Background

Acanthamoeba keratitis (AK) is a rare but serious eye infection caused by a microscopic organism called Acanthamoeba. This amoeba is commonly found in water sources, including tap water, swimming pools, hot tubs, and even contact lens solution. AK usually affects people who wear contact lenses, particularly those who use them improperly or do not follow proper hygiene practices.

When the amoeba comes into contact with the eye, it can penetrate the cornea and cause a range of symptoms, including eye pain, redness, blurred vision, sensitivity to light, and excessive tearing. AK is a serious condition that can cause permanent damage to the eye if left untreated.

Treatment typically involves the use of antifungal and antiprotozoal medications, as well as measures to improve eye hygiene and prevent reinfection. In severe cases, corneal transplant may be necessary to restore vision.

Epidemiology

The epidemiology of AK varies depending on the region and population studied. AK is a rare but serious eye infection that occurs more frequently in contact lens wearers than in non-wearers. Studies have shown that the incidence of AK among contact lens wearers ranges from 1 to 33 cases per million wearers per year, with higher rates reported in some countries, such as the United Kingdom and Singapore.

AK is also more common in people who use certain types of contact lenses, such as soft contact lenses, and those who do not follow proper hygiene practices. Other risk factors for AK include exposure to contaminated water, such as swimming or showering while wearing lenses, and trauma to the cornea.

While AK is a rare disease, its incidence appears to be increasing in some regions, possibly due to changes in contact lens use and hygiene practices. In addition, AK can be difficult to diagnose, and delays in diagnosis and treatment can lead to permanent vision loss.

Anatomy

Pathophysiology

Acanthamoeba keratitis (AK) occurs when the microscopic organism Acanthamoeba infects the cornea of the eye. The pathophysiology of AK involves several stages. First, the Acanthamoeba organism comes into contact with the cornea, typically through contaminated water or contact lens solution. The organism then penetrates the epithelial layer of the cornea and invades the stroma, the middle layer of the cornea.

Once inside the cornea, the Acanthamoeba organism begins to feed on the corneal tissue, leading to inflammation, tissue destruction, and eventually corneal ulceration. The inflammatory response can cause pain, redness, and sensitivity to light, while the tissue destruction can lead to vision loss and even blindness.

In addition to the direct effects of the organism on the cornea, Acanthamoeba can also produce toxins that contribute to tissue damage and inflammation. The immune response to the infection can also contribute to tissue damage and further inflammation. The pathophysiology of AK can be further complicated by delays in diagnosis and treatment, which can allow the infection to progress and cause more extensive damage to the cornea.

In severe cases, corneal transplant may be necessary to restore vision. Overall, the pathophysiology of AK involves a complex interplay between the Acanthamoeba organism, the immune system, and the cornea itself. Prompt diagnosis and treatment are essential to prevent serious complications and preserve vision.

Etiology

Acanthamoeba keratitis (AK) is caused by infection with Acanthamoeba, a free-living amoeba commonly found in the environment, including in soil, dust, and water sources such as swimming pools, hot tubs, and tap water. The infection typically occurs when Acanthamoeba comes into contact with the cornea of the eye, most commonly in people who wear contact lenses.

Contact lens wearers may be at increased risk of AK if they do not follow proper lens hygiene practices, such as failing to disinfect lenses properly or exposing lenses to contaminated water. Other risk factors for AK include exposure to contaminated water, such as when swimming or showering while wearing lenses, and trauma to the cornea, such as from a foreign body or a scratch. While Acanthamoeba is the primary cause of AK, other microorganisms such as bacteria and fungi may also contribute to the infection in some cases.

In addition, certain factors, such as a weakened immune system or the use of corticosteroid eye drops, may increase the risk of AK or complicate its course. Overall, the etiology of AK is multifactorial, involving the presence of Acanthamoeba in the environment, contact lens wear and hygiene practices, and other individual and environmental risk factors. Preventing AK requires good hygiene practices and avoiding exposure to contaminated water, while prompt diagnosis and treatment are essential to prevent serious complications.

Genetics

Prognostic Factors

The prognosis of Acanthamoeba keratitis (AK) can vary depending on the severity and duration of the infection, as well as the promptness of diagnosis and initiation of treatment. In general, early diagnosis and treatment can lead to a more favorable prognosis, while delayed or inadequate treatment can lead to more severe complications and poorer outcomes.

With appropriate treatment, many cases of AK can be resolved within several weeks to months, although some people may experience long-term visual impairment or other complications, such as corneal scarring or recurrent infections. In some cases, surgical intervention may be necessary to remove damaged or infected tissue from the cornea.

