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Mpox and the Eye: Understanding the Risks and Impact on Ocular Health

Wed, 15 Jan 2025 00:55:51 GMT

Mpox and the Eye: Understanding the Risks and Impact on Ocular Health

The global outbreak of mpox (formerly known as monkeypox) has emerged as a significant public health challenge. The World Health Organization (WHO) Director-General, Dr. Tedros Adhanom Ghebreyesus, declared mpox a “public health emergency of international concern” (PHEIC) twice, first in May 2022 and again in August 2024. As this viral disease continues to spread, understanding its implications, particularly concerning ocular health, is crucial. This article provides a comprehensive overview of mpox, its ocular manifestations, and what eye care professionals and high-risk groups need to know to effectively manage and prevent its spread.

Understanding mpox and High-Risk Groups

Mpox is a viral zoonosis caused by the mpox virus (MPXV), a double-stranded DNA virus of the orthopoxvirus genus. While its natural host remains unknown, various animals can contract the virus. Historically confined to parts of Central and Western Africa, the 2022 outbreak saw cases emerge globally, prompting the WHO to declare it a “public health emergency of international concern.” As the virus continues to spread, it is important to understand its potential impact on various aspects of health, including ocular health, and to identify who is most at risk.

Historical Timeline of mpox

– 1958: Mpox virus first discovered in research monkeys in Denmark.

– 1970: First reported human case in a 9-month-old boy in the Democratic Republic of the Congo (DRC).

– 1980: Eradication of Smallpox and cessation of global Smallpox vaccination.

– 1980s-1990s: Gradual emergence of mpox in central, east, and west Africa.

– 2003: Outbreak in the United States linked to imported wild animals (Clade II).

– 2005-present: Thousands of cases reported annually in the DRC.

– 2017: Re-emergence of mpox in Nigeria, leading to ongoing local transmission and international travel-related cases.

– 2022: Global outbreak, primarily affecting non-endemic countries.

High-Risk Groups for Mpox Transmission

Men who have sex with men (MSM): Currently the most affected group in the 2022 and 2024 outbreaks, with close skin-to-skin contact during sexual activity being a primary transmission route. Unfortunately, there may be stigma and discrimination against infected individuals because of this.

Healthcare workers: Especially those in direct contact with mpox patients or handling potentially contaminated materials, including doctors, nurses, laboratory technicians, and cleaning staff in healthcare settings.

Veterinarians and animal handlers: Those working with animals that may carry the virus, particularly in endemic regions of Africa.

Close contacts of infected individuals: Family members, roommates, or others in close physical proximity to someone with Mpox.

Immunocompromised individuals: People with weakened immune systems due to conditions like HIV/AIDS, cancer, or certain medications that cause immune dysfunction. They are at higher risk of severe disease if infected, and deaths have occurred in this group.

Pregnant women and young children: May be at higher risk of severe disease, though data is limited.

Individuals who have traveled to endemic areas: Those who have recently been to regions where Mpox is common, particularly parts of Central and West Africa.

Laboratory workers: Those handling mpox samples or conducting research on the virus.

Prevention strategies should focus on these high-risk groups, including targeted vaccination campaigns, enhanced surveillance, and directed public health messaging. The virus is classified into two distinct genetic “clades”: Clade I (formerly known as the Congo Basin clade) and Clade II (formerly the West African clade). The current global outbreak is primarily associated with Clade II, which is generally considered less severe than Clade I.

Mpox typically presents with fever, intense headache, muscle aches, and a characteristic rash that progresses from macules to papules, vesicles, pustules, and finally scabs. While mpox is generally self-limiting, it can lead to severe complications, particularly in immunocompromised individuals and children.

Ocular Manifestations of Mpox

As mpox continues to spread, it’s becoming increasingly clear that the virus can affect various parts of the body, including the eyes. Understanding these ocular manifestations is important for early detection, proper management, and prevention of vision-threatening complications. Approximately 20-30% of infected individuals will manifest ocular signs and symptoms. Here are the key ocular symptoms associated with mpox:

Periorbital and Orbital Rash: The most common ocular symptom of mpox is the characteristic rash around the eyes. This can manifest as small, raised bumps or fluid-filled blisters in the periorbital (around the eye) and orbital areas. In some cases, up to 25% of patients with mpox may develop these rashes in the ocular region.

Eyelid Involvement: MPXV can affect the eyelids, causing swelling, redness, and the formation of small vesicles or pustules on the eyelid margins. This can be uncomfortable and may interfere with normal eyelid function.

