After a 75-year-old male, who pursued gardening as a hobby, noticed decreased vision in his left eye, he visited an ophthalmologist in September of 2015. He had a history of hypertension, colon cancer and metastatic hepatic tumor. As an ophthalmologic examination revealed macular edema in his left retina resulting from branch retinal vein occlusion (BRVO), he underwent a posterior STTA injection in his left eye to treat the macular edema. After routine disinfection of the lid margins and conjunctival sac with 10% and 0.625% (16-fold dilution) povidone iodine, respectively, the procedure was performed uneventfully. The patient once again visited his ophthalmologist in November due to complaints of ocular pain and hyperemia in his left eye. The symptoms did not improve even though he received oral and topical antibiotic treatment for 3 days. Computed tomography of the orbit was performed and revealed a peribulbar high density lesion of the left eyeball. Due to a suspected peribulbar infection, he was subsequently referred to our hospital in the middle of November.\nAt his first visit, best corrected visual acuity (BCVA) (decimal) was 1.2 in the right eye and 0.15 in the left eye. Intraocular pressures were normal. Although the upper and lower eyelids of his left eye were swollen, we observed no restrictions of his eye movement. Slit lamp examination of the left eye showed ciliary injection, cells in the anterior chamber and a subtenon abscess in the superotemporal quadrant, which corresponded to the site of the posterior STTA (Fig. ). While our fundus examination did not reveal any intravitreal involvement, it did find macular edema and BRVO, which had been reported by his previous doctor. The right eye exhibited no abnormal findings, including both the anterior and posterior segments. The patient had no fever. The orbital magnetic resonance imaging (MRI) revealed the presence of a peribulbar high intensity lesion that corresponded to the subtenon abscess (Fig. ). The MRI did not detect any paranasal sinus or intracranial invasion. The serologic test, which included white blood cells, C-reactive protein and beta-D-glucan, only revealed a slight elevation of C-reactive protein (1.11 mg/dL). To determine the causative pathogen, incision and drainage of the subtenon abscess were performed, with the obtained purulent fluid submitted for bacterial and fungal cultures. While the smears revealed polymorphonuclear leukocytes and a large number of round or oval conidia-like structures, a fungal filamentous appearance was not observed (Fig. ). Based on these results, we suspected fungal infectious scleritis induced by STTA. Therefore, the patient was initially started on 1% voriconazole (VRCZ) and 1.5% levofloxacin (LVFX) eye drops that were each administered six times per day in an outpatient department. Inflammation of the anterior chamber of the left eye worsened after 4 days, with choroidal detachment observed in the temporal region of the fundus. The fungal culture found an early colony of a filamentous fungus. Based on the definitive diagnosis of infectious scleritis by filamentous fungi, we then performed debridement of the infected sclera and Tenon’s capsule. The resected scleral tissue was submitted for further pathological examination. The conjunctival sac of the left eye was irrigated with 0.625% povidone iodine, followed by hospitalization for treatments with 1% natamycin ointment, 1% atropine eye drops and intravenous VRCZ. Ten days after the initial visit, we noted improvement in both his ocular pain and inflammation of the anterior chamber. As a result, we switched the voriconazole from an intravenous to an oral administration. Histopathological examination using Grocott staining revealed infiltration of branching hyphae into the sclera (Fig. ). Due to a novel subtenon abscess of the adjacent upper region of the left eyeball that developed at 18 days after the initial visit, we once again performed scleral debridement. The fungal species, Scedosporium apiospermum, was identified by DNA sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA amplified by polymerase chain reaction (PCR) with ITS1F and ITS1R primers []. The strain was sent to Teikyo University for complete species identification. The susceptibility testing of the antifungal agents was performed using the broth microdilution method based on CLSI M38-A2 []. Results indicated low minimum inhibitory concentrations against micafungin, VRCZ and miconazole (Table ). Based on the antifungal susceptibility test findings, the natamycin ointment was discontinued. Topical and systemic voriconazole administrations were continued for 2 and 1 months, respectively, and then stopped once the ciliary injection subsided. However, 1 month after the discontinuation of topical VRCZ, the subtenon abscess recurred at the same place (superotemporal quadrant). Incision and drainage of the abscess was performed three times. Light microscopic examination of the smears of the subtenon abscess revealed that septate hyphae were still present. As a result, we resumed the 1% VRCZ and 1.5% LVFX eye drops for 2 weeks and then stopped the administration. No recurrence was observed after the final treatment. Due to the prolonged macular edema, however, the final BCVA (decimal) of the left eye was 0.2 as of April 2016 (Fig. ).\nCharacteristics of the colonies found on the potato dextrose agar incubated at 28 °C for 21 days included a grayish white and cottony appearance with an umbonate center on the surface, and a reverse side showing a brownish dark wrinkle appearance in the center and a yellow-white appearance on the margin (Fig. ). Microscopic features observed when using the slide culture technique on potato dextrose agar at 10 days included septate hyphae that were 2 μm in diameter and branching irregularly, along with the production of lateral and terminal conidia, which were round or oval (3 to 5 by 5 to 10 μm) (Fig. ). We also observed a Graphium synanamorph that produced a brush of cylindrical conidia (3 by 12 μm) (Fig. ).\nIn order to confirm the species identification using a molecular approach, the BUT locus of the β tubulin gene was also amplified by PCR using Bt1a/Bt1b primers [, ] and then applied to DNA sequencing [, ]. The obtained DNA sequencing was compared by using the Basic Local Alignment Search Tool. Both the ITS and the BUT exhibited 100% homology with that reported by Zouhair et al. for Scedosporium apiospermum (GenBank accession no. JQ690950 and JQ691056) []. Based on the current and previous results, we were finally able to identify the causative fungal strain as Scedosporium apiospermum sensu stricto.
