Grand Rounds at the New England Eye Center

Young man presents with sudden loss of vision

The right eye showed an inferior altitudinal defect and some thickening of the retinal nerve fiber layer.

A 31-year-old man was referred to the neuro-ophthalmology service for 3 weeks of cloudy vision in the right eye and intermittent headaches. He felt that this came on suddenly one morning and described darkening of the lower portion of his visual field.

His medical history was significant for obesity and surgical history included tonsillectomy. He was aware that he snored but did not know if he stopped breathing periodically while sleeping. He was taking no medications.

Fundus photos
Figure 1. Fundus photo of the right eye showing mild disc edema. Fundus photo of the left eye is normal.

Source: Jarod Santoro, MD, and Thomas R. Hedges III, MD

Humphrey visual field 
Figure 2. Humphrey visual field 30-2 of the right eye showing an inferior altitudinal defect. The left eye is normal.
ganglion cell complex 
Figure 3. Ganglion cell complex showing normal thickness.

Examination

Best corrected visual acuity was 20/30 in the right eye and 20/20 in the left eye. The patient identified all Ishihara color plates in both eyes but had some difficulty with the right eye. There was a 2+ right relative afferent pupillary defect. IOP was 13 mm Hg in the right eye and 14 mm Hg in the left. Motility was full. External and slit lamp findings were normal. On dilated exam of the right eye, the optic nerve showed mild disc edema with a normal macula and vessels. The left optic nerve was pink with a small cup-to-disc ratio (Figure 1). Automated visual field (Humphrey 30-2, Allergan) of the right eye showed an inferior altitudinal defect (Figure 2).

OCT showed some thickening of the retinal nerve fiber layer (RNFL) on the right but a normal ganglion cell complex (GCC) (Figure 3).

What is your diagnosis?

See answer on next page.

Sudden loss of vision

The differential diagnosis of apparently sudden loss of vision in one eye with associated RNFL thickening in a young man includes demyelinating optic neuritis, antibody-mediated optic neuritis and sarcoidosis, as well as infection such as syphilis. An infiltrative or compressive process of the optic nerve must also be considered. Although this patient is young, nonarteritic ischemic optic neuropathy (NAION) should also be on the differential as he had small cup-to-disc ratios and was overweight with possible sleep apnea. The patient had not seen a primary care physician over the last few years, and it was unknown if he had developed other risk factors such as hypertension or diabetes.

Additional workup

The patient was sent to primary care for blood pressure monitoring and to check hemoglobin A1c, which was normal. A sleep study was also recommended to evaluate for obstructive sleep apnea.

MRI of the orbits and brain with and without contrast was ordered mainly to look for optic nerve enhancement and intracranial demyelinating lesions. This revealed a heterogeneously enhancing mass filling the sphenoid sinus with extension to the clivus. The mass extended along the right optic nerve in the optic canal. There were also two enhancing lesions in the cerebellum (Figure 4).

The patient was then evaluated by neurosurgery and underwent endoscopic transsphenoidal biopsy of the mass, which was found to be metastatic cutaneous melanoma.

MRI of a heterogeneously enhancing mass
Figure 4. MRI of a heterogeneously enhancing mass filling the sphenoid sinus. Axial cut shows the mass extended along the right optic nerve in the optic canal.

Discussion

Our patient presented with apparently sudden unilateral decreased vision and optic disc edema. The most common causes of this presentation are optic neuritis and NAION. A retrospective study by Lee and colleagues identified eight patients who were originally diagnosed with optic neuritis or NAION and were later found to have compressive lesions. All eight patients in this study were found to have atypical features of each disease at presentation. Atypical features of optic neuritis consist of progressive course, older age, absence of pain and lack of improvement within 3 weeks. Atypical features of NAION consist of progressive visual loss, presentation at a younger age, lack of vasculopathic risk factors, absence of a relative afferent pupillary defect and absence of disc edema in the acute phase. In our patient, his young age, lack of periocular pain exacerbated by eye movement and unknown vasculopathic risk factors would be an atypical presentation for either optic neuritis or NAION.

