Abstract & Commentary

Candida Chorioretinitis and Endophthalmitis

By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford University, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Synopsis: While 16% of patients with candidemia had possible or probable ocular involvement, only 6 of 370 (1.6%) developed endophthalmitis.

Sources: Oude Lashof AM, et al. Ocular manifestations of candidemia. Clin Infect Dis 2011;53:262-268.

Oude Lashof and colleagues examined the incidence and outcomes of patients with ocular involvement in a randomized, clinical trial comparing treatment of non-neutropenic patients with candidemia with either voriconazole or amphotericin B followed by fluconazole.1 In that study, no significant differences in overall outcome between treatment arms were detected in the 370 patients who constituted the modified intent-to-treat population and who are the subjects of this substudy. All patients underwent dilated retinal examination at baseline, 7 days, 2 weeks, and 6 weeks after the end of treatment.

Abnormalities thought to be consistent with ocular candidiasis were detected in 60 patients (16%). The ocular lesions were detected at baseline in 49 of the 60 patients (81.7%), while the remaining abnormalities were first seen at follow-up examinations. Twenty had possible, and 40 had probable ocular candidiasis. Among those with probable disease, only 6 had endophthalmitis, with vitritis or "fluffy" lesions extending into the vitreous. One of these patients, with negative retinoscopy at days 1 and 8, and whose central venous catheter was not removed until day 10 of therapy, was first detected after 18 days of treatment. The remaining 36 with probable ocular candidiasis had chorioretinitis defined as deep focal white infiltrates in the retina or hemorrhages, Roth spots, or cotton wool spots with absence of other explanation, such as diabetes mellitus or hypertension, present. If these chorioretinal findings were seen in patients with diabetes, hypertension, or bacteremia, as was true in 20 patients (33.3%), they were classified as possible ocular candidiasis. Designation as proven ocular candidiasis required vitreous sampling, which was not performed in any patient.

Ocular involvement was associated with a somewhat more prolonged duration of candidemia. The median interval from the day of randomization to a first negative blood culture was 4 days (range, 1-18 days) in those with and 3 days (range, 1-26 days) in those without ocular involvement, a difference that was statistically significant (P = 0.026). When compared to infection with other species, patients with bloodstream infection with Candida albicans were more likely to have ocular involvement, while those infected with Candida parapsilosis were less likely to develop this complication.

Of the 6 patients with endophthalmitis, 2 died before repeat retinal examination was performed, 3 had resolution, and 1 (the patient in whom extension of the infection into the vitreous was detected at day 18 of therapy after failure to remove his central venous catheter until day 10) was classified as a therapeutic failure when treatment was discontinued for unknown reasons.

Treatment of probable Candida chorio-retinitis was successful in 24 of 34 patients (71%), unevaluable in 9, and classified as a failure in 1 patient whose candidemia relapsed with a new retinal lesion after apparently successful initial therapy. No patient with chorioretinitis progressed to endophthalmitis during systemic treatment.

None of the patients received intra-vitreous therapy, so all responses were presumably the result of systemic therapy with the study drugs, whose administration was not apparently prolonged in response to the detection of ocular lesions. The antifungals were administered for a median of 14 days after the first negative blood culture in both those with and without eye involvement.

Commentary

The phrase "Candida endophthalmitis" often is inappropriately used to describe all forms of endogenous infection of the eye with this fungus. This study illustrates the importance of maintaining the distinction between infection restricted to chorioretinal layers and involvement of the vitreous, for which the term endophthalmitis in this context should be reserved.

The frequency of detection of ocular lesions in patients with candidemia has been reported to be 0%-78%,2 an absurdly broad range. Nonspecific retinal lesions, such as cotton wool spots and superficial retinal hemorrhages, have been reported to be present in 11%-20% in most recent studies. The picture is further clouded by the fact that such lesions have been reported in 12%-26% of patients with bacteremia in the absence of candidemia. In these reports, however, many patients had confounding illnesses, such as diabetes mellitus.

In this study, as in most others, ocular candidiasis was most often asymptomatic. Thus, at baseline, only 1 patient reported decreased visual acuity, while only the 1 patient in whom endophthalmitis developed during treatment complained of visual loss. This observation is, of course, complicated by the inclusion of critically ill patients in whom visual changes may be underreported.

Ocular lesions were first detected after initial negative examinations in one-fifth of affected patients. Patients whose fungemia persists longer than 3 days after the initiation of therapy may be at increased risk of ocular involvement, as may patients whose infection is caused by C. albicans. Infection with C. parapsilosis appears to be associated with a lesser risk of eye involvement. The authors recommend that performance of dilated fundoscopy in all patients with candidemia be performed at least 1 week after the initiation of systemic antifungal therapy and that all patients with ocular involvement have follow-up examinations.

It can, however, be asked whether careful and repeated retinal examinations affect outcome. In this study, all patients with chorioretinitis had favorable ocular outcomes. In addition, only 1.6% of patients had endophthalmitis and there was no evidence that its presence necessitated alteration of the planned therapy, with no need for intravitreal therapy or prolongation of systemic administration of antifungals. Similarly, in a study comparing caspofungin to amphotericin B in patients with invasive candidiasis (approximately 80% were candidemic), ocular lesions consistent with Candida endophthalmitis (not clearly defined) were detected in 7 of 217 (3.7%) and all resolved after the end of therapy, without added intervention.3

References

  1. Kullberg BJ, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: A randomised non-inferiority trial. Lancet 2005;366:1435-1442.
  2. Rodríguez-Adrián LJ, et al. Retinal lesions as clues to disseminated bacterial and candidal infections: Frequency, natural history, and etiology. Medicine (Baltimore) 2003;82:187-202.
  3. Mora-Duarte J, et al; Caspofungin Invasive Candidiasis
  4. Study Group. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002;347:2020-2029.