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 represents intraocular dissemination of a systemic fungal infection. Among the different fungal species, Candida species is the most common cause of infection, followed by Aspergillus species. [1] Risk factors include immunosuppression, intravenous drug abuse, bacterial sepsis, prolonged hyperalimentation, systemic antibiotics, corticosteroid therapy, recent abdominal surgery, malignancy, alcoholism, diabetes mellitus, trauma, and hemodialysis. [2, 3, 4]
Exogenous infections usually are secondary to trauma or surgery. A variety of fungi, including Paecilomyces, Acremonium, and Sporothrix species, has been associated with endophthalmitis following intraocular surgery or trauma. Fungal endophthalmitis is a rare complication after cataract surgery. The most common causative fungal pathogens implicated in fungal endophthalmitis after cataract surgery include Candida species and molds such as Aspergillus and Fusarium species. [5] There have been outbreaks of fungal endophthalmitis associated with contaminated compounded brilliant blue G and triamcinolone. [6]
Pathophysiology
Candidal endophthalmitis
Even though Candida albicans is by far the most common cause of endogenous endophthalmitis, [7] other non– C albicans species, in particular C tropicalis, have also been implicated in intraocular infections. [8] The most common risk factors are those that predispose to candidemia (eg, a prior history of gastrointestinal surgery, hyperalimentation, and diabetes mellitus). [9]
Surprisingly, immunosuppression alone does not significantly increase the risk of Candida entering the bloodstream (eg, candidal chorioretinitis is an uncommon ophthalmic condition in AIDS patients). Furthermore, Candida endophthalmitis can occur after abdominal surgery or in diabetic patients without granulocytopenia. Rao and Hidayat have suggested that Candida overgrowth in the gastrointestinal tract and the increased availability of glucose seen in diabetic patients promote the growth of Candida. [9] The intravitreal concentration of glucose is higher in diabetic patients when compared with nondiabetic patients, which may explain Candida' s predilection for the vitreous. [10]
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 Aspergillus, A flavus and A fumigatus are the most common pathogenic organisms in humans. They are ubiquitous organisms found in soil, decaying matter, water, and organic debris. Its conidia, the asexual spores of aspergilli organisms are airborne, so inhalation is an important route of entry into the human body. When conidia enter the terminal alveoli of the lung, they may be engulfed by mononuclear phagocytes. If conidia are not destroyed by this first line of defense, they germinate and extend mycelial structures that are associated with tissue invasion. Neutrophils constitute the second line of defense and kill the mycelia.
In patients who are at risk, such as those patients with chronic pulmonary diseases or those patients with orthotopic liver transplants, renal transplants, leukemia and other hematologic disorders, Goodpasture syndrome, alcoholism, prematurity, and bone marrow transplants, disseminated aspergillosis may result. The most common predisposing factors include intravenous drug abuse, prior cardiac surgery, and being an organ transplant recipient. The common denominator in these patients appears to be granulocytopenia. [9] The fungus usually gains access to the eye as it spreads from the lungs to the choroid.
Cryptococcal 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.
Epidemiology
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% of patients developed endogenous fungal endophthalmitis. A prospective cohort study that enrolled 125 inpatients with positive fungal blood culture results showed a 5.6% rate of chorioretinitis and 1.6% rate of endophthalmitis. [11] Despite modern antifungal therapy, fungal chorioretinitis and endophthalmitis continue to occur in patients with positive fungal culture results.
International
In countries with temperate climates, endophthalmitis usually results from an infectious organism such as bacteria. Fungal endophthalmitis remains a relatively rare condition. [12] However, in countries with tropical climates, fungal endophthalmitis is not an infrequent finding. In India, fungi were isolated in 22% of culture-proven endophthalmitis. [13]
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 Joaquin Valley) and Northern Mexico. It also has been reported in Honduras, Venezuela, and Colombia.
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.
Prognosis
The prognosis of fungal endophthalmitis depends on the virulence of the organism, the extent of intraocular involvement, and the timing and mode of interventions. Regardless of the organism, one of the most important prognostic factors for vision was the baseline visual acuity. [14]
Infections secondary to molds have a worse outcome than those due to yeasts. [3]
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.
In cases of candidal endophthalmitis, prognostic factors include baseline visual acuity and location of the lesions. Early vitrectomy reduces the risk for retinal detachment. [15]
The prognosis following fungal endophthalmitis depends on the virulence of the organism, the extent of intraocular involvement, and the timing and mode of interventions.
A retrospective study of 17 eyes in 9 patients diagnosed with endogenous C albicans and C tropicalis fungal endophthalmitis showed that early ophthalmic consultation, better initial visual acuity, and use of effective systemic antifungal treatment might lead to relatively good visual outcomes in these patients. A final visual acuity of 20/200 or more was achieved in 69.2% of the eyes in this study. [16] In contrast, in a Chinese series of 32 eyes, a poor visual outcome was seen, particularly if the presenting visual acuity was less than counting fingers or molds were involved. [17]
