoidosis is a known, but less described, manifestation of the disease. In a large prospective cohort study, 52 patients with sarcoid-associated optic neuropathy were followed over 20 years. The mean age at diagnosis was 42.5 years, and 61% of patients were female. The majority of patients presented with a subacute optic neuropathy, resembling an optic neuritis. MRI showed evidence of optic nerve involvement in 75% of cases, which was not a finding seen on our patient’s neuroimaging. ACE levels were normal in 43% of patients followed in this series. The majority of patients were treated with systemic corticosteroids, with a reported substantial improvement in vision after treatment. Patients with widespread neurologic involvement tended to have a poorer prognosis and visual outcome.

A retrospective case series from the University of Iowa described 20 patients with biopsy-proven sarcoidosis with neuro-ophthalmic manifestations. Optic nerve involvement was the most common neuro-ophthalmic manifestation reported, with 14 patients in the series presenting with an optic neuropathy. Eight patients presented with optic disc edema, five with optic disc pallor and one with an optic disc granuloma. Additional neuro-ophthalmic findings included cranial neuropathies, Horner’s syndrome, tonic pupil and optic tract involvement. Similar to the previously described study, MRI showed contrast enhancement of the optic nerve in the majority of patients. ACE levels were normal in 67% of patients who subsequently went on to have biopsy-proven sarcoidosis. Chest imaging was abnormal in 67% of patients. All patients were treated with systemic corticosteroids, with five patients requiring additional immunosuppressive therapy to control their disease.

Sarcoidosis is a known cause of optic neuropathy and must be considered in the diagnosis of a unilateral papillitis. Optic nerve involvement can be the presenting symptom of sarcoidosis, emphasizing the importance of ophthalmologists in the detection and diagnosis of this multisystemic disease. Serum ACE levels are not sufficient to rule out this disease because levels can be normal despite active inflammation. Chest imaging has shown improved detection, but ultimately tissue diagnosis is required in cases in which suspicion is high. Corticosteroids remain the mainstay of treatment, with consideration of additional immunosuppressive therapy for those with a relapsing or chronic disease course.