The intersection of ROCM and COVID-19 in patients with diabetes

Investigators find that successful outcomes may depend on the awareness of red-flag symptoms and signs.

Reviewed by Mrittika Sen, MD, FICO, MRCSEd

Rhino-orbital-cerebral mucormycosis (ROCM) has reached endemic proportions in India, in association with the COVID-19 pandemic.

Clinicians from the Centre for Sight in Hyderabad, India, led by Santosh Honavar, MD, FACS, FRCOphth; and Mrittika Sen, MD, FICO, MRCSEd, that rhino-orbital-cerebral mucormycosis (ROCM) that develops after moderate-to-severe COVID-19 in patients with uncontrolled diabetes, 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,” Sen said, adding that the advent of the COVID-19 pandemic resulted in a surge of ROCM cases to epidemic proportions.

Identifying the at-risk patients

Sen and her colleagues conducted a retrospective, interventional study in 2 centers—the Centre for Sight in Hyderabad and Grant Government Medical College and JJ Group of Hospitals in Mumbai, India—that included all consecutive patients with clinically and microbiologically proven ROCM and either concurrent or a previous history of COVID-19 between August 1 and December 15, 2020. This study was conducted when there were only 3 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.

Treatment was with intravenous liposomal amphotericin B, and posaconazole oral suspension was added for patients who were intolerant of or refractory to amphotericin B. Aggressive debridement of paranasal sinuses was done. Orbital exenteration was done in patients with extensive orbital involvement not improving within 72 hours of initiation of intravenous amphotericin B.

All 6 patients were men (mean age, 60.5 years) who had type 2 diabetes (mean blood glucose level, 222.5 mg/dL). Only 1 patient had concurrent COVID-19 at presentation, and he was not treated with systemic steroids. The other 5 patients received either oral prednisolone or intravenous dexamethasone or methylprednisolone for the management of COVID-19.

Sen reported that the mean duration between COVID-19 diagnosis and the onset of mucor symptoms was 15.6 days. At presentation, 5 patients had no light perception vision and 1 patient had a best-corrected vision of 6/60. The clinical findings included periocular edema, complete ptosis, ophthalmoplegia, proptosis, conjunctival congestion, and severe chemosis.

Imaging showed intracranial extension with cavernous sinus involvement and all cases underwent sinus debridement. The eyes were salvaged in 4 cases and all patients survived. All patients continued treatment with amphotericin B with or without posaconazole.

COSMIC: The large follow-up study of COVID-19–associated ROCM

The investigators proposed a staging system for ROCM to customize patient care. The staging system was published in the Indian Journal of Ophthalmology.1 This was based on the natural anatomic progression of the disease from the nose to the paranasal sinuses, orbit, and brain. The management guidelines are based on the disease stage.

The investigators later went on to conduct a collaborative OPAI-IJO study on mucormycrosis in COVID-19 (COSMIC) during the second COVID-19 wave, which included 2826 patients with COVID-19-associated ROCM from 118 centers 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,” Sen said.

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

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

Sen noted that this was the first case series in COVID-19 that identified associated ROCM.

“The series of 6 cases and [the] COSMIC study found that corticosteroids and diabetes are the most important predisposing factors in the development of COVID-19–associated ROCM,” Sen 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 Sen’s presentation at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Louisiana. 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(6):1361-1365. doi:10.4103/ijo.IJO_1165_21

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(7):1670-1692. doi:10.4103/ijo.IJO_1565_21