Objective:: With coronavirus disease 2019 (COVID-19) pandemic across the world, there had been an exponential increase in rhino-orbito-cerebral mucormycosis (ROCM). Extension of infection to cavernous sinus leads to cavernous sinus syndrome (CSS). This study aims to describe incidence, clinicoradiological profile, and outcome of CSS positive along with comparative analysis of CSS negative COVID-19-associated ROCM. Material and Method:: This was a prospective and observational study conducted from May 1, 2021, to July 31, 2021. Subjects included ROCM with active or recovered COVID-19 (past 6 weeks) and were categorized and staged. CSS was defined as involvement of two or more of third, fourth, fifth, or sixth cranial nerve with one each direct and indirect qualitative neuroradiological features. Clinicoradiological features of CSS-positive and negative COVID-19-associated ROCM groups were compared. Results:: Incidence of CSS with COVID-19-associated ROCM was 28%. Mean age of subjects was 44 15 years with 60% being males and 73% were proven ROCM. Significant differences seen across the CSS-positive and negative groups were ocular, nasal, and cerebral findings including eyelid and periocular discoloration, ptosis, proptosis, ophthalmoplegia, nasal discharge, mucosal inflammation, and fever. Oculomotor, trochlear, and abducens nerves were significantly involved more in CSS-positive group. Significant radiological findings across two groups included indirect features in orbit, nose, and paranasal sinuses along with direct features in cavernous sinus. Surgical intervention was more common in CSS-positive group. Mortality in CSS-positive group at 824 weeks was 13 and 27%, respectively. Conclusion:: Extension of ROCM to CSS was more common in young males in advanced stages of proven ROCM with concurrent COVID-19. CSS-positive group had significant difference in clinicoradiological features involving orbit, nose, paranasal sinuses, and central nervous system as compared to CSS-negative group. This study highlights the need to develop an objective scoring system considering clinical and radiological features for diagnosis of CSS with COVID-19-associated ROCM.
