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.
A 48-year-old man with diabetes mellitus who had failed to adhere to his treatment presented to the emergency department with complaints of a right-sided headache and toothache for two weeks, with nausea and vomiting for two days prior to presentation. The patient was managed for septic shock secondary to dental abscesses. Non-contrast brain computed tomography (CT) was performed. The CT scan showed no significant intracranial abnormality other than pansinusitis, without obvious retro-orbital fat streakiness (Figure ). Four days later, tooth number 17 and 18 in the left mandibular region, both of which had abscesses, were extracted. The patient noted progressive painless blurring of the vision in his right eye post-extraction of the abscessed teeth and was referred to the ophthalmology team two days later. At this time, the patient was receiving day five of treatment with intravenous (IV) amoxicillin-clavulanate, (1.2 g three times a day), with the addition of IV metronidazole (400 mg twice a day).\nThe visual acuity (VA) in his right eye was 4/60, with no improvement in the pinhole test. A relative afferent pupillary defect was present, with an associated decrease in the optic nerve function, in addition to ophthalmoplegia and restrictions in the superior and lateral gaze. No proptosis, ptosis or lid swelling was present, and all other anterior segment findings were normal. A fundus examination of the right eye showed only proliferative diabetic retinopathy. The VA in the patient’s left eye was 6/18 and 6/9 in the pinhole test. An examination of the anterior segment was unremarkable. Moderate non-proliferative diabetic retinopathy was detected in the posterior segment. Dental caries were present in the upper molars, with mucopurulent discharge from the right sphenoid sinus region. The clinical diagnosis was OAS, and emergency functional endoscopic sinus surgery and septoplasty were performed by the ear, nose and throat (ENT) team. Intra-operatively, pus (6cc) was drained from the right sphenoid sinus. The pus breached the anterior sphenoid wall, tracked down to the septum polypoidal mucosa over the right maxillary sinus and right anterior and posterior ethmoid sinuses.\nEmpirical treatment with IV ceftriaxone (1 g twice a day) and IV fluconazole (400 mg once a day) was started. Despite the commencement of IV antibiotic and antifungal treatment, the patient’s condition deteriorated, and the VA in this right eye was classified as no perception of light (NPL) and almost total ophthalmoplegia four days post-presentation (Figure ). Treatment with IV methylprednisolone was not started in view of the infective nature of the disease and the possibility of a fungal infection, which could worsen his condition.\nMethicillin-resistant Staphylococcus aureus was isolated from the pus and from a nasal swab. IV vancomycin (1 g twice a day) and IV metronidazole (400 mg twice a day) were added. An urgent non-contrast CT brain scan was repeated and revealed features suggestive of fungal pansinusitis, with the involvement of the right orbital apex and right orbital contents (Figure ). No suspicious intracranial lesion was seen. The patient underwent emergency nasal debridement for the second time and septotomy. A bony dehiscence was noted over the right posterior ethmoid supralaterally, exposing the orbital apex.\nOn day 13 after the first surgical drainage, tissue culture from the septal wall yielded S. apiospermum. IV amphotericin B (35 mg once a day) was commenced. However, the patient’s renal profile deteriorated following the amphotericin B treatment. Thus, the antifungal regime was changed to oral voriconazole (200 mg twice a day), but the patient failed to respond to the treatment. Forty days after the initial presentation, he developed invasive pansinusitis, with disease progression involving the base of the skull (both orbits) and intracranial extension.\nAt this stage, the VA in the patient’s right eye was classified as NPL in all four quadrants, with almost total ophthalmoplegia. The VA in his left eye was 6/12, with full extraocular movement. The neurosurgical team decided against any surgical intervention. Functional endoscopic sinus surgery was performed for the third time, with nasal toileting. Intra-operatively, minimal crusting was observed over the right nasal cavity. The right sphenoid, pterygoid, maxillary sinuses and the frontal sinuses were clear, with no pus. The mucosa was healthy, with minimal bleeding. The left maxillary sinus was also clear.\nIV amphotericin B was restarted, but the patient developed gastrointestinal intolerance. The antifungal treatment was again changed to oral voriconazole (200 mg twice a day). Fifty-seven days after the initial presentation, the VA in the patient’s left eye decreased suddenly to 6/30 (reduced Snellen chart), and his colour vision decreased. A plain and contrast-enhanced CT scan of the brain, orbit and the paranasal sinuses showed invasive pansinusitis, with bilateral orbital apex involvement (Figure ). It also showed an increasing intracranial extension involving the right cavernous sinus anteriorly, the roof of the sphenoid sinus, the floor of the anterior cranial fossa and right medial cranial fossa anteriorly, as well as osteomyelitis changes at the base of the skull. In view of the acute progression of the infection, surgical intervention was considered. However, the area of the lesion was too extensive and was beyond ophthalmology coverage. Following a reassessment by the neurosurgical team, a decision was made to continue medical treatment rather than perform a surgical intervention.\nSIxty-seven days after the initial presentation, the patient’s VA decreased to NPL in both eyes. Although his Glasgow coma scale was full, his general condition worsened, with lethargy, irritability and dizziness, accompanied by nausea and vomiting. The patient decided to discharge himself from the hospital (at own risk discharge) and subsequently failed to attend an appointment in the ophthalmology clinic.