Purpose: To describe 2 patients with mpox keratouveitis and evaluate their contrasting clinical phenotypes in the context of baseline immune function. Methods: Both patients were subject to longitudinal care by providers at our institution. Qualitative polymerase chain reaction (PCR) analysis was used to confirm their diagnoses, and interval slit-lamp photography was used to document their clinical progression. For case 2, histologic analysis was performed on a corneal biopsy specimen. Results: Case 1 describes a 31-year-old immunocompetent man with cutaneous mpox who developed a unilateral keratouveitis after a cutaneous lesion of the ipsilateral eyelid. His keratitis resolved over 1 week with application of trifluridine eye drops. An anterior uveitis persisted but resolved by 2 weeks after treatment with topical prednisolone and oral tecovirimat. Case 2 describes a 27-year-old man with HIV and a declining CD4+ count who was coinfected with monkeypox virus. Over 3 months, he developed a progressive unilateral keratouveitis that resulted in corneal melt requiring tectonic keratoplasty to preserve globe integrity. On histology, the patient's corneal biopsy specimen was devoid of lymphocytes. Conclusions: Contrary to immunocompetent patients, individuals with profound cell-mediated immunodeficiencies may be unable to mount sufficient lymphocytic responses in corneal tissue to contain mpox lesions. A progressive keratouveitis can develop, leading to corneal melt with an atypical local immune signature. The clinical and histologic phenotype of the cornea in this scenario is analogous to progressive vaccinia of the skin, a rare clinical entity that develops after smallpox vaccination of immunocompromised hosts.
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