Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Long-term outcomes of transcutaneous retrobulbar amphotericin B in COVID-19-associated mucormycosis.

Purpose: To describe the long-term outcomes of transcutaneous retrobulbar amphotericin B (TRAMB) in COVID-19-associated mucormycosis. Methods: In total, 18 cases of COVID-19-associated mucormycosis were reviewed. In addition to the recommended treatment protocol, all patients were to be given 3.5 mg/ml/day of TRAMB for five days. Results: Of the 18 patients, 2 presented with stage 3a disease, 13 had stage 3c disease, and 3 patients had central nervous system (CNS) involvement (stage 4a and 4c). In addition to planned retrobulbar doses, five patients were given more while two patients received fewer injections (i.e., <5). At the last mean follow-up of 34.67 (±8.88) weeks, 11 patients were in radiological regression and 4 had stable disease while 2 patients had to undergo exenteration; one mortality was observed because of disease progression. Clinical regression in terms of visual and ptosis improvement was seen in seven and nine patients, respectively. Conclusion: Rhino-orbito-cerebral mucormycosis is a serious condition which warrants an aggressive treatment strategy. In unprecedented situations witnessed recently, TRAMB turned out to be an effective and economical alternative. Though large randomized studies are needed to establish its efficacy, TRAMB still manages to halt progression and salvage the globe in significant number of patients, and hence its use should be encouraged on a case-to-case basis especially in developing countries with limited resources.

Exploring the globe salvaging treatment options in patients of COVID-19-associated mucormycosis with orbital involvement.

Purpose: To explore the various globe salvaging treatment strategies for patients with coronavirus disease 2019-associated mucormycosis (CAM). Methods: This was a prospective: interventional analytical study conducted at a Medical College in rural India. A total of 84 patients of CAM admitted between May 2021 and August 2021 were enrolled for the study. Patients with histologically proven CAM with clinical and/or radiological evidence of orbital involvement were divided into three treatment categories based on the site and extent of the lesion. Re-assessment was performed after 7 days. For patients who worsened with the primary approach, orbital exenteration was considered based on a Sion Hospital Scoring System. A novel approach to intra-orbital anti-fungal therapy, site-centered peri-bulbar injection of amphotericin B (SCPeriAmB), was also explored. All the patients were followed up for at least 3 months. Convenience sampling with descriptive statistics was used. Results: Six patients had to finally undergo exenteration by the end of the study period. The rest of the patients were reported to be stable or improved. No mortalities were reported on delaying the exenteration. No adverse events were noted in patients who were given SCPeriAmB. Conclusion: Globe salvaging treatment options should be advocated as a primary approach in patients with CAM. Site-centered peri-bulbar injections can be considered as an approach for delivering intra-orbital anti-fungal therapy in selected patients.

Retrobulbar Injection of Amphotericin B in Patients With COVID-19 Associated Orbital Mucormycosis: A Systematic Review.

PURPOSE: Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery. One of the potential interventions for globe salvage in these patients is retrobulbar injections of amphotericin B. This study was conducted to review protocols, outcomes, and side effects of retrobulbar injection of amphotericin B in patients with COVID-19 associated rhino-orbito-cerebral mucormycosis (CAM). METHODS: The PubMed, Scopus, Web of Science, and Embase databases were searched using a comprehensive string of relevant keywords. All English studies with the confirmed diagnosis of CAM infection were included. We excluded all studies in which retrobulbar injection of amphotericin B was not implemented in any of the patients or there was a lack of clarified and detailed data about this procedure among participants. RESULTS: A total of 647 cases had a history of retrobulbar injection(s) of amphotericin B in 13 reviewed studies with 3,132 subjects of CAM. The most common protocol was the retrobulbar injection of 1 ml of 3.5 mg/ml liposomal amphotericin B for 3 doses daily or on alternate days. We discerned that the globe salvage rate was 95.0% in eyes with a history of retrobulbar injection(s). The total rate of orbital exenteration was 14.9%, regardless of the history of retrobulbar injection of the drug. Other outcomes of this intervention were vision salvage and reduced major ophthalmic complaints, including pain, swelling, chemosis, ptosis, and ophthalmoplegia. The side effects of this intervention were not serious, and most of them were transient. They included swelling at the injection site, restriction of ocular motilities, exacerbation of orbital inflammation, and even intensification of visual impairment in a few cases. CONCLUSIONS: Retrobulbar injection of amphotericin B should be considered a nearly safe and protective intervention against orbital exenteration in patients with CAM. It may also be effective in saving vision. Since the effectiveness of orbital exenteration in the survival of patients is not ascertained, retrobulbar injections can be considered an alternative intervention.

