Introduction

Amid the ongoing global monkeypox outbreak, the World Health Organization’s Director-General has declared the disease a Public Health Emergency of International Concern [1]. This places urgency on the clinical need to understand the full spectrum of complications associated with the infection. While potential systemic complications like cardiovascular and dermatological components are already well-recognized, the ophthalmological complications of monkeypox remain poorly described in the literature [2, 3].

What is Monkeypox infection

Monkeypox is a zoonotic illness caused by the monkeypox virus, which is classified as an Orthopoxvirus. Most patients present with a systemic illness characterized by fever, myalgia, and a distinctive rash. Potential complications of monkeypox infection that have previously been reported in the literature include severe bacterial infection from unresolved skin lesions, pneumonia to bacterial superinfection (refer to Fig. 1). Currently, no exclusive treatment has been approved for monkeypox infection. Supportive care is generally advised for most patients with monkeypox infection who have intact immune systems with little to no systemic involvement. Regarding its implications for the wider community, the Monkeypox virus is undeniably an infection of global health significance. Monkeypox infections have been reported across several countries on different continents. In Africa, the Democratic Republic of Congo (DRC) remains one of the most severely affected nations, with approximately 22,000 reported cases attributed to monkeypox. Meanwhile, in North America, the United States has documented around 30,000 infections to date. [4, 5]. Despite such widespread incidence across various countries, most studies investigating the ophthalmological complications of monkeypox have been limited to small cohorts with short follow-up periods.

Fig. 1: Brief overview of monkeypox virus transmission and associated complications.
figure 1

a The reservoir for the monkeypox virus includes rodents, which can transmit the virus to other animals, such as monkeys. These animals, in turn, can spread the virus to humans through exposure to bodily fluids. Additionally, interspecies transmission between humans can occur in a similar manner, further facilitating the spread of the virus. b Known complications of monkeypox virus include a range of manifestations. These can be nonspecific, such as fever, and cutaneous, like mucocutaneous lesions. Gastrointestinal symptoms, including nausea and diarrhea, are also common, as well as pneumonia. Ophthalmological complications, such as keratitis and conjunctival lesions, have been reported, though the relationship with uveitis remains unclear.

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Implications for ophthalmologist

Previous case reports and meta-analyses have highlighted various ophthalmologic manifestations of monkeypox infection, including anterior uveitis, eyelid or corneal lesions. Notably, a meta-analysis by Rojas-Carbabali et al. identified corneal lesions as a common feature among monkeypox cases. Building on this, one of the largest studies to date on monkeypox-related ophthalmologic complications, conducted by Hsu et al., analyzed a cohort of 5449 patients across all age groups. It should also be noted that this study also utilized propensity score matching to compare the monkeypox cohort with a control group of similar characteristics, thereby controlling for various confounding factors. Key factors accounted for in the propensity score matching included age, sex, ethnicity, and comorbidities such as diabetes, cardiovascular diseases, and steroid use. Due to their thorough study design, which enhances the validity of their findings, it is important to highlight the findings of Hsu et al. in this discussion. Their findings revealed a significant association between monkeypox infection and uveitis (HR: 2.14, CI: 1.17–3.94), particularly anterior uveitis [6]. These findings align with previously reported case studies, which suggest an increased risk of ophthalmologic complications, including uveitis, among monkeypox patients. This raises critical concerns regarding the potential global ophthalmological implications of this infection. [7, 8] This association between monkeypox infection and uveitis has also been suggested in laboratory studies, which have demonstrated an attenuation of T-helper 2 cell activity among monkeypox patients, leading to elevated levels of interleukins such as IL-4 and IL-6, among other cytokines [9]. These inflammatory mediators may then ultimately contribute to the development of uveitis, a form of intraocular inflammatory disorder.

Another notable finding from Hsu et al. was that monkeypox patients with concomitant HIV infections were not at an increased risk for uveitis. This is particularly interesting, as the presence of such infections and an immunosuppressive state did not appear to elevate the risk of uveitis in these patients, despite previous reports indicating a higher risk of uveitis among individuals with HIV. However, future studies are needed to validate and further explore these findings.

However, it is troubling that current clinical guidelines, such as those issued by the European and Australian health authorities, make no mention of uveitis-related complications [2, 3]. Such lack of mention from among guidelines could be because current studies to date are limited either by their retrospective nature or relatively small sample sizes. Therefore, future research involving larger prospective studies is needed to validate these findings further.

However, in light of these emerging findings, we emphasize the importance of heightened vigilance among clinicians and ophthalmologists managing monkeypox patients, particularly for potential uveitis-related sequelae. Prompt detection and management of intraocular inflammation are crucial to minimizing diagnostic delays and improving visual outcomes in this at-risk population. Clinicians should monitor for key signs of intraocular inflammation, including anterior chamber cells, vitreous haze, and hypopyon. Moreover, a multidisciplinary approach is vital when managing suspected cases of monkeypox, given its potential to affect multiple systems beyond the eye. Collaboration between ophthalmologists, infectious disease specialists, and internal medicine physicians are essential to optimize patient outcomes and ensure comprehensive care.