Mpox-Related Ophthalmic Disease: A Rare Case Report

Introduction

Monkeypox virus (mpox), a double-stranded DNA virus belonging to the Orthopox genus, which includes the variola virus, vaccine virus, and cowpox virus, was first reported as a zoonotic infection transmitted from animals to humans in 1958, with the first human case being diagnosed in 1970. It was declared a pandemic by the World Health Network (WHN) on June 22, 2022, the disease mostly affecting men who-have-sex-with-men and people living with HIV (PLWHA). ^{1 –3} According to CDC 2022 outbreak global map, between January 1, 2022, and December 13, 2022, there have been documented 82,550 mpox cases worldwide, 46 cases in Romania, from which almost half (22 cases) in Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest. ⁴ Most diagnosed patients were mild cases, with discrete skin lesions, none or only mild ocular symptoms. Although in our clinic, there were two patients that needed ophthalmological examination and only one patient had an advanced stage of Mpox-related ophthalmic disease (mpoxROD) (severe pain, photophobia with ulcerative conjunctival and corneal lesions) associated with a severe form of confirmed mpox infection. The aim of this article is to aggregate from an ophthalmologic point of view what is presently known about mpoxROD and to present a particular case with severe ocular complications.

Background

The mpox virus can affect vulnerable anatomic sites, including the eyes, causing a mpoxROD, which seems to be rarer in the 2022 pandemic than in historical outbreaks. ⁵

The incubation period of mpox is typically 7–17 days, but may last up to 21 days. The rash begins with macular lesions, which then evolve to papules, vesicles, and pustules which often involve the periorbital and orbital skin, similar to a varicella-zoster rash (all mpox lesions are typically in the same stage), eventually affecting the conjunctiva and cornea. In addition, ophthalmologists should be aware of any new ocular complaints following confirmed mpox. ^1,6,7

The mpox virus may enter the eye via autoinoculation and cause multiple problems from mild lesions including conjunctivitis, blepharitis, keratitis, to severe ones such as corneal ulcers, corneal scarring, and rarely loss of vision. ⁷ Such symptoms should be recognized by health workers, particularly ophthalmologists, because it can be a vision-threatening condition that may require urgent and specific therapeutic management.

We suggest that ophthalmologists take into consideration mpox as a part of their differential diagnosis when they encounter cases presenting with ocular manifestations such as conjunctivitis, blepharitis, keratitis, or corneal lesions, in patients with a high index of clinical suspicion.

Complications of mpoxROD were mostly observed in unvaccinated individuals and PLWHA.

The most common consequences of ocular involvement of mpox infection are bacterial superinfection of corneal ulcerations, corneal scarring, and vision loss. All patients should be considered for urgent ophthalmologic evaluation and initiation of mpox-directed treatment.

Methods

The ophthalmologist evaluated the severity of ocular mpox infection with a slit lamp examination and dilated funduscopic examination, which was helpful for determine whether anterior segment structures (conjunctiva, cornea, iris) or posterior segment structures (retina, optic nerve, choroid) were involved.

Swabs from both skin and conjunctival lesions were collected to examine whether PCR values of ocular swabs correlate with infectivity similarly to skin lesions swabs. It is known that both lesions sites are acceptable specimens for real time-PCR testing to confirm the diagnostic of mpox and to determine the cycle threshold value (Ct). ⁸ We correlated Ct values for each specimen source separately (a Ct threshold [≥33] predicts a poor or noninfectious specimen). ⁹

All the investigations and procedures that have been used to write this article, had permission from the ethical board of “Dr. Victor Babes Clinical Hospital of infectious and Tropical Diseases” and for obtaining all the data and images for this case report, the patients gave full consent.

Case Report

We present a 41-year-old, white, bisexual, HIV positive male, who was admitted into our clinic with multiple skin and oral lesions, ocular pain, and photophobia (Fig. 1A, B). He was first examined in another emergency department, and given topical chloramphenicol, dexamethasone, and lubricants four times a day for a suspected conjunctivitis.

