Ocular signs and symptoms of monkeypox virus infection, and possible role of the eye in transmission of the virus

Abstract

Dear Editor, This study wishes to bring to the attention of your readers the ocular signs and symptoms of Monkeypox infection and the possible involvement of the eye in the transmission of this virus. Monkeypox is a zoonotic disease caused by a member of the Poxviridae family called the monkeypox virus (MPXV). Before May 2022, infections with this virus were limited to Africa, where it is endemic [1]. In the middle of 2022, a sudden multinational outbreak of MPXV was reported that led the World Health Organization (WHO) to declare the disease a pandemic. There have been 71,437 laboratory-confirmed cases and 29 deaths as of 19th October 2022 [2]. MPVX is commonly spread by respiratory droplets, contact with bodily fluids, and skin lesions from an infected individual [1]. In the endemic areas of MPXV infections, ocular involvement has been reported in both the early and late stages of the disease. In the early stages, 71 % of patients have enlarged lymph nodes including the pre-auricular nodes [3], and 25 % have a vesicular rash involving the orbital and peri-ocular skin [4]. Blepharitis and conjunctivitis have been reported in 30 % of unvaccinated and 7 % of vaccinated patients [5] and focal conjunctival lesions occur in 17 % of unvaccinated compared and 14 % of vaccinated patients [6]. In the later stages of the disease, 22.5 % of patients complain of photophobia [4], up to 7.5 % develop keratitis [4], [7], corneal ulceration occurs in 4 % of unvaccinated and 1 % of vaccinated patients [7], and up to 10 % of cases can result in vision loss [7]. A literature search was performed of four electronic databases (PubMed, Scopus, Google Scholar, and Chinese biomedical database (CNKI)) using the keyword search terms “monkeypox” AND “ocular” OR “eyes”. As of 22nd September 2022, there have been six reports of MPXV isolated from ocular swabs, and several cases with ocular signs and symptoms. It appears that the first publication of ocular involvement in the current pandemic was published in July 2022 [8]. The last two cases contained in this article were from the USA and reported by the Centers for Disease Control and Prevention (CDC) on October 17, 2022 [9]. Table 1 summarises all cases reporting the isolation and identification of the monkeypox virus from the eyes to October 2022. The most common ocular events produced by this virus are conjunctivitis (red eyes), itchiness, pain, photophobia, and vision changes very similar to those previously reported for earlier endemic cases [4], [5], [6], [7]. Conjunctivitis (Fig. 1 A–B) often with ulceration and with umbilicated papillae on the tarsal and bulbar conjunctiva, the fornix, and at the temporal limbus (Fig. 1C–D) can appear some days (2–7 days) after the appearance of rashes on other parts of the body [8], [9], [10], [11]. Ocular signs and symptoms may last for 1–2 months. Table 1 Overall summary of cases reporting the presence of monkeypox virus in ocular sites. Case No. and reference Gender Age(years) Country Dateof publication Ocular signs and symptoms Collection site Virus detection method* Ocular Treatment and time to resolution 1 [8] Male 39 Italy July 29, 2022 Conjunctivitis of the left eye; a small vesicle on the lower eyelid; resolved into a single whitish ulcer (10 mm) on the medial bulbar conjunctiva, with regular edges. Swabs of ocular vesicles PCR Neomycin (3500 IU/mL), polymyxin B (6000 IU/mL), and dexamethasone (1 mg/mL).After 3 weeks the ocular vesicles were no longer visible and the eye had almost healed, although some redness remained. 

 2 [10] Male 39 – August 13, 2022 Red-eye; itchiness; conjunctival follicular reaction with small white vesicles on the nasal bulbar conjunctiva. Swabs of conjunctiva and eye secretion PCR – 

 3 [11] Male 26 Italy August 17, 2022 Multiple papular lesions in the right eyelid with progressive periorbital and conjunctival involvement Swabs of eyelid and conjunctiva RT-PCR, cell culture Initially intravenous antibiotic therapy with topical steroid therapy. Changed to cidofovir (5 mg/kg weekly with oral probenecid and fluid support), anti-inflammatory, and vitamin A-based eye drops. Steroid local therapy was stopped.Resolved approximately-two months after onset. 