Conjunctivitis: Inflammation of the conjunctiva (the clear membrane covering the white part of the eye and inner surface of the eyelid) is a common ocular manifestation of mpox. Conjunctivitis due to MPXV infection can present in various forms, including conjunctival ulcers, disseminated blistering or papular conjunctival lesions, conjunctival follicular reactions, and pseudomembranous or subconjunctival nodules. Some studies have reported that up to 23% of mpox patients may develop conjunctivitis. Interestingly, patients with conjunctivitis often report more frequent systemic symptoms such as nausea, chills, sweats, mouth ulcers, sore throats, fatigue, and lymphadenopathy.

Keratitis and Corneal Ulceration: While less common, corneal involvement is arguably the most severe ocular complication of mpox. Keratitis (inflammation of the cornea) and corneal ulceration can lead to permanent vision loss and corneal scarring if not promptly treated. Studies have reported corneal infections in about 3-7% of mpox cases. The severity can range from mild corneal pitting to severe ulceration and potential blindness.

Other Potential Ocular Complications: While not yet reported in mpox cases, eye care professionals should be aware that other poxviruses have been associated with conditions such as retinitis, chorioretinitis, optic neuritis, and extraocular muscle palsy. These potential complications underscore the importance of comprehensive eye examinations in mpox patients.

Diagnosis and Detection of MPXV in Ocular Secretions

Accurate diagnosis of mpox, especially in cases with ocular involvement, is vital for proper management and prevention of transmission. The gold standard for confirming MPXV infection is polymerase chain reaction (PCR) testing of various specimens, including those from ocular sources. For patients presenting with eye symptoms, ophthalmologists can collect conjunctival swabs or samples of eyelid lesion fluid for PCR testing. This method allows for precise analysis of even small amounts of ocular samples.

Importantly, studies have shown that MPXV can be detected in conjunctival swabs and even isolated in cell culture, indicating the potential for ocular transmission of the virus. One case report described a patient whose viral load in conjunctival and ocular secretions was similar to that in cutaneous lesions. This finding highlights the importance of appropriate personal protective measures for healthcare workers during ophthalmic examinations of suspected or confirmed mpox cases.

Treatment Approaches for Mpox Eye Infections

Currently, there is no standard treatment specifically approved for mpox. Most cases are mild and self-limiting, with management focusing on supportive care and symptom relief. However, for severe cases or in immunocompromised patients, several antiviral treatments, originally developed for Smallpox, may be considered:

Tecovirimat (Tpoxx): This antiviral drug, developed for smallpox treatment, has shown effectiveness against various orthopoxviruses, including MPXV. It is licensed for use in mpox, smallpox and cowpox by the European Medicines Agency. However, recent evidence on its effectiveness has been ambiguous and the FDA has not yet approved it for treatment of patients. Infected patients may still be able to access it through the STOMP trial.

Cidofovir and Brincidofovir: These antivirals have shown promise in animal studies and may be considered for severe cases.

Vaccinia Immune Globulin (VIG): This antibody preparation may be used in certain cases, although it’s contraindicated for isolated vaccinia keratitis.

For ocular symptoms, treatment approaches may include:

– Lubricating eye drops to prevent corneal dryness and promote healing.

– Antibiotic eye drops to prevent secondary bacterial infections (if indicated).

– Careful monitoring of corneal health to detect and manage any ulceration early.

– Topical trifluoridine has been used anecdotally but its efficacy has not been established.

It is important to note that the use of steroid eye drops in mpox patients with ocular involvement is controversial. Some reports suggest that steroids may prolong viral shedding and potentially worsen outcomes. Therefore, their use should be carefully considered and monitored by an eye care professional.

Vaccination and Its Impact on Ocular Mpox

While there’s no specific vaccine for mpox, smallpox vaccines have shown cross-protection against MPXV infection. Two vaccines are currently available for mpox prevention:

JYNNEOS (also known as MVA-BN, Imvamune, or Imvanex): This is a third generation, modified, attenuated vaccine that has been licensed in the US, Europe, and Canada. It is considered the primary vaccine for Mpox prevention in the current outbreak.

ACAM2000: This is an older smallpox vaccine that may provide some protection against Mpox but carries a higher risk of side effects.

Vaccination appears to be effective in reducing the risk of ocular complications from mpox. One study found that only 7% of smallpox-vaccinated individuals developed conjunctivitis and blepharitis from mpox, compared to 30% of unvaccinated individuals. Vaccine strains can occasionally cause unintended infections, including ocular complications. Healthcare workers, especially those at high risk of exposure to MPXV, are recommended to consider vaccination.

