This is a literature report for the following literature source(s): "Orbital Inflammation Following COVID-19 Vaccination", Ophthalmic plastic and reconstructive surgery, 2022; DOI:10.1097/IOP.0000000000002161. The authors report 3 cases of orbital inflammation occurring within days of the BNT162b2 mRNA (Pfizer/BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccine which is suggestive of an association. A 13-year-old boy with a history of recurrent idiopathic orbital inflammation which was quiescent for over a year presented with left periorbital swelling, erythema, and pain 1 day after his first dose of COVID-19 vaccine (BNT162b2 mRNA, Pfizer/BioNTech). Prior episodes of orbital inflammation were triggered by upper respiratory tract infections. Examination at the time of presentation revealed visual acuities of 20/20 in the OD and 20/40 in the OS, normal IOP, and no rAPD or dyschromatopsia. The OS was noted to have moderately restricted supraduction and abduction, 3 mm of proptosis, conjunctival injection and chemosis, and left upper and lower eyelid edema and erythema (External photographs demonstrating periorbital edema, erythema, and conjunctival injection and chemosis). The remainder of the ophthalmic examination was unremarkable. MRI of the orbits with contrast revealed recurrent orbital inflammation with left lacrimal gland enlargement and intraconal fat stranding in a similar pattern to prior episodes of orbital inflammation, but not noted on surveillance MRI of the orbits several weeks prior (MRI orbits with contrast, with T1 fat-suppressed coronal (left) and axial (right) sections demonstrating left preseptal edema, intraconal fat stranding, enlarged lacrimal gland, and globe proptosis (arrows).). A laboratory workup including CBC, BMP, ESR, CRP, ACE, lysozyme, IgG subclass, ANA, ANCA, TSH, thyroxine (T4), complement C3, complement C4, and Lyme screen with reflex was unremarkable. In all 3 cases, an extensive infectious and inflammatory laboratory work-up was unremarkable. Signs and symptoms of orbital inflammation improved promptly in all cases after initiation of treatment with 60 mg of oral prednisone. All patients achieved complete resolution after prednisone taper over the span of 1 month and have remained in remission at 6 to 11 months follow-up after completion of treatment. The third patient's taper was prophylactically maintained at 20 mg of oral prednisone at the time of his second vaccination dose, without recurrent inflammation or subsequent COVID-19 infection. A rapid corticosteroid course starting at 20 mg of oral prednisone will be initiated 2 days prior to his third vaccination to minimize the risk of recurrent inflammation. [Discussion] This is the first report documenting orbital myositis and dacryoadenitis following the COVID-19 vaccination. The onset of symptoms within 1 week of vaccination is in line with previous literature. The exact immune-mediated mechanism by which COVID-19 targets orbital tissue remains yet to be elucidated. However, inflammation following vaccination suggests an immunological process targeting orbital tissue rather than direct viral infiltration, which has been hypothesized by some to be the underlying mechanism of COVID-19 infection-associated ophthalmic diseases. Although rare, orbital myositis or dacryoadenitis may occur within days after administration of the COVID-19 vaccine. If no underlying etiology is identified after extensive workup, an inflammatory postvaccine etiology may be considered as an alternative to a presumed idiopathic diagnosis. As in 2 of the 3 reported cases, a history of orbital inflammation may be a predisposing factor. Though causation cannot be proven, the temporal relationship between vaccination and onset of orbital inflammatory symptoms in the reported cases, in combination with an extensive unrevealing workup, is highly suggestive of an association. Ophthalmologists should be aware of this possible association to appropriately counsel patients, particularly those with underlying orbital inflammatory conditions, of signs and symptoms that may warrant early examination. Prophylactic treatment with corticosteroid prior to vaccination may be considered for patients with previous orbital inflammation. However, it remains yet to be elucidated whether such treatment may diminish vaccine efficacy. Sender's Comments: Based on the current available limited information in the case provided, the causal association between the event and the use of suspect product BNT162B2 cannot be fully excluded. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to RAs, Ethics Committees, and Investigators, as appropriate. Linked Report(s): US-PFIZER INC-202200506766 Same drug/Event and different patient.