Endogenous fungal endophthalmitis following COVID-19 infection with microbiological and molecular biological correlation - A report of two cases.

This case report describes three eyes of two patients, who were diagnosed to have endogenous fungal endophthalmitis post coronavirus disease 2019 (COVID-19) infection. Both patients underwent vitrectomy with intravitreal anti-fungal injection. Intra-ocular samples confirmed the fungal etiology by conventional microbiological investigations and polymerase chain reaction in both cases. The patients were treated with multiple intravitreal and oral anti-fungal agents; however, vision could not be salvaged.

Endogenous Fungal Endophthalmitis following COVID-19 Hospitalization: Evidence from a Year-Long Observational Study.

PURPOSE: To describe cases of endogenous fungal endophthalmitis (EFE) post-recovery from or hospitalization for coronavirus disease 2019 (COVID-19). METHODS: This prospective audit involved patients with suspected endophthalmitis referred to a tertiary eye care center over a one-year period. Comprehensive ocular examinations, laboratory studies, and imaging were performed. Confirmed cases of EFE with a recent history of COVID-19 hospitalization±intensive care unit admission were identified, documented, managed, followed up, and described. RESULTS: Seven eyes of six patients were reported; 5/6 were male, and the mean age was 55. The mean duration of hospitalization for COVID-19 was approximately 28 days (14-45); the mean time from discharge to onset of visual symptoms was 22 days (0-35). All patients had underlying conditions (5/6 hypertension; 3/6 diabetes mellitus; 2/6 asthma) and had received dexamethasone and remdesivir during their COVID-related hospitalization. All presented with decreased vision, and 4/6 complained of floaters. Baseline visual acuity ranged from light perception (LP) to counting fingers (CF). The fundus was not visible in 3 out of 7 eyes; the other 4 had "creamy-white fluffy lesions" at the posterior pole as well as significant vitritis. Vitreous taps were positive for Candida species in six and Aspergillus species in one eye. Anti-fungal treatment included intravenous amphotericin B followed by oral voriconazole and intravitreal amphotericin B. Three eyes underwent vitrectomy; the systemic health of two patients precluded surgery. One patient (with aspergillosis) died; the others were followed for 7-10 months - the final visual outcome improved from CF to 20/200-20/50 in 4 eyes and worsened (hand motion to LP) or did not change (LP), in two others. CONCLUSION: Ophthalmologists should maintain a high index of clinical suspicion for EFE in cases with visual symptoms and a history of recent COVID-19 hospitalization and/or systemic corticosteroid use - even without other well-known risk factors.

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.

Rhino-orbital mucormycosis in a patient with no susceptibility following P.vivax malaria infection-a case report.

BACKGROUND: Mucormycosis is a potentially lethal, angioinvasive fungal infection caused by the Mucoracea family comprising Mucor, Rhizopus, and Absidia species. It is commonly associated with uncontrolled diabetes mellitus, the use of corticosteroids, immunosuppressive drugs, and Covid-19 infection. The occurrence of mucormycosis in an immunocompetent patient is rare. Also, only a few case reports have been published where patients developed mucormycosis with associated malarial infection. CASE PRESENTATION: A young female presented with a 3-weeks history of painful swelling and outward protrusion of the right eye with complete loss of vision. She had a history of P.vivax malaria two weeks before her ocular symptoms. On ocular examination, there was proptosis and total ophthalmoplegia with loss of corneal sensations in the right eye. Hematological examination revealed normocytic normochromic anemia and thrombocytopenia. MRI was suggestive of right-sided pansinusitis and orbital cellulitis with right superior ophthalmic vein thrombosis and bulky cavernous sinus. Nasal biopsy was negative for fungal culture. An emergency surgical debridement of all the sinuses was done with right orbital exenteration. Histopathology confirmed the diagnosis of mucormycosis and the patient improved post-operatively on systemic antifungals. CONCLUSION: Such an association of mucormycosis with malaria infection is rarely reported in the literature and is hypothesized to be a result of immunosuppression caused by malaria. Also, emphasis is laid upon having a high index of suspicion for fungal infection in the setting of pansinusitis even if the risk factors are absent. We hereby report a case of rhino-orbital mucormycosis following P.vivax malaria in a 20-year-old female with anemia and thrombocytopenia.

Clinical profile of keratitis treated within 3 months of acute COVID-19 illness at a tertiary care eye centre.

