Mpox Virus and its ocular surface manifestations

Abstract

The Mpox virus (MPXV) is the causative agent of human Mpox disease - a debilitating rash illness similar to smallpox. Although Clade I MPXV has remained endemic to West and Central Africa, Clade II MPXV has been responsible for many outbreaks worldwide. The most recent outbreak in 2022 resulted from the rapid spread of a new clade of MPXV, classified into Clade IIb - a distinct lineage from the previously circulating viral strains. The rapid spread and increased severity of Mpox disease by the Clade IIb strain have raised the serious public health imperative of better understanding the host and viral determinants during MPXV infection. In addition to typical skin rashes, including in the periorbital area, MPXV causes moderate to severe ophthalmic manifestations - most commonly, ocular surface complications (e.g., keratitis, conjunctivitis, blepharitis). While ocular manifestations of Clade I Mpox within the Congo basin have been well-reported, global incidence trends of ocular Mpox cases by Clade IIb are still emerging. Given the demonstrated ability of all MPXV strains to auto-inoculate ocular tissue, alongside the enhanced transmissibility of the Clade IIb virus, there is an urgent need to elucidate the mechanisms by which MPXV causes ocular anomalies. In this review, we discuss the viral and genomic structures of MPXV, the epidemiology, and pathology of systemic and ocular Mpox, as well as potential prophylactic and therapeutic interventions.

Keywords: Cidofovir; Monkeypox; Mpox; Ocular; Ophthalmic; Orthopoxvirus; Tecovirimat (TPOXX).

Figure 1.. Global Transmission of Mpox.

A) A graphic history of MPXV spread. B) A color map recording the case counts of the 2022 MPXV outbreak. Case counts acquired from the United States Centers for Disease Control and Prevention, 2022–2023 Global Map & Case Count (last updated March 5, 2024). Grey = no data. Images created with BioRender.

Figure 1.. Global Transmission of Mpox.

A) A graphic history of MPXV spread. B) A color map recording the case counts of the 2022 MPXV outbreak. Case counts acquired from the United States Centers for Disease Control and Prevention, 2022–2023 Global Map & Case Count (last updated March 5, 2024). Grey = no data. Images created with BioRender.

Figure 2.. Various Replication Stages of Mpox Virus.

Two major pathways exist for MPXV entry and egress steps based on the two major circulating viral particle types. Internal mature virions (IMVs) are unenveloped viruses that enter via micropinocytosis and exit via cell lysis. Extracellular enveloped virions (EEVs) enter the cell via interactions between viral envelop surface proteins and host cell surface receptors. Following viral entry and genome replication, the viral particles are assembled in the cytoplasmic viral factories by the structural proteins encapsidating the viral genome, resulting in the formation of IMVs. These non-enveloped particles acquire membranes by budding through the Golgi network, forming intracellular enveloped viruses (IEVs), which serve as an intermediate to cell-associated enveloped viruses (CEV) and EEV particles. IEVs are released from the cell via endocytosis to become freely circulating EEVs. Image created with BioRender.

Figure 3.. Ocular Surface Complications of Mpox Pathologies.

(A) The clinical manifestations of MPXV include conjunctivitis, blepharitis, and keratitis. In addition, MPXV can cause secondary systemic infections in various organs via transmission through the nasolacrimal duct. Image created with BioRender. (B) Images of two ocular Mpox patients with unilateral conjunctivitis with corneal opacification. Images generously provided by Dr. Devina Bhamray-Sanchez et al. and IDCases.

Figure 3.. Ocular Surface Complications of Mpox Pathologies.

(A) The clinical manifestations of MPXV include conjunctivitis, blepharitis, and keratitis. In addition, MPXV can cause secondary systemic infections in various organs via transmission through the nasolacrimal duct. Image created with BioRender. (B) Images of two ocular Mpox patients with unilateral conjunctivitis with corneal opacification. Images generously provided by Dr. Devina Bhamray-Sanchez et al. and IDCases.

Figure 4.. Ophthalmic Findings of Ocular Mpox in Three Patients.

Clinical images of three ocular Mpox patients. (A-B) Patient 1 presented with (A) epithelial keratitis, which was stained with fluorescein (green), and (B) anterior uveitis with granulomatous keratic precipitates (indicated by red arrow). (C) Patient 2 developed keratitis with corneal edema and hypopyon. (D) Patient 3 presented with diffuse ocular hyperemia with keratitis and corneal opacities. Images generously provided by Dr. Luciana P.S. Finamor et al. and the International Journal of Infectious Diseases.

Figure 5.. Ocular Mpox Pathologies Evolve with Treatment.

Images of various ocular Mpox pathologies among five patients. (A-D) Patient 1 demonstrates (A) acute conjunctivitis and (B) geographic corneal ulcers that progressed to (C) severe corneal thinning after eight days, with (D) improvements in corneal lesions after one month of treatment with TPOXX. (E-H) Patient 2 presents with (E) eyelid papules and (F) membranous conjunctivitis with focal conjunctival erosions in the left eye that extended over time. (G) Twenty days after treatment with povidone-iodine and oxytetracycline plus polymyxin plus hydrocortisone ointment, the patient showed corneal involvement with semilunar corneal ulceration and Dellen, which (H) infiltrated over the next five days with stromal corneal edema. (I-K) Patient 3 shows (I) eyelid papules with (J) membranous and mucopurulent conjunctivitis and (K) conjunctival erosions that resolved after 28 days. (L-N) Patient 4 presents with (L) severe unilateral eyelid edema, (M) membranous conjunctivitis, and (N) demonstrated cellulitis with restriction of the medium rectus. (O-Q) Patient 5 presents with (O, P) peripheral corneal semilunar infiltrates, which progressed to (Q) corneal thinning with stromal edema. Images generously provided by Dr. José L. Blanco and Ophthamology¹³⁴7/5/2024 4:43:00 AM.