Grand Rounds at the New England Eye Center

Older woman presents with new-onset diplopia

She also reported a 2-week history of occipital headaches associated with scalp tenderness.

A 78-year-old woman with a medical history of hypertension, hyperlipidemia, diet-controlled type 2 diabetes, gout, osteopenia and herpes zoster presented with a 4-day history of new-onset constant binocular double vision.

The patient had binocular double vision that varied between horizontal and vertical. She denied both amaurosis and vision loss. Her ocular history included a lamellar hole in the right eye and cataract surgery in the right eye. The patient was a daily cigarette smoker and drank alcohol on occasion.

On presentation in the emergency room for a suspected right third nerve palsy, a CT of the brain was performed and showed no acute pathology. An MRI of the brain with and without contrast for the third nerve palsy was performed and showed questionable enhancement of the right distal canalicular segment of the third cranial nerve. Ophthalmology was consulted to assess the patient’s new-onset diplopia.

On further questioning, the patient endorsed a 2-week history of occipital headaches associated with scalp tenderness that resolved with ibuprofen. Additionally, she endorsed difficulty chewing to the point where she was limiting the foods she was eating. She complained of mild neck stiffness and aching. She denied fevers, fatigue and myalgias.

ocular alignment

Source: Alison Lauter, MD, and Geetha Athappilly, MD

Examination

On examination, best corrected visual acuity was 20/40-1 in the right eye and 20/30-2 in the left eye. HRR color plates were full in both eyes. Pupils were equal in size and briskly reactive to light with no afferent pupillary defect present. IOPs were within normal limits in both eyes. Extraocular movements and confrontational visual fields were full in both eyes. Ocular alignment as tested with a Maddox rod is noted in Figure 1. There was no ptosis. There was no tenderness or nodularity to bilateral temporal arteries. Anterior slit lamp exam was unremarkable except for a posterior chamber IOL in the right eye and a nuclear sclerotic cataract in the left eye. Dilated posterior exam revealed a lamellar hole on the right without evidence of ischemia to the optic nerve or retina.

What is your diagnosis?

See answer on next page.

Binocular diplopia

Our patient was found to have binocular vertical diplopia. On exam, the patient exhibited a right hypertropia in all fields of gaze that was not alternating and did not follow the three-step Parks-Bielschowsky test. The differential diagnosis for new-onset diplopia in an elderly patient includes an ischemic cranial nerve palsy, vasculitis such as giant cell arteritis, infectious causes such as meningitis, inflammation such as sarcoidosis, myasthenia gravis or infiltrative process such as a lymphoma.

MRI of the orbit with gadolinium
Figure 2. T1 fat-saturation MRI of the orbit with gadolinium showing perineural enhancement of the right optic nerve.

The patient’s constellation of symptoms was concerning for giant cell arteritis. A C-reactive protein was elevated at 48.1 g/mL. A basic metabolic panel and complete blood count were within normal limits. Given the high suspicion for giant cell arteritis based on her symptoms and elevated C-reactive protein, she was started on intravenous methylprednisolone 1 g daily. A temporal artery biopsy was performed by vascular surgery. Due to motion artifact limiting the quality of the original MRI, a repeat MRI of the brain and orbits with and without contrast was ordered and showed perineural enhancement of the right optic nerve concerning for a perineuritis (Figure 2).

Discussion

Giant cell arteritis (GCA) is a systemic inflammatory vasculitis that affects both medium- and large-sized arteries. GCA most commonly affects the superficial temporal artery, ophthalmic artery, posterior ciliary arteries and vertebral arteries. Ischemic complications occur as the vasculitis leads to luminal occlusion. GCA typically occurs in the elderly population with peak incidence between the ages of 70 and 80 years old. The majority of patients affected are women, accounting for 65% to 75% of cases.

The clinical presentation of GCA can vary vastly among patients; therefore, it should be in the differential even when the symptoms and findings are not typical. GCA can present with systemic symptoms such as unilateral or bilateral headaches localized to the temple or occipital region, fatigue, myalgias, fever, weight loss, jaw claudication or scalp tenderness. A variety of systemic, neurologic and ophthalmologic complications can occur due to the disease. Rapidly progressive visual loss is the most severe ocular complication and can become permanent. Partial or complete vision loss in one or both eyes occurs in 20% of patients due to retinal artery occlusions and anterior ischemic optic neuropathy. Ischemic optic neuropathy in GCA causes vision loss in about 10% to 15% of patients. Less frequently, the vasculitis can present with diplopia. Patients can present with predominantly ocular symptoms, which is termed occult GCA.

Prompt diagnosis and treatment of GCA is paramount to preserving vision and preventing life-threating complications. In cases of amaurosis or vision loss, a fluorescein angiogram can show characteristic features of patchy choroidal filling and delayed arterial and choroidal filling pathognomonic for GCA. The gold standard for diagnosis is a temporal artery biopsy. In general, a 2-cm biopsy specimen of the temporal artery is recommended to prevent false negative biopsy due to skip lesions. A biopsy should always be done to justify the prolonged treatment with steroids.

