Addressing COVID-19-associated fungal eye disease in India

Reviewed by Dr Mrittika Sen.

The advent of the COVID-19 pandemic has resulted in a surge of cases of the potentially lethal fungal infection rhino-orbital-cerebral mucormycosis (ROCM) in India. The symptoms of this infection are often non-specific and can vary in severity. Patients may initially complain of headache, nausea, fever and weakness.

Purulent discharge with the onset of sinusitis, congestion and decreased nasal sensation can also occur, along with nasal ulceration and necrosis. Other symptoms reported are facial pain and numbness and double or blurred vision, as well as partial or complete loss of vision in one or both eyes. Altered consciousness, seizures and/or an unstable gate point to the progression of brain involvement.

Clinicians from the Centre for Sight in Hyderabad, India, led by Dr Santosh Honavar and Dr Mrittika Sen, reported that the development of ROCM following moderate-to-severe COVID-19 in patients with uncontrolled diabetes who are treated with corticosteroids is a recipe for a life-threatening scenario. “This infection is typically a rare opportunistic occurrence in patients with uncontrolled diabetes, neutropenia, blood malignancies and organ transplants. ROCM is associated with mortality rates exceeding 50% despite treatment,” Dr Sen said.

Identifying at-risk patients

Dr Sen and her colleagues conducted a retrospective interventional study in two centres—the Centre for Sight in Hyderabad and JJ Hospital at Grant Medical College in Mumbai, India—that included all patients with clinically and microbiologically proven ROCM and either a concurrent or a previous history of COVID-19 between 1 August and 15 December 2020. This study was conducted when there were only three isolated case reports from around the world, and the association between COVID-19 and ROCM was unknown.

The study goals were to determine the population at risk, clinical features and possible early diagnosis and management strategies. All six patients in the study were men (mean age 60.5 years) who had type 2 diabetes (mean blood glucose level 222.5 mg/dL). Five of the patients received either oral prednisolone or intravenous dexamethasone or methylprednisolone for the management of COVID-19. Only one patient had concurrent COVID-19 at presentation, and he was not treated with systemic corticosteroids.

Dr Sen reported that the mean duration between COVID-19 diagnosis and the onset of mucormycosis symptoms was 15.6 days. At presentation, five patients had no light perception vision and one patient had a best-corrected vision of 6/60. The clinical findings included periocular oedema; complete ptosis; ophthalmoplegia; proptosis; conjunctival congestion; and severe chemosis.

Treatment was with intravenous liposomal amphotericin B; posaconazole oral suspension was added for patients who were intolerant of or refractory to amphotericin B. Aggressive debridement of paranasal sinuses was performed. Orbital exenteration was carried out on patients with extensive orbital involvement that did not improve within 72 hours of initiation of intravenous amphotericin B.

Imaging showed intracranial extension with cavernous sinus involvement and all cases underwent sinus debridement. The eyes were salvaged in four cases and all the patients survived and continued treatment with amphotericin B with or without posaconazole.

The investigators proposed a staging system for ROCM to customise patient care. This four-stage system was based on the natural anatomical progression of the disease from the nose to the paranasal sinuses, orbit and brain, with management guidelines for each disease stage. It was published in the Indian Journal of Ophthalmology.¹

The investigators later went on to conduct a collaborative OPAI-IJO study on mucormycosis in COVID-19 (COSMIC) during the second COVID-19 wave, which included 2,826 patients with COVID-19-associated ROCM from 102 centres in India.2 “The primary result showed that diabetes was present in 78% of patients, 87% had been treated with steroids and 44% had delayed onset beyond 14 days of a COVID-19 infection,” Dr Sen said.

Based on the management recommended in the staging system, 73% of patients received intravenous amphotericin B, 56% underwent functional endoscopic sinus surgery or paranasal sinus debridement, 15% underwent orbital exenteration and 22% received an intraorbital injection of amphotericin B. The overall mortality at the time of reporting was 14%.

Patients with disease stage 3b and higher with diffuse orbital involvement had a poorer prognosis. However, paranasal sinus debridement and orbital exenteration reduced the mortality from 52% to 39% in those who had stage 4 disease with intracranial extension.

Dr Sen noted that this was the first case series in COVID-19 that identified associated ROCM. “The series of six cases and [the] COSMIC study found that corticosteroids and diabetes are the most important predisposing factors in the development of COVID-19-associated ROCM,” she said.

“Successful outcomes depend on awareness of the red flag symptoms and signs, a high index of clinical suspicion, prompt diagnosis and early treatment with amphotericin B; aggressive surgical debridement of the paranasal sinus; and orbital exenteration where indicated, with coordinated effort between different departments. Intraorbital amphotericin B does seem to have a role in reducing the need for orbital exenteration.”

Mrittika Sen, MD, FICO, MRCSEd

E: mrittika24sen@gmail.com

This article was adapted from Dr Sen’s presentation at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Louisiana, United States. She has no financial interest in this subject matter.

References

1. Honavar SG. Code mucor: guidelines for the diagnosis, staging and management of rhino-orbito-cerebral mucormycosis in the setting of COVID-19. Indian J Ophthalmol. 2021;69:1361-1365.

2. Sen M, Honavar SG, Bansal R, et al. Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India – collaborative OPAI-IJO study on mucormycosis in COVID-19 (COSMIC), report 1. Indian J Ophthalmol. 2021;69:1670-1692.