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FIG. 1.

Slit lamp examination of the right eye in a patient with HIV-associated immune compromise and ocular monkeypox, with conjunctivitis and nasal conjunctival ulcer, peripheral ulcerative keratitis earlier in the course of monkeypox illness (A), slit lamp examination of the left eye under blue cobalt light with fluorescein staining, revealing nasal conjunctival ulcer and peripheral keratitis earlier in the course of monkeypox illness (B). Photo: Malciolu-Nica M.A. Patient permission for the use of the clinical images was obtained.

After 4 days, he was referred to our clinic, in a deteriorated state, with multiple severe mucosal and skin papulo-nodular lesions, with conjunctival and peripheral corneal ulcers, similar to a peripheral ulcerative keratitis, and blepharoconjunctivitis that had evolved into a single white ulcer of about 6 mm with regular edges on the medial bulbar conjunctiva (Fig. 2A, B). The anterior chamber was clear, and there was no inflammatory reaction, and the fundoscopy was normal.

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FIG. 2.

Slit lamp examination under blue cobalt light with fluorescein staining of the right eye in a patient with HIV-associated immune compromise and ocular monkeypox, with conjunctivitis and temporal conjunctival lesion earlier in the course of monkeypox illness (A), slit lamp examination of the left eye under blue cobalt light with fluorescein staining revealing temporal conjunctival ulcer and peripheral ulcerative keratitis earlier in the course of monkeypox illness (B). Photo: Malciolu-Nica MA. Patient permission for the use of the clinical images was obtained.

Viral swabs of eye lesions returned PCR-positive for mpox (monkeypox DNA) with Ct values of 19.51. Laboratory tests were negative for hepatitis C virus a (enzyme-linked immunosorbent assay [ELISA]), Treponema pallidum (chemiluminescence assay), Chlamydia trachomatis DNA, and Neisseria gonorrhoeae (multiplex PCR).

We decided to stop the previous treatment and administer topical antivirals (acyclovir, since trifluridine—which shows some promise in mpoxROD—was unavailable), antibiotics (for prevention of bacterial superinfection of the corneal ulcers) five times a day, mydriatics (to reduce ciliary spasm and ocular pain) and lubricants hourly. The evolution was stationary after 2 weeks of treatment with a persistent corneal ulcer (central and peripheral) and conjunctival hyperemia (Fig. 3 A,B). Moreover, during the examinations, we noticed that the patient had a poor hygiene (not washing his hands and rubbing his eyes), thus the epithelial defects increased.

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FIG. 3.

Slit lamp examination of the right eye in a patient with HIV-associated immune compromise and ocular monkeypox, with perikeratic hyperemia and central corneal ulcerations 2 weeks after administration in our clinic (A), slit lamp examination of the left eye with conjunctivitis and peripheral ulcerative keratitis with central corneal erosion in the course of monkeypox illness (B). Photo: Malciolu-Nica MA. Patient permission for the use of the clinical images was obtained.

After 3 weeks of the aforementioned topical treatment and still persistent bilateral corneal ulcer, we added systemic Tecovirimat (time needed for the legal approval of the substance, previously unavailable in our country), and after 5 days of treatment, ocular discomfort and lesions started to decrease, Ct-value in swabs from eye lesions was 36.58 (showing decreased viral replication), but corneal scarring and peripheral pannus were already present (Fig. 4A, B).

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FIG. 4.

Slit lamp examination of the right eye in a patient with HIV-associated immune compromise and ocular monkeypox, with perikeratic hyperemia and discrete central corneal erosions (A), slit lamp examination of the left eye with mild conjunctivitis and mild central corneal erosion in the course of monkeypox illness (B). Photo: Malciolu-Nica MA. Patient permission for the use of the clinical images was obtained.