Factors that may impact the prognosis of AK include the following:

• Severity of the infection: The extent and severity of the infection can influence the likelihood of successful treatment and recovery.
• Duration of the infection: Prolonged infection can lead to more severe complications and poorer outcomes.
• Promptness of diagnosis and treatment: Early diagnosis and treatment are critical for a favorable prognosis.
• Underlying health conditions: People with compromised immune systems or other underlying health conditions may be at higher risk for more severe or recurrent infections.
• Adherence to treatment: Compliance with medication and other treatment regimens is important for successful treatment outcomes.

Clinical History

Clinical history

The clinical history of Acanthamoeba keratitis (AK) typically involves a gradual onset of symptoms, which may be present for several weeks or even months before the diagnosis is made. The following are common clinical features of AK:

• Eye pain: AK often causes severe eye pain, which may be described as a burning, stinging, or sharp sensation.
• Redness: The eye may appear red and inflamed due to the immune response to the infection.
• Photophobia: Sensitivity to light is common in AK, and exposure to bright light can exacerbate symptoms.
• Blurred vision: AK can cause blurred or distorted vision, particularly in the later stages of the infection.
• Foreign body sensation: Some people with AK may feel as though there is a foreign body, such as a grain of sand, in their eye.
• Contact lens wear: AK is more common in people who wear contact lenses, particularly those who do not follow proper lens hygiene practices.
• Exposure to contaminated water: People who have been exposed to contaminated water, such as when swimming or using tap water to rinse lenses, may be at increased risk of AK.

The clinical history of AK can be similar to other types of eye infections, which can make diagnosis challenging. However, the gradual onset of symptoms, presence of severe pain and photophobia, and history of contact lens wear or exposure to contaminated water can help to raise suspicion for AK. Prompt evaluation by an ophthalmologist is essential for accurate diagnosis and treatment.

Physical Examination

Physical examination

The physical examination of a patient with suspected Acanthamoeba keratitis (AK) typically involves a comprehensive eye exam performed by an ophthalmologist. The following are some of the key elements of a physical exam for AK:

• Visual acuity test: This test measures how well the patient can see at various distances and is an essential component of any eye exam.
• Slit-lamp exam: A slit-lamp is a specialized microscope that allows the ophthalmologist to examine the structures of the eye in detail. In AK, the ophthalmologist may observe corneal infiltrates (white or gray patches on the cornea), epithelial defects (areas where the outer layer of the cornea has been damaged), or radial keratoneuritis (inflammation of the corneal nerves).
• Tissue scrapings and cultures: The ophthalmologist may take a sample of the corneal tissue for analysis to confirm the diagnosis of AK. The sample may be examined under a microscope for the presence of Acanthamoeba or sent to a laboratory for culture.
• Sensitivity to light: The ophthalmologist will assess the patient’s sensitivity to light by shining a bright light into the eye.
• Eye movement: The ophthalmologist will evaluate the patient’s ability to move their eyes in different directions, which can be affected by inflammation or other eye conditions.
• Intraocular pressure: The ophthalmologist may measure the pressure inside the eye, which can be elevated in some cases of AK.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential diagnosis

The clinical presentation of Acanthamoeba keratitis (AK) can be similar to other types of eye infections, which can make it difficult to diagnose. The differential diagnosis of AK includes:

Bacterial keratitis: This is a common type of eye infection that can cause similar symptoms to AK, such as eye pain, redness, and sensitivity to light. Bacterial keratitis is typically treated with antibiotic eye drops.

Fungal keratitis: This is another type of eye infection that can cause similar symptoms to AK, particularly in people who wear contact lenses. Fungal keratitis is typically treated with antifungal medications.

Herpes simplex keratitis: This is a viral infection that can affect the cornea and cause similar symptoms to AK, including eye pain, redness, and sensitivity to light. Herpes simplex keratitis is typically treated with antiviral medications.

Allergic conjunctivitis: This is an allergic reaction that can cause eye redness, itching, and swelling, which can be mistaken for the symptoms of AK. Allergic conjunctivitis is typically treated with antihistamines and other allergy medications.

Dry eye syndrome: This is a chronic condition that can cause dryness, irritation, and redness of the eyes, which can be mistaken for the symptoms of AK. Dry eye syndrome is typically treated with artificial tears and other lubricating eye drops.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Diagnosis: Prompt and accurate diagnosis is crucial. A corneal scraping or biopsy may be performed to confirm the presence of Acanthamoeba. 

Medication: 

• Topical Antimicrobial Agents: The mainstay of treatment involves the use of topical medications, such as biguanide antiseptics (e.g., polyhexamethylene biguanide or PHMB), diamidines (e.g., propamidine isethionate), or azoles (e.g., ketoconazole). These medications are often prescribed in various combinations to enhance efficacy. 
• Oral Medications: In some cases, oral antifungal medications like voriconazole or itraconazole may be prescribed to complement the topical treatment. 