An 80-year-old male with diabetes mellitus, mild diabetic retinopathy, and mild dementia underwent reported uncomplicated, bilateral FESS for chronic sinusitis with polyposis at an outside hospital. He was provided an outpatient prescription for amoxicillin-clavulanic acid upon outpatient surgical discharge. Initial pathology specimen within the immediate postoperative period from the outside hospital was reported as non-invasive Aspergillus. He was seen by his original surgeon at the outside facility on postoperative day 3 without visual complaints or unexpected facial pain. On postoperative day 4, the patient reported sudden right-sided vision loss and presented to the walk-in ophthalmology clinic at the primary author’s tertiary care facility. An ophthalmology exam found no perception of light on the right and an abducens nerve palsy. Pupils were equal and reactive to light bilaterally with no pallor of the optic disc and normal ocular pressures. He was sent immediately to the emergency department for imaging, whereupon the otolaryngology team evaluated the patient. Intranasal exam by otolaryngology was only notable for moderate edema of the nasal mucosa without necrosis or pallor. There was no decreased sensation of the palate or midface. Computed tomography was performed and notable for violation of the lamina papyracea (Figure ). Preoperative imaging from the outside facility was not available for comparison. Magnetic resonance imaging suggested acute ischemic findings of the right optic nerve with diffusion restriction at the proximal optic nerve without evidence of thrombosis or hemorrhage. Subsequent imaging after admission noted an abnormal T2 signal without canalicular segment enhancement. There was, however, some adjacent enhancement extending to involve the optic and nerve sheaths in the orbital apex and superior orbital fissure. The enhancement of the right-sided nerve sheaths was thought to be contributing both to the vision loss and the abducens nerve palsy that was defining the OAS. In addition to those mentioned, the neurosurgery, neurology, and internal medicine teams evaluated the patient. It should be noted that repeated images were obtained at several time points due to poor images from motion artifact that did delay care. The clinical and radiologic findings were determined by the treating teams to be most suggestive of the surgical trauma from the FESS at the outside facility and not of an infectious origin. A non-surgical approach was initially pursued. The patient was provided broad-spectrum antibiotics and high-dose steroids to decrease inflammation with close neurologic monitoring. Re-evaluation by otolaryngology on flexible nasal endoscopy did not show any change in findings of the nasal mucosa.\nOn postoperative day 9 from the original FESS, the patient developed sudden vision loss of the left eye. An ophthalmology exam noted no light perception bilaterally, worsening ophthalmoplegia on the right with decreased supraduction, adduction, and infraduction in addition to the complete abducens palsy. These findings suggested now the involvement of the oculomotor and trochlear nerves. The posterior ocular exam now showed mild optic nerve pallor on the right with good color on the left and no evidence of edema. Repeat computed tomography and magnetic resonance imaging noted no new bony destruction; however, there was persistent inflammation of the right optic canal. An emergent multidisciplinary team meeting was held between all consulting specialties and infectious disease was also consulted as the initial diagnosis of traumatic neuropathy was questioned. The patient then underwent emergent FESS with otolaryngology and neurosurgery with decompression of both optic nerves, sphenoidotomy, septectomy, and mucosal stripping (Figure ). The lamina papyracea and bone adjacent to the root of the right orbital apex were dehiscent as had been suggested on imaging (Figure ). Additionally, there was a large amount of absorbable packing in the posterior ethmoid cavity on the right.\nA final culture from the initial FESS at the outside hospital was re-evaluated by the infectious disease team, which revised the diagnosis of Aspergillus to that of S. apiospermum. This pathologic diagnosis was made on postoperative day 10 (postoperative day 1 from emergent FESS). The patient was started on high-dose voriconazole and amphotericin B. The patient continued on maximum medical therapy and continued to worsen clinically and radiologically regarding the infection. Unfortunately, after prolonged hospitalization, he suffered a myocardial infarction and subsequent severe gastrointestinal bleeding. He passed away on postoperative day 47 from the initial FESS after being transferred to inpatient hospice services.