COVID-19-Related Rhino-Orbital-Cerebral Mucormycosis in a Renal Transplant Recipient.

Coronavirus disease 2019 increases transplant recipients' susceptibility to rare opportunistic infections as a consequence of the impairment that COVID-19 can cause in the immune system. Mucormycosis is a rare complication but has a high risk of fatal outcome. A 50-year-old woman who received a kidney transplant 10 years previously was admitted to the hospital with COVID-19. During follow-up by the inpatient service, the patient developed pain, edema, and proptosis in the right eye. She was diagnosed with rhino-orbitalcerebral mucormycosis. This is the first reported case of rhino-orbital-cerebral mucormycosis in a renal transplant recipient with COVID-19 infection.

Clinico-Radiological-Pathological Correlation of Visual Loss in COVID-Associated Rhino-Orbito-Cerebral Mucormycosis.

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.

Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients.

PURPOSE: To report a series of 13 immunocompetent patients who developed new-onset uncontrolled diabetes mellitus (DM) following COVID-19 infection and presented as rhino-orbital mucormycosis (ROM). METHOD: Retrospective study. RESULTS: A total of 127 patients of COVID-19 Associated Mucormycosis (CAM) were evaluated at four centres in India. All patients underwent endoscopic sinus debridement surgery and received systemic amphotericin-B therapy. Five patients (5/13; 38.4%) received retrobulbar amphotericin-B injections. Orbital exenteration was performed in advanced orbital involvement or progression of orbital disease in spite of maximal medical therapy. In his cohort, 13/127 (10.2%) patients presented with new onset DM, where one patient had bilateral disease. The mean age was 35.9 years (range: 20-51 years) and the mean duration from diagnosis of COVID-19 to the diagnosis of mucormycosis was 14.2 days. While 7/13 (53.8%) of the patients received systemic corticosteroids during the course of their treatment for COVID-19, six patients received no steroids or immunomodulators. The mean follow-up period was 9.2 weeks (range: 3-18 weeks) following discharge. Life salvage was possible in 100% of the cases. While overall globe salvage was possible in 42.8% (6/14 eyes), the globe could be preserved in 4/5 patients who received retrobulbar amphotericin-B injections. CONCLUSIONS: Those involved in the care of COVID-19 patients should be aware about the possibility of recent-onset DM, even in patients without a history of corticosteroid therapy. Rarely, recent-onset DM following COVID-19 may present as rhino-orbital mucormycosis, which requires aggressive surgical and medical intervention.

COVID-19 triggering mucormycosis in a susceptible patient: a new phenomenon in the developing world?

A middle-aged woman with diabetes presented with left-sided facial pain, complete ptosis and fever of short duration. On presentation, she had hyperglycaemia without ketosis. There was total ophthalmoplegia of the left eye with a visual acuity of 6/36. She incidentally tested positive for COVID-19. CT paranasal sinus and MRI brain revealed left-sided pansinusitis with acute infarct in the left parieto-occipital region without angioinvasion. An emergency functional endoscopic sinus procedure was done, which confirmed mucormycosis on histopathological examination. After 1 week of conventional amphotericin B and antibiotics, repeat CT brain showed improvement in mucosal thickening and sinusitis. This case is a rare presentation of mucormycosis associated with rapid progression to orbital apex syndrome with brain infarction in a patient with non-ketotic diabetes and COVID-19. Early diagnosis and treatment are essential to prevent further end-organ damage. It is also interesting that there was no angioinvasion and transient periarterial inflammation was attributed to brain infarction.

Rhino-orbital mucormycosis during steroid therapy in COVID-19 patients: A case report.

