Monkeypox is a smallpox-like virus that can cause dermatologic, mucosal, and even ophthalmic manifestations. As the number of cases of monkeypox increases, it is important that eyecare providers remember this virus in their list of differential diagnoses.
From eyelid and orbital lesions to conjunctivitis and corneal disease, it can mimic multiple common etiologies like Herpes zoster ophthalmicus, dry eye syndrome, blepharitis/blepharoconjunctivitis, or other types of viral conjunctivitis.
This article will offer an overview of the monkeypox virus and highlight possible ocular pathologies, along with diagnosis protocol and treatment options.
Overview of the monkeypox virus
Epidemiology
Monkeypox is a double-stranded DNA virus that belongs to the Orthopoxvirus genus classification. In 1958 this zoonotic virus was reported as transferable from animals to humans, with the first actual human-to-human transmission not occurring until 1996 in the Democratic Republic of Congo. Initially, the primary route of transmission was through direct contact with men who had sex with other men.
However, it is now known that transmission of the virus also occurs through respiratory particles and any direct contact with infected individuals. It is not limited to men who have sex with men.
The monkeypox virus re-emerged in early 2022, with over 9,000 cases in 56 countries. In June 2022, the World Health Network declared monkeypox a pandemic.1 According to the World Health Organization, the mortality rate due to monkeypox is 0.03% globally.2
Clinical characteristics
Symptoms of the infection usually occur within 3 weeks of exposure to the virus and last up to 4 weeks. The monkeypox virus usually starts with prodromal symptoms that are flu-like. This can include headache, fever, chills, fatigue, nausea, muscle ache, and back pain. It can also cause swollen lymph nodes. The characteristic monkeypox cutaneous and mucosal lesions will typically present 1 to 3 days after the first symptoms.3
“Early on, skin lesions can appear macular or papular, and more vesicular or pustular appearance later, finally scabbing over at the end of their course.”
Oral and/or mucosal lesions may present slightly earlier than dermatologic lesions. There tends to be a greater density of skin lesions on the face and extremities. The anogenital region is also commonly involved (upwards of 70% of cases).2
Possible ocular manifestations of monkeypox
Cutaneous symptoms
Monkeypox skin lesions can present in the orbital and periorbital areas in up to 25% of cases.4 This viral rash can resemble (and be misdiagnosed as) varicella-zoster vesicles, which makes taking a thorough case history of utmost importance. If lesions are present along or at the eyelid margin, this can cause temporary lid edema.1
Conjunctivitis
Conjunctivitis can be present with or without eyelid involvement. It has been proposed that skin lesions of the eyelid can autoinoculate the conjunctiva, thus spreading the infection. Monkeypox conjunctivitis can involve follicles and pseudo-membranes.2
Conjunctivitis is more prevalent among those who are not vaccinated and those with more pronounced general symptoms, such as fever or malaise. It was also more frequently noted in patients with oral sores, lymphadenopathy, and sore throat.
Some reports have identified conjunctivitis as a predictor of illness severity since those with conjunctivitis tended to have more severe cases.5
Corneal symptoms
Photophobia related to ocular surface disruption was present in up to 20% of patients. Corneal complications of monkeypox, such as severe keratitis (approximately 7% of cases) and ulceration with scarring, are possible albeit rare (about 4% of cases).1 Neurotrophic keratitis and immune stromal keratitis have also been noted in patients with monkeypox.2
Other symptoms
Frontal headaches behind the eyes, photophobia without an identifiable cause, and preauricular lymphadenopathy can also be present.6
Overall permanent vision loss from monkeypox-induced ocular disease ranges from 5 to 10%. Permanent vision loss can result from corneal infection and ulceration, seen in very severe cases.7
Transmission of monkeypox
Monkeypox can be contracted through direct, close contact with an infected person. This can occur through skin-to-skin contact with a monkeypox rash, scabs, or bodily fluids. Prolonged face-to-face contact, contact with respiratory secretions, hugging, kissing, and any sexual contact can also spread the monkeypox virus.
“Monkeypox can even be spread through contaminated surfaces such as bedding, towels, clothing, or any other non-disinfected items used by a person with monkeypox.”
The virus can be spread to a fetus from a pregnant person. It can also be contracted from an infected animal through bites, scratches, preparing raw meat, eating meat from an infected animal, or using products made from an infected animal. An infected person is contagious from when the symptoms start up until the rash has completely healed and a new layer of skin is present, which can take up to a month.3
Viral transmission of monkeypox
Viral transmission from patients with monkeypox conjunctivitis has been noted, but it remains unclear if the virus can be spread via conjunctival secretions by a person with monkeypox who does not have conjunctivitis. In a rat model, corneal and conjunctival secretions did contribute to viral transmission.
