The Difficulty of Diagnosing Invasive Aspergillosis Initially Manifesting as Optic Neuropathy

Abstract

Background: Invasive aspergillosis is often fatal. Here, we report a patient with invasive aspergillosis primarily involving the optic nerve diagnosed on autopsy.

Case presentation: A 77-year-old female with underlying diabetes mellitus, hyperlipidemia, and hypertension presented with disc swelling of the left eye. Although mini-pulse steroid therapy improved visual acuity (VA) of the left eye, it abruptly decreased to no light perception within a month, followed by a decrease in VA of the right eye to 0.5. At referral, VA was 0.3 in the right eye, and there was no light perception in the left eye.

Results: Fundus examination revealed optic disc swelling of both eyes. Goldmann perimetry showed irregular visual field defects, whereas magnetic resonance imaging (MRI), general, and cerebrospinal fluid (CSF) examinations revealed no distinct abnormalities. We suspected anterior ischemic optic neuropathy and invasive optic neuropathy. As with the left eye, steroid pulse therapy temporarily improved VA of the right eye and then decreased to 0.2. Additional anticoagulant therapy did not improve VA. Concurrent to therapy, the patient became febrile with depressed consciousness. Repeat MRI identified suspected midbrain infarction, and CSF examination indicated cerebral meningitis. In spite of administering transfusions and antibiotics, she died on hospital day 40. Autopsy revealed large amounts of Aspergillus hyphae mainly localized in the dura mater of the optic nerve and destruction of the cerebral artery wall, suggesting an etiology of subarachnoid hemorrhage.

Conclusions: When examining refractory and persistent disc swelling, we should rule out fungal infections of the optic nerve.

Keywords: Autopsy; Fungal infections; Invasive aspergillosis; Optic neuropathy; Steroid pulse therapy.

Fig. 1

Ophthalmic examination findings. Fundus photograph (a) and GP (b) of the left eye at initial onset. The optic disc was reddish and mildly swollen. GP showed lower horizontal hemianopia. Fundus photograph of the right eye (c) and the left eye (d), fluorescein angiography of the right eye (e) and left eye (f), and GP of the right eye (g) with onset in the right eye. The optic disc was reddish and mildly swollen with splinter hemorrhage, and the optic disc of the left eye was markedly swollen with mild retinal hemorrhage. Hyperfluorescence in the left eye was much more intense than in the right eye. Delay of choroidal circulation was detected in the lower retina (arrowheads). Time after initiation of the right eye and left eye was 113 and 65 s, respectively.

Fig. 2

Brain MRI STIR image (a) at the initial onset when the left eye was affected, T1WI (WI) at the onset when the right eye was affected (b), and STIR image at the onset when the right eye was affected (c). There was no the apparent swelling or high-intensity area in the optic nerve at the occurrence of disc swelling in both eyes. d T2WI of the brain at the time when the patient was febrile with depressed consciousness; e DWI; f ADC map. There was a high-intensity area around the cerebral aqueduct in the midbrain on T2WI, representing a high-intensity area on DWI and a low-intensity area on the ADC map (arrows in d–f). DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient.

Fig. 3

Microphotograph of optic nerve sections. The transverse section of the optic nerve was stained with H&E (a low magnification image, b high magnification image). c, d The transverse section of the optic nerve stained with PAS. Scale bar indicates 500 µm in a and c and 100 µm in b and d. A large amount of PAS-positive A. hyphae and inflammatory cells densely accumulated in the dura mater (arrowheads). PAS, periodic acid-Schiff.