Man presents with daily headaches and blurry vision
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A 39-year-old man presented to the comprehensive ophthalmology service at the New England Eye Center with 6 weeks of daily headaches and blurry vision.
The headaches radiated from his neck to his forehead and temples and were throbbing in nature, not associated with changes in position. The blurry vision was bilateral, occurring at both distance and near, and present for the past month. He also endorsed having occasional nausea. He denied having fevers, pulse-synchronous tinnitus and diplopia. His ocular history was notable for mild myopia of –2.5 D in both eyes. His medical history was notable for hyperthyroidism and gastroesophageal reflux disease. His medications included methimazole and omeprazole. He had no known drug allergies and did not use alcohol, tobacco or recreational drugs.
Examination
Best corrected visual acuity was 20/40 in each eye with a hyperopic shift noted. The pupils were symmetric, round and briskly reactive, with no afferent pupillary defect. IOPs were within normal limits in each eye. Confrontational visual fields noted a superotemporal defect in the right eye. Motility was full and painless bilaterally. Slit lamp examination was notable only for complexion-associated melanosis on the conjunctiva of each eye. The optic nerves of both eyes had Frisén grade 5, 360° optic disc edema with blurred margins and obscuration of the vasculature, as well as peripapillary flame-shaped hemorrhages and cotton wool spots (Figure 1). Macular edema was present bilaterally (Figure 2). The retinal vessels were of normal caliber and appearance bilaterally. There was a focal region of myelinated retinal nerve fiber layer superotemporal to the macula in the left eye. Retinal periphery appeared unremarkable bilaterally.
Source: Nisha S. Dhawlikar, MD, MPH, Melina Morkin, MD, Thomas R. Hedges III, MD, and Yosbelkys Martin-Paez, MD
Humphrey visual field 30-2 testing was obtained to further evaluate the patient’s visual field deficit. Testing was reliable in each eye and revealed a left homonymous hemianopsia, worse superiorly, with a possible enlarged blind spot in the right eye (Figure 3). OCT of the macula revealed subretinal fluid tracking from the optic nerve (Figure 4).
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Bilateral disc edema
Bilateral disc edema, regardless of whether visual function is affected, gives rise to a large differential diagnosis including intracranial processes, infectious etiologies, vascular etiologies, autoimmune conditions and drug toxicity. Given the patient’s visual field defects and neurologic symptoms of headaches and nausea, secondary intracranial hypertension was highest on the differential, such as from an intracranial tumor. Idiopathic intracranial hypertension was considered as well; however, the patient was not obese and did not have recent weight gain.
Infectious etiologies such as cryptococcal meningitis, although rare, could mimic a tumor because secondary increased intracranial pressure could lead to papilledema and its ocular manifestations. However, the patient was afebrile and did not have a stiff neck, seizures, altered mental status or diplopia. Papillitis was lower on the differential as it most often presents with unilateral findings, and the patient had no recent travel history or exposure to pets.
Malignant systemic hypertension could cause bilateral optic disc edema. However, our patient’s flame-shaped hemorrhages and cotton wool spots were localized to the peripapillary region rather than along the arcades or in the periphery, and the patient’s blood pressure was within normal limits.
Obstruction of venous outflow such as in venous sinus thrombosis was lower on the differential, and the patient did not have any known hypercoagulable risk factors. The patient’s presentation was also unlikely to be toxicity/medication-related as he did not recently ingest methanol, ethanol, ethylene glycol, tetracyclines or steroid medications.
Further workup and management
Given the patient’s homonymous visual field defect in the setting of new onset of headache and nausea, an urgent MRI of the head with and without contrast was obtained. This revealed a nonenhancing T2/FLAIR hyperintense mass centered in the right temporal lobe with significant midline shift, mass effect and uncal herniation, with the appearance most characteristic for a low-grade glioma (Figure 5). The patient was sent to the emergency room for intravenous steroids and was admitted to the neurosurgery team.
Three days later, he underwent right temporal mass resection with frozen section biopsy showing a glial tumor (Figure 6). The final pathology report indicated an anaplastic astrocytoma (WHO grade III), isocitrate dehydrogenase (IDH)-mutant. Postoperatively, the patient was started on levetiracetam daily for seizure prophylaxis as well as dexamethasone to reduce postoperative cerebral edema, and he was discharged home.
Three weeks post-resection, the patient was seen in the New England Eye Center neuro-ophthalmology clinic. His best corrected visual acuity improved from 20/40 to 20/20, and his left homonymous hemianopia improved, with Humphrey visual field 30-2 noting residual left superior quadrantanopia (Figure 7).