“All infected patients should be reminded to practice frequent and thorough handwashing and avoidance of eye rubbing.”
The likelihood of transmission through corneal grafting is not exactly known; therefore, the Eye Bank Association of America has precautionarily excluded donors who tested positive for monkeypox within 21 days, unexplained Orthopoxvirus positivity on testing, known exposure to a person with monkeypox, or a rash that is suspicious for monkeypox.2
Prevention of monkeypox
The best ways to prevent the spread of the monkeypox virus are maintaining good handwashing and hygiene habits as well as safe sexual and intimate practices. Avoid skin contact and areas where bodily fluids, especially scab secretions or particles from a person with the virus or a suspected case.
The CDC recommends personal protective equipment for healthcare providers treating patients with monkeypox. This includes a gown, gloves, eye protection with side coverage, and an N95 filter at minimum. Hospital-grade disinfectant with viral pathogen inactivation is recommended for cleaning.2
There are two vaccines available for monkeypox. Both JYNNEOS and ACAM2000 have been effective in preventing and reducing the severity of monkeypox viral infections. While they are actually smallpox vaccines, they have been up to 85% effective for monkeypox.
The sooner a patient can get vaccinated after a known exposure, the better. Getting vaccinated within 4 days of the known exposure will have the best outcome; however, the vaccine can still be given up to 14 days after the exposure with a reasonable likelihood of lessening the severity of illness. JYNNEOS is a newer vaccine and is considered to have less serious side effects than ACAM2000.3
Diagnosis of monkeypox
Skin lesions consistent with monkeypox with or without additional symptoms warrant testing. This involves swabbing the skin in the affected area, which is then sent to a lab. The exudate or crusting from the rash can also be sent as a specimen. If possible, the CDC recommends healthcare providers take samples from a few different areas or lesions.3
Conjunctival swabs have been shown to carry similar viral loads to those of skin lesions; however, at this time, cornea or conjunctiva are not recommended sample locations.2 Proper infection control and personal protective equipment are needed for the provider taking the sample. Specific guidance for collecting samples for providers can be found here.
The CDC has established three categories for patient classification:
- A suspect case is any patient showing characteristics consistent with monkeypox.
- A probable case is a patient who tests positive for orthopoxvirus on PCR, immunohistochemistry, electron microscopy, or IgM within 45 days of a skin rash but did not have any known exposure.
- A confirmed case is a patient with positive PCR or positive culture.2
If a positive monkeypox case is identified, it should be reported to the local or state health department for public health monitoring. The patient can be directed to fill out a CDC case report survey to gather more information. That form can be found here.
Treatment for monkeypox
Systemic treatment
Monkeypox is usually self-limiting. In otherwise healthy people, no treatment may be needed, or using over-the-counter pain relievers could be sufficient. For those with severe underlying health conditions or at high risk of severe disease, swelling or scarring treatment can be indicated. This includes anyone who is immunocompromised, has a severe skin condition, or has developed infections of the monkeypox rash.
Since monkeypox is similar to smallpox, antivirals targeting smallpox have effectively treated it. This includes the antiviral medication tecovirimat, which is FDA approved for treating smallpox in children and adults.
Cidofovir, brincidofovir and vaccinia immune globulin IV may also be used.2 There are no antivirals specific for monkeypox at this time, so the smallpox medications are considered “off-label.” The STOMP (Study of Tecovirimat for Human Monkeypox Virus) trial is currently underway to investigate the true safety and efficacy of tecovirimat for monkeypox.3
Ocular treatment
Viral keratitis associated with monkeypox has been treated with trifluridine, which has been effective in vitro against orthopoxvirus but has unknown efficacy against monkeypox.2
Corneal compromise should be treated with topical antibiotics to prevent secondary infection; similar protocols should be used with orbital and periorbital lesions to prevent superinfection.
Otherwise, a lubrication regimen can be used alone if photophobia or general irritation is present without evidence of severe ocular surface compromise.2
In conclusion
In suspected cases of monkeypox, patients should be counseled, referred for testing, and provided sources for reliable health information. Any patient with a known exposure should be monitored for 21 days for symptoms and consider vaccination if within the recommended window.
Severe sequelae are significantly more likely in unvaccinated people compared to vaccinated, at roughly 70% versus 30%, respectively.1 Patients should isolate themselves from other people (and pets) and avoid sharing any items that could be contaminated. Isolation should continue until skin lesions have scabbed over and new skin has replaced the area.2
By improving recognition, eyecare providers can provide appropriate counseling, initiate appropriate treatment, and mitigate transmission of the monkeypox virus.