Diplopia in GCA is rare and reported to occur in 2% to 15% of patients. Diplopia can occur due to vasculitic occlusion or due to ischemia of the extraocular muscles or oculomotor nerves. Ischemia can also occur in the brainstem ocular motor nuclei or its fascicles, supranuclear or internuclear pathways associated with ocular motility. Diplopia typically precedes vision loss and may be an early indication of GCA. It can either be constant or transient and usually resolves with treatment. Isolated diplopia in elderly patients presents a diagnostic predicament due to the extensive differential diagnosis, but it is important to keep GCA in the differential.

Radiologic manifestations in patients with GCA are uncommon, and an MRI is not typically a component of the initial workup for the vasculitis. Rarely are there either cranial or optic nerve findings that correlate with the visual symptoms. However, there are reports of cranial nerve enhancement with double vision. In our case, the initial MRI was of poor quality, and after review, the enhancement of the right third nerve seemed to be due to artifact. The optic nerve sheath enhancement seen on repeat MRI was not due to artifact and has been reported with GCA. Typically, these patients do not have the profound vision loss seen with ischemic events to the optic nerve; however, prompt initiation of systemic corticosteroids is necessary for preservation of vision.

Clinical course continued

Temporal artery biopsy
Figure 3. Temporal artery biopsy showing a mononuclear cell infiltration and granulomatous inflammation with multinucleated giant cells surrounding the vessel.

Our patient was continued on high-dose intravenous steroids for 5 days using the C-reactive protein as a guide. Her blood sugars were closely monitored during this time given her diabetes, and she was started on insulin for adequate control of blood sugar. She was also started on a proton pump inhibitor for gastrointestinal protection. Her C-reactive protein trended down daily and was 0.6 g/mL after completion of the intravenous steroid course. She was discharged home on prednisone 100 mg daily, which was managed by rheumatology. Her temporal artery biopsy (Figure 3) showed a mononuclear cell infiltration and granulomatous inflammation with multinucleated giant cells surrounding the vessel consistent with GCA.

On 3-day follow-up after discharge from the hospital, the patient had persistent diplopia and mild improvement of her deviation. She was given a Fresnel 4 diopter base down prism over the right eye for symptomatic management of her right hypertropia. At her 2-month follow-up, the patient’s diplopia resolved and she no longer needed the Fresnel prism. She was gradually tapered off of prednisone over the course of 10 months. She did not experience any further episodes of diplopia or suffer permanent vision loss due to GCA.

A 78-year-old woman with a medical history of hypertension, hyperlipidemia, diet-controlled type 2 diabetes, gout, osteopenia and herpes zoster presented with a 4-day history of new-onset constant binocular double vision.

The patient had binocular double vision that varied between horizontal and vertical. She denied both amaurosis and vision loss. Her ocular history included a lamellar hole in the right eye and cataract surgery in the right eye. The patient was a daily cigarette smoker and drank alcohol on occasion.

On presentation in the emergency room for a suspected right third nerve palsy, a CT of the brain was performed and showed no acute pathology. An MRI of the brain with and without contrast for the third nerve palsy was performed and showed questionable enhancement of the right distal canalicular segment of the third cranial nerve. Ophthalmology was consulted to assess the patient’s new-onset diplopia.

On further questioning, the patient endorsed a 2-week history of occipital headaches associated with scalp tenderness that resolved with ibuprofen. Additionally, she endorsed difficulty chewing to the point where she was limiting the foods she was eating. She complained of mild neck stiffness and aching. She denied fevers, fatigue and myalgias.

ocular alignment

Source: Alison Lauter, MD, and Geetha Athappilly, MD

Examination

On examination, best corrected visual acuity was 20/40-1 in the right eye and 20/30-2 in the left eye. HRR color plates were full in both eyes. Pupils were equal in size and briskly reactive to light with no afferent pupillary defect present. IOPs were within normal limits in both eyes. Extraocular movements and confrontational visual fields were full in both eyes. Ocular alignment as tested with a Maddox rod is noted in Figure 1. There was no ptosis. There was no tenderness or nodularity to bilateral temporal arteries. Anterior slit lamp exam was unremarkable except for a posterior chamber IOL in the right eye and a nuclear sclerotic cataract in the left eye. Dilated posterior exam revealed a lamellar hole on the right without evidence of ischemia to the optic nerve or retina.

What is your diagnosis?

See answer on next page.

PAGE BREAK

Binocular diplopia

Our patient was found to have binocular vertical diplopia. On exam, the patient exhibited a right hypertropia in all fields of gaze that was not alternating and did not follow the three-step Parks-Bielschowsky test. The differential diagnosis for new-onset diplopia in an elderly patient includes an ischemic cranial nerve palsy, vasculitis such as giant cell arteritis, infectious causes such as meningitis, inflammation such as sarcoidosis, myasthenia gravis or infiltrative process such as a lymphoma.

