Acute Visual Loss Related to Retinal Vascular Occlusion Secondary to Visual Pathway Primary Glioblastoma

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Acute Visual Loss Related to Retinal Vascular Occlusion Secondary to Visual Pathway Primary Glioblastoma Marta L. Muñoz-Cardona, MD, Yuliana Llano-Naranjo, MD, Francisco LondoñoOcampo, MD, Esteban E. Preciado-Mesa, MD, Feliza Restrepo, MD, Lina García, MD, Beatriz Pineda-Arrieta, MD, Beatriz Lopera-Marín, MD, Germán A. Reyes-Botero, MD M alignant gliomas are invasive tumors originating in glial cells of the central nervous system (CNS); their origin primary visual pathways gliomas are very infrequent (1). Optic gliomas can be benign or malignant tumors and represent approximately 1% of intracranial tumors and 65% of optic nerve primary tumors (2). Optic gliomas have a benign course in 90% of cases and are diagnosed in patients under 20 years of age; the most common type is pilocytic astrocytoma (WHO Grade I), which can be associated with neurofibromatosis Type 1 between 10% and 70% of cases (2). On the other hand, malignant optic nerve gliomas occur mainly in people over 50 years and have aggressive clinical course, fast growth, and very poor prognosis (3). At onset, unilateral or bilateral decreased vision occurs in 70% of patients, leading to blindness usually within 3 months and death in less than 1 year (4). Here, we present a patient that presented with painful acute visual loss secondary to malignant optic glioma. Informed consent was obtained for publication. A 61-year-old woman with a medical history of mild hypertension and hypothyroidism presented to the emergency department after 2 days of acute visual loss of the right eye, orbital pain, and right side headache. Physical examination of the right eye showed the following findings: a. decreased visual acuity limited to light perception, b. mild palpebral ptosis, c. relative afferent pupillary defect, d. painful ocular movements, e. mild vitreal hemorrhage, f. optic disc edema with exudates and peridiscal hemorrhages, and g. multiple retinal hemorrhages and vascular tortuosity (Fig. 1A). Intraocular pressure was normal in Department of Neuro-ophthalmology (MLM-C), Universidad Pontificia Bolivariana, Medellín, Colombia; Department of Ophthalmology (YL-N), Universidad Pontificia Bolivariana, Medellín, Colombia; Department of Neurosurgery (FL-O), Hospital Pablo Tobón Uribe, Medellín, Colombia; Department of Neurosurgery (EEP-M), Universidad de Antioquia, Medellín, Colombia; and Departments of Neuroradiology (FR, LG), Radiotherapy (BP-A), Pathology (BL-M), and Department of Neuro-oncology (GAR-B), Hospital Pablo Tobón Uribe, Medellín, Colombia. The authors report no conflicts of interest. Address correspondence to Yuliana Llano-Naranjo, Department of Ophthalmology, Universidad Pontificia Bolivariana, Medellín, Colombia, 78B Higt Street # 72A-159, Medellín, Colombia 050040; E-mail: [e-mail] e142 both eyes. Left eye examination was normal. The clinical presentation was interpreted as an atypical anterior optic neuritis associated with central retinal vein occlusion. A systemic workup including blood test and cerebrospinal fluid was performed, and it did not show evidence of infection, immunologic disorders, vasculitis, or metabolic abnormalities. Brain MRI showed a hyperintensity signal in T2-weighted sequences at the right optic nerve in intraorbital, intracanalicular, and prechiasmatic portions associated with contrast enhancement after gadolinium injection (Fig. 1). Moreover, brain MRI also showed a T2 hyperintensity signal at the right temporal uncus, hypocampus, and thalamus (Fig. 1B-E). An inflammatory cause was suspected because of brain involvement reported in MRI, and the patient was treated with intravenous methylprednisolone (1 g a day for 5 days), but visual acuity did not recover and she was discharged. Two weeks later, she presented with chemosis and visual deterioration. The clinical exploration right eye showed complete visual loss, optic nerve atrophy, arteriolar and vein atherosclerosis, bloodless vessels, and retinal pallor suggesting a combined central arterial and vein retinal occlusion (Fig. 1F) and eye contralateral hemianopsia. A brain MRI was performed, and it showed findings of high-grade tumor originating in the right visual pathways (Fig. 1G–J). A stereotaxic brain biopsy at the right temporal lobe was performed, and the anatomopathology analysis reported a glioblastoma (Fig. 2). The patient was treated with intensity-modulated radiation therapy 6 MV photons at planning target volume of 2 Gy/day (total dose 60 Gy) concomitant to temozolomide followed by mensual temozolomide as 5/28 days schedule. However, after 4 cycles of chemotherapy, brain MRI showed increase of tumoral size and mass effect due to tumor progression because she developed a left hemiplegia and central neuropathic thalamic pain syndrome (Fig. 3). Bevacizumab was added to treatment, but she presented a severe pulmonary embolism after 1 cycle and secondary clinical deterioration leading to chemotherapy interruption, and she died 12 months from diagnosis. Malignant gliomas (anaplastic