Discussion
It is important to realize that patients with serious neurologic problems may walk into a general ophthalmology clinic. Papilledema can be a sign of real emergency, and thus it is important for any ophthalmologist to know when to send these patients to the emergency room for urgent neurologic workup and management. One method of grading papilledema is with the Frisén scale, graded 0 to 5, with grade 0 indicating a normal optic disc and grade 5 indicating severe optic disc swelling with obliteration of vessels on and leaving the disc. Higher grades are more visually significant and can present with decreased visual acuity and field defects of blind spot enlargement or worse. Presence of Frisén grade 4 or 5 disc edema in the presence of any focal neurologic signs warrants urgent imaging. In our patient’s case, the visual field defect, along with the severity of the papilledema, prompted us to refer the patient for urgent MRI of the brain because we were fairly certain that he had a space-occupying lesion.
One of the interesting features of this case was the presence of subretinal fluid associated with papilledema. This may have been the reason for his decreased visual acuity rather than the elevated intracranial pressure from the brain tumor itself, as the patient did not appear to notice the hemianopia. Subretinal fluid in the setting of papilledema has been reported previously. Hyperopic shifts may be seen secondary to the presence of subretinal fluid as in our patient, who no longer required glasses for near vision. Treatment of the papilledema leads to resolution of the subretinal fluid with improvement in visual acuity.
Brain tumors may present with localizing or nonlocalizing signs and symptoms, based on size, location, cell of origin and mechanical effects. In adults, tumors tend to develop in the cerebral hemispheres vs. the posterior fossa in children. Papilledema and diplopia may occur with intracranial tumors in any location if there are changes in cerebrospinal fluid dynamics or due to mass effect. Tumors of the optic nerve lead to slowly progressive and painless visual loss, visual field defects and early-stage disc edema, with eventual optic nerve atrophy. Intraorbital tumors may cause proptosis, orbital congestion, diplopia and resistance to retropulsion. Cavernous sinus involvement may result in ophthalmoplegia with or without pain. Tumors near the optic chiasm may reveal bitemporal visual field defects. Tumors of the parietal and temporal lobes may involve the visual pathway and produce oftentimes non-congruent visual field defects. Parietal lobe tumors may present with contralateral inferior homonymous hemianopias, whereas temporal lobe tumors may produce contralateral homonymous hemianopias from lesions of the optic tract or contralateral superior homonymous quadrantanopias if involving the inferior optic radiating fibers (Meyer’s loop). Occipital lobe tumors produce congruous visual field defects but spare central vision.
In our patient, the left homonymous hemianopsia localized to the right optic radiations, which corresponded to the location of the right temporal lobe mass found on MRI. The nonenhancing T2/FLAIR hyperintense nature of the mass was most consistent with a glioma, which accounts for the majority of primary tumors originating from the brain parenchyma. Histologically, these tumors have features similar to normal glial cells such as astrocytes, oligodendrocytes and ependymal cells.
The final surgical pathology for our patient revealed anaplastic astrocytoma grade III. Diffuse astrocytomas are classified by grade II to IV, with a higher grade indicating more abnormal tumor cell appearance and aggressive growth rate. Anaplastic astrocytomas have a low prevalence, accounting for 1.7% of all primary brain tumors. Some may have genetic signatures, such as the IDH-mutant if IDH1 or IDH2 mutations are present, which can affect prognosis and treatment. IDH mutations tend to occur in younger patients with brain tumors, most commonly between 20 to 40 years of age, and may serve as a biomarker to guide aggressive surgical resection. The primary treatment is “maximal safe resection,” with the goal to surgically remove as much tumor as possible while protecting critical brain function. As anaplastic astrocytomas have a tendency to spread to adjacent healthy tissue, radiation or chemotherapy may be recommended to treat residual tumor cells. Gamma knife or intensity-modulated radiation therapy may also help target remaining tumor cells while reducing radiation exposure to healthy tissue.
Anaplastic astrocytoma survival rates vary based on numerous factors including specific molecular alternations and age. Across all ages, the average 5- and 10-year survival rates are 29.85% and 20.8%, respectively, with the highest survival rates in the 20- to 44-year age group, at 55.1% and 39.7%, respectively. Anaplastic astrocytomas grade III are likely to progress to glioblastoma (grade IV), which has a 5-year survival rate of 5.5%. Thus, patients are regularly and closely monitored for tumor recurrence and/or progression.
- References:
- Basic and Clinical Science Course. Book 5. Neuro-Ophthalmology. American Academy of Ophthalmology. 2019-2020.
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- Louis DN, et al. Acta Neuropathol. 2016;doi:10.1007/s00401-016-1545-1.
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- For more information:
- Nisha S. Dhawlikar, MD, MPH, Melina Morkin, MD, Thomas R. Hedges III, MD, and Yosbelkys Martin-Paez, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Christine Benador-Shen, MD, and Malgorzata Dymerska Peterson, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.