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Candidal Endophthalmitis After Keratoplasty

Merchant, Amyna M.D.; Zacks, Charles M. M.D.; Wilhelmus, Kirk M.D., M.P.H.; Durand, Marlene M.D.; Dohlman, Claes H. M.D., Ph.D.

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Fungal endophthalmitis after keratoplasty is uncommon but well documented. 1–12 We report an unusually precipitous postoperative endophthalmitis in a patient whose graft donor eye grew abundant yeast.


The donor was a 68-year-old patient who died from chronic heart failure, chronic obstructive pulmonary disease, and chronic vascular disease. Death-to-preservation time was 5 hours and preservation-to-surgery time was 5 days. The preservation method used Optisol-GS (Bausch & Lomb Surgical, Rochester, NY, U.S.A.) at 4°C.

The patient was a 58-year-old woman with keratoconus who underwent a fifth penetrating keratoplasty of her right eye for a previously failed graft. One day postoperatively the visual acuity was counting fingers at 2 feet. The corneal graft was edematous, and a microhyphema and a mild fibrinous reaction were present in the anterior chamber. She was discharged with a treatment of 1% topical prednisolone acetate every 2 hours and 0.3% ofloxacin drops four times daily. The same afternoon, the microbiology report of the residual donor rim was reported to be positive for abundant Candida. The patient was immediately called back from another state.

The next day the patient's vision had deteriorated to counting fingers at 6 inches, the graft was edematous, and the anterior chamber was full of fibrin and a large fluffy white exudate (Fig. 1A). The vitreous was clear on ultrasonography. An anterior chamber tap revealed budding yeast in the aqueous humor and cultures subsequently grew Candida albicans. Treatment included an intracameral injection of 5 μg of amphotericin B, 400 mg of oral fluconazole daily, and 0.3% topical amphotericin drops every hour for 24 hours. Repeat keratoplasty and anterior chamber washout were performed the next day, and a second injection of 5 μg of amphotericin B was given intracamerally. Cultures of the donor cornea and aqueous grew C. albicans.

FIG. 1.
FIG. 1.:
A:C. albicans endophthalmitis on second postoperative day. The corneal graft was edematous and the anterior chamber was full of fibrin and contained a large fluffy white exudate. B: Repeat corneal graft failed, and a dense fibrinous pupillary membrane formed.
Figure 1
Figure 1:

Despite immediate recognition of contamination and prompt treatment with a repeat keratoplasty and intraocular, topical, and parenteral antifungal medication, the second graft failed and the pupil was covered with a fibrinous membrane (Fig. 1B). The patient was left with bare hand-motion vision.


Published cases were identified by an electronic searching strategy of MEDLINE from 1966 to 1998 and of EMBASE from 1974 to 1998, without language restrictions. The reference lists of primary reports, review articles, and corneal textbooks were searched for additional relevant reports. Data extracted from the full articles included demographic information of donor and recipient, the donor's cause of death, the recipient's indication for keratoplasty, and the postoperative outcome.

Cases of postkeratoplasty fungal endophthalmitis after procedures performed from 1991 to 1998 were identified in the Adverse Reaction Registry of the Eye Bank Association of America (EBAA), a reporting system of postoperative events that may be related to donor eye tissue. Extracted data for candidal endophthalmitis included microbiologic data of the infected recipient eye and of the donor rim or medium.


Over 100,000 corneal transplants are done yearly worldwide. 13 Infection is among the most serious donor-related complications and fungi (especially Candida) are important causes of postkeratoplasty endophthalmitis. A summary of previously reported cases is presented in Table 1. Candida (especially C. albicans) accounts for nearly all cases of postkeratoplasty fungal endophthalmitis that are potentially attributable to the donor tissue and reported in the literature (Table 2) and to the EBAA (Table 3). Most had the same organism isolated from the donor rim or medium, and about one third involved pairs from a single donor. Each year, between 2 to 3 cases are reported to the EBAA, although 12 cases were reported in 1997–1998. 14Candida accounts for approximately 15% to 20% of endophthalmitis cases reported to the EBAA and may be emerging as one of the more common serious complications of corneal transplantation.

Summary of postkeratoplasty fungal endophthalmitis cases reported in the literature 1978–1998
Summary of linkage between contaminating organism and the causative organism in postkeratoplasty fungal endophthalmitis cases reported in the literature 1978–1998
Summary of linkage between contaminating organism and the causative organism in postkeratoplasty fungal endophthalmitis cases reported to the EBAA (1991–1998)

The prevalence of fungi on the normal conjunctival flora varies from 3% to 28%, 14–16 and fungi have been isolated in 2.5% to 6.5% of donor corneoscleral rims. 4,7,8,10,17 The prevalence of fungi may be increased with ocular surface disease and in environments conducive to fungal growth. For example, donors who have been on a ventilator for a prolonged period of time are more prone to harbor fungi, 18 and fungal ocular contamination may be more common in warm, humid climates.

The risk of developing fungal endophthalmitis after keratoplasty is related to the occurrence and concentration of fungal contamination of the donor eye or preservation medium. Several banking measures and fungicidal agents have been suggested to eradicate fungal contaminants. 18–22 Povidone-iodine rinse is used by many eye banks to reduce microbial contamination of donor eye tissue. Monitoring the color and turbidity of the storage medium is also done, despite its limitation in detecting fungal contaminants. 23 Although the conjunctival flora of the recipients cannot be excluded as a possible source of fungi for the endophthalmitis, the striking concordance of donor rim culture and recipient intraocular culture makes this unlikely.

Two techniques of storage of corneas for keratoplasty are available. In North America, where approximately 35,000 corneal transplants are performed yearly, cold storage at 4°C is widely practiced . In Europe, where approximately 22,000 transplants are done each year, organ culture at 34°C is more common. 24 Fungal contamination of organ-cultured corneas is variable, with a prevalence of 0.25% to more than 5%. 20,21,25 However, no case of fungal endophthalmitis has been reported in the literature using organ-cultured corneas, perhaps because amphotericin B is added to the organ culture media and microbiological screening is routinely performed before using the tissue. All reported cases of candidal endophthalmitis after keratoplasty are from donor corneas preserved with the cold-storage method.

Cold storage is more convenient and less costly but may carry a higher risk of transmitting fungal contaminants. Given the devastating outcome of candidal endophthalmitis, consideration must be given to the need for antifungal supplementation of cold storage media that is effective against Candida and other yeast and fungi, stable at various temperatures, and nontoxic to donor and recipient eyes. Amphotericin B 0.25 μg/mL has been successfully used in organ-culture media and may be a useful alternative to cold storage media. 23,24C. albicans, the prevalent cause of postkeratoplasty fungal endophthalmitis, is generally susceptible to a dose of less than 2 μg/mL. 26 Improved monitoring of fungal contamination during cold storage of donor corneas may also be warranted. These and other preventative strategies for reducing the risk of donor-to-host transmission of microbial infection should be a high priority for eye bankers and corneal researchers.


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Fungal endophthalmitis; Candida albicans; Keratoplasty; Storage medium; Eye banking

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