PURPOSE: To report the spectrum of keratitis treated within 3 months of acute COVID-19 infection. METHODS: Retrospective, descriptive case series study of 19 eyes of 16 patients who presented at tertiary eye care centre in Southern India. RESULTS: Median age of the patients was 43(IQR 35-55.5) years. Majority (15/16, 93.75%) were males. Unilateral affliction was predominant (13/16, 81.25% patients). Nine had a history of hospitalization, five had received oxygen supplementation and five had been treated with steroids during COVID-19 illness. The median duration between COVID-19 diagnosis and the ocular symptoms in the eye was 29 (IQR 22-57) days. Microbiological diagnosis consisted of microsporidia in nine eyes of seven patients, fungus in six patients, Pythium in one patient, and herpes zoster ophthalmicus in one patient. One patient had neurotrophic keratitis. Therapeutic penetrating keratoplasty was performed in five patients, glue application in two patients and three were managed with tarsorrhaphy with/without amniotic membrane grafting or tenonplasty. There was medical and surgical cure in all patients. CONCLUSIONS: Microsporidia was the commonest cause of keratitis, followed by fungal infection. Majority of the microsporidia infections were keratoconjunctivitis. The fungal isolates identified were Aspergillus and Mucor species. All patients responded to conventional management guidelines with favourable outcomes.

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.

Endogenous Fungal Endophthalmitis in a Patient Admitted to Intensive Care and Treated with Systemic Steroid for COVID-19

A 61-year-old woman presented to our clinic with complaints of decreased visual acuity, pain, and redness in her left eye. Best corrected visual acuity (BCVA) was 20/20 in the right eye and counting fingers at 3 meters in the left eye. On slit-lamp examination, 1+ cells were detected in the anterior chamber. Fundus examination revealed 1+ haze in the vitreous and multiple creamy-whitish lesions in the retina and vitreous. Her history included a diagnosis of coronavirus disease 2019 (COVID-19) one month earlier, for which she was hospitalized in the intensive care unit for 20 days and received systemic corticosteroid treatment. Vitreous culture yielded Candida albicans. The patient's nasopharyngeal swab sample was positive for COVID-19 by reverse transcription polymerase chain reaction test. BCVA was improved to 20/40 after amphotericin therapy (via intravitreal injection and intravenous routes), and the vitritis and chorioretinitis lesion regressed after 2 weeks of treatment. Two weeks later, intravenous amphotericin was discontinued and oral fluconazole treatment was started at a dose of 400 mg/day. At 3-month follow-up, her BCVA was 20/25 and no inflammatory reaction was observed in the anterior chamber and vitreous.

Localized surgical debridement for the management of orbital mucormycosis.

PURPOSE: To describe the role of localized debridement and instillation of amphotericin B for the management of orbital mucormycosis post COVID-19 infection with a view to avoid exenteration. METHODS: The records of all patients with orbital mucormycosis post COVID-19 infection in the last 6 months from December 2020 to June 2021 were evaluated, and ten patients were identified who were successfully managed with localized debridement, that is, removing the fungal tissue and necrotic material and amphotericin B gel instillation locally. MRI scan was used to identify the area of fungal infiltration and presence of necrotic material. Early surgery in the form of transconjunctival orbitotomy was performed for disease in the infraorbital fissure area, and superior transcutaneous lid crease approach was employed for disease in the superomedial orbit or medial orbit. Most patients had lid edema, ptosis, and proptosis; this resolved with the medication. Systemic antifungals were given and the follow-up ranged from 1 to 5 months. RESULTS: The ptosis, proptosis, and lid edema subsided in all, except in one patient who had residual ptosis and in one who had residual ophthalmoplegia. Vision deficit did not occur in any patient. All patients were successfully discharged on oral antifungal medication. CONCLUSION: Localized clearance of the fungal tissue and the necrotic material is a good option to avoid exenteration in cases of orbital mucormycosis, avoiding disfigurement and mental trauma to the patient.

Adjunctive use of saturated solution of potassium iodide (SSKI) with liposomal amphotericin B (L-AMB) in mucormycosis achieves favorable response, shortened dose and duration of amphotericin: A retrospective study from a COVID-19 tertiary care center.

