Fungal Endophthalmitis

What is Fungal Endophthalmitis?

Endophthalmitis is a rare but serious eye disease that causes inflammation and can lead to blindness. In particular, fungal endophthalmitis is caused by fungal infections in the eye. These infections can either be external, coming from injuries or surgeries, or internal, spreading through the bloodstream. Fungal endophthalmitis is especially hard to diagnose because its symptoms are very similar to other conditions such as bacterial infections, non-infectious diseases, and cancers within the eye.

Without a proper diagnosis and if steroids are used without the right antifungal treatment, there’s a higher risk of significant vision loss. This is why it’s extremely important for doctors to detect fungal endophthalmitis early and to start the right antifungal treatment as soon as possible.

What Causes Fungal Endophthalmitis?

Exogenous endophthalmitis is an eye infection caused by bacteria or other microorganisms on the surface of the eye or from the environment. This condition can be triggered by eye surgery, an injury that pierces the eyeball, or by the spread of an infection from nearby tissues. There are three types of this condition caused by fungi: post-surgery, after an injury, or from a specific condition called fungal keratitis.

Most often, this condition occurs after eye surgery, making up 40%-80% of all cases. It’s uncommon for fungi to be the cause. Still, when they are, species like Aspergillus and Candida are usually responsible. Eye infections that happen after an injury make up the second most common type, accounting for 25% of cases. Bacteria are typically the cause, but the Aspergillus fungus is common too. The spread of fungal keratitis is the least common cause of endophthalmitis.

Endogenous endophthalmitis is a different type of eye infection. It’s quite rare, making up only 5%-15% of all cases. This condition typically happens when infectious agents in the blood breach the natural barrier between the blood and the eye. Patients with this condition are usually those whose immune system is compromised or those who use illicit drugs intravenously that cause fungal infection in their blood.

This contrasts with the more common types of endophthalmitis, where bacteria are typically the cause. In endogenous endophthalmitis, fungi, especially Candida albicans, are usually the culprits. Other species of Candida have been reported as well, including C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, and C. pelliculosa. Aspergillus and Fusarium are the most commonly involved molds.

Risk Factors and Frequency for Fungal Endophthalmitis

Endogenous endophthalmitis, an infection inside the eye, is commonly caused by a widespread Candida infection. The risk of a person with a Candida infection developing endophthalmitis ranges between 0% to 40%, depending on the study. However, recent studies have shown that the number of cases is as low as 0 to 2.2%, possibly due to better preventive measures and treatment strategies.

The infection typically starts in the choroid, which is a densely packed blood vessel network located towards the back of the eye, and progresses towards the retina at the front. As the infection worsens, it can infect the vitreous, the jelly-like substance inside the eye. This makes the progression of the infection quite slow.

People who have a weakened immune system, or conditions that increase the chances of a bloodstream infection, are at risk of developing endogenous fungal endophthalmitis. This doesn’t mean that having a suppressed immune system guarantees that the Candida will have access to the bloodstream. However, having a suppressed immune system does increase the severity of the ocular infection when candidemia (presence of Candida in the blood) is present.

Conditions that put you at risk for endogenous fungal endophthalmitis include:

• HIV and other diseases that weaken the immune system.
• Underlying malignant conditions.
• Using broad-spectrum antibiotic therapy.
• Using corticosteroids and other medications that suppress the immune system.
• Having experienced trauma or surgery in the gastrointestinal tract.
• Needing parenteral nutrition, or feeds given via a vein.
• Use of long-term or temporary venous catheters.
• Abusing drugs via intravenous route.
• Having neutropenia, the decrease in a type of white blood cells.
• Diabetes.
• Kidney insufficiency.
• Recent stints in a hospital.
• Organ transplantation.
• Hemodialysis.
• Pregnancy, abortion, or recent childbirth.
• Lung diseases, specifically when Aspergillus is involved.