Metastatic melanomas to the eye and orbit are rare, usually occur in patients with widely disseminated metastases and represent only 3% to 20% of all metastatic tumors to the orbit. Metastatic orbital melanomas have a poor prognosis, and treatment is usually palliative, with survival ranging from 5.7 to 19.7 months. In the unusual patient in whom metastatic melanoma is the presenting feature, symptoms may include proptosis, ophthalmoplegia and optic nerve compression. Cutaneous melanoma most often metastasizes to the lung, liver, brain and bone. In a study by Shields and colleagues, patients with orbital metastases who also had brain metastases had the worst prognosis, averaging 6 months’ survival.

The treatment of orbital metastases is palliative and aimed at improving the patient’s comfort and relieving symptoms. Different modalities such as surgery, radiotherapy or chemotherapy can be used to help control symptoms such as diplopia or proptosis and also can be used to reduce vision impairment when there is compression of the optic nerve. Radiotherapy can reduce tumor load and alleviate bothersome symptoms but can cause other ocular side effects including radiation optic neuropathy or retinopathy and corneal scarring. Surgical resection, even if incomplete, may provide palliative effects for the remainder of the patient’s life.

Our patient had a dense inferior field defect and a full GCC. In a study by Tieger and colleagues, patients with visual field defects but relatively preserved GCC thickness tended to have a better postoperative recovery of vision.

Newer immunotherapies such as ipilimumab have shown an improved overall survival in patients with previously treated metastatic melanoma. Ipilimumab is a humanized monoclonal antibody that potentiates the activity of T cells, which enhances the immune system to inhibit tumor growth. Unfortunately, these drugs have significant side effects. Patients taking ipilimumab have had immune-related adverse events (IRAE) at a 10% to 15% higher rate compared with traditional chemotherapeutic drugs. However, one study showed ophthalmic IRAE only occurred in less than 1% of patients and included uveitis and orbital myositis. As there are increased complication rates with these new drugs, patients should be monitored closely and treated appropriately when adverse events arise.

Clinical course

After the diagnosis of metastatic cutaneous melanoma, our patient received a CT of the chest and abdomen, which revealed multiple masses within the lungs, liver and left kidney. The patient continued to have visual deterioration of the right eye and had decompressive neurosurgery with almost complete improvement in his vision. He was started on immunotherapy with the goal of comprehensive global reduction of the tumor, including within the cranium. If the patient does not respond to immunotherapy, then he will be offered conformal fractionated radiotherapy or radiosurgery to address the intracranial metastasis.

A 31-year-old man was referred to the neuro-ophthalmology service for 3 weeks of cloudy vision in the right eye and intermittent headaches. He felt that this came on suddenly one morning and described darkening of the lower portion of his visual field.

His medical history was significant for obesity and surgical history included tonsillectomy. He was aware that he snored but did not know if he stopped breathing periodically while sleeping. He was taking no medications.

Fundus photos
Figure 1. Fundus photo of the right eye showing mild disc edema. Fundus photo of the left eye is normal.

Source: Jarod Santoro, MD, and Thomas R. Hedges III, MD

Humphrey visual field 
Figure 2. Humphrey visual field 30-2 of the right eye showing an inferior altitudinal defect. The left eye is normal.
ganglion cell complex 
Figure 3. Ganglion cell complex showing normal thickness.

Examination

Best corrected visual acuity was 20/30 in the right eye and 20/20 in the left eye. The patient identified all Ishihara color plates in both eyes but had some difficulty with the right eye. There was a 2+ right relative afferent pupillary defect. IOP was 13 mm Hg in the right eye and 14 mm Hg in the left. Motility was full. External and slit lamp findings were normal. On dilated exam of the right eye, the optic nerve showed mild disc edema with a normal macula and vessels. The left optic nerve was pink with a small cup-to-disc ratio (Figure 1). Automated visual field (Humphrey 30-2, Allergan) of the right eye showed an inferior altitudinal defect (Figure 2).

OCT showed some thickening of the retinal nerve fiber layer (RNFL) on the right but a normal ganglion cell complex (GCC) (Figure 3).

What is your diagnosis?

See answer on next page.

PAGE BREAK

Sudden loss of vision

The differential diagnosis of apparently sudden loss of vision in one eye with associated RNFL thickening in a young man includes demyelinating optic neuritis, antibody-mediated optic neuritis and sarcoidosis, as well as infection such as syphilis. An infiltrative or compressive process of the optic nerve must also be considered. Although this patient is young, nonarteritic ischemic optic neuropathy (NAION) should also be on the differential as he had small cup-to-disc ratios and was overweight with possible sleep apnea. The patient had not seen a primary care physician over the last few years, and it was unknown if he had developed other risk factors such as hypertension or diabetes.