PURPOSE: Second wave of COVID-19 pandemic was associated with an unprecedented rise in cases of mucormycosis, treatment of which has been challenging owing to the availability and side effects associated with amphotericin. METHODS: All patients presenting with rhino-orbital cerebral mucormycosis (ROCM) following COVID-19 infection between April 2021 to June 2021 were included in this retrospective interventional study. Primary objective was to assess the clinical response with combination of intravenous liposomal amphotericin B (4-5 mg/kg/day) and saturated solution of potassium iodide (SSKI) given orally along with surgical debridement. RESULTS: Twenty-five patients of ROCM were treated with the regimen. Mean age and fasting blood sugar levels were 53.48 years and 239.64 mg/dL respectively. All patients had history of intake of steroids with a mean daily dose of 86.39 mg of prednisolone equivalent. 88% of patients had a "proven" diagnosis of mucormycosis. Cultures were positive in 52% of patients with Rhizopus arrhizus as the predominant species. The mean daily dose of amphotericin received was 268 mg/day with a mean duration of 9.52 days. Mean daily dose of SSKI was 2.57 g. 21 patients (84%) had stabilization of disease at week 8 and achieved cure at the end of treatment whereas the mortality rate was 16%. Factors that significantly affected outcome were eye and central nervous system (CNS) involvement on presentation. CONCLUSION: SSKI, with its remarkably low cost and safety profile, makes it a potential adjuvant drug that may help achieve the twin benefits of shortened duration and dose of LAMB.

A clinico-pathological study of COVID-19 associated rhino-orbital-cerebral mucormycosis.

Purpose: Known predisposing factors for mucormycosis are neutropenia and diabetes. Though COVID-19 is associated with hyperinflammatory response, a high surge in rhino-orbital-cerebral mucormycosis (ROCM) cases was observed during the second wave. The histopathological features reflect the background pathogenesis. This study analyzes the histopathological features and clinical presentation of COVID-19-associated ROCM. Methods: In this retrospective observational study, the clinical details of 89 proven ROCM patients treated during May-July 2021 were collected from the case records. Histopathological features were correlated with clinical staging groups and outcomes. The mean neutrophil-to-lymphocyte ratio (NLR) of clinical and outcome groups were compared. Results: The mean age was 54.71 ± 11.03 years, with male patients constituting a majority (78.7%). Uncontrolled diabetes mellitus was noted in 70.8% of patients, and 3.4% had normal range of blood sugar. The mean blood sugar was 298.08 ± 99.51 mg/dL. The mean duration of onset of symptoms of mucormycosis from the diagnosis of COVID-19 was 17.36 ± 7.392 (3-45) days. Poor outcome with disease progression or death occurred in 21.3% of patients. Clinical group II patients (44.9%) with ROCM stages 3c and above had poor outcomes (P = 0.005). Histopathological analysis showed minimal inflammation in 25.8%, neutrophil extracellular trap (NET) in 75.3%, and angio-invasion in 28.1% of patients. Minimal inflammation was associated with clinical group II (P = 0.004) and poor outcome (P = 0.001). Angio-invasion correlated with poor outcome (P = 0.007). Patients with severe clinical group and poor outcome had higher mean NLR with P = 0.017 and P = 0.007, respectively. Conclusion: Vision loss and cerebral involvement had poor outcomes. The histopathologic features such as inflammation and angio-invasion along with NLR aid as prognostic indicators in the management of ROCM. The role of NET in the pathogenesis of COVID-19-associated ROCM needs further studies.

Outcome of transcutaneous retrobulbar injection of liposomal amphotericin B in post-COVID-19 rhino-orbito-cerebral mucormycosis: Our experience.

Purpose: To assess the outcome and response of transcutaneous retrobulbar injection of amphotericin B (TRAMB) in post-coronavirus disease of 2019 (COVID-19) rhino-orbito-cerebral mucormycosis (ROCM) and to establish a scoring system in guiding treatment modalities. Methods: An interventional, prospective study was done on 82 eyes of post-COVID-19 ROCM from May 2021 to July 2021. A comprehensive multi-departmental evaluation along with detailed ophthalmic examination, laboratory investigations, and radiological examination was done. Scoring points were given to each symptom, sign, and radiological features of orbit and the total score was taken. Based on these scores, severity of disease was grouped into A, B, and C corresponding to mild, moderate, and severe orbital ROCM. One milliliter of reconstituted liposomal amphotericin B was given to all patients every alternate day as three doses. Efficacy of these injections was assessed in all groups, even though other treatment modalities like orbital debridement and exenteration were considered for moderate and severe cases. Patients were followed up for a period of 8 weeks. Results: Out of 82 eyes, symptomatic improvement was seen in a major proportion (72%) of patients. A statistically significant improvement in scores was noted in group A (93% improved) with a P value of 0.002, while 68.4% showed improvement in group B (P-value- 0.0001). Group C with severe disease showed minimal improvement in post-injection scores of 41% (P-value 0.086), necessitating surgical intervention. No serious adverse effect of the drug or procedure was noted. Conclusion: Significant improvement in scores of groups A and B highlights TRAMB as an effective and safe treatment modality in mild to moderate ROCM. It is an effective adjunct in severe cases, along with other interventions. Also, the scoring system helps in assessing the severity and guiding in management strategies.

