Microsporidial Keratitis

What is Microsporidial Keratitis?

Keratitis is a condition where the cornea (the front part of the eye) becomes inflamed. This can often be caused by an injury or infection. There is a rare form of keratitis caused by microsporidia, which were originally referred to as “corneal nosematosis”. Microsporidia are parasites, similar to fungi, that infect various creatures including insects, birds, fish, and mammals — including humans. However, only seven types of such parasites are known to infect humans.

Microsporidia most commonly cause stomach infections, but they can also infect the eyes, brain, and muscles. Risk factors for eye infections include wearing contact lenses, eye injury or surgery, use of steroid eye drops, and exposure to soil, mud, unclean water, or hot springs. Eye infections from microsporidia often lead to keratoconjunctivitis (inflammation of the cornea and conjunctiva) or deep stromal keratitis (a more serious inflammation of the cornea).

The first case of microsporidia causing keratitis was reported in a child in Sri Lanka in 1973. Its incidence increased during the AIDS epidemic in the 1990s, especially among patients with weakened immune systems. Since the early 2000s, more and more healthy individuals have been affected, and most cases occur in Asia. The disease can be challenging to detect and manage due to its various symptoms and how it progresses.

The hardy microsporidia spores can survive in the environment for several months and still be infectious. Humans can get infected by eating, breathing in, or intimate contact with the spores. Although we are not certain how microsporidia infect the human eye, the most accepted theory suggests contact with contaminated water or direct trauma is a cause. For example, there have been reported cases following exposure to floodwaters.

To diagnose this infection, doctors use methods like optical microscopy and a test known as polymerase chain reaction (PCR) to confirm the presence of the parasite. Treatment often involves eye drops, but sometimes surgery may be necessary. If left untreated, this infection could cause serious vision loss and even a hole in the cornea. Without understanding the exact way this disease is transmitted, prevention is difficult. That’s why, if a patient has keratitis but the cause is unclear, doctors should consider if it could be microsporidia, especially if the patient has recently travelled to or returned from Asia, particularly in the rainy season.

What Causes Microsporidial Keratitis?

Microsporidia are small organisms that form spores and can be found almost anywhere in nature. Previously, they were grouped with protists, but recent research has shown they’re more like fungi. Among over 1700 species of Microsporidia, the ones that most commonly infect humans are Enterocytozoon bieneusi and certain types of Encephalitozoon. Two species in particular, Microsporidium and Vittaforma corneae, are usually the culprits when it comes to an eye condition called microspordial stromal keratitis. Meanwhile, Encephalitozoon is usually responsible for another eye condition called microspordial keratoconjunctivitis.

Interestingly, Microsporidia have features of both simple and complex organisms. They have basic genetic material and tiny structures that play a functional role, like the protozoa, but lack other structures, like energy-producing mitochondria. This mix of features has led scientists to categorize them now as fungi instead of protists.

Microsporidia are often found in water and can cause disease when people come into contact with water that’s been contaminated with them. For example, they can be in lakes, swamps, swimming pools, or spring water. In humans, they can affect various body parts like the digestive system, brain, eyes, muscles, bones, and lungs. Notably, they can cause various eye conditions, with keratoconjunctivitis and stromal keratitis being the most common.

Originally, it was thought that only people with weak immune systems, particularly those with HIV, could get microsporidial keratoconjunctivitis. However, recent research has shown that even people with healthy immune systems can get this condition. Interestingly, stromal keratitis is most commonly seen in people with strong immune systems.

Risk Factors and Frequency for Microsporidial Keratitis

Ocular microsporidiosis is an infection, uncommon but important to note, that has a noticeable impact specifically in Southeast and South Asian countries like Thailand, Taiwan, Singapore, and India. Studies show that nearly 20% of all cases of infective keratitis (a type of eye infection) in these areas are caused by microsporidia, especially during the rainy season.