Preventing Nosocomial Infections in Eye Care Settings

Given the potential for MPXV transmission through close contact and through ocular secretions such as tear fluid, implementing strict infection control measures in eye care settings is important. Here are some key recommendations from the Centers for Disease Control (CDC):

For Patients:

– Practice regular hand hygiene.

– Avoid touching or rubbing eyes, especially if skin lesions are present.

– Discontinue contact lens use during active infection.

For Eye Care Professionals:

– Use appropriate personal protective equipment (PPE), including respiratory protection, when examining suspected or confirmed mpox cases.

– Thoroughly disinfect all reusable ophthalmic equipment (e.g., slit lamps, ophthalmic lenses) according to local infection control guidelines.

– Consider vaccination if at high risk of exposure to MPXV.

For Healthcare Facilities:

– Implement screening protocols to identify potential Mpox cases before they enter the general waiting area.

– Ensure proper isolation procedures for suspected or confirmed cases.

– Provide training to staff on Mpox recognition, PPE use, and infection control measures.

Special Considerations for High-Risk Groups

Each high-risk group requires specific precautions and considerations. For example:

– MSM should be aware of symptoms and consider temporary changes in sexual practices during outbreaks, including the use of condoms. Participate in vaccination programs if eligible.

– Healthcare workers should strictly adhere to infection control protocols, use appropriate PPE, especially when examining patients’ eyes, and consider pre-exposure vaccination.

– Immunocompromised individuals should be extra vigilant about symptoms and seek medical attention early. Discuss preventive strategies with healthcare providers and consider vaccination, weighing potential benefits and risks.

– Pregnant women and young children should exercise caution and avoid close contact with suspected or confirmed cases. Consult healthcare providers about risk mitigation strategies.

– Travelers to endemic areas should be aware of the risk and take preventive measures. Consider vaccination before travel if recommended.

Conclusion

The current mpox outbreak serves as a reminder of the ever-present threat of emerging infectious diseases and their potential impact on various aspects of health, including ocular health.

As eye care professionals and members of the public, staying informed and vigilant is crucial in effectively managing and preventing the spread of mpox. Ongoing research and collaboration between healthcare specialties will be vital in developing more effective prevention, diagnosis, and treatment strategies.

@floridalionseyeclinic and #floridalionseyeclinic

Avastin in Ophthalmology: A Revolutionary Journey from Cancer Treatment to Saving Sight

Fri, 15 Mar 2024 00:58:15 GMT

Avastin in Ophthalmology: A Revolutionary Journey from Cancer Treatment to Saving Sight

When I was training as an ophthalmology resident in the 1990s, I remember seeing countless patients losing their vision due to a condition called age-related macular degeneration (AMD). Many of these patients developed a form of AMD known as “wet” AMD, characterized by the growth of new blood vessels underneath the retina that leaked fluid and sometimes bled suddenly, leading to catastrophic central vision loss.

Patients often found they could not recognize faces, read, or even tell the time on their watch. At the time, treatments were limited. Photodynamic therapy (PDT) was available but expensive, and I had to watch helplessly as many people went blind.

The Breakthrough: Avastin

In response to the devastating effects of AMD, pharmaceutical companies worked diligently to find a solution. One treatment that has since revolutionized ophthalmology is Avastin (bevacizumab). Originally developed as a treatment for colon cancer, Avastin has found critical applications in eye care, particularly for conditions involving abnormal blood vessel growth.

What is Avastin?

Avastin is part of a class of drugs known as anti-VEGF agents. VEGF stands for Vascular Endothelial Growth Factor , a protein produced by oxygen-deprived (ischemic) tissue that stimulates the growth of new blood vessels. The “mab” in bevacizumab indicates that it was initially derived from mouse antibodies.

While the production of VEGF is crucial for normal bodily functions, excessive VEGF can lead to abnormal blood vessel growth, which is a hallmark of several eye conditions, including wet AMD and diabetic retinopathy.

Mechanism of Action

Developed by Genentech (now part of Roche ), Avastin works by inhibiting VEGF. It binds irreversibly to the protein, slowing or halting the growth of new blood vessels. Interestingly, its effectiveness in treating eye conditions was discovered accidentally by ophthalmologists at the Bascom Palmer Eye Institute in Miami, Florida.

Avastin’s Journey from Cancer to Eye Care

Initially, Avastin was approved by the FDA in 2004 for treating metastatic colorectal cancer. It worked by inhibiting angiogenesis – the formation of new blood vessels – depriving tumors of the nutrients and oxygen they need to grow. Clinical trials proved its effectiveness in combination with chemotherapy for various cancers, including lung, breast, kidney, and brain cancers.

