Overview
Candida can be implicated as causes of both exogenous endophthalmitis (following surgery or trauma) and endogenous endophthalmitis due to hematogenous seeding of the eye. Candidal exogenous endophthalmitis is comparatively rare. Reported cases have been linked to eye surgery (keratoplasty, cataract extraction), traumatic ulcers, and contaminated ophthalmic irrigation solutions [210, 1166, 1293, 1477, 2434]. Most cases of exogenous endophthalmitis have a bacterial etiology.
Conversely, Candida is recognized as the most common cause of endogenous endophthalmitis and that will be the focus of our discussion here. Embolic seeding of Candida spp. into the retina may cause both retinal and vitreal lesions that can leave important visual sequela. Interestingly an appropriate immune response seems to be necessary for this condition to become manifest [1023]. Neutropenic patients rarely develop clinically apparent candidal endogenous endophthalmitis.
Epidemiology
Up to 78% of cases of autopsy-proven invasive candidiasis show signs of retinal involvement [650]. Prospective studies performed during the 1980’s reported variable incidence of candidal endophthalmitis (range 5-78%, median 29%) among non-neutropenic populations with, or at high risk for, candidemia [324, 1022, 1723].
| Reference | # Cases with candidemia | # Cases with classic retinal lesions | Incidence(%) |
|---|---|---|---|
| [1212] | 21 | 11 | 53 |
| [1022] | 9 | 7 | 78 |
| [1723] | 38 | 11 | 29 |
| [993] | 43 | 2 | 5 |
| [324] | 32 | 9* | 22 |
| TOTAL | 143 | 40 | Median: 29 |
* 2 cases of Roth’s spots in patients without bacteremia were included in this study.
It seems that the early use of antifungal agents in patients with candidemia has reduced both the incidence and severity of this complication [198, 607]. Data from a randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in non-neutropenic patients, revealed an incidence of classic progressive candidal endophthalmitis of only 1% [1904].
Intravenous drug abusers represent a unique population at risk for candidemia in whom symptomatic and advanced endophthalmitis is usually a marker of invasive candidiasis [24, 463, 1063, 1281, 1514, 2007, 2120, 2133, 2156, 2173].
Candida Endophthalmitis and Candida species
C. albicans is responsible for most cases [1142].
| Reference | #Cases with endophthalmitis | Frequency per species(%) | ||||
|---|---|---|---|---|---|---|
| C. abicans | C. tropicalis | C. glabrata | C. parapsilosis | Other species | ||
| [1212] | 11 | 81 | 0 | 19 | 0 | 0 |
| [1022] | 7 | 100 | 0 | 0 | 0 | 0 |
| [1723] | 11 | 91 | 9 | 0 | 0 | 0 |
| [993] | 2 | 50 | 50 | 0 | 0 | 0 |
| [324] | 9 | 67 | 0 | 0 | 1 | 2* |
* 2 non-specified “non-albicans” species
Clinical Manifestations
Typical lesions of candidal endophthalmitis are whitish chorioretinal spots with filamentous borders protruding into the vitreous and causing vitreal haze. These lesions can be single or multiple, isolated or confluent, and preceded or not by other less specific findings, including cotton wool spots, retinal hemorrhages, and white centered hemorrhages (also known as Roth spots).
In an outstanding review of 76 cases of Candida endophthalmitis, Edwards et al. noticed that one quarter of cases also had exudates with associated hemorrhages. However, because of the unspecificity of these retinal lesions and the overlap of underlying medical conditions (diabetes, hypertension, bacterial sepsis, retinopathy of AIDS, etc.) that produce the same type of lesions among patients at high risk to develop candidemia, they are of limited clinical applicability [1947].
Occasionally embolic lesions can affect other eye structures producing conjunctivitis [650], episcleritis [2133], iritis [1529], or iris abscesses [1529]. Severe vitritis and anterior chamber involvement are classically seen in advanced stages of the disease, usually related to a delay in initiation of appropriate therapy [24, 247].
If a funduscopic exam is performed at the time that candidemia is either suspected or proven, the large majority of patients with positive findings will be asymptomatic [324]. Also, patients who are severely ill or incapable of communicating (e.g., neonates) will of course offer no complaints.
Therefore, by the time Candida endophthalmitis becomes symptomatic, about two thirds of patients have bilateral disease and more than half have multiple lesions and vitreous involvement [650, 904]. Symptoms at this stage of the disease include decreased vision (either related to macular involvement or to large vitreous lesions), eye discomfort, foreign body sensation (associated with iridocyclitis), floaters, eye redness in cases with advanced iritis, and pain in cases with advanced iritis.
Specific Diagnostic Strategies
A funduscopic examination with pupillary dilatation should be routinely performed in patients with candidemia. While some authors have suggested use of eye examinations in cases of suspected invasive candidiasis [2407], we find these examinations to have low sensitivity. It is preferable this examination be done by an ophthalmologist, as small lesions are easily overlooked.
If an eye examination is performed early during the course of invasive candidiasis, most identified lesions will be limited to the retina. If disease is found that extends beyond the retina, a diagnostic and therapeutic vitrectomy is useful. Centrifugation of vitreous specimen or passage through a millipore filter for subsequent stain and culture is recommended. Calcofluor white staining can help to identify small numbers of fungi.
Blood cultures should be performed as well. However, if the patient is presenting with symptomatic eye disease, these cultures are usually negative. Concomitant endocarditis is possible, especially among IV drug abusers [247].
Therapies
All data for the treatment of candidal endophthalmitis come from case reports and animal models. No data is available to recommend with certainty which agent, procedure, or length of therapy is the best. We suggest systemic fungal therapy as for invasive candidiasis with close ophthalmologic follow-up. If lesions extend into the vitreous or progress into the vitreous despite adequate antifungal therapy, therapeutic pars plana vitrectomy should be considered. [463, 1450, 2120].
Amphotericin B has poor vitreal penetration. Intravitreal administration of this drug is recommended at the time of performing vitrectomy. A dose of 5 micrograms should be used [2156].
Fluconazole penetrates freely into the eyes, specially if tissue is inflammed [2035]. Although, animal models have not been very encouraging about the efficacy of this drug [729, 1140], Akler et al. recently reported on 16 infected eyes, 15 of which were cured after receiving fluconazole as sole therapy at ~200 mg/d for approximately two months [35].
Very limited data exist on the use of lipid preparations of Amphotericin B for the treatment of Candida endophthalmitis [2328].