January 08, 2020
8 min read
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Elderly woman presents with presumed orbital cellulitis

The patient had experienced acute-onset left eye ptosis, discomfort, discharge, eyelid swelling and vision decline.

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An 83-year-old woman with diet-controlled type 2 diabetes presented to Lahey Medical Center as a transfer from Bermuda for presumed orbital cellulitis.

Alison J. Lauter
Alison J. Lauter
Sarah E. Thornton
Sarah E. Thornton

Ten days before presentation to our institution, the patient developed acute-onset left eye ptosis, discomfort, discharge and subjective eyelid swelling. She was seen by her local ophthalmologist with a visual acuity of 20/40 in the involved eye from a baseline vision of 20/20 and was prescribed topical antibiotic/steroid drops. She was seen 4 days later with vision decline in the left eye to count fingers at 1 foot, prompting admission to the hospital in Bermuda given concern for orbital cellulitis. She was afebrile and hemodynamically stable with a mild leukocytosis on admission labs. Blood cultures were negative. CT of the head and orbits showed left ethmoid sinus disease and left retro-orbital soft tissue enhancement concerning for an infectious orbital cellulitis. Treatment with intravenous piperacillin/tazobactam and dexamethasone was initiated. On hospital day 3, she was noted to have light perception vision in the left eye, complete ptosis and restricted extraocular motility, which prompted transfer to our institution for care.

Of note, the patient was a well-controlled diabetic with last known HbA1c less than 7 and had not required medication management for almost 2 years. Her ophthalmic history includes panretinal photocoagulation (PRP) in both eyes with quiescent proliferative diabetic retinopathy (PDR) and pseudophakia in both eyes.

Extraocular motility restriction
Figure 1. Extraocular motility restriction and ophthalmoplegia of the left eye. The right eye moves through all cardinal directions.

Source: Allison V. Coombs, DO, and Geetha Athappilly, MD

Examination

left retro-orbital enhancing soft tissue with medial orbital wall involvement
Figure 2a. MRI of the orbits after contrast, axial T1 FS showing left retro-orbital enhancing soft tissue with medial orbital wall involvement and ethmoid sinus enhancement.
left orbital apex soft tissue enhancement with optic nerve involvement
Figure 2b. MRI of the orbits after contrast, coronal T1 FS showing diffuse left orbital apex soft tissue enhancement with optic nerve involvement and medial wall involvement.

Upon transfer to our institution, the patient’s best corrected visual acuity was 20/30 in the right eye and no light perception in the left eye. The right pupil was briskly reactive while the left pupil was unreactive with a 4+ afferent pupillary defect. IOP was 9 mm Hg in both eyes. Her extraocular motility was intact in the right eye; however, the left extraocular motility was grossly abnormal with nearly complete ophthalmoplegia and only a slight flick of infraduction (Figure 1). Trigeminal nerve sensory testing revealed subjective difference to tactile sensation inferior and superior to the left orbital rim, suggesting involvement of V1 and V2 on the left side. On external examination, the left upper lid was completely ptotic. There was no proptosis. The anterior segment examination was unremarkable for conjunctival injection, chemosis or anterior chamber cell. Fundus exam revealed complete PRP in both eyes with quiescent PDR. She had no optic nerve edema, optic nerve pallor or retinal whitening.

MRI of the orbits and brain with and without contrast (Figures 2a and 2b) performed upon arrival at our institution showed infiltrating, enhancing soft tissue within the inferior and posterior left orbit extending posteriorly through the orbital apex, orbital fissures, optic nerve canal and inferiorly through left pterygopalatine fossa. Adjacent bone erosion was noted involving the lateral wall of the left posterior ethmoid sinus, superolateral wall of the left sphenoid sinus and the lesser wing of the sphenoid bone involving the optic canal/optic strut. The left posterior ethmoid and sphenoid sinuses were completely opacified. Additionally, there was severe compression of the left optic nerve in the orbital apex and optic canal. MRV and MRA were both negative.

