After the Storm: Ophthalmic Manifestations of COVID-19 Vaccines

Abstract

Several COVID-19 vaccines have been developed and approved for use around the world from December 2020, to combat the pandemic caused by the novel SARS-CoV-2 virus. Several ophthalmic manifestations of the COVID-19 vaccines have been reported by ophthalmologists. This review was undertaken to recognize, encourage active reporting and determine the pathogenesis and time of appearance for better awareness and understanding of the ophthalmic manifestations of COVID-19 vaccines. A literature search was performed for publications on the ophthalmic manifestations of COVID-19 vaccines between January 1, 2021 and November 7, 2021. 23 case reports, 17 letters to editors, 3 ophthalmic images, 4 brief communications, 4 retrospective cohort studies and 2 case control studies were included. Posterior segment, including the uvea, choroid and retinal vasculature, was most commonly affected and the reported clinical features developed at a median of four days from the time of vaccination. The possible mechanisms include molecular mimicry of the vaccine components with host ocular tissues, antigen-specific cell and antibody-mediated hypersensitivity reactions to viral antigens and adjuvants present in the vaccines. The causal relationship of the ocular signs and symptoms and COVID-19 vaccines has not been established and requires long-term and large multicentre data. Most of the reported manifestations are mild, transient and adequately treated when diagnosed and managed early. The benefits of COVID-19 vaccination outweighs the reported rare adverse events and should not be a deterrent to vaccination.

Keywords: COVID-19; COVID-19 vaccine; Corneal graft rejection; SARS-CoV-2; inactivated vaccine; mRNA vaccine; ophthalmic manifestations; vascular occlusion; vector based vaccine.

Figure 1

Purpuric lesions on the upper eyelids in patient 2 (a and b) and patient 1 (c and d). (Reproduced with permission from Mazzatenta C, Piccolo V, Pace G, Romano I, Argenziano G, Bassi A. Purpuric lesions on the eyelids developed after BNT162b2 mRNA COVID-19 vaccine: another piece of SARS-CoV-2 skin puzzle?. Journal of the European Academy of Dermatology and Venereology. 2021 May 28.)

Figure 2

Early acute endothelial rejection post-DMEK following vaccination. Slit-lamp image at presentation on day 7 postvaccination with rejection and corneal edema (a), and on day 14 postvaccination and intensive treatment with topical dexamethasone showing improved stromal transparency (b). Anterior segment OCT on day 7 post-DMEK, indicating full graft attachment and CCT of 525 μm (c), on day 21 post-DMEK (day 7 postvaccination) at presentation with rejection and CCT of 652 μm corresponding to observed stromal edema and inflammation (d), and on day 28 post-DMEK (day 14 post-vaccination), following increased frequency of topical steroids and CCT of 526 μm (e). (Reproduced with permission from Phylactou M, Li JP, Larkin DF. Characteristics of endothelial corneal transplant rejection following immunization with SARS-CoV-2 messenger RNA vaccine. British Journal of Ophthalmology. 2021 Jul 1;105(7):893-6.)

Figure 3

A case of acute corneal endothelial graft rejection after COVID-19 vaccine. A, B Slit-lamp photography demonstrating conjunctival hyperemia, corneal graft haze, diffuse corneal epithelial, and stromal edema (within the graft), Descemet’s folds, scattered keratic precipitates (KPs), and 1+ cells in the anterior chamber. An unusual distribution of fluorescein staining with coarse punctate epitheliopathy over the corneal graft was observed. The central corneal thickness (CCT) was 730 μm. C, D At 3-week post-treatment, the corneal graft rejection was successfully treated with considerable improvement in the graft transparency, reduction in epithelial and stromal edema, and resolution of epitheliopathy and anterior chamber inflammation. The best-corrected visual acuity improved to 6/12, with a CCT of 609 μm (Reproduced with permission from Rallis KI, Ting DS, Said DG, Dua HS. Corneal graft rejection following COVID-19 vaccine. Eye. 2021 Aug 23:1-2.)

Figure 4

(a) Fundoscopy, (b) autofluorescence, and (c) fluorescein angiography of both eyes showing serous retinal detachment, optic disc hyperemia, and choroidal inflammation in a patient with Vogt-Koyanagi-Harada syndrome after COVID-19 vaccination. (Reproduced with permission from Saraceno JJ, Souza GM, dos Santos Finamor LP, Nascimento HM, Belfort R. Vogt-Koyanagi-Harada Syndrome following COVID-19 and ChAdOx1 nCoV-19 (AZD1222) vaccine. International Journal of Retina and Vitreous. 2021 Dec;7(1):1-7.)

Figure 5

Clinical evaluation of a patient with unilateral central serous retinopathy. The right eye (left column) and left eye (right column) are shown. Fundus photography of the posterior pole (a) of the right eye shows an inferotemporal parafoveal depigmented lesion. The left eye fundus was normal. Optical coherence tomography (b) of the right eye shows a serous detachment of the neurosensory retina in the central macula. (Reproduced with permission from Fowler N, Martinez NR, Pallares BV, Maldonado RS. Acute-onset central serous retinopathy after immunization with COVID-19 mRNA vaccine. American Journal of Ophthalmology Case Reports. 2021 Sep 1;23:101136.)

Figure 6

Color fundus photograph of the left eye of a patient with central retinal vein occlusion following COVID-19 vaccination showing dot-blot and flame-shaped hemorrhages, dilated tortuous veins, and blurred margins in the disc, especially in the temporal quadrant (Reproduced with permission from Endo B, Bahamon S, Martínez-Pulgarín DF. Central retinal vein occlusion after mRNA SARS-CoV-2 vaccination: A case report. Indian Journal of Ophthalmology. 2021 Oct 1;69 (10):2865-6.)

Figure 7

lL of facial symmetry, incomplete right eye closure, loss of nasolabial fold, and drooping of the angle of the mouth of the right side suggestive of right-sided Bell’s palsy (Reproduced with permission from Ish S, Ish P. Facial nerve palsy after COVID19 vaccination – A rare association or a coincidence. Indian J Ophthalmol 2021;69:2550-2.)

Figure 8

MRI of an inflammatory left cavernous sinus process consistent with Tolosa-Hunt syndrome T2 axial FLAIR (a) and FSE coronal (c) images showing bulky perineural tissue extending into the left cavernous sinus. The perineural tissue has heterogeneous postcontrast enhancement and slightly decreased enhancement centrally consistent with a component of thrombosis on postcontrast T1 axial (b) and coronal (d) images (Reproduced with permission from Chuang TY, Burda K, Teklemariam E, Athar K. Tolosa-Hunt Syndrome Presenting After COVID-19 Vaccination. Cureus. 2021 Jul; 13 (7).)

Figure 9

Timeline showing the onset of signs and symptoms from the time of COVID-19 vaccination (Day 0)