Mpox (monkeypox) is a zoonotic disease caused by the monkeypox virus (MPXV), an orthopoxvirus. It presents with symptoms similar to smallpox. It was first identified in 1958 in African monkeys transported to Denmark.
The name “monkeypox” is somewhat a misnomer. The natural reservoir is thought to be unidentified rodents (e.g., Gambian pouched rats, rope squirrels) 1).
MPXV has two clades: the Congo Basin (CB) clade and the West African (WA) clade. The CB clade has higher mortality and morbidity compared to the WA clade 1). Since May 2022, a global outbreak including non-endemic countries has occurred 1).
Ophthalmic complications are called monkeypox-related ophthalmic disease (MPXROD). It mainly affects the external eye (eyelids, conjunctiva, cornea). In past endemic regions, ocular complications were reported in 9–23% of cases, but in the 2022 outbreak, they were reported in less than 1%.
Both belong to the Orthopoxvirus genus, but there are important differences. The presence of lymphadenopathy in monkeypox is a key distinguishing feature from smallpox. Additionally, the fatality rate of monkeypox (about 10.6% for the Congo Basin clade and 3.6% for the West African clade) is lower than that of smallpox (about 30%). Smallpox was declared eradicated in 1980, but monkeypox is difficult to eradicate due to the existence of animal reservoirs.
The incubation period is usually 7–14 days (up to 3 weeks). Prodromal symptoms include fever, malaise, headache, and lymphadenopathy 2). Ocular symptoms include eye pain, redness, tearing, and decreased vision.
Skin lesions progress through stages: macules → papules → vesicles → pustules → scabs 2). The distribution is centrifugal, with dense clustering on the face and extremities. In the 2022 outbreak, the anogenital area was most commonly affected (73%).
Eyelids and Adnexa
Vesiculopustular lesions: Affect the eyelids in up to 25% of patients. They progress through stages: macules → papules → vesicles → pustules → scabs.
Eyelid edema: Appears with inflammation of surrounding soft tissues.
Preseptal cellulitis: May be accompanied by secondary bacterial infection.
Sequelae: May result in scarring or deformity of the eyelids.
Conjunctiva, Cornea, and Others
Conjunctivitis: Observed in about 20% of patients. Presents with follicular reaction, vesicular/papular conjunctival lesions, and pseudomembrane.
Keratitis: Ulcerative keratitis is reported in 3–4% of CB clade cases. Immune stromal keratitis and neurotrophic keratitis may also occur.
Anterior uveitis: Seven cases have been reported, mostly associated with corneal lesions.
Scleral lesions: Scleral injection associated with subconjunctival nodules has been reported in a few cases.
Severe cases may lead to corneal perforation, corneal scarring, secondary bacterial infection, and permanent visual impairment.
Serious systemic complications include encephalitis3), myocarditis/pericarditis4), and fetal death in the perinatal period5).
In past African outbreaks, ocular complications were reported at a relatively high frequency of 9–23%. However, in the 2022 global outbreak, they were reported at less than 1%. This difference may be due to clade differences (CB clade is more severe than WA clade), vaccination rates, healthcare access, and reporting systems.
MPXV is an enveloped double-stranded DNA virus2). Routes of transmission include broken skin, droplets, and body fluids. Sexual contact has also been confirmed as a route of transmission. Occupational infection via needlestick injury in healthcare workers has been reported6).
Known risk factors in endemic areas are as follows:
| Vaccine | Type | Administration |
|---|---|---|
| ACAM2000 | Replication-competent | Single dose by percutaneous scarification |
| JYNNEOS | Non-replicating | Two doses by subcutaneous injection |
JYNNEOS is a non-replicating vaccine that uses modified vaccinia virus Ankara (MVA) and can be safely used in immunocompromised patients 7). ACAM2000 uses a replicating vaccinia virus, so there is a risk of vaccinia infection 7).
The smallpox vaccine is about 85% effective against mpox. JYNNEOS is used for both pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in high-risk groups. Early vaccination after exposure can prevent disease onset or reduce severity 6)7).
Check for known contact with mpox cases, travel history to endemic or outbreak countries. Sexual history is also important.
Check for vesicles or pustules on the eyelids and periorbital area. Examine the conjunctiva, cornea, and sclera in detail with a slit lamp. Also assess for anterior uveitis.
| Differential Diagnosis | Key Differentiating Features |
|---|---|
| Chickenpox | Centered on trunk |
| Herpes simplex | Unilateral and recurrent |
| Herpes zoster | Distribution along dermatomes |
Other differential diagnoses include smallpox, molluscum contagiosum, syphilis, cowpox, and vaccinia. The presence or absence of lymphadenopathy characteristic of mpox is useful for distinguishing it from smallpox.
The course of mpox is usually self-limiting. Symptomatic treatment is the mainstay of therapy 1). Antiviral drugs are used in severe cases or in patients at high risk of severe disease.
Treatment for ocular symptoms is as follows:
Mild cases are managed primarily with artificial tears for lubrication and topical antibiotics to prevent secondary infection. Trifluridine eye drops have been used against related vaccinia virus and may be considered for MPXROD. Severe corneal lesions may require systemic antiviral drugs (e.g., tecovirimat). Corneal transplantation is necessary if corneal perforation occurs.
MPXV enters through broken skin, respiratory mucosa, or mucous membranes (eyes, nose, mouth)2). It causes primary viremia via the lymphatic system and progresses to systemic infection2).
NK cells play an important role in innate immunity2). NK cells are activated or inhibited through interaction with MHC class I molecules. They trigger inflammatory responses via production of IFN-γ and TNF-α, and activate T helper cells through dendritic cells2).
Skin pathology shows Guarnieri bodies characteristic of poxviruses within keratinocytes. Histological features include proliferation of basal keratinocytes, epidermal necrosis, spongiosis, pallor of keratinocytes, and inflammatory cell infiltration with vasculitis.
Routes of ocular entry include direct contact infection (self-inoculation via hands) or hematogenous dissemination from systemic infection. The mechanism of corneal lesions is presumed to involve both direct viral cytopathic effects and immune-mediated inflammatory responses, similar to smallpox.
Since the outbreak in 2022, research on mpox has progressed rapidly.
Evidence on the efficacy of tecovirimat is accumulating. In a case of occupational infection, the combination of post-exposure JYNNEOS vaccination and tecovirimat administration prevented systemic dissemination and limited the infection to a local site6).
A case of combined encephalitis and transverse myelitis as neurological complications of mpox has been reported, with improvement following treatment with tecovirimat, cidofovir, steroids, and plasma exchange3). Cardiovascular complications such as myocarditis and pericarditis have also been reported4).
Perinatal mpox infection carries a high risk of fetal death, highlighting the importance of infection management in pregnant women5).
In the ophthalmology field, evidence on the mechanism and optimal treatment of MPXROD remains limited. Future challenges include evaluating the efficacy of antiviral eye drops, elucidating the long-term prognosis of MPXROD, and establishing ophthalmic screening guidelines.
