International meta-analysis highlights elevated ocular risk in Clade I Monkeypox

A large international study¹ published in the British Journal of Ophthalmology has extended the knowledge about monkeypox (mpox), which since 2024 has been considered by the World Health Organization (WHO) as a Public Health Emergency of International Concern.

The study reviewed the ocular manifestations of mpox and found higher proportions in clade I (Ia/Ib), a specific genetic lineage of the mpox virus that is more virulent than clade II (IIa/IIb), and greater disease severity in patients who have advanced HIV, according to first author Oscar Kallay, MD, who is from the Ophthalmology Department, Centre Médical de l’Alliance, Braine-l’Alleud, Walloon Brabant, Belgium.

Clade I has an estimated case fatality ratio of 10.6%, compared with 1% to 3.6% for clade II.²

Within the previous 5 months, the WHO reported substantial global transmission of the virus, with 43,000 confirmed cases in Africa alone in the previous 12 months, followed by the Democratic Republic of the Congo with 22,222, Uganda with 7,979, and Sierra Leone with 5,245, the most affected countries. More current data are available on the WHO Global Mpox Dashboard and in situation reports.^3-5

In addition to the skin and systemic features of mpox that include fever, rash, and lymphadenopathy, mpox can cause substantial morbidity and visual impairment.⁶ “Ocular involvement may result from direct viral invasion or immune-mediated mechanisms, ranging from mild conjunctivitis and blepharitis to keratitis, which can cause corneal scarring and vision loss if untreated, in patients with, or who have had, mpox.⁷ In severe cases, these complications may culminate in permanent visual disability, with major implications for patients affected, health systems, and communities,”⁸ according to Dr Kallay and colleagues.

Prior to their study, they explained that no study had quantified the global burden of the virus or examined clade-specific and region-specific differences in ocular outcomes, and they specifically wanted to determine the proportion of ocular manifestations among mpox cases, clade-specific variations, HIV-related risks, and the influence of the healthcare infrastructure.

They carried out an umbrella review and meta-analysis that included identifying studies that mentioned ophthalmic manifestations in PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from inception to September 2025.

What did the review and meta-analysis reveal?

Dr Kallay and colleagues identified 5 systematic reviews that included a total of 36 primary studies and 28,139 patients.

The primary findings were as follows. “The pooled proportion of conjunctivitis was 8.9% (95% confidence interval 4.8 to 13.9), highest in clade I (21.9%) and lowest in clade IIb (2.7%). Keratitis (1.5%), eyelid lesions (3.3%), conjunctival lesions (8.4%), and corneal ulceration (3.3%) varied by clade. Visual impairment occurred in 4.5% overall; unilateral (0.9%) and bilateral (0.4%) blindness were reported only with clade I. Across reviews, people living with advanced HIV experienced disproportionately higher rates of severe and persistent ocular complications than HIV-negative individuals,” the investigators reported.

The study findings emphasized that ocular disease associated with the mpox virus can cause substantial and potentially preventable visual disability. This recognition is especially important in areas of the world with limited resources.

They emphasized the necessity of including ocular health in the “mpox preparedness and response,” including early recognition and referral, integrated HIV-mpox services, and assured access to vaccines and antivirals. The priorities should focus on children and immunocompromised populations in resource-limited settings, and future research should address clade-specific risks, long-term sequelae, and interactions with comorbidities such as HIV,” the authors concluded.

The study findings support enhanced ophthalmic surveillance in clade I-endemic regions, integration of HIV and mpox services to address syndemic risk, and incorporation of eye health into outbreak preparedness, vaccination strategies, and clinical care pathways.

References

1. Kallay O, Ji L, Uthman OA, et al. Clade-specific ophthalmic manifestations of mpox: an umbrella review and meta-analysis of systematic reviews. Br J Ophthalmol. 2025;published online on 30 December. doi: 10.1136/bjo-2025-328294

2. Beer EM, Rao VB. A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl Trop Dis. 2019;13:e0007791. doi:10.1371/journal.pntd.0007791

3. World Health Organization. Global Mpox dashboard. 2025.

4. World Health Organization. Mpox situation reports. 2025.

5. World Health Organization. Mpox: multi-country external situation report no. 57. Geneva World Health Organization; 2025.

6. Abdelaal A, Reda A, Hassan AR, et al. Monkeypox-associated manifestations and complications involving the eye: a systematic review and meta-analysis of previous and current outbreaks. Asia Pac J Ophthalmol (Phila). 2023;12:326–37. doi:10.1097/APO.0000000000000608

7. Abdelaal A, Serhan HA, Mahmoud MA, et al. Ophthalmic manifestations of monkeypox virus. Eye (Lond). 2023;37:383–5. doi:10.1038/s41433-022-02195-z

8. Chenchula S, Ghanta MK, Amerneni KC, et al. A systematic review to identify novel clinical characteristics of monkeypox virus infection and therapeutic and preventive strategies to combat the virus. Arch Virol. 2023;168:195. doi:10.1007/s00705-023-05808-4