Some advanced techniques, like different kinds of staining and a process called PCR, have helped with faster and more accurate detection of this disease. However, it’s believed that many cases are still unreported. This is likely due to two reasons: first, microsporidial keratoconjunctivitis (an eye condition similar to pink eye caused by microsporidia) often clears up on its own; second, thorough examinations aren’t always performed on everyone with conjunctivitis.

One study from South India examined over 10,000 individuals suffering from conjunctivitis, revealing that a good number of them were affected by microsporidial keratoconjunctivitis. Thus, large-scale studies are needed to uncover more about where this disease is common, how it varies from place to place, and how it spreads.

Signs and Symptoms of Microsporidial Keratitis

Examining the eye for microsporidial keratitis, an infection of the cornea, involves looking at various aspects. These include the patient’s eye symptoms, overall health history, and potential risk factors for getting the infection. Doctors typically assess a patient’s sight and use a special tool called a slit-lamp biomicroscope to closely examine the cornea. This helps to spot key signs such as sores in the skin layer of the eye, signs of infection in the deeper layers of the cornea, and inflammation of the conjunctiva. Doctors also look for other symptoms, such as redness in the eye, watery eyes, sensitivity to light and a feeling of having something in the eye.

When caused by the Encephalitozoon species, the infection usually stays in the corneal and conjunctival cells. Symptoms show up 1 to 2 weeks after being exposed and are often linked to contact with contaminated water or physical injury to the eye. This is more common in the rainy season. Other risk factors may include exposure to pool water, natural springs, infected soil, eye drops containing steroids, insect bites, interacting with pets, or water sports.

Patients often complain of symptoms like reddened eyes, decreased vision, tearing eyes, swollen eyelids, eye pain and feeling like there’s something in their eye. Usually, one eye is affected first, but the infection can spread to both eyes. This can happen at the same time or one after the other within a span of 1 week to 3 months. People with weaker immune systems are more likely to experience this double-eye infection, which appears in about 32% of healthy people too.

In medical examinations, details of the infection can include:

• Several small to big, raised patchy lesions on the corneal skin layer that look stuck-on
• Lesions take stain variably with fluorescein (a coloring agent)
• Lesions located on the edges, center, or all over the cornea
• Significant inflammation of the conjunctiva
• Typically no pus
• Possible inflammation and protein deposits in the anterior chamber of the eye

Sometimes the disease mimics an adenoviral eye infection, which may callback from multiple punctate formations under the skin layer. Throughout the illness, based on presenting features, it can be graded from 1 to 4:

• Grade 1: Pale, less than 10 lesions, mostly at the edges of the cornea
• Grade 2: Central lesions, 10 to 20 in number, elevated skin layer lesions
• Grade 3: 21 to 40 lesions
• Grade 4: Mostly peripheral lesions with infiltrates beneath the skin layer

If the disease progresses, it may lead to superficial punctate keratitis or surface damage to the cornea, which may finally result in scarring beneath the epithelium or skin layer. Unusual displays of microsporidial keratoconjunctivitis can show unique corneal patterns or conditions that look like other eye diseases.

Microsporidial stromal keratitis impacts the corneal stroma, including the keratocytes, mostly in healthy individuals. This infection is typically associated with Vittaforma corneae and Microsporidium infections. The history and impact resemble that of microsporidial keratoconjunctivitis, but those affected may have a record of multiple episodes of improvements and worsening symptoms. While clinical features include multifocal, mid to deep stromal infiltrates with the overlying epithelium remaining intact. Stromal infiltrates are nonspecific and often associate with edema with or without deep stromal vascularization. The stromal infiltrate can at times be ulcerative. Chronic disease can be overlooked due to its uncommon nature and difficulty of diagnosis.

Testing for Microsporidial Keratitis

To confirm if someone has microsporidial keratitis, a disease affecting the eyes, doctors usually take small samples from the conjunctiva or cornea, which are then tested in a lab to detect microsporidia spores.