To illustrate the risks above, two different studies found that 90% of patients with this condition had one or more predisposing conditions. However, it is also possible for individuals with no predispositions or illnesses to develop endogenous fungal endophthalmitis.

It is also worth noting that despite HIV and other conditions causing candidemia, endophthalmitis is uncommon in HIV patients or AIDS patients without these other risk factors.

Candida fungi are one of the main causes of hospital-acquired bloodstream infections, with C. albicans being the most common cause of endogenous fungal endophthalmitis. It is not clear why the eye is a frequent target in cases of fungemia (fungal bloodstream infections). One study on rabbits shown C. albicans has a marked preference for eyes, similar to its preference for kidneys and cells lining the blood vessels.

Neonatal endophthalmitis (in newborns) is very rare. Candida is the most common cause, with risk factors including preterm birth, retinopathy of prematurity (a potentially blinding eye disorder), and long hospital stays.

Moving onto exogenous endophthalmitis, this typically happens in otherwise healthy people. Risk factors include eye surgery, penetrating eye injuries, and fungal keratitis. This type of infection generally affects the fluid-filled front part of the eye first, instead of starting in the back of the eye like endogenous endophthalmitis.

Acute and chronic postoperative endophthalmitis, and post-keratoplasty (corneal transplant) endophthalmitis, although uncommon, often result from fungal infections. Instances of fungal endophthalmitis following certain surgeries or injections into the eye are minimal, but have occurred due to contamination of the compounds used.

Fungal keratitis, a type of fungal corneal infection, can lead to endophthalmitis if the fungal infection spreads from the cornea into the front chamber of the eye. Certain factors like wearing contact lenses, eye trauma with organic material, and LASIK can raise the risk of getting fungal keratitis. Interestingly, although only a small percentage of eyes with corneal infections progress to endophthalmitis, a majority of these are due to fungal infections, most commonly Fusarium molds.

Signs and Symptoms of Fungal Endophthalmitis

Endogenous fungal endophthalmitis is a type of eye infection that can be difficult to diagnose due to varying symptoms. Typically, affected individuals may experience a subtle onset of vision loss, floating spots in their line of sight, redness in the eye, eye pain, discomfort, and sensitivity to light. Often, these symptoms are seen in people with weak immune systems or certain risk factors. Occasionally, those with early or outer edged fungal lesions may not show any symptoms and are referred for an eye test due to a positive blood culture or diagnosis of a Candida infection in the body.

Upon physical examination, the patient might display symptoms like eyelid swelling, redness around the white part and corners of the eye, inflammation in the front area of the eye with or without a pus-filled swelling, loss of the red reflex, cloudy deposits in the jelly-like substance in the back of the eye, and bleeding within the layers of the retina. These observations on inspection of the back of the eye can be made difficult due to the inflammation inside the eye obscuring the view.

The key to diagnosing Candida chorioretinitis, a type of eye infection, is the presence of creamy white lesions at the level of the choroid (layer of blood vessels and connective tissue) and retina. These lesions are associated with clouding in the jelly-like substance in the back of the eye and increase in size if left untreated, causing scarring that may result in tension and detachment of the retina. These lesions are often numerous and can occur in both eyes in two-thirds of cases. Additionally, Candida endophthalmitis can manifest with abscesses within the jelly-like substance of the eye.

Aspergillus endophthalmitis, another type of eye infection, shows yellow-white lesions in the back of the eye that are often larger, more severe, and prone to bleeding. Aspergillus typically invades the blood vessels of the retina and choroid, potentially causing tissue death of the retina

Fungal endophthalmitis that follows eye surgery usually develops several weeks or months post-procedure with symptoms similar to endogenous endophthalmitis.

Posttraumatic fungal endophthalmitis may develop within hours or several weeks following a traumatic injury, particularly when contaminated with soil, filthy objects, or plant material. Patients present with decreased vision, an amount of eye pain that seems excessive compared to their physical examination, eyelid swelling, corneal ulcer, inflammation in the anterior chamber of the eye, pus in the front area of the eye, inflammation of the jelly-like substance in the back of the eye, or clear pus. The extent of injury can influence all these clinical findings.