astrocytoma, anaplastic oligodendroglioma, oligoastrocytoma, and glioblastoma according to WHO classification 2016) (3) are diffuse CNS Muñoz-Cardona et al: J Neuro-Ophthalmol 2021; 41: e142-e144 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. Initial funduscopy of the right eye showing mild vitreal hemorrhage, optic disc edema, peridiscal hemorrhages, and intraretinal hemorrhages suggesting central retinal vein occlusion. Brain MRI at onset of symptoms (T1-weighted postcontrast B–E) and T2-weighted (FLAIR) sequence (D) showing contrast enhancement in the right optic nerve and right temporal lobe hyperintensity. A. Funduscopy of the right eye 2 weeks later showing optic nerve atrophy, bloodless retinal vessels, and retinal pallor suggesting combined retinal central vein and artery occlusion. Brain MRI follow-up showing increase of initial findings (B, C) and right temporal lobe tumour infiltration (D, E). tumors mostly affecting cerebral lobes, which rarely present in the optic nerve (1). Despite a variety of different strategies to treat malignant glioma, the results are still unsatisfactory showing an overall medial survival of about 12 months (4). Optic nerve tumor involvement (known as malignant optic nerve glioma) was reported by Hoyt in 1973, and it is characterized by unilateral or bilateral visual loss leading rapidly to blindness in 5–6 weeks associated with retinal vascular involvement simulating an optic neuritis (5). Although symptoms of malignant optic nerve and visual pathways glioma vary depending on the nervous structures affected (optic nerve or chiasm), visual outcome and poor prognosis are similar. Visual impairment is usually progressive from weeks to months. Ocular pain is also frequent, and typical findings on ophthalmological exploration are optic disc edema, vascular retinal abnormalities, and optic nerve atrophy (4). If the tumor grows toward the optic chiasm, bilateral visual disturbances, alterations in the visual fields test, and normal appearing fundus may be found (4). Previous reports propose about pathological features that tumor cells infiltrate the optic nerve at subpial and subretinal levels reaching blood vessels leading to blood supply obstruction, optic disc edema, and necrosis. The tumor FIG. 2. Brain biopsy. Upper panel: Hematoxylin and eosin stain (·40) showing (A) hypercellularity, (B) abundant mitosis, pseudopalisading necrosis, and (C) endothelial vascular proliferation. Lower panel: Immunostaining showing (D) PGFA positive, (E) p53 positive, (F) Ki67: 30%–40% confirmed a histological diagnosis of glioblastoma. Muñoz-Cardona et al: J Neuro-Ophthalmol 2021; 41: e142-e144 e143 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 3. Upper panel: Normal brain MRI (T2-weighted axial sequence) illustrating the visual pathways (yellow line: a. optic nerve, b. optic chiasma, c. optic tract, d. lateral geniculate nucleus, e. Meyer’s loop, f. optic radiations). Lower panel: Patient’s brain MRI after tumor progression to radiotherapy and chemotherapy (T1-weighted postcontrast axial sequence) shows tumor infiltration involving optic nerve, chiasma, optic tract, and midbrain. infiltration, inflammation, and ischemic optic nerve involvement cause acute visual loss and severe pain simulating an atypical optic neuritis refractory to corticosteroids (5). This case was initially interpreted as a severe optic neuritis with central retinal vein occlusion due to its severe optic disc edema and multiple retinal hemorrhages. However, a progressive visual deterioration and the brain MRI findings led to perform a histological confirmation of a malignant visual pathways glioblastoma. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: G. A. Reyes-Botero, M. L. MuñozCardona, and Y. Llano-Naranjo; b. Acquisition of data: G. A. ReyesBotero, M. L. Muñoz-Cardona, and Y. Llano-Naranjo; c. Analysis and interpretation of data: G. A. Reyes-Botero, Y. Llano-Naranjo, M. L. Muñoz-Cardona, F. Restrepo, F. Londoño-Ocampo, and B. LoperaMarín. Category 2: a. Drafting the manuscript: G. A. Reyes-Botero, Y. Llano-Naranjo, M. L. Muñoz-Cardona, and E. E. Preciado-Mesa; b. Revising it for intellectual content: G. A. Reyes-Botero, M. L. Muñoz- e144 Cardona, and Y. Llano-Naranjo. Category 3: a. Final approval of the completed manuscript: G. A. Reyes-Botero, Y. Llano-Naranjo, M. L. Muñoz-Cardona, L. García, B. Pineda-Arrieta, and B. Lopera-Marín. REFERENCES 1. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359:492–507. 2. Dutton JJ. Gliomas of the anterior visual pathway. Surv Ophthalmol. 1994;38:427–452. 3. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO Classification of Tumours of Central Nervous System, Revised 4th Edition. Lyon, France: IARC, 2016. 4. Traber GL, Pangalu A, Neumann M, Costa J, Weller M, HunaBaron R, Landau K. Malignant optic glioma - the spectrum of disease in a case series. Graefes Arch Clin Exp Ophthalmol. 2015;253:1187–1194. 5. Hoyt WF, Meshel LG, Lessell S, Schatz NJ, Suckling RD. Malignant optic glioma of adulthood. Brain J Neurol. 1973;96:121–132. Muñoz-Cardona et al: J Neuro-Ophthalmol 2021; 41: e142-e144 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.