Historically, a technique known as transmission electron microscopy played a key role in understanding human microsporidia infections. This method can identify microsporidia based on the presence of a special structure called a polar tubule. However, because this technique is complicated and not widely available, it’s not typically used in everyday clinical diagnostics.

In diagnosing microsporidiosis, doctors often rely on optical microscopy, as microsporidia are intracellular organisms, meaning they live inside a host cell. These organisms can’t be grown in common laboratory settings and need special cell cultures for growth. Given these challenges, doctors often use direct smear findings, which involves staining samples to identify microsporidia spores.

If diagnosing microsporidial stromal keratitis, a form of the disease that affects deeper layers of the eye tissue, taking samples from the corneal surface may not provide enough information. In these cases, a corneal biopsy or a specific kind of eye surgery may be used to diagnose the condition.

A tool known as PCR is helpful for diagnosing microsporidial infections and identifying the specific species causing the infection. This technique uses a specifically designed set of molecules to amplify the DNA of the pathogen, making it easier to identify.

Because microsporidia can only grow inside cells, they can only be cultivated in cell culture systems. Vero cell line, a type of monkey cell line, has proven to be the most effective for growing different microsporidia species. However, this method has yet to be standardized for regular diagnosis of microsporidial keratoconjunctivitis.

Antigen detection is another common technique used to identify a variety of infectious diseases. However, many researchers feel this technique is less sensitive than PCR and is better used as a supplement to other conventional methods.

Imaging techniques such as anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy are used to visualize the cornea in high detail. Impressions cytology is another method used, in which a piece of cellulose acetate filter paper is applied to the eye’s surface to collect cells for analysis, offering a less invasive alternative to corneal smear tests. However, these methods have not been extensively documented in the literature, and their potential benefits and drawbacks are still being explored.

Treatment Options for Microsporidial Keratitis

There’s no widely accepted standard for treating microsporidial keratitis, an infection of the cornea (the clear front surface of the eye) caused by the microsporidia group of parasites. However, various treatment methods are available and can be used on their own or in combination, based on the specifics of a patient’s condition.

For superficial infections, or those on the surface of the eye, it’s sometimes enough for the body’s immune system to take care of it, or it can be treated medically. However, if the infection spreads deeper into the corneal tissue, surgery may be required to get rid of the infection and restore vision. Lubricants can be effective for relieving symptoms, and their usage can be adjusted according to the patient’s discomfort levels.

Topical, or externally applied, antimicrobial agents such as fumagillin and different types of fluoroquinolones are frequently used to treat this condition. Fluoroquinolones interfere with enzymes that parasites need to reproduce, and several variations of these drugs have been found effective against microsporidia. It’s worth noting, though, that much of this evidence is anecdotal or comes from laboratory studies, rather than large clinical trials.

Fumagillin, a compound produced by a type of mold, combats microsporidia by blocking production of their RNA, a key part of their reproductive process. Some reports suggest that in some cases, the infection may return after treatment with fumagillin is ended.

Two other types of substances, called biguanides, have also proven to be effective in treating this condition. Polyhexamethylene biguanide (PHMB) and chlorhexidine gluconate are both disinfectants and can be used alongside debridement, a process of removing infected tissue. Despite their effectiveness, these substances are not readily available in the concentrations typically used in treatment.

Topical steroids or other inflammation-modulating agents can also be used if the disease remains recurrent or persistent. Tacrolimus and cyclosporine are two such drugs that suppress inflammation in the cornea and hence, can alleviate symptoms. Topical steroids can also be administered if complications like inflammation of eye tissues occur.

Since microsporidia are closely related to fungi, certain antifungal agents called ‘azoles’ are used to treat this condition. Azoles inhibit the production of a component essential for fungi survival. A scientific study shows that a specific azole named fluconazole, can significantly help restore the patient’s visual acuity.