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Sudden vision loss

The patient’s clinical examination and imaging findings were concerning for orbital apex syndrome manifesting in complete ophthalmoplegia, which can result from infectious, inflammatory, infiltrative, neoplastic or vascular etiologies.

Infectious etiologies resulting in orbital apex syndrome most commonly originate from bacterial or fungal entities. The most common fungal etiologies include Mucor or Aspergillus. Common inflammatory etiologies include giant cell arteritis, granulomatosis with polyangiitis and sarcoidosis; however, giant cell arteritis would not reveal infiltrating enhancement of soft tissue on imaging. Neoplastic processes include paranasal sinus tumors invading into the orbit, primary orbital tumors, lymphoma, metastasis and sellar tumors. Vascular etiologies include carotid-cavernous fistulae, aneurysms within the Circle of Willis or cavernous sinus thrombosis; however, with a negative MRA and MRV, vascular etiologies were less likely in this case.

Given the patient’s rapid deterioration on antibiotic therapy and IV steroids, coupled with the imaging findings of a destructive lesion involving the adjacent sinuses and orbit, an invasive fungal process with Aspergillus was highest on our differential. The patient’s history of well-controlled diabetes made us less concerned for Mucor.

Case continued

Given high suspicion for fungal infection, empiric antifungal therapy was initiated with intravenous liposomal amphotericin. Additionally, bacterial coverage was broadened to intravenous vancomycin and ampicillin/sulbactam. All steroids in any form were discontinued immediately upon arrival to our institution.

postsurgical sinus changes
Figure 3. MRI of the orbits after contrast, axial T1 FS showing diffuse left retro-orbital soft tissue enhancement with postsurgical sinus changes and extension of enhancement into right orbital apex.

Otolaryngology was consulted to perform bedside endoscopy for examination of the sinuses. Endoscopy was unrevealing, which prompted need for functional endoscopic sinus surgery (FESS) to acquire a tissue culture and biopsy. ENT found well-perfused mucosa throughout the sinonasal cavities; however, there was sphenoethmoid material suspicious for allergic fungal elements and bony changes to the left sphenoid. Two days after surgery, the tissue cultures and biopsy revealed a positive fungal culture for Aspergillus fumigatus. Amphotericin was changed to oral voriconazole following pathogen sensitivities.

The patient was doing well after surgery until hospital day 4 when there was a marked cognitive decline. The patient became lethargic, disoriented and complained of new, severe headache. Ophthalmic examination was concerning for new right eye involvement. The patient had difficulty tracking with the right eye, and visual acuity dropped from 20/30 to 20/80. Given concern for disease progression and the risk for central nervous system (CNS) dissemination, an urgent CT of the brain and MRI of the orbit and brain (Figure 3) were obtained. The CT was negative for acute intracranial bleeding. The MRI showed diffuse left retro-orbital soft tissue enhancement with postsurgical sinus changes, extension of enhancement into bilateral cavernous sinuses and right orbital apex, and left superior ophthalmic vein thrombosis (SOVT).

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Given the findings of disease progression on imaging and the patient’s clinical deterioration, surgical intervention for further debridement and potential exenteration of the left orbit for control of the invasive infection was recommended. Anticoagulation was initiated for the left SOVT. ENT and oculoplastics proceeded with repeat FESS for further washout and exenteration of the left eye and orbit.

The patient stabilized after surgery. Cognitive changes, headache and right eye symptoms resolved over the course of 2 days, and the patient was discharged on a 6-week course of isavuconazole. Two weeks after hospital discharge, visual acuity in the right eye was 20/25 with full extraocular motility.

Discussion

Invasive sino-orbital aspergillosis is a rare but potentially fatal diagnosis that is most commonly seen in severely immunocompromised individuals. However, at least 20 cases have been reported in immunocompetent patients since the 1950s. The presentation of sino-orbital invasive aspergillosis is variable, and the disease is most often misdiagnosed as bacterial orbital cellulitis. Morbidity and mortality of invasive aspergillosis ranges between 40% and 90% in literature; therefore, physicians should have a high clinical suspicion for invasive mycoses in cases presenting with orbital apex syndrome.

