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

Published:December 28, 2022DOI:https://doi.org/10.1016/j.clae.2022.101808

      Keywords

      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 [
      • Peter O.J.
      • et al.
      Transmission dynamics of Monkeypox virus: a mathematical modelling approach.
      ]. 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 [

      WHO. Multi-country outbreak of monkeypox, External situation report #5 - 7 September 2022. 2022; Available from: https://www.who.int/publications/m/item/multi-country-outbreak-of-monkeypox--external-situation-report--5---7-september-2022.

      ].
      MPVX is commonly spread by respiratory droplets, contact with bodily fluids, and skin lesions from an infected individual [
      • Peter O.J.
      • et al.
      Transmission dynamics of Monkeypox virus: a mathematical modelling approach.
      ]. 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 [
      • Huhn G.D.
      • et al.
      Clinical characteristics of human monkeypox, and risk factors for severe disease.
      ], and 25 % have a vesicular rash involving the orbital and peri-ocular skin [
      • Ogoina D.
      • et al.
      Clinical course and outcome of human monkeypox in Nigeria.
      ]. Blepharitis and conjunctivitis have been reported in 30 % of unvaccinated and 7 % of vaccinated patients [
      • Damon I.K.
      Status of human monkeypox: clinical disease, epidemiology and research.
      ] and focal conjunctival lesions occur in 17 % of unvaccinated compared and 14 % of vaccinated patients [
      • Ježek Z.
      • et al.
      Human monkeypox: clinical features of 282 patients.
      ]. In the later stages of the disease, 22.5 % of patients complain of photophobia [
      • Ogoina D.
      • et al.
      Clinical course and outcome of human monkeypox in Nigeria.
      ], up to 7.5 % develop keratitis [
      • Ogoina D.
      • et al.
      Clinical course and outcome of human monkeypox in Nigeria.
      ,
      • Jezek Z.
      • et al.
      Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.
      ], corneal ulceration occurs in 4 % of unvaccinated and 1 % of vaccinated patients [
      • Jezek Z.
      • et al.
      Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.
      ], and up to 10 % of cases can result in vision loss [
      • Jezek Z.
      • et al.
      Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.
      ].
      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 [

      Benatti SV, et al., Ophthalmic manifestation of monkeypox infection. Lancet Infect Dis, 2022;22(9):1397 doi: 10.1016/S1473-3099(22)00504-7. Epub 2022 Jul 30.

      ]. 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 [
      • Meduri E.
      • Malclès A.
      • Kecik M.
      Conjunctivitis with monkeypox virus positive conjunctival swabs.
      ]. 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 [
      • Ogoina D.
      • et al.
      Clinical course and outcome of human monkeypox in Nigeria.
      ,
      • Damon I.K.
      Status of human monkeypox: clinical disease, epidemiology and research.
      ,
      • Ježek Z.
      • et al.
      Human monkeypox: clinical features of 282 patients.
      ,
      • Jezek Z.
      • et al.
      Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.
      ]. Conjunctivitis (Fig. 1A–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 [

      Benatti SV, et al., Ophthalmic manifestation of monkeypox infection. Lancet Infect Dis, 2022;22(9):1397 doi: 10.1016/S1473-3099(22)00504-7. Epub 2022 Jul 30.

      ,
      • Meduri E.
      • Malclès A.
      • Kecik M.
      Conjunctivitis with monkeypox virus positive conjunctival swabs.
      ,
      • Mazzotta V.
      • et al.
      Ocular involvement in monkeypox: description of an unusual presentation during the current outbreak.
      ,

      Scandale P, Raccagni AR, Nozza S, Unilateral blepharoconjunctivitis due to monkeypox virus infection. Ophthalmology, 2022;129(11):1274 doi: 0.1016/j.ophtha.2022.08.013.

      ]. Ocular signs and symptoms may last for 1–2 months.
      Table 1Overall summary of cases reporting the presence of monkeypox virus in ocular sites.
      Case No. and referenceGenderAge

      (years)
      CountryDate

      of publication
      Ocular signs and symptomsCollection siteVirus detection method
      PCR = polymerase chain reaction; RT-PCR = real time polymerase chain reaction.
      Ocular Treatment and time to resolution
      1

      Benatti SV, et al., Ophthalmic manifestation of monkeypox infection. Lancet Infect Dis, 2022;22(9):1397 doi: 10.1016/S1473-3099(22)00504-7. Epub 2022 Jul 30.

      Male39ItalyJuly 29, 2022Conjunctivitis 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 vesiclesPCRNeomycin (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
      • Mazzotta V.
      • et al.
      Ocular involvement in monkeypox: description of an unusual presentation during the current outbreak.
      Male39August 13, 2022Red-eye; itchiness; conjunctival follicular reaction with small white vesicles on the nasal bulbar conjunctiva.Swabs of conjunctiva and eye secretionPCR
      3

      Scandale P, Raccagni AR, Nozza S, Unilateral blepharoconjunctivitis due to monkeypox virus infection. Ophthalmology, 2022;129(11):1274 doi: 0.1016/j.ophtha.2022.08.013.

      Male26ItalyAugust 17, 2022Multiple papular lesions in the right eyelid with progressive periorbital and conjunctival involvementSwabs of eyelid and conjunctivaRT-PCR, cell cultureInitially 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
      • Ly-Yang F.
      • et al.
      Conjunctivitis in an individual with monkeypox.
      Male35ItalyAugust 27, 2022Unilateral 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 swabRT-PCROcular papillae resolved in 3 days following the administration of a single intravenous dose of cidofovir (5 mg/kg).
      5
      • Cash-Goldwasser S.
      Ocular monkeypox—United States, July–September 2022.
      Male42September 7, 2022Left-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



      PCRSystemic 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
      • Meduri E.
      • Malclès A.
      • Kecik M.
      Conjunctivitis with monkeypox virus positive conjunctival swabs.
      Male20–29USAOctober 17, 2022Initially 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.
      Conjunctival

      Swab
      PCR; immuno-histochemistryIntravenous 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
      • Meduri E.
      • Malclès A.
      • Kecik M.
      Conjunctivitis with monkeypox virus positive conjunctival swabs.
      Male30–39USAOctober 17, 2022rashes with symptoms of redness, pain, and eyelid swelling on the right eye.Eye swabPCRInitially, 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.
      Figure thumbnail gr1
      Fig. 1Ocular 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.

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