Upon examination, if the cornea shows infiltrates with unclear or feathery borders and tiny satellite lesions, this can be a strong sign of a mould infection. Other strong signs might include tree-like projections from the back of the cornea into the aqueous or a dense clump of material in the aqueous, these can indicate progression of fungal keratitis into endophthalmitis.

Testing for Fungal Endophthalmitis

The process of diagnosing a condition known as fungal endophthalmitis, which is an infection within the eye, can be a challenge as it does not have specific symptoms. The diagnosis depends on a detailed patient history and an in-depth eye exam. If the doctors suspect it to have been caused externally, they’ll ask about recent eye surgeries or any inflicted eye injuries. If it’s suspected to be internal, your recent health history such as surgeries, hospital stays, use of immune suppressing drugs, or intravenous drug use will be considered. Here’s how doctors usually go about diagnosing fungal endophthalmitis:

They may use a method called Ultrasound B-scan, especially if they are not able to clearly see the back of your eye. This won’t specifically diagnose fungal endophthalmitis, but it can help provide crucial information such as how serious the infection is, where it’s located, and if there’s any retinal detachment or abscesses – all important information in order to come up with a treatment plan.

They will also examine samples of your eye fluids in the lab, particularly in cases where blood tests have turned out negative but your symptoms still indicate fungal endophthalmitis. Certain methods for obtaining these fluid samples work better than others, and in some cases, the results may not always be accurate, as there have been instances when some samples are not able to grow cultures in the lab.

Generally, a full-body assessment for possible systemic fungal infection is carried out, including blood cultures and an ultrasonic scan of your heart to look for possible sources of infection. However, normal blood cultures do not always exclude fungal endophthalmitis – in one type of endophthalmitis caused by a fungus called Candida, only about half to three-quarters of patients have positive blood cultures. It’s important that anyone diagnosed with a systemic fungal infection consult an ophthalmologist promptly for a comprehensive eye exam, even if the initial exam was negative.

Polymerase chain reaction (PCR) is another potential test. It has its advantages over traditional culture tests as it can rapidly identify cases of fungal endophthalmitis with better accuracy. Moreover, it has the ability to detect fungal DNA in eye fluid samples, which is a less invasive method.

Finally, measuring the levels of a substance called beta-D-glucan in the eye fluids can also be indicative of fungal endophthalmitis, though it can’t identify the specific fungal species causing the infection.

Treatment Options for Fungal Endophthalmitis

If you’re identified with a fungal eye infection known as fungal endophthalmitis, you’ll be immediately referred to an eye inflammation specialist, known as a uveitis specialist. Mild cases, where the infection is mainly outside the blood-retina barrier, can be managed with medications designed to fight fungal infections. However, moderate or severe cases with more significant involvement of the eye’s internal jelly (vitreous) will most likely need a combination of medications and treatments injected directly into the eye.

A surgery called vitrectomy, which involves the removal of some or all of the vitreous, is usually recommended in severe cases, as it can reduce the risk of the retina detaching later on.

As these infections are often part of a more widespread, systemic infection, you will also be given an anti-fungal treatment that works throughout your whole body. These medications should be able to cross the blood-retina barrier (the natural defence that protects the eye from certain substances in the blood) to fight the infection. Fluconazole is often the preferred choice for this, but voriconazole can also be used, especially in cases where the infection is believed to be resistant to fluconazole. However, voriconazole is more expensive, requires regular blood tests to adjust the dose, and can cause liver toxicity more commonly compared to fluconazole.

When it comes to therapies injected directly into the eye, voriconazole is preferable as it has a wide spectrum and lower risk of causing damage to the retina. Another drug, called AMB, remains a viable alternative when voriconazole isn’t feasible, particularly for infections caused by yeast.

