Medical Care

In vitro, minimum inhibitory concentration (MIC) data do not always correlate with in vivo MIC values. Therefore, these should only be used as a guideline.

The following drugs are used in the treatment of fungal endophthalmitis:

Amphotericin B
Fluconazole
Ketoconazole
Miconazole
Flucytosine
Itraconazole
Caspofungin

Systemic amphotericin has been the treatment of choice because of its broad-spectrum coverage; however, the penetration of the vitreous cavity is poