eMedicine Specialties > Ophthalmology > Infectious Disease

Endophthalmitis, Fungal

Author: Lihteh Wu, MD, Consulting Surgeon, Department of Ophthalmology, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica
Coauthor(s): Teodoro Evans, MD, Retina Fellow, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica; Rafael Alberto García, MD, Chief of Outpatient Services, Department of Ophthalmology, Hospital México of San José, Costa Rica
Contributor Information and Disclosures

Updated: Jul 24, 2007

Introduction

Background

Fungi are eukaryotic organisms that are ubiquitous in nature. The following 3 classes of fungi are important ocular pathogens: molds, yeasts, and diphasic fungi. Molds, also known as filamentous fungi, are multicellular organisms that form a tangled mass known as the mycelium. From this mass, filamentous projections, known as hyphae, branch out. The hyphae may be septate or nonseptate. Septate hyphae have true divisions, subdividing them into several cells, while nonseptate hyphae have no true divisions. Common septate filamentous fungi are Aspergillus, Fusarium, Cephalosporium, Paecilomyces, and Penicillium species. The nonseptate filamentous fungi include the Mucor species.

Yeasts are unicellular organisms that may develop pseudohyphae. Candida and Cryptococcus are the important ocular pathogens. The diphasic fungi exist in 2 forms, yeast and mold. Important ocular pathogens include Histoplasma, Blastomyces, and Coccidioides.

Endophthalmitis refers to intraocular inflammation involving the vitreous and anterior chamber of the eye. In most cases, endophthalmitis results from an infectious organism. Fungal endophthalmitis can be divided into the less common endogenous infections and the more common exogenous infections.

Endogenous fungal endophthalmitis is frequently an ocular manifestation of a systemic disease. Endogenous infections usually occur in patients with 1 or more of the following risk factors: immunosuppression, intravenous drug abuse, bacterial sepsis, prolonged hyperalimentation, systemic antibiotics, corticosteroid therapy, recent abdominal surgery, malignancy, alcoholism, diabetes mellitus, trauma, and hemodialysis. Candida albicans is by far the most common pathogen isolated in endogenous fungal endophthalmitis. Other pathogens include Aspergillus, Coccidioides, Cryptococcus, Blastomyces, and Sporothrix species.

Exogenous infections usually are secondary to trauma or surgery. A variety of fungi, including Paecilomyces, Acremonium, and Sporothrix species, have been associated with endophthalmitis following intraocular surgery or trauma.

Pathophysiology

Candida endophthalmitis

C albicans is by far the most common cause of endogenous endophthalmitis. They are commensal organisms that reside in the human body and are found normally in the female genital tract, the gastrointestinal tract, and the respiratory tract.

These fungi are kept in check by the host's normal immune response. When a breakdown in the host's immune system occurs, fungi may spread throughout the body. Many organs, including the eye, can be affected by this spread of fungi through the bloodstream. However, immunosuppression alone does not increase significantly the risk of fungi entering the bloodstream. For instance, candidal chorioretinitis is an uncommon ophthalmic condition in AIDS patients. Neutrophils are apparently important in the first-line defense against candidal organisms. Infection probably starts in the choroid and spreads to the retina and vitreous.

Patients who are at risk include patients with longstanding indwelling catheters; persons who use intravenous drugs; postpartum women; premature infants; patients undergoing hyperalimentation; patients with a history of recent abdominal surgery; and patients with debilitating diseases, such as diabetes mellitus, postorgan transplantation, or malignancies.

Aspergillus endophthalmitis

Of the more than 200 species of aspergilli, Aspergillus flavus and Aspergillus fumigatus are the most common pathogenic organisms in humans. They are ubiquitous organisms found in soil, decaying matter, water, and organic debris. Its conidia are airborne, so inhalation is an important route of entry into the human body. In patients who are at risk, such as those patients with chronic pulmonary diseases or those patients with orthotopic liver transplants, renal transplants, and bone marrow transplants, disseminated aspergillosis may result. In these patients, the fungus usually spreads from the lungs to the eye. Persons who use intravenous drugs may present with ocular symptoms only.

