Anticoagulation and the risk of central retinal artery occlusion in post-COVID rhino-orbital-cerebral mucormycosis

Dear Editor, Central retinal artery occlusion (CRAO) is an uncommon but devastating complication of post-COVID rhino-orbital-cerebral mucormycosis (ROCM). During the second wave of COVID-19, an unprecedented number of ROCM cases were encountered, frequently among diabetics receiving corticosteroids.[1] While these risk factors are well established, the role of systemic anticoagulation in preventing vascular events such as CRAO remains inadequately explored.[2,3] We retrospectively analyzed 369 consecutive ROCM patients managed at a tertiary care center [Table 1]. All patients had a confirmed history of COVID-19 and histopathologically proven mucormycosis. 23 (6.2%) patients developed CRAO during their disease course. Of these, 21/23 (91.3%) had orbital involvement, and all were diabetic, similar to earlier other reports of CRAO in post-COVID mucormycosis.[4] Sphenoid or ethmoid sinus involvement was present in 48/369 (13.0%), and among them, 23/48 (47.9%) developed CRAO, highlighting the anatomical proximity of these sinuses to the ophthalmic vasculature.Table 1: Table showing patient demographics, systemic illnesses, and clinical features in post-COVID mucormycosisThe key observation was a clear difference in CRAO incidence between those who had received anticoagulation during acute COVID-19 and those who had not. Low-molecular-weight heparin (LMWH) (Enoxaparin 1 mg/kg subcutaneously BID for 7–14 days) was used prophylactically in 158/369 (42.8%) patients; a small subset also received Oral aspirin 150 mg once daily.[5] CRAO occurred in only 3/158 (1.9%) of anticoagulated patients, compared with 20/211 (9.5%) who had not received any anticoagulants [Table 2]. None of the anticoagulated patients developed major bleeding complications. LMWH, such as Enoxaparin (1 mg/kg subcutaneously BID), is usually the anticoagulant of choice in mucor-related CRAO. It acts quickly, has predictable pharmacokinetics, and is generally safe to use alongside antifungal therapy or during surgical debridement. Once the patient is stable, it can be switched to an oral anticoagulant. In contrast, unfractionated heparin demands close monitoring and carries a greater risk of bleeding, which can complicate surgery. Direct oral anticoagulants are not preferred in the acute phase as they could be less effective in the intense prothrombotic state and can interact with azole antifungals that modify their metabolism. The other types of anticoagulants that are used for mucor patients include Unfractionated Heparin (80 U/kg IV bolus followed by 18 U/kg/h infusion, aPTT 2–2.5×), which is used when close monitoring is required. Oral anticoagulants include Warfarin (5 mg OD, INR 2–3) or direct oral anticoagulants such as Apixaban 5 mg BID, Rivaroxaban 15–20 mg OD, and Dabigatran 150 mg BID, for 3 months. Adjunct aspirin 150 mg ± clopidogrel 75 mg OD enhances antiplatelet protection. The markedly lower incidence of CRAO among anticoagulated patients supports a potential protective association, possibly by mitigating the combined thromboinflammatory effects of COVID-19 and mucormycosis. This observation reflects the effect of appropriately administered, guideline-directed prophylactic anticoagulation in hospitalized, high-risk patients, rather than advocacy for its universal use.[6]Table 2: Anticoagulant usage versus CRAO statusWhile anticoagulation cannot prevent fungal invasion, it may reduce secondary thrombotic occlusion of the central retinal artery and preserve vision in high-risk patients.[2,5] Our findings emphasize the importance of early risk stratification, strict glycemic control, adequate antifungal therapy, and risk-adapted prophylactic anticoagulation during acute COVID-19 in patients predisposed to ROCM. Serial ocular examinations during active disease are also crucial as 16 of our CRAO cases developed visual loss after initially normal fundus findings within 1 week [Fig. 1].Figure 1: Bedside retcam fundus examination showing cherry-red spot in the maculaIn summary, prophylactic anticoagulation with LMWH during COVID-19 illness was associated with a fivefold lower risk of CRAO in subsequent ROCM. Incorporating anticoagulation into multidisciplinary management may help prevent vision-threatening vascular complications in post-COVID mucormycosis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.