Aspergillus Endophthalmitis - An Overview

Introduction

Fungi, as ocular pathogens, are mold, yeasts, and biphasic fungi. Endophthalmitis is an inflammation of ocular tissues and fluids. It is a medical emergency, and there is a risk of loss of vision due to the involvement of the cornea, orbit, sclera, eyelid, lacrimal apparatus, and internal structures. Endophthalmitis caused by Aspergillus is endogenous or exogenous.

What Are the Types of Endophthalmitis?

1. Endogenous endophthalmitis is caused by a systemic fungal infection invading the eye in immunosuppressed patients. Aspergillus is the second most common fungal infection.

2. Exogenous endophthalmitis is caused by trauma or surgery. Endophthalmitis after cataract surgery is rare, but there are reported cases of infection with Aspergillus. Depending on the onset time, the endophthalmitis can be acute or chronic.

What Is the Pathophysiology of Aspergillus Endophthalmitis?

Aspergillus flavus and fumigatus are known to cause ocular infection in humans. Other species detected in ophthalmic infection include A niger, A terreus, and A glaucus. These fungi are found in soil, decaying matter, water, and organic debris. In addition, the asexual spores of aspergillus called conidia are airborne and inhaled by humans. These spores are engulfed by mononuclear phagocytes when they enter terminal alveoli if the first line of defense does not destroy the fungi. Conidia further establish themselves by forming mycelium. Neutrophil forms a second line of defense and attack mycelium. If the fungus survives, it starts to increase in the body. The fungi infect the eye through the choroid as it spreads from the lungs.

What Is the Risk Factor for Aspergillus Infection?

Patients with chronic pulmonary disease, orthotopic liver transplant, renal transplant, leukemia, hematological disorders, Goodpasture syndrome (an autoimmune condition affecting lung and kidneys), alcoholism, prematurity, and bone marrow transplant. Other common factors are intravenous drug abuse, prior cardiac surgery, and organ transplant recipients or individuals with suppressed immunity. In addition, granulocytopenia (decrease in peripheral blood) is seen in individuals with aspergillus infection. The progression of the infection is rapid.

Aspergillus endophthalmitis is common in tropical countries, and its incidence has increased in the United States due to an increase in immunosuppressed patients. The incidence is greater in males who work in the open air. The aspergillus endophthalmitis has two peaks among the age group. The initial peak is in patients younger than one year, and the second is in middle-aged patients.

What Are the Features of Eye Infection?

• Iridocyclitis (inflammation of the iris and ciliary body) with or without hypopyon (layering of white blood cells in the anterior chamber) is seen.

• Yellow subretinal and retinal infiltrates affect the macula.

• Pseudohypopyon may be seen as inflammatory cells in the infiltrate that may layer secondary to gravity.

• With the progression of the disease, the fundus gets concealed due to the severely affected vitreous chamber. In addition, there may be scarring of macular lesions.

• The tendency of Aspergillus to invade vasculature causes thrombosis and necrosis.

• Invasion of choroidal vessels leads to exudative retinal detachment, progressing to retinal necrosis.

What Are the Symptoms of Aspergillus Endophthalmitis?

• Visual loss- patients are asymptomatic if the peripheral retina is involved. Visual loss is not a diagnostic feature of the disease.

• Red eye.

• Photophobia (eye discomfort in bright light).

• Pain.

• Floaters (black or gray spots in vision).

• Scotoma (a blind spot that obstructs part of vision).

• Burning and foreign body sensation.

• Tearing.

• Hyperemia (increased blood flow to the eye).

• Blurred vision.

How Is Aspergillus Endophthalmitis Diagnosed?

• Blood cultures, urine cultures, sputum cultures, and cerebrospinal fluid cultures (CSF) are obtained to isolate aspergillus fungi. Blood culture is negative in most cases of aspergillus endophthalmitis.

• Polymerase chain reaction (PCR) is used to detect fungi due to high sensitivity and faster results.

• DNA (deoxyribonucleic acid) microarray analysis is useful for faster detection.

• X-ray is done to detect pulmonary involvement.

• A cardiac workup is done as aspergillus endophthalmitis is often associated with aspergillus endocarditis.

• Pars plana vitrectomy is useful in obtaining samples of aspergillus fungi for culture and sensitivity.

• Aspergillus fungi, once isolated, grow on Sabouraud and Czapek solutions. The colonies are viewed with Gomori- methenamine- silver (GMS) or periodic- acid Schiff (PAS) stains. Aspergilli in the initial stage appear flat, white, and filamentous. After 48 hours, the aspergillus spores called conidia are seen with changes in pigmentation.

• In imaging studies such as fluorescein angiography, the chorioretinal lesion appears hyperfluorescent in the initial stage, and leakages are seen in later stages.

• Slit lamp examination and fundus examination revealed the extent of fungal invasion. Therefore, an ultrasound examination is done in case of poor visibility with a slit lamp or fundus examination.

How Is Aspergillus Endophthalmitis Treated?

The medications used are

• Amphotericin B intravitreal or systemic medication is used. Systemic medication may be toxic to the retina and have poor intravitreal penetration. In addition, resistance to the medication is a limiting factor.

• Imidazoles.

• Fluconazole is effective against Aspergillus and has a good cerebrospinal fluid (CSF) and intravitreal penetration. In addition, this drug is fungistatic (inhibits fungal growth without killing).

• Ketoconazole has fungistatic activity with limited action against Aspergillus.

• Itraconazole is a synthetic fungistatic.

• Miconazole is a second line of treatment against Aspergillus. The drug is administered intravenously as GI absorption is poor. In addition, the drug is used in Amphotericin B-resistant cases.

• Voriconazole is used in treatment against invasive aspergillosis.

• Corticosteroids, intravitreal dexamethasone use as an adjunct is indicated in a few studies to control inflammation.

• Chemotherapeutic agents inhibit cell growth and proliferation. Flucytosine is effective against a few strains of aspergillus fungi. The drug is used as a combination therapy since the drug alone carries the risk of developing resistance.

• Echinocandins and Caspofungin help in treating refractory invasive aspergillosis. The action is through the inhibition of cell wall synthesis.

Surgery:

A vitrectomy is done if the response to intravitreal infection is poor or if there is a development of keratitis. Effective treatment is achieved when vitrectomy is combined with intravitreal antifungals.

• Vitreous Tap:

Without suitable treatment, vitreous inflammation spreads to the anterior chamber. There are no guidelines on the duration of the disease. Studies suggest four to six weeks of treatment with systemic medication. Intravitreal injection requires administration every 48 hours.

What Are the Complications?

• Choroidal neovascularization at the chorioretinal scar region.

• Epiretinal membranes.

• Tractional retinal detachment.

• Conjunctivitis.

• Vitritis.

• Uveitis.

• Ulcerative keratitis.

• Necrotizing scleritis.

• Orbital inflammation.

What Is the Differential Diagnosis?

• Acute retinal necrosis.

• Bacterial endophthalmitis.

• Ophthalmic Manifestation of leukemia.

• Postoperative endophthalmitis.

What Is the Prognosis?

The prognosis for aspergillus endophthalmitis is poor due to macular involvement. In addition, delayed diagnosis and ineffective ocular penetration of antifungal drugs cause limitations in treating the condition.

How to Prevent Disease?

Individuals with a weakened immune system are advised to use a mask or shield while working outdoors. Avoid going to areas where molds are present.

Conclusion

The fungal infection is challenging to treat. Therefore, early diagnosis is important to preserve visual function. Since the diagnosis is difficult, the physician must carry out appropriate diagnostics in suspected cases.