Retrobulbar injection of amphotericin B using intravenous cannula for post-COVID-19 rhino-orbital mucormycosis.

Rhino-orbital mucormycosis has seen a huge resurgence in patients post COVID-19 infection. In patients with minimal orbital disease and especially with preserved vision, retrobulbar injections of amphotericin B can be of great help in controlling the disease. Instead of giving daily injections of amphotericin B using needles every time, we used an 18-gauge intravenous (IV) cannula with injection port and suture holes to deliver the amphotericin into the orbital space for a period of 5 days. Patients were more compliant and less distressed with this method compared with being given an injection with a needle daily. We got a good response in terms of orbital disease regression with this method. In our review of the literature, we did not come across any such case of amphotericin B injection using an IV cannula. Injection of amphotericin B into the orbit using an IV cannula is a viable and easy treatment option for cases of rhino-orbital mucormycosis.

A case of endogenous candida endophthalmitis with incidental cytomegalovirus infection and optic neuropathy in a patient recovered from severe COVID-19.

A 62-year-old female diabetic recovered from COVID-19 pneumonia after receiving a prolonged course of steroids. She presented with a clinical picture of left-eye panuveitis with white cotton ball chorioretinal lesions and RAPD suggesting an optic neuropathy (VA HM). Diagnostic vitrectomy was performed to take samples for infective screen and to give intravitreal voriconazole empirically. Smear, culture, and PCR for viral DNA confirmed mixed infection of endogenous Candida endophthalmitis and incidental CMV infection. With further treatment, her corrected vision improved to 6/18 with regressing fungal lesions in serial fundus photographs. Prompt diagnosis and intervention preserved her vision and prevented potential life-threatening complications.

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.

Risk factors and outcomes of COVID associated mucormycosis in kidney transplant recipients.

BACKGROUND: Invasive mucormycosis (IM) is a life-threatening fungal infection occurring mostly in solid organ transplant (SOT) recipients, patients with hematological malignancies, and diabetes. A sudden spurt of mucormycosis has been reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in India; however, there is little data about coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) in kidney transplant recipients (KTRs). METHODS: We describe the clinical presentations, risk factors, treatment and outcomes of 11 mucormycosis cases in KTRs post-COVID-19 infection from February 2020 to June 2021 at a single center in India. RESULTS: Mucormycosis was seen in 11/102 (10.7%) KTRs during the pandemic. Six patients had mild disease and rest five had moderate disease. Seven patients had pre-existing diabetes mellitus and four developed new onset hyperglycemia after receiving steroids for COVID-19 infection. All had poorly controlled sugars at the time of presentation. Most common presentation was rhino-orbital-cerebral mucormycosis (ROCM) in 10/11 (89%) patients and one has pulmonary mucormycosis. All patients received combination of amphotericin B and surgical debridement/excision of affected tissue followed by posaconazole prophylaxis. Nine patients recovered, however two patients succumbed to their illness after median of 14 (7-21) days from diagnosis. One patient developed acute T-cell-mediated rejection during the course of recovery. At last follow up, the mean serum creatinine was 2.05 mg/dl as compared to 1.4 mg/dl at presentation. CONCLUSIONS: IM is a common fungal infection in transplant recipients in India after COVID-19. Early diagnosis and prompt treatment with combination of surgical debridement and liposomal amphotericin B are key to better outcomes in CAM. Judicious use of steroids and control of hyperglycemia is key to avoid flaring up of the fungal infection.

Endogenous fungal endopthalmitis treated with intravitreal caspofungin in a COVID-19 recovered patient: A case report.

We present a case of endogenous fungal endophthalmitis in a nondiabetic, nonhypertensive patient who recovered from COVID-19 infection. Endogenous fungal endophthalmitis in an immunocompetent individual is quite uncommon. The organism in our patient was resistant to amphotericin and voriconazole and was successfully treated with intravitreal caspofungin. The rarity of an opportunistic nosocomial infection in an immunocompetent person with a drug-resistant organism prompted us to write this report.