Additional workup

The patient was sent to primary care for blood pressure monitoring and to check hemoglobin A1c, which was normal. A sleep study was also recommended to evaluate for obstructive sleep apnea.

MRI of the orbits and brain with and without contrast was ordered mainly to look for optic nerve enhancement and intracranial demyelinating lesions. This revealed a heterogeneously enhancing mass filling the sphenoid sinus with extension to the clivus. The mass extended along the right optic nerve in the optic canal. There were also two enhancing lesions in the cerebellum (Figure 4).

The patient was then evaluated by neurosurgery and underwent endoscopic transsphenoidal biopsy of the mass, which was found to be metastatic cutaneous melanoma.

MRI of a heterogeneously enhancing mass
Figure 4. MRI of a heterogeneously enhancing mass filling the sphenoid sinus. Axial cut shows the mass extended along the right optic nerve in the optic canal.

Discussion

Our patient presented with apparently sudden unilateral decreased vision and optic disc edema. The most common causes of this presentation are optic neuritis and NAION. A retrospective study by Lee and colleagues identified eight patients who were originally diagnosed with optic neuritis or NAION and were later found to have compressive lesions. All eight patients in this study were found to have atypical features of each disease at presentation. Atypical features of optic neuritis consist of progressive course, older age, absence of pain and lack of improvement within 3 weeks. Atypical features of NAION consist of progressive visual loss, presentation at a younger age, lack of vasculopathic risk factors, absence of a relative afferent pupillary defect and absence of disc edema in the acute phase. In our patient, his young age, lack of periocular pain exacerbated by eye movement and unknown vasculopathic risk factors would be an atypical presentation for either optic neuritis or NAION.

Metastatic melanomas to the eye and orbit are rare, usually occur in patients with widely disseminated metastases and represent only 3% to 20% of all metastatic tumors to the orbit. Metastatic orbital melanomas have a poor prognosis, and treatment is usually palliative, with survival ranging from 5.7 to 19.7 months. In the unusual patient in whom metastatic melanoma is the presenting feature, symptoms may include proptosis, ophthalmoplegia and optic nerve compression. Cutaneous melanoma most often metastasizes to the lung, liver, brain and bone. In a study by Shields and colleagues, patients with orbital metastases who also had brain metastases had the worst prognosis, averaging 6 months’ survival.

PAGE BREAK

The treatment of orbital metastases is palliative and aimed at improving the patient’s comfort and relieving symptoms. Different modalities such as surgery, radiotherapy or chemotherapy can be used to help control symptoms such as diplopia or proptosis and also can be used to reduce vision impairment when there is compression of the optic nerve. Radiotherapy can reduce tumor load and alleviate bothersome symptoms but can cause other ocular side effects including radiation optic neuropathy or retinopathy and corneal scarring. Surgical resection, even if incomplete, may provide palliative effects for the remainder of the patient’s life.

Our patient had a dense inferior field defect and a full GCC. In a study by Tieger and colleagues, patients with visual field defects but relatively preserved GCC thickness tended to have a better postoperative recovery of vision.

Newer immunotherapies such as ipilimumab have shown an improved overall survival in patients with previously treated metastatic melanoma. Ipilimumab is a humanized monoclonal antibody that potentiates the activity of T cells, which enhances the immune system to inhibit tumor growth. Unfortunately, these drugs have significant side effects. Patients taking ipilimumab have had immune-related adverse events (IRAE) at a 10% to 15% higher rate compared with traditional chemotherapeutic drugs. However, one study showed ophthalmic IRAE only occurred in less than 1% of patients and included uveitis and orbital myositis. As there are increased complication rates with these new drugs, patients should be monitored closely and treated appropriately when adverse events arise.

Clinical course

After the diagnosis of metastatic cutaneous melanoma, our patient received a CT of the chest and abdomen, which revealed multiple masses within the lungs, liver and left kidney. The patient continued to have visual deterioration of the right eye and had decompressive neurosurgery with almost complete improvement in his vision. He was started on immunotherapy with the goal of comprehensive global reduction of the tumor, including within the cranium. If the patient does not respond to immunotherapy, then he will be offered conformal fractionated radiotherapy or radiosurgery to address the intracranial metastasis.