PURPOSE: To report two cases of COVID-19 under treatment with a corticosteroid; in one case rhino-orbitocerebral mucormycosis and in another one rhino-orbital mucormycosis developed. CASE PRESENTATION: A 40-year old woman and a 54-year old man with severe COVID-19 underwent corticosteroid therapy for immune-related lung injuries. The first case presented with a bilateral visual loss and complete ophthalmoplegia of the right eye. The second case presented with vision loss, proptosis, orbital inflammation, and complete ophthalmoplegia on the left side. Histopathologic, nasal endoscopic examinations, and radiologic findings confirmed mucormycosis in both patients. The patients denied orbital exenteration and were managed with systemic amphotericin B and daily endoscopic sinus debridement and irrigation with diluted amphotericin B. Because of the intracranial space involvement, the first case died. The second case was successfully managed surgically and medically. CONCLUSION: Rhino-orbital/cerebral mucormycosis may be developed in COVID-19 patients under treatment with corticosteroid, and requires prompt diagnosis and management.

Eye Protection for Patients With COVID-19 Undergoing Prolonged Prone-Position Ventilation.

Importance: Critically ill patients with coronavirus disease 2019 (COVID-19) who are unresponsive to maximum optimal ventilator settings may be in a prone position for at least 16 hours per day to improve oxygenation. This extended duration of prone positioning puts patients at risk of developing orbital compartment syndrome if direct pressure to the orbit and the globe occurs and concomitant protection of the eyes is not undertaken. Objective: To report 2 cases of orbital compartment syndrome, as well as optic disc edema and retinal hemorrhages, in the setting of prolonged prone positioning of patients in the intensive care unit during the COVID-19 pandemic. Design, Setting, and Participants: The cases took place from April 27, 2020, to May 4, 2020, at a COVID-19 intensive care unit of a tertiary care hospital. Four of 16 patients in the intensive care unit required prolonged prone-position ventilation. A bedside eye examination was performed on 4 selected patients due to the observed presence of substantial periorbital edema. Main Outcomes and Measures: Intraocular pressures and fundus findings of 4 patients with periorbital edema. Results: Two of 4 patients who were in the prone position for extended periods of time had bilateral fundoscopic findings of optic disc edema and retinal hemorrhages, possibly consistent with a papillophlebitis. Additionally, both patients had a substantial increase in intraocular pressure of 2- to 3-fold in the prone position compared with the supine position. Conclusions and Relevance: Prolonged prone positioning of patients with COVID-19 can be associated with elevated intraocular pressure from periorbital edema, direct compression on the eye, and increased orbital venous pressure. Orbital compartment syndrome can be avoided by the use of protective cushioning around the eyes and maintaining the patient's head position above heart level during prone positioning. Patients with COVID-19 may also develop papillophlebitis with optic disc edema and retinal hemorrhages, which may be associated with a hypercoagulable state caused by COVID-19. These observations suggest awareness for the possible presence of these ophthalmic findings while treating severely ill patients with COVID-19.

Ocular Complications in the Prone Position in the Critical Care Setting: The COVID-19 Pandemic.

PURPOSE: Ocular complications are common in the critical care setting but are frequently missed due to the focus on life-saving organ support. The SARS-CoV-2 (COVID-19) pandemic has led to a surge in critical care capacity and prone positioning practices which may increase the risk of ocular complications. This article aims to review all ocular complications associated with prone positioning, with a focus on challenges posed by COVID-19. MATERIALS AND METHODS: A literature review using keywords of "intensive care", "critical care", "eye care", "ocular disorders", "ophthalmic complications," "coronavirus", "COVID-19," "prone" and "proning" was performed using the electronic databases of PUBMED, EMBASE and CINAHL. RESULTS: The effects of prone positioning on improving respiratory outcomes in critically unwell patients are well established; however, there is a lack of literature regarding the effects of prone positioning on ocular complications in the critical care setting. Sight-threatening ophthalmic disorders potentiated by proning include ocular surface disease, acute angle closure, ischemic optic neuropathy, orbital compartment syndrome and vascular occlusions. CONCLUSIONS: COVID-19 patients may be more susceptible to ocular complications with increased proning practices and increasing demand on critical care staff. This review outlines these ocular complications with a focus on preventative and treatment measures to avoid devastating visual outcomes for the patient.