Frequency and Duration of Medication: Topical medications are typically applied hourly during waking hours, and the frequency can be adjusted based upon the severity of the infection. Treatment duration is often prolonged, spanning several weeks to months. 

Cycloplegics and Analgesics: Cycloplegic agents may be prescribed to alleviate pain and reduce ciliary spasm. Analgesic eye drops may be recommended to manage pain. 

Contact Lens Discontinuation: Individuals with Acanthamoeba keratitis are usually advised to discontinue the use of contact lenses during the course of treatment. 

Corneal Debridement: In some cases, therapeutic corneal debridement may be performed to remove infected tissue and improve the effectiveness of topical medications. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

non-pharmacological-treatment-of-acanthamoeba-keratitis

Lifestyle modifications: 

Contact Lens Hygiene: 

• Discontinuation of Contact Lenses: Patients are typically advised to discontinue the use of contact lenses during the treatment period. 
• Strict Hygiene Practices: If contact lens use is resumed, strict hygiene practices are emphasized. This includes thorough handwashing before handling lenses and using appropriate cleaning solutions. 

Eye Protection: 

• Avoidance of Water Exposure: Patients should avoid exposing their eyes to water, especially tap water, hot tubs, and swimming pools, as Acanthamoeba is commonly found in water sources. 
• Protective Eyewear: Consider wearing protective eyewear (goggles) when engaging in activities where water exposure is likely. 

Good Ocular Hygiene: 

• Avoid Eye Rubbing: Minimize eye rubbing, as this can potentially introduce contaminants to the eyes. 
• Proper Eye Care: Follow recommended eye care practices, including regular eye exams, to monitor eye health and detect any early signs of infection or other issues. 

Environmental Modifications: 

• Clean Living Spaces: Maintain clean living spaces to reduce the risk of environmental contamination. 
• Air Quality: Consider using air purifiers to maintain good air quality, especially if there are concerns about environmental allergens or contaminants. 

Nutrition and Overall Health: 

• Balanced Diet: Adopt a balanced and nutritious diet to support overall health, including eye health. 
• Stay Hydrated: Ensure proper hydration, as it contributes to overall well-being. 

Regular Follow-Up: 

• Adherence to Medical Advice: Adhere closely to the prescribed treatment plan, including the use of topical and oral medications as directed. 
• Regular Ophthalmic Check-ups: Attend regular follow-up appointments with the ophthalmologist for ongoing monitoring of eye health and to detect any signs of recurrence. 

Use of topical antimicrobial agents in the treatment of Acanthamoeba Keratitis

Biguanide Antiseptics: 

• Polyhexamethylene Biguanide (PHMB): PHMB is a commonly used biguanide antiseptic in the treatment of Acanthamoeba keratitis. It has broad-spectrum antimicrobial properties, targeting a variety of microorganisms, including Acanthamoeba. PHMB is often used in combination with other agents for enhanced efficacy. 

Diamidines: 

• Propamidine Isethionate: Propamidine isethionate is a diamidine compound with antiprotozoal activity. It is effective against Acanthamoeba and is used as a topical agent in the treatment of Acanthamoeba keratitis. Diamidines work by disrupting the cell membranes of the protozoa, leading to their destruction. 

Azoles: 

• Ketoconazole: Azoles, commonly known as antifungal agents, have shown efficacy against Acanthamoeba. Ketoconazole, an azole antifungal, has been used topically in the treatment of Acanthamoeba keratitis. Azoles work by inhibiting the ergosterol synthesis, an essential component of fungal and Acanthamoeba cell membranes. 

Administration of Topical Antimicrobial Agents: Topical antimicrobial agents are typically administered as eye drops at regular intervals throughout the day. The frequency of administration may vary based on the severity of the infection and the specific agent used. 

Combination Therapy: In many cases, a combination of these antimicrobial agents may be prescribed to enhance the efficacy and decrease the risk of resistance. Combination therapy is often tailored to the individual patient’s response and the characteristics of the infecting Acanthamoeba strain. 

Corneal Debridement: In some cases, therapeutic corneal debridement may be performed to remove infected tissue and improve the penetration of topical antimicrobial agents. 

Use of Topical Immunomodulator in the treatment of Acanthamoeba Keratitis

Oral antifungal medications, particularly voriconazole and itraconazole, are sometimes employed in the treatment of Acanthamoeba keratitis to complement topical antimicrobial therapy.  

