The pathophysiology of COVID-19 involves systemic immune responses, with massive production of inflammatory mediators.2,3 The coronavirus enters host cells by binding its spike (S) protein to host ACE2 receptors, and the transmembrane serine protease 2 (TMPRSS2) facilitates viral fusion with the human cell.2,3,9 Although the ACE2 receptor and TMPRSS2 are particularly expressed in type 2 alveolar epithelial cells, they have also been identified in several other tissues such as the conjunctiva, limbus, and cornea.2,3
The human body's immune reaction to SARS-CoV-2 infection involves innate and adaptive responses.9 An intracellular cascade signal leads to the production of numerous proinflammatory cytokines such as tumour necrosis factor (TNF), interleukin 1 (IL-1) and 6 (IL-6), and interferons (IFNs).2,9 IFNs typically protects the host from viral replication by inducing apoptosis of infected cells, although this cytokine can be supressed by SARS-CoV-2 proteins.9 In the reported patient's case, we believe that an intense immunological response caused by viral particles led to severe injury to the corneal stroma, resulting in IK. This mechanism would be akin to that of stromal keratitis secondary to the herpes simplex virus, in which case herpes virus replication in the cornea triggers an immune signaling cascade and production of cytokines.10 The resulting influx of inflammatory cells and antigen presenting cells result in both acute and chronic corneal inflammation and vascularization.10
Approximately 11% of COVID-19 patients have ocular findings.1 The most common ocular feature of this disease is viral conjunctivitis,1 and other anterior segment manifestations of COVID-19 include keratoconjunctivitis,11 episcleritis,4 and acute corneal graft rejection.5 Additional ophthalmic manifestations include acute dacryoadenitis,12 cotton wool spots and retinal microhemorrhages,13 posterior scleritis,14 oculomotor nerve palsy,15 optic neuritis,16 Guillan-Barre syndrome,17 Miller Fisher syndrome,18 ophthalmic artery occlusion,19 and retinal vein occlusion.20 As ophthalmic findings may precede systemic disease, knowledge of the ocular manifestations of COVID-19 is vital to permit early diagnosis and treatment.
IK involves chronic and nonulcerative inflammation of the corneal stroma with variable neovascularization, usually without epithelial or endothelial involvement.21 The pathogenesis typically involves an immune-mediated response to foreign antigens, which are usually bacterial, viral, or parasitic.21 At one institution in the United States, the most common identified causes of IK were herpes simplex virus and syphilis.22 However, the vast majority of bilateral cases were either idiopathic or secondary to syphilis.22 Other etiologies include Lyme disease, tuberculosis, Epstein-Barr virus, and acanthamoeba.21 The results of laboratory tests for our patient were non-confirmatory. Although it is a possibility that our patient had IK related to herpetic infection, the bilateral nature of his disease as well as no prior herpetic history makes this less likely.
The management of IK typically involves topical inflammatory therapy and treatment of the underlying etiology, when identified.23 ln our case, the patient was able to achieve functional vision with rigid gas permeable contact lenses. In conclusion, we present a rare case of bilateral IK after the onset of COVID-19 resulting in corneal scarring and decreased vision. We hope that this case highlights the importance of ocular evaluation in patients with COVID-19, as early management of this complication may reduce ocular morbidity.