Aspergillus infections are characterized by the breakdown of neutrophil and mononuclear phagocytic defenses. The first line of defense is the mononuclear phagocyte, which engulfs the conidia, the asexual spores of aspergilli organisms. Neutrophils constitute the second line of defense, which kill the mycelia. Most likely, the choroid is the first ocular site where aspergilli organisms gain access to the eye.

Cryptococcus endophthalmitis

Pigeons play an important role in the pathogenesis of cryptococcosis. Cryptococci spores can survive up to 2 years in pigeon droppings. Spores gain access to the human body through inhalation. From the lungs, the fungus is disseminated hematogenously and preferentially affects the central nervous system. It is the most common cause of fungal meningitis. Cryptococci organisms reach the eye through either direct extension from the optic nerve sheath or hematogenously from a distant focus. The choroid is probably the first site of ocular infection.

Coccidioides endophthalmitis

Coccidioides endophthalmitis results from the inhalation of Coccidioides immitis arthroconidia, which are found in the dust of endemic areas. Agricultural workers and constructions crews are at risk. In most patients, the inhalation of the spores leads to a self-limited respiratory disease. In few patients who are reexposed to the fungus, a chronic respiratory disease ensues. Hematogenous dissemination to the eye can occur.

Frequency

United States

Compared to previous decades, the incidence of endogenous endophthalmitis appears to have increased in the past few decades. This may be secondary to an increase in intravenous drug use; the advent of chemotherapy for cancer patients; and the increased ability to care for more debilitated patients with hyperalimentation, indwelling catheters, and potent antibiotics.

Prospective studies of hospitalized patients with candidemia reveal that 9-37% of patients developed candidal endophthalmitis. In studies where prompt treatment of a systemic fungal infection is instituted, only 3-9% patients developed endogenous fungal endophthalmitis.

International

Because it is commensal in the human body, Candida species are found throughout the world. Cryptococci and aspergilli also are present worldwide and found in both urban settings and rural settings.

C immitis is endemic in the southwestern United States (the San JoaquinValley) and Northern Mexico. It also has been reported in Honduras, Venezuela, and Colombia.

Mortality/Morbidity

• The prognosis of fungal endophthalmitis depends on the virulence of the organism, the extent of intraocular involvement, and the timing and mode of interventions.
• Prompt therapy following early diagnosis helps to reduce significant visual loss in all forms of fungal endophthalmitis.
• The visual outcome of Aspergillus endophthalmitis usually is poor because of the preferred macular involvement by the fungus.

Race

No racial predisposition has been observed.

Sex

A male preponderance is reported for endogenous fungal endophthalmitis.

Age

With regard to endogenous fungal endophthalmitis, there are 2 incidence peaks: one in patients younger than 1 year, and the other in middle-aged patients.

Clinical

History

• Risk factors for Candida endophthalmitis
  
  
  • The most common risk factor for the development of endogenous Candida endophthalmitis is intravenous drug abuse.
  • Other risk factors include patients with long-standing indwelling catheters; postpartum women; premature infants; patients undergoing hyperalimentation; patients with a history of recent abdominal surgery; and patients with debilitating diseases, such as diabetes mellitus, postorgan transplantation, or malignancies.
• Risk factors for Aspergillus endophthalmitis
  