• Voriconazole: Voriconazole is a broad-spectrum antifungal agent that inhibits the ergosterol synthesis, an essential component of fungal and Acanthamoeba cell membranes. It is administered orally in the form of tablets or liquid suspension. The dosage and duration of voriconazole therapy are determined on the severity of infection and the patient’s response to treatment. Close monitoring is necessary to assess for potential side effects and treatment efficacy. 
• Itraconazole: Itraconazole is an azole antifungal that also inhibits ergosterol synthesis. It is administered orally in the form of capsules. The dosage and duration are individualized based on the patient’s condition and treatment response. Regular monitoring is essential to evaluate the patient’s response and manage any adverse effects. 

Combination Therapy: Oral antifungal medications are often used in combination with topical antimicrobial agents to achieve a more comprehensive treatment approach. The choice between voriconazole and itraconazole, as well as the decision to use combination therapy, is based on the specific circumstances of the infection and the patient’s medical history. 

corneal transplantation in the treatment of Acanthamoeba Keratitis

Corneal transplantation, also known as keratoplasty, may be considered in cases of severe Acanthamoeba keratitis where the infection has caused significant corneal damage that cannot be managed with medications alone. Corneal transplantation involves replacing the damaged corneal tissue with a healthy donor cornea. 

• Indications for Corneal Transplantation: Corneal transplantation is considered when the Acanthamoeba infection leads to extensive corneal scarring, thinning, or perforation. The decision for transplantation is based on the severity of the infection, the extent of corneal damage, and the potential for visual improvement. 
• Types of Corneal Transplantation: 

• Penetrating Keratoplasty (PKP): In PKP, the entire cornea is replaced with a donor cornea. 
• Deep Anterior Lamellar Keratoplasty (DALK): DALK involves replacing the outer layers of the cornea while preserving the inner layers (endothelium). It may be preferred in cases where the infection has not reached the endothelium. 

• Timing of Transplantation: The timing of corneal transplantation is carefully considered. It may be performed after the infection is controlled with antimicrobial therapy. In some cases, therapeutic keratoplasty (combined removal of infected tissue and transplantation) may be considered. 
• Postoperative Care: Following corneal transplantation, patients require diligent postoperative care to monitor for the signs of infection and ensure proper healing. Topical and sometimes systemic medications may be continued postoperatively to prevent infection and rejection of the donor tissue. 
• Visual Rehabilitation: Visual recovery after corneal transplantation is a gradual process. Visual rehabilitation may involve the use of glasses or contact lenses. In some cases, additional procedures or adjustments may be needed to optimize visual outcomes. 

management-of-acanthamoeba-keratitis

Acute Phase: 

• Diagnosis: Prompt and accurate diagnosis is crucial. Acanthamoeba keratitis is diagnosed through a combination of clinical examination, corneal scrapings for microscopy and culture, and molecular diagnostic techniques. 
• Topical Antimicrobial Therapy: Initiate aggressive topical antimicrobial therapy to target Acanthamoeba. Commonly used agents include biguanide antiseptics (e.g., polyhexamethylene biguanide or PHMB), diamidines (e.g., propamidine isethionate), and azoles (e.g., ketoconazole). 
• Oral Antifungal Medications: In certain cases or when the infection is not responding adequately to topical therapy, oral antifungal medications such as voriconazole or itraconazole may be prescribed. 
• Pain Management: Manage pain and discomfort with analgesics, as Acanthamoeba keratitis can be associated with significant ocular pain. 
• Corneal Debridement: In some cases, therapeutic corneal debridement may be performed to remove infected tissue and improve the penetration of antimicrobial agents. 

Chronic Phase: 

• Topical Therapy Continuation: Continue topical antimicrobial therapy even as the infection begins to resolve. The duration may extend for several weeks to months. 
• Oral Antifungal Medications: They may be continued in the chronic phase, especially in cases with persistent or recurrent infections. 

• Corticosteroids: Topical corticosteroids may be introduced to control inflammation and minimize scarring. However, their use is cautious and typically initiated after the infection is under control. 
• Visual Rehabilitation: Address visual rehabilitation needs, which may involve glasses or contact lenses. Visual recovery is often a gradual process. 
• Corneal Transplantation: In cases of severe corneal damage, corneal transplantation (keratoplasty) may be considered in the chronic phase to restore visual function. This is often performed after the infection is controlled. 
• Long-Term Follow-Up: Long-term follow-up with the ophthalmologist is crucial to monitor for any signs of recurrence, manage complications, and ensure the ongoing health of the cornea. 

Medication

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References

Acanthamoeba keratitis – Clinical signs, differential diagnosis and treatment 

Acanthamoeba Keratitis – StatPearls