A 38-year-old male presented to the emergency medicine department of our urban academic tertiary care center with painless left eye swelling for the last seven days. He also complained of progressive limitation of left eye movement with drooping of left eyelid, ultimately causing inability to open left eye over last week. He complained of having double vision while looking sideways. While looking himself in mirror two days ago, he also noticed his mouth deviating towards the right side of his body. He had history of high-grade fever, mostly at nighttime, in the last fifteen days, which was responsive to oral antipyretics, as well as few episodes of bloody sputum. His wife also noticed his body excessively sweating at night for the last few weeks and his significant weight loss in the last few months.
The patient had suffered from diabetes mellitus for the last seven years, non-compliant to orally administered anti-hyperglycemic agents (OHA) treatment. His past medical history revealed having been diagnosed with pulmonary tuberculosis two years back, for which he took regular treatment only for four months. He has smoked (30 pack years), consumes alcoholic beverages four days a week, and occasionally uses opium. There was no history of trauma, involuntary body movements, pus or watery discharge from ear, epistaxis, alteration in sensorium or behavior, dysphagia, or change in voice. No history of any recent surgery was present. 
The patient was conscious with Glasgow coma score (GCS) of E3V4M5, afebrile (temp 99.6 F), blood pressure of 100/80 mmHg, pulse rate of 89/min, and respiratory rate of 22/min, cooperative with physician. Neurological examination revealed deviation of angle of mouth to the right side with absent wrinkling of forehead on left side, abnormal grimace with hypoesthesia in distribution of V1, V2 branches of left trigeminal nerve (Figure 1). On blowing of mouth air, leak was present from left side. Left eye ptosis, immobility, fixed mid-dilated non-reactive pupil and complete loss of accommodation, and loss of left corneal sensation were noted. Fundoscopy revealed normal disc and macula. He had bilateral lower and upper limb power of 5/5 with normal reflexes and no other cranial nerve deficit was noted. Nasal discharge from left nostril was seen, which was not blood stained. No infraorbital necrosis, ulcer, or perforation of hard palate were present. Gag reflex was intact.
Based on clinical findings, after ruling out possibility of trauma, a differential diagnosis of cerebrovascular accident (CVA), intracranial space occupying lesion, tuberculoma or diabetes mellitus-related neuropathy with tuberculosis reactivation were considered. Initial Non-Contrast computed tomography (CT) scan (NCCT) of the head revealed left maxillary sinusitis. Hematological and biochemical workup done in emergency department revealed anemia, raised total leukocyte count (TLC), and high random blood glucose without ketoacidosis (Table 1). Cerebrospinal fluid examination was unremarkable. Electrocardiogram (ECG) was not suggestive of any abnormality. Urine and blood culture were sterile. Sample for assessing KOH mount of nasal secretion was sent. His sputum was sent for acid fast bacilli (AFB) staining as well as fungal evaluation. Patient was admitted to the emergency medicine ward and started on intravenous (IV) antibiotics empirically, and insulin for glycemic control, as further diagnostic evaluations continued. As per local guideline, his high nasal and oropharyngeal swab were sent for RTPCR for COVID-19, which came negative. His chest radiograph revealed fibrotic bands along with cavitary lesion with surrounding consolidation and air crescent sign present in both hemi thoraces (figure 2).
Contrast-enhanced magnetic resonance imaging (CEMRI) of brain, orbit, and paranasal sinuses (PNS) was done to look for intracranial pathology. It demonstrated acute left maxillary sinusitis with posterolateral wall erosion, prominent left optic nerve sheath, and skull base osteomyelitis with cavernous sinus thrombosis (Figure 2). In view of chest X-ray findings, after pulmonary consultation contrast-enhanced CT scan (CECT) of chest was performed to aid in decision regarding initiation of anti-tubercular therapy, which suggested tuberculosis reactivation (Figure 2). Patient's KOH mount of nasal secretion showed non-septate ribbon-like hyphae.
Based on cumulative results of initial evaluation, a primary diagnosis of invasive rhino-orbito-cerebral mucormycosis with pulmonary tuberculosis reactivation was made. Anti-tubercular treatment (ATT) was started and ear, nose, throat (ENT) review was sought for assessing need for urgent endoscopic debridement, taking in account intra-orbital and intracranial fungal extension causing multiple cranial nerve palsies threatening vision. Nasal endoscopic debridement and left orbital decompression were performed the next day. Histopathological examination (HPE) of excised tissue revealed broad aseptate hyphae with right angle branching invading both nerves and vessel wall, confirming diagnosis of invasive mucormycosis (Figure 2).
Patient was started on amphotericin B, optimal anticoagulation, and insulin therapy for optimization of glycemic control. His biochemistry was regularly monitored for any nephrotoxicity, hematotoxicity, and other infusion-related adverse effects. A repeat endoscopic debridement was performed after a period of seven days. Meanwhile, serial fundoscopy was performed by ophthalmologist to look for possible optic nerve involvement, any optic disc changes, papilledema, or decrease in visual acuity and field. A week after the second debridement and thirteen days of amphotericin B cumulative dose 1425 milligrams, patient complained of severe pain in left side of face, predominant in the orbital region with increased swelling on waking up from sleep. Fundus examination revealed a cherry red spot, optic disc edema with complete retinal opacification, suggesting central retinal artery occlusion in left eye. Patient was started on topical timolol 0.5% and systemic acetazolamide alongside intermittent digital ocular massage with the aim of reducing intraocular pressure. He did not respond to the above measures and decision for left eye exenteration alongside repeat decompression and debridement was made. Post-exenteration monitoring for involvement of right eye and other signs of raised intraocular and intracranial pressures continued alongside antifungal therapy. His condition remained satisfactory and gradual improvement followed. His right eye vision remained unaltered and serial fundoscopy did not reveal any alarming features. Optimal glycemic control was achieved with insulin therapy. He was ultimately discharged home after 48 days of hospital stay in a stable state with residual left facial nerve palsy, written advice to follow up for dressing, ocular prosthesis, and further treatment optimization.