  
  • Patients with a history of renal transplantation who are receiving corticosteroids, leukemia and other hematological disorders, Goodpasture syndrome, alcoholism, and prematurity.
  • The most common predisposing factor is intravenous drug abuse.
  • Notably, chest x-ray film findings are normal in up to 20% of patients with invasive pulmonary aspergillosis.
  • Aspergillus endogenous endophthalmitis tends to present more acutely than Candida endophthalmitis and to progress more rapidly.
  • Aspergillus endocarditis is often found together with Aspergillus endophthalmitis; therefore, a thorough cardiac workup is necessary.
• Risk factors for Cryptococcus endophthalmitis
• • Patients who are known to be at risk of developing this condition are those with lymphoproliferative diseases, collagen vascular diseases, sarcoidosis, tuberculosis, diabetes mellitus, Cushing syndrome, or AIDS; those who are pregnant or abuse drugs; and those who have had organ transplants.
  • A few cases of cryptococcosis have been reported in individuals with no known risk factors or immune deficiencies.
  • Since the arthroconidia of C immitis are found in the dust of endemic areas, agricultural workers and construction crews are at risk of acquiring the infection. 
• Symptoms include the following:
• • Visual loss may be present; however, several studies have shown that visual acuity is not a useful factor in assessing the presence of endogenous fungal endophthalmitis in patients who are at risk. 
  • In addition, patients may be asymptomatic if the lesion is in the peripheral retina or if the patient is moribund. 
  • Red eye 
  • Photophobia 
  • Pain 
  • Floaters 
  • Scotoma

Physical

• Candida endophthalmitis
  
  
  • Candida chorioretinitis typically presents as several, small, creamy white, circumscribed chorioretinal lesions with overlying vitreous inflammation.
  • In certain cases, these chorioretinal lesions may be surrounded by hemorrhage, giving them the appearance of a white-centered hemorrhage (Roth spot). 
  • In the area of the lesion, the retinal vessels may be sheathed.
  • The vitreous opacities resemble fluffy balls, and they may be linked to each other by strands giving them the so-called string of pearls appearance. 
  • If the infection is not suspected and the disease advances, epiretinal membranes may develop, leading to vitreoretinal traction and retinal detachment. 
  • As the lesions heal with treatment, chorioretinal scarring evolves in the areas of prior inflammation. 
  • Choroidal neovascular membranes may develop at the site of these scars. 
  • Two thirds of patients have bilateral disease, and more than one half of patients have vitreous involvement. 
  • Iridocyclitis often is present, and a hypopyon also may be present. 
  • Infection of the iris and ciliary body is rare. 
• Aspergillus endophthalmitis
• • In Aspergillus endophthalmitis, an iridocyclitis with or without a hypopyon may be present; yellow subretinal and retinal infiltrates that preferentially affect the macula are observed. 
  • Inflammatory cells within the infiltrate may layer secondary to gravity, thereby creating a pseudohypopyon. 
  • As the disease progresses, the vitreous becomes severely involved, concealing all fundus details. With time, the macular lesions scar. 
  • In addition, Aspergillus species have a propensity for vascular invasion, leading to thrombosis and necrosis. 
  • If the fungus invades the choroidal vessels, an exudative retinal detachment may result. 
  • When the retinal vessels become involved, retinal necrosis may occur.
• Cryptococcus endophthalmitis
• • Cryptococcus neoformans usually presents intraocularly as a multifocal chorioretinitis characterized by discrete yellow-white lesions of different sizes. 
  • Retinal vessels may be sheathed, and a vitritis of variable intensity may develop. 
  • Retinal necrosis accompanied by retinal hemorrhage and exudative retinal detachments also have been known to occur. 
  • If the central nervous system is involved, papilledema is present. 
  • A mild inflammatory reaction is present in the anterior segment. 
  • If treatment is not instituted, iris neovascularization and cataract may result. 
• Coccidioides endophthalmitis

• Ocular coccidioidomycosis is an uncommon finding in patients with disseminated disease.
• Usually, a severe granulomatous iridocyclitis characterized by mutton-fat keratic precipitates is present.
• Multifocal choroiditis, typified by several, scattered, discrete, yellow-white lesions measuring less than the disc diameter in size, is observed. 
• Occasionally, vascular sheathing, vitreous haze, serous retinal detachment, and retinal hemorrhage also may be seen.

Causes

• C albicans is by far the most common cause of endogenous fungal endophthalmitis.
• Other organisms that can cause fungal endophthalmitis include the following:
  
  
  • Aspergillus species
  • Cryptococcus neoformans
  • Coccidioides immitis

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