The typical demographic and risk factors for invasive aspergillosis include patients with compromised immune systems, patients with a nidus for infection such as joint prostheses or patients who have been inoculated via trauma. Aspergillus is considered endemic in tropical and subtropical climates.

Ocular findings vary depending on the extent of anatomic involvement and may present with similar findings to bacterial cellulitis, including nonspecific periorbital edema and erythema. Findings may progress to include ptosis, proptosis, ophthalmoplegia and optic neuropathy.

In addition to invasive aspergillosis, there are noninvasive forms of Aspergillus that involve the orbit and sinuses. Noninvasive aspergillosis is rare and may manifest as an orbital mass or may be misdiagnosed as a paranasal sinus tumor. As with pulmonary Aspergillosis, an intact immune response can localize the Aspergillus infection and create aspergilloma. This may cause mass effect within the orbit and can also lead to orbital apex syndrome. Orbital aspergilloma is a rare entity with six cases reported in the literature. Orbital aspergilloma may become invasive if misdiagnosed and mismanaged.

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Initial imaging for suspected invasive aspergillosis should include CT of the orbit to evaluate the extent of retro-orbital/orbital involvement, bony erosion and sinus contents. MRI is often necessary to better characterize the orbital changes. Aspergillosis characteristically appears as hypointense enhancement on T1- and T2-weighted images.

Definitive diagnosis requires biopsy and culture. Aspergillus includes 200 species, with 20 known to inoculate humans. The most common is Aspergillus fumigatus. Aspergillus is a septate hyphae with acute 45° branching and typically takes 2 to 3 days to result in culture. There is a high rate of false negative biopsy with aspergillosis, which warrants repeat sampling if clinical suspicion is high.

Management includes optimization of immune status, empiric treatment with systemic antifungals and surgical debridement. Antifungal selection includes empiric management with intravenous liposomal or regular amphotericin B, oral or intravenous voriconazole, and long-term maintenance therapy with itraconazole. There is notable resistance to azole antifungals, and sensitivities should be assessed if possible. Steroids should be avoided in fungal processes. Given that orbital aspergillosis is often misdiagnosed, steroid therapy that is erroneously used in such cases is well documented to cause progression of disease and propagate inflammatory cascade, leading to local tissue destruction.

Surgical management includes functional endoscopic sinus surgery with sinus debridement and washout. The sphenoid and ethmoid sinuses are most commonly involved in aspergillosis, likely attributable to their low oxygen content and acidic environment. Orbital exenteration is warranted in cases of progressive disease for source control, as with our case.

Complications of sino-orbital aspergillosis include invasive spread to the cavernous sinus and the brain, which can result in brain abscesses, mycotic aneurysm formation, CNS dissemination, and optic neuropathy from compression, infiltration, thrombosis and ischemia.

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Mortality rates in cases of invasive sino-orbital aspergillosis range from 40% to 90% and are most commonly attributed to rupture of a mycotic aneurysm, resultant subarachnoid hemorrhage and CNS dissemination. Progressed, fulminant aspergillosis can ultimately resemble mucormycosis and may create black eschar and tissue necrosis due to invasion of blood vessels and subsequent thrombosis.

In our case, the patient initially presented with what was described by the outside institution as orbital cellulitis but rapidly progressed to orbital apex syndrome with complete ophthalmoplegia and optic nerve involvement. As with most cases of orbital aspergillosis, this case most likely disseminated from contiguous spread from paranasal sinuses due to a granulomatous reaction that eroded to the orbit.

Orbital apex syndrome may result from many etiologies, and physicians should have a high clinical suspicion of invasive mycosis in cases of rapidly progressive ophthalmoplegia and severe vision loss. Management decisions in such cases should avoid steroids and initiate antifungals empirically as delaying management can result in blinding and fatal complications.