Itraconazole, another oral antifungal medication, and Albendazole, an antiprotozoal drug, are also recommended to treat this condition. Albendazole acts by affecting the parasite’s cell division process. However, their overall effectiveness in treating microsporidial keratitis has not been definitively proven.

Surgical intervention, such as corneal debridement, can be used to remove the infected tissue or collect samples for laboratory evaluation. Swabbing the cornea using cotton swabs is a less invasive method that has proven to be effective. However, if the drugs administered aren’t effective enough, a specific type of eye surgery called therapeutic penetrating keratoplasty may be the only option left to manage the disease.

What else can Microsporidial Keratitis be?

When a doctor is diagnosing eye conditions like microsporidial keratoconjunctivitis and microsporidial stromal keratitis, there are several other conditions they need to rule out because they have similar symptoms.

For microsporidial keratoconjunctivitis, these may be:

• Adenoviral keratoconjunctivitis
• Thygeson superficial punctate keratitis
• Dry eye disease
• Filamentary keratitis
• Vesicular stage of herpes simplex virus epithelial keratitis
• Acanthamoeba keratitis
• Atypical mycobacterial keratitis
• Viral keratoconjunctivitis
• Bacterial conjunctivitis

Thygeson superficial punctate keratitis is an example of a condition that can be confused with microsporidial keratoconjunctivitis. This condition often shows up in both eyes, with noticeable lesions located in the central eye area. Luckily, this condition often responds well to treatment with eye drops containing steroids.

For microsporidial stromal keratitis, conditions to rule out may include:

• Herpetic stromal keratitis
• Fungal corneal ulcer
• Bacterial corneal ulcer

What to expect with Microsporidial Keratitis

Microsporidial stromal keratitis, a condition that affects the cornea, typically comes and goes until it is surgically removed through a procedure called penetrating keratoplasty. On the other hand, microsporidial keratoconjunctivitis, a different condition that affects both the cornea and the conjunctiva (the thin layer covering the front of the eye), usually heals without any lasting damage.

In a study of 332 patients treated for microsporidial keratoconjunctivitis, 49 came back for a second check at 6 weeks. Out of these individuals, 16 (or about 4.8%) came back due to symptoms of microsporidial keratoconjunctivitis. The rest had other eye-related issues not related to microsporidial keratoconjunctivitis, such as problems with vision and dacrocystitis, an inflammation of the tear sac.

Of those who were experiencing symptoms of microsporidial keratoconjunctivitis, three different signs of persisting disease were found: superficial punctate keratitis (small, pinpoint inflammations on the cornea), sub-epithelial infiltrates (accumulation of certain cells under the surface of the cornea), and uveitis (inflammation of the middle layer of the eye). These 16 patients received additional treatment and were able to overcome the disease, although some did see the condition return at a later time.

Vision usually comes back to normal after successful treatment, with 70% to 100% of patients seeing their sight return. However, if the subepithelial infiltrates or cell accumulations under the corneal surface aren’t resolved, it can lead to a worsening of vision.

Possible Complications When Diagnosed with Microsporidial Keratitis

“Nummular” scars (round or coin-like scars) can last for a long time when a person’s keratoconjunctivitis, an eye condition caused by infection, isn’t adequately treated. In situations where the infection affects the thick, middle layer of the eye, each subsequent inflammation usually leads to more scarring and swelling of the cornea (the clear, front surface of the eye). Increasing pressure inside the eye is another complication, possibly due to the use of topical corticosteroid medications. Other possible aftereffects of the infection include inflammation of the connective tissue in the eye (limbitis), inflammation of the inner layer of the eye (endotheliitis), and small, whitish specks on the cornea (keratic precipitates). These conditions can be addressed with topical steroids – medicines you put directly on your skin or eye.