The most challenging part was communicating with the patient and making him understand the unpredictable evolution of the disease, despite giving him specific and maximal treatment (subject to availability) and the importance of the basic rules of hygiene. He was discharged from the hospital with no local pain or redness and with a visual acuity of 20/25 due to corneal scarring (Fig. 5 A,B).

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FIG. 5.

Slit lamp examination of the right eye in a patient with HIV-associated immune compromise and ocular monkeypox, with complete epithelization of corneal surface, and paracentral corneal scarring (A), slit lamp examination of the left eye with complete corneal surface epithelization with peripheral corneal scarring (B). Photo: Malciolu-Nica MA.

Although the information from this case report have some limitations, we can only generate hypotheses on the general outcome. First, the case described might not be representative of patients with ocular mpox or the frequency of these severe ocular manifestations. Second, the treatment was nonspecific at first, so the outcome of ocular lesions is unclear. However, the clinical findings in these patients were similar with descriptions of ocular mpox from other studies.

Discussions

This article presents the first reported case in Romania, of severe mpoxROD, with clinically relevant information for infectious disease doctors and especially for ophthalmologists.

This report highlights the severity of clinical manifestations of ocular mpox and the importance of prompt evaluation and treatment to prevent sight-threatening complications.

There is little research on these types of lesions in literature, Mpox being usually a self-limited disease with symptoms lasting from 2 to 4 weeks, ³ but historical data suggested that mpoxROD may be underestimated. ¹ While in other case studies, the majority of patients presented with mild skin lesions (rash or pustule) and ocular manifestations from mild conjunctivitis to severe eyelid and corneal ulcerations, ^1,6,10 our patient presented with severe face and body pustular and vesicular rash, penile necrosis, and ocular involvement with the threat of corneal perforation. Regardless of the initial nonspecific treatment, prolonged hospitalization, and poor collaboration from the patient, evolution was favorable.

There is no available topical ophthalmic antiviral agent specific for mpox infection, and the data suggest that generous topical lubrication remains an important component of supportive ocular therapy. ^1,11 Topical trifluridine for patients with ocular mpox is recommended in cases of keratitis, in consultation with an ophthalmologist or specialist in infectious diseases, although there is no available evidence of its efficacy in mpox cases specifically. ^1,8

Despite the fact that the patient presented with ocular lesions suggesting peripheral ulcerative keratitis for which the first line of treatment is topical steroids, after the positive PCR test for mpox, and confirming the diagnosis, the topical steroids were stopped to avoid corneal damage and prevent viral persistence.

Additionally, in patients with corneal disease, topical lubricants and antibiotics should be considered to prevent bacterial superinfection, which can be a vision-threatening complication of a corneal ulcer. There is limited data on the effectiveness of currently available therapeutics and on the outcomes of ocular mpox.

Tecovirimat (TPOXX) is often given for systemic therapy in collaboration with the infectious disease doctor. There is currently no pharmacokinetic data on the levels of Tecovirimat penetration on the surface or in the deeper structures of the eye, but in our case, under this treatment, the patient's ocular lesions resolved in days after the administration. ^6,12,13

The potential benefits of relatively simple therapies for ocular complications, such as generous topical lubrication or antibiotics, could be considered along with prompt systemic antiviral therapy. ^6,12,13

For patients with monkeypox that develop severe ocular signs or symptoms (e.g., vision changes or eye pain, itching, redness, swelling, or foreign body sensation) and lesions near the eye, we suggest that an urgent referral for ophthalmological evaluation and prompt antiviral therapy be taken in consideration.

Conclusions

Several strategies might help prevent ocular monkeypox and associated complications:

Prompt topical and systemic antiviral therapy in all mpox patients with severe ocular lesions.

In summary, ocular mpox is a potentially sight-threatening infection and should be treated urgently to prevent poor outcomes. mpox should be included in the differential diagnosis of patients with vesicular and pustular eye lesions, especially in the presence of epidemiological links or risk factors.