MRI of the orbit with gadolinium
Figure 2. T1 fat-saturation MRI of the orbit with gadolinium showing perineural enhancement of the right optic nerve.

The patient’s constellation of symptoms was concerning for giant cell arteritis. A C-reactive protein was elevated at 48.1 g/mL. A basic metabolic panel and complete blood count were within normal limits. Given the high suspicion for giant cell arteritis based on her symptoms and elevated C-reactive protein, she was started on intravenous methylprednisolone 1 g daily. A temporal artery biopsy was performed by vascular surgery. Due to motion artifact limiting the quality of the original MRI, a repeat MRI of the brain and orbits with and without contrast was ordered and showed perineural enhancement of the right optic nerve concerning for a perineuritis (Figure 2).

Discussion

Giant cell arteritis (GCA) is a systemic inflammatory vasculitis that affects both medium- and large-sized arteries. GCA most commonly affects the superficial temporal artery, ophthalmic artery, posterior ciliary arteries and vertebral arteries. Ischemic complications occur as the vasculitis leads to luminal occlusion. GCA typically occurs in the elderly population with peak incidence between the ages of 70 and 80 years old. The majority of patients affected are women, accounting for 65% to 75% of cases.

The clinical presentation of GCA can vary vastly among patients; therefore, it should be in the differential even when the symptoms and findings are not typical. GCA can present with systemic symptoms such as unilateral or bilateral headaches localized to the temple or occipital region, fatigue, myalgias, fever, weight loss, jaw claudication or scalp tenderness. A variety of systemic, neurologic and ophthalmologic complications can occur due to the disease. Rapidly progressive visual loss is the most severe ocular complication and can become permanent. Partial or complete vision loss in one or both eyes occurs in 20% of patients due to retinal artery occlusions and anterior ischemic optic neuropathy. Ischemic optic neuropathy in GCA causes vision loss in about 10% to 15% of patients. Less frequently, the vasculitis can present with diplopia. Patients can present with predominantly ocular symptoms, which is termed occult GCA.

Prompt diagnosis and treatment of GCA is paramount to preserving vision and preventing life-threating complications. In cases of amaurosis or vision loss, a fluorescein angiogram can show characteristic features of patchy choroidal filling and delayed arterial and choroidal filling pathognomonic for GCA. The gold standard for diagnosis is a temporal artery biopsy. In general, a 2-cm biopsy specimen of the temporal artery is recommended to prevent false negative biopsy due to skip lesions. A biopsy should always be done to justify the prolonged treatment with steroids.

PAGE BREAK

Diplopia in GCA is rare and reported to occur in 2% to 15% of patients. Diplopia can occur due to vasculitic occlusion or due to ischemia of the extraocular muscles or oculomotor nerves. Ischemia can also occur in the brainstem ocular motor nuclei or its fascicles, supranuclear or internuclear pathways associated with ocular motility. Diplopia typically precedes vision loss and may be an early indication of GCA. It can either be constant or transient and usually resolves with treatment. Isolated diplopia in elderly patients presents a diagnostic predicament due to the extensive differential diagnosis, but it is important to keep GCA in the differential.

Radiologic manifestations in patients with GCA are uncommon, and an MRI is not typically a component of the initial workup for the vasculitis. Rarely are there either cranial or optic nerve findings that correlate with the visual symptoms. However, there are reports of cranial nerve enhancement with double vision. In our case, the initial MRI was of poor quality, and after review, the enhancement of the right third nerve seemed to be due to artifact. The optic nerve sheath enhancement seen on repeat MRI was not due to artifact and has been reported with GCA. Typically, these patients do not have the profound vision loss seen with ischemic events to the optic nerve; however, prompt initiation of systemic corticosteroids is necessary for preservation of vision.

Clinical course continued

Temporal artery biopsy
Figure 3. Temporal artery biopsy showing a mononuclear cell infiltration and granulomatous inflammation with multinucleated giant cells surrounding the vessel.

Our patient was continued on high-dose intravenous steroids for 5 days using the C-reactive protein as a guide. Her blood sugars were closely monitored during this time given her diabetes, and she was started on insulin for adequate control of blood sugar. She was also started on a proton pump inhibitor for gastrointestinal protection. Her C-reactive protein trended down daily and was 0.6 g/mL after completion of the intravenous steroid course. She was discharged home on prednisone 100 mg daily, which was managed by rheumatology. Her temporal artery biopsy (Figure 3) showed a mononuclear cell infiltration and granulomatous inflammation with multinucleated giant cells surrounding the vessel consistent with GCA.

On 3-day follow-up after discharge from the hospital, the patient had persistent diplopia and mild improvement of her deviation. She was given a Fresnel 4 diopter base down prism over the right eye for symptomatic management of her right hypertropia. At her 2-month follow-up, the patient’s diplopia resolved and she no longer needed the Fresnel prism. She was gradually tapered off of prednisone over the course of 10 months. She did not experience any further episodes of diplopia or suffer permanent vision loss due to GCA.

PAGE BREAK