In 2005, ophthalmologists realized that the same mechanism could benefit patients with eye conditions involving abnormal blood vessel growth. In these conditions, VEGF overproduction leads to leaky blood vessels in the retina, causing fluid accumulation, bleeding, and vision loss. Avastin reduces this fluid, controls inflammation, and halts the growth of abnormal vessels.

How is Avastin Administered?

Avastin is delivered via an intravitreal injection – a small amount of the drug is injected directly into the vitreous humor (the jelly-like substance filling most of the eyeball).

Eye Conditions Treated with Avastin

Avastin has shown effectiveness in managing several sight-threatening conditions:

1. Age-Related Macular Degeneration (Wet AMD)

Wet AMD involves abnormal blood vessel growth under the retina, causing fluid leakage and rapid vision loss. Avastin helps reduce these abnormal vessels and fluid buildup, preserving central vision.

2. Diabetic Retinopathy and Diabetic Macular Edema

Diabetic retinopathy damages retinal blood vessels due to diabetes. In advanced stages, fluid leaks into the macula (diabetic macular edema), impairing central vision. Avastin reduces this fluid and helps manage the disease.

3. Retinal Vein Occlusion

This condition occurs when a major retinal vein is blocked, causing widespread damage and fluid leakage. Avastin reduces macular edema associated with both branch and central retinal vein occlusions.

4. Neovascular Glaucoma

In this rare form of glaucoma, abnormal blood vessels grow on the iris, blocking drainage channels and increasing eye pressure. Avastin helps reduce vessel growth, giving surgeons time to perform laser treatment (PRP).

5. Retinopathy of Prematurity (ROP)

ROP affects premature infants and involves abnormal retinal blood vessel growth. Avastin can be used as an initial treatment until laser therapy (PRP) can be performed.

Benefits of Avastin

Effectiveness: Studies, including a 2011 New England Journal of Medicine study, found Avastin as effective as the more expensive drug Lucentis for AMD treatment.

Cost-Effectiveness: Avastin is significantly more affordable than other anti-VEGF medications, making it accessible to more patients, especially in resource-limited healthcare systems.

Versatility: Avastin is effective for multiple eye conditions, making it a versatile tool for ophthalmologists.

Rapid Action: Many patients notice vision improvements within weeks of starting treatment.

Potential Risks and Side Effects

While Avastin is generally safe, it does carry some risks:

1. Eye-Related Complications

Severe eye infection (endophthalmitis)

Retinal detachment

Temporary increase in eye pressure

Inflammation inside the eye

2. Systemic Side Effects

Increased risk of blood clots (especially in patients with a history of stroke or heart attack)

High blood pressure

Gastrointestinal perforations

3. Allergic Reactions

Though rare, allergic reactions can occur.

Off-Label Use Controversy

Avastin’s use in ophthalmology is “off-label” in many countries, including the United States. This means it’s FDA-approved for cancer but not specifically for eye treatments.

Proponents: Avastin’s efficacy and affordability make it indispensable for many patients.

Critics: Concerns remain about potential risks and lack of FDA oversight.

Compounding pharmacies prepare Avastin for ophthalmic use by dividing large cancer-treatment vials into smaller doses for eye injections.

Conclusion

Avastin’s transformation from a cancer drug to a revolutionary ophthalmic treatment showcases the power of innovation and adaptability in medicine. It provides an affordable, effective solution for sight-threatening conditions like wet AMD and diabetic retinopathy, helping millions preserve their vision.

While debates about off-label use persist, extensive clinical research supports Avastin’s role in eye care. As always, patients should consult qualified ophthalmologists to weigh potential risks and benefits.

Staying informed about treatments like Avastin empowers patients to take an active role in their eye health.

References

CATT Research Group (2011). Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration. New England Journal of Medicine, 364(20), 1897-1908.

CATT Research Group (2012). Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: Two-Year Results. Ophthalmology, 119(7), 1388-1398.

American Academy of Ophthalmology (2015). Policy Statement: Intraocular Use of Bevacizumab (Avastin).

Avery, R. L., et al. (2006). Intravitreal Bevacizumab (Avastin) in the Treatment of Proliferative Diabetic Retinopathy. Ophthalmology, 113(10), 1695-1705.e6.

Michels, S., et al. (2005). Intravitreal Bevacizumab (Avastin) for Persistent Neovascular Age-Related Macular Degeneration after Previous Treatment. Retina, 25(6), 713-720.

Duker, J., & Liang, M. (2024). Anti-VEGF Use in Ophthalmology. CRC Press.