Persistent ocular mpox infection in an immunocompetent individual

Ocular involvement because of mpox (formerly known as monkeypox) infection has been described, including blepharitis, conjunctivitis, and keratitis.1Benatti SV Venturelli S Comi N et al.Ophthalmic manifestation of monkeypox infection.Lancet Infect Dis. 2022; 221397 Summary Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 2Carrubba S Geevarghese A Solli E et al.Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analogues.Lancet Infect Dis. 2023; (published online Jan 23.)https://doi.org/10.1016/S1473-3099(22)00869-6Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 3Cash-Goldwasser S Labuda SM McCormick DW et al.Ocular Monkeypox - United States, July-September 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 1343-1347Crossref PubMed Google Scholar, 4Mitjà O Alemany A Marks M et al.Mpox in people with advanced HIV infection: a global case series.Lancet. 2023; 401: 939-949Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar Tecovirimat is the first-line antiviral therapy for severe mpox, but treatment failures have been reported.4Mitjà O Alemany A Marks M et al.Mpox in people with advanced HIV infection: a global case series.Lancet. 2023; 401: 939-949Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar Here, we present an individual with persistent mpox ocular involvement over 8 months, who was poorly responsive to multiple tecovirimat cycles, and was successfully administered a combined antiviral treatment of tecovirimat and cidofovir (figure; appendix). This individual provided written informed consent. In July 2022, an immunocompetent man aged 35 years, who had sex with men, and had no comorbidities, reported the appearance of only three pustular lesions on the left hand and the trunk without systemtic symptoms, after close non-sexual contact with another individual later diagnosed with mpox. Because the lesions resolved without treatment, diagnostic tests were initially not performed. He recalled concurrent accidental self-injury of the left eye with foreign body puncture, resulting in conjunctivitis and periocular oedema. Topical moxifloxacin and tobramycin (2 weeks) followed by polymyxin (1 week) were administered with topical steroids (3 weeks). After steroid withdrawal, he complained of photophobia and vision loss; he had a new paracentral dendritic corneal ulcer, with rolled edges, perilesional corneal epithelial defects, and stromal infiltration noted on the slit-lamp examination. Oral empirical therapy with fluconazole (1 week), voriconazole (2 weeks), acyclovir (2 weeks), doxycycline (1 week), topical moxifloxacin (2 weeks), and azithromycin (1 week) was administered with topical dexamethasone (4 months). In September 2022, given the persistence of corneal signs and photophobia, the individual underwent screening for autoimmunity and bacterial, viral, and fungal infections (negative PCR on conjunctival swabs for 18S rDNA, Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, adenovirus, herpes simplex virus type 1 and 2, varicella zoster virus, cytomegalovirus, and bacterial and fungal cultures). Monkeypox virus PCR on the conjunctival swab resulted positive (cycle threshold, 34; indicating possible low infectiousness). Monkeypox virus PCR on plasma and HIV testing were negative. Oral tecovirimat was prescribed for 14 days, resulting in corneal ulcer repair and vision improvement to 20/30. Upon the discontinuation of topical dexamethasone in November 2022, photophobia and eye redness worsened and, after receiving a single dose of mpox vaccination, corneal ulcers relapsed. Monkeypox virus testing was repeated on the conjunctival swab, and the results were positive (cycle threshold, 29); HIV testing was negative. A second course of oral tecovirimat was prescribed for 14 days in December 2022, in addition to topical steroids, resulting in partial photophobia and eye redness control; a negative conjunctival swab was obtained in January 2023. 3 weeks after treatment, ulcerative keratitis relapsed and a positive monkeypox virus conjunctival swab was obtained in February 2023 (cycle threshold, 27). A third course of oral tecovirimat was prescribed for 14 days, with partial corneal ulcer repair and regression of photophobia and eye redness. Intravenous cidofovir (5 mg/kg) was administered at the end of tecovirimat. The ulcerative keratitis completely resolved after cidofovir, with residual minimal surface staining and stromal opacity. Vision was 20/50, despite best refractive correction. Monkeypox virus testing on the conjunctival swab was negative in March 2023, and no symptoms or corneal involvement were noted over 2 months of follow-up. This case represents an atypical mpox infection, with mainly ocular involvement persisting for 8 months, in an immunocompetent individual. To our knowledge, no other reported cases were characterised by such a long persistence of monkeypox virus in a specific site, which was possibly related to hypothetic viral sanctuaries, such as in the eye. In this individual, ocular signs were responsive to oral tecovirimat and topical steroids, but they recurred after treatment withdrawal. Viral DNA was documented on conjunctival swabs at each relapse.4Mitjà O Alemany A Marks M et al.Mpox in people with advanced HIV infection: a global case series.Lancet. 2023; 401: 939-949Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar Administered topical medications might also have resulted in signs worsening. Treatment with oral tecovirimat and intravenous cidofovir resulted in the resolution of ocular signs and apparent infection clearance. The effectiveness of the combined treatment might be related either to the different pharmacokinetics of the two antivirals, with dissimilar delivery to the corneal epithelium, or their alleged synergy.5Siegrist EA Sassine J Antivirals with activity against mpox: a clinically oriented review.Clin Infect Dis. 2023; 76: 155-164Crossref PubMed Scopus (39) Google Scholar In conclusion, mpox ocular involvement might result in a noteworthy reduction of life quality and requires multidisciplinary management to face possible clinical and therapeutic challenges. TC and ARR visited the individual and contributed to writing the article. SN and MR visited the individual and contributed to the reviewing of the article. MVC performed ophthalmological evaluations. AC coordinated clinical activities and contributed to the reviewing of the article. All authors have read and agreed to the published version of the manuscript. All authors have seen and approved of the final text. ARR, TC, and SN had directly accessed and verified the underlying data reported in the manuscript. SN and AC were responsible for the decision to submit the manuscript. AC has received personal fees for advisory boards, speaker panels, and educational materials from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, Theratechnlogies, and ViiV Healthcare. SN has received personal fees for advisory boards, speaker panels, and educational materials from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. All other authors declare no competing interests. All data collected in the study are available upon reasonable request, after approval of the proposal, to the corresponding author ([email protected]). The data can be requested from publication onwards. The data are not publicly available for ethical reasons. Download .pdf (.54 MB) Help with pdf files Supplementary appendix Ophthalmic manifestation of monkeypox infectionA 39-year-old, White, bisexual male attended our sexual health clinic with proctitis and a cluster of vesicles (2–3 mm) in the anal region, which had presented 3 days previously. He declared having had multiple unprotected sexual encounters and being on pre-exposure prophylaxis for HIV prevention since 2019. Over the previous 3 weeks, he had travelled to France and Germany, before returning to Italy. Full-Text PDF Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analoguesWHO has declared human mpox (formerly known as monkeypox) a global public health emergency since July, 2022. When case numbers were increasing, so did clinicians' exposures to new elements of the disease. Additionally, the burden of mpox is particularly apparent in immunocompromised patients, who can have more variable and severe manifestations of disease across organ systems. In this Grand Round, we report novel and severe oculocutaneous manifestations of mpox in this population, which are both sight and life threatening. Full-Text PDF