List of Possible Eye Condition Complications:

• Long-lasting “nummular” scars
• Repeated corneal scarring and swelling
• Increased eye pressure due to medication use
• Inflammation of the eye’s connective tissue (limbitis)
• Inflammation of the eye’s inner layer (endotheliitis)
• Small, whitish specks on the cornea (keratic precipitates)

Recovery from Microsporidial Keratitis

After treatment for microsporidial keratitis, a type of eye infection, both the care given after surgery and the recovery and strengthening process are crucial for your eyesight and recovery. This process usually involves carefully watching the surgical site, taking prescribed medicines on time, and strictly following all the instructions given by your doctor.

Your post-surgery care might look something like this:

Medications: As a first step, a medication known as topical fumagillin is typically used to treat microsporidial keratitis, but it might not always be available. In its absence, other possible medications include oral albendazole, itraconazole, and a topical medicine known as propamidine isethionate. You should avoid corticosteroids, or use them carefully, as they can make the infection worse. If they are used, they should always be used alongside therapy to control any inflammation.

Regular check-ups: Regular check-ups are key to keep an eye on the healing process, spot any complications early, and make sure the treatment is working. Tests, including slit-lamp examinations, can help monitor the keratitis condition of your eye.

Eye care after the infection: Once the infection has cleared, some people may still have corneal scarring, which can affect vision. Depending on your situation, you may need corrective glasses or contact lenses. If the scarring is serious, a corneal transplant or surgical repair of the cornea might be necessary to restore vision.

Protection: After an infection, wearing sunglasses can help reduce sensitivity to light. Using protective glasses, particularly in environments where there’s a risk of eye injury, can help prevent future episodes.

Education: It’s important to understand why you need to complete your medication regimen, even if you start to feel better. You also need to be aware of how to prevent microsporidial keratitis in the future.

Physical Therapy: If you’ve been bedridden or severely debilitated because of the infection or another health condition, you may need physical rehabilitation to regain muscle strength and function.

Mental Health: Dealing with eyesight problems, or having a serious eye condition can be very stressful. Counseling or mental health resources can be very helpful for your emotional well-being.

Nutrition: Good nutrition is key for healing. Make sure to maintain a balanced diet to support your body during the healing process.

Preventing Microsporidial Keratitis

Microsporidia are a rare type of germs that are often mistakenly identified when they cause infection in the eye. When these germs infect the eye, it usually shows up as an inflammation or irritation of the eye’s surface and the tissue underneath, which is known as keratoconjunctivitis or stromal keratitis. As a patient, it’s key to understand how to lower your chances of catching this infection.

Here are some ways you can guard against this infection:

* Don’t use water that might be polluted

* Wear goggles or some form of eye protection when swimming or doing water sports

* Wash your hands often with soap and water, particularly after you’ve been pinching soil, gardening, or touching animals

* Try not to rub your eyes with dirty hands.

If you wear contact lenses, these tips can also help:

* Always wash your hands before you handle your lenses
* Use clean solutions, specially made for contact lenses, to clean and store them
* Clean the container for your lenses every day, and get a new one every now and then
* Don’t sleep in your lenses unless they’re designed to be safe for overnight use.

Signs that you might have an infection caused by microsporidia are redness, pain, watery eyes, sensitivity to light, blurry vision, and feeling like there’s something in your eye. There are a number of ways to treat this infection, such as eye drops, oral drugs, and even surgery. Most people who get this kind of eye inflammation will get better on their own. Some treatments that might help include wiping away the germs with a cotton swab and managing your symptoms with eye lubricants, antibacterial eye drops, and oral antifungal and anti-parasite medications.

If the tissue beneath the surface of your eye is affected, your outlook may not be as good, and you might need to have a corneal transplant surgery. It’s very important for patients to take all of their medication as directed, return for all of their follow-up appointments, and call your doctor if you notice any signs that the infection might be coming back.

We encourage you to tell your loved ones about this type of eye infection, particularly if they might be at risk. With the right prevention strategies and learning more about the infection, you have a better chance of avoiding it, and if you do get it, of having a better outcome. Remember, it’s always important to consult with your healthcare providers for early detection and effective management of any health conditions.