 4 [12] Male 35 Italy August 27, 2022 Unilateral ocular pain and photophobia, multiple umbilicated papillae on the tarsal and bulbar conjunctiva, the fornix, and at the temporal limbus. The fellow eye was uninvolved. Conjunctival swab RT-PCR Ocular papillae resolved in 3 days following the administration of a single intravenous dose of cidofovir (5 mg/kg). 

 5 [13] Male 42 – September 7, 2022 Left-eye lacrimation, pain, and photophobia, with ulcers on the eyelid margin, mucoid whitish conjunctival discharge, and serpiginous infiltrative lesions with conjunctival thickening.Conjunctival pseudomembranes developed in the second week of treatment, which was removed. Conjunctival swab PCR Systemic treatment with 600 mg tecovirimat every 12 h and intravenous acyclovir, 1 g every 8 h, plus topical zinc sulfate every 8 h on the skin lesions. Ocular topical treatment with 0.2 % chlorhexidine, 0.5 % ganciclovir, moxifloxacin (dose unknown), and 1 % povidone-iodine eye drop, applied 5 times a day. Topical fluorometholone treatment 4 times a day started after the appearance of pseudomembranes. Conjunctival lesions resolved after 4 weeks. 

 6 [9] Male 20–29 USA October 17, 2022 Initially pain, itching, swelling, discharge, foreign body sensation, photosensitivity, and vision changes (20/40) for the left eye (resolved with treatment).One month later presented with conjunctivitis, keratitis, and a vision of 20/300 in the left eye. ConjunctivalSwab PCR; immuno-histochemistry Intravenous tecovirimat and topical trifluridine with antiretroviral therapy (ART). Discharged once ocular symptoms improved, and advised to take regular medication (oral tecovirimat, topical trifluridine, and ART). After reoccurrence, intravenous tecovirimat with one week’s course of topical trifluridine and povidone-iodine for the left eye. At the time of writing status and any vision recovery unspecified. 

 7 [9] Male 30–39 USA October 17, 2022 rashes with symptoms of redness, pain, and eyelid swelling on the right eye. Eye swab PCR Initially, empiric antibiotics for suspected bacterial infection. After two days, trifluridine for 5 days; antibacterial drops to the right eye. Oral tecovirimat (14-day course) after discharge * PCR = polymerase chain reaction; RT-PCR = real time polymerase chain reaction. Fig. 1 Ocular manifestations of monkeypox virus infection. 1Figure A–B Reprinted from Ophthalmology, Vol 129 Issue 10, Meduri, E., A. Malclès, and M. Kecik, Conjunctivitis with Monkeypox Virus Positive Conjunctival Swabs, Pages No. 1095, Copyright (2022), with permission from Elsevier. 2Figure C–D Reprinted from Ophthalmology, Vol 129 Issue 11, Scandale, P., A.R. Raccagni, and S. Nozza, Unilateral Blepharoconjunctivitis due to Monkeypox Virus Infection, Pages No. 1274, Copyright (2022), with permission from Elsevier.). Along with ocular signs and symptoms, this report outlines the possibility of viral transmission from ocular sites. Seven cases were reported detecting MPXV nucleic acid from ocular sites. Eye care practitioners should follow protective and prophylactic measures and be aware of the general and ocular signs and symptoms, as well as patient histories (for example the current outbreak appears to be commonly associated with men who have sex with men, but that could change if the pandemic intensifies) that can help diagnose the disease and stop transmission. Ocular involvement in the monkeypox virus pandemic demands more attention from the researcher and believe this work will grab the attention of those who have an interest in viral eye infections. Funding statement This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.