Vitrectomy surgery might be used not only to remove a sample of the vitreous for diagnosis but also to treat complications associated with fungal endophthalmitis, such as retina detachment. However, it’s not entirely clear whether early vitrectomy helps to control inflammation. While some studies suggest that early surgery doesn’t significantly reduce the risk of severe vision loss, it appears to decrease the risk of the retina detaching fivefold.

Moreover, whether the surgery is performed immediately or after some delay seems not to influence the prospects of the vision improving to a certain level.

What else can Fungal Endophthalmitis be?

If a person who has a weakened immune system, has been recently hospitalized, or has a history of injecting drugs suffers from inflammation inside the eye – specifically in the back part of the uvea or the overall interior of the eye – a disease called Candida chorioretinitis or Candida endophthalmitis might be considered by doctors.

However, many other possible conditions could be causing these symptoms, including:

• Non-infectious inflammation of the uvea:
  • Sarcoidosis
  • Behçet syndrome
  • Sympathetic ophthalmia
  • Juvenile idiopathic arthritis
  • Vogt-Koyanagi-Harada disease
• Infections of the choroid and retina:
  • Bacterial inflammation of the entire interior of the eye (endophthalmitis) caused by:
    • Coagulase-negative staphylococci
    • Staphylococcus aureus
    • Streptococci
    • Tuberculosis
    • Syphilis
  • Viral inflammation of the entire interior of the eye caused by:
    • Herpes simplex virus
    • Varicella-zoster virus
    • Epstein-Barr virus
    • Cytomegalovirus
  • Inflammation of the choroid and retina caused by the parasite Toxoplasma
• Cancer inside the eye:
  • Intraocular lymphoma
  • Retinoblastoma – largely affecting children

Therefore, doctors need to carefully test for and rule out these other conditions before settling on suspected Candida chorioretinitis or endophthalmitis.

What to expect with Fungal Endophthalmitis

Generally, fungal endophthalmitis, which is an inflammation inside the eye caused by a fungus, tends to have poor outcomes, often leading to complete loss of vision. This is particularly true if the condition is not diagnosed and treated promptly. Consequences can be especially severe if the patient’s vision is already compromised to start with, or if the infection is located in the central part of the eye.

Moreover, the severity of this eye condition can largely depend on the type of fungus causing the infection. For example, eye infections caused by Aspergillus and other types of mold are typically more serious than those caused by yeast. This is because infections with these types of molds often lead to more aggressive forms of endophthalmitis which can worsen the prognosis for the patient’s vision.

Possible Complications When Diagnosed with Fungal Endophthalmitis

Patients with Candida endophthalmitis, an eye infection, often recover enough sight to have a final visual acuity of 6/60 or more. However, patients suffering from candidemia, a yeast infection in the blood, have a high overall death rate. This high mortality rate reflects the severity of both the fungal infection and any other underlying health issues.

Among all the causes of exogenous fungal endophthalmitis, an external fungal infection of the eye, infections occurring after trauma have the worst effect on a person’s vision. A study reported that 70% of eyes with endophthalmitis related to open-globe injury (an injury involving full-thickness wound of the eye) needed enucleation- a surgery to remove the eye.

Common Outcomes:

• Improved sight for patients with Candida endophthalmitis
• High death rate for patients with candidemia
• Poor visual outcomes after trauma-related fungal infections
• Surgical eye removal in 70% of open-globe injury cases with endophthalmitis

Preventing Fungal Endophthalmitis

If you are diagnosed with fungal endophthalmitis, which is a type of eye infection, it’s crucial that you fully follow the prescribed medication routine. In simple terms, failing to complete the treatment can lead to severe consequences. The medication can be costly and uncomfortable, as they are often delivered via direct injections into the eye. Particularly, a drug called voriconazole can be very expensive. This discomfort and cost are the common reasons why some patients may not follow their treatment plan properly. However, it’s important you understand that early and aggressive treatment of this eye infection can result in better health results. If left untreated or not treated fully, the eye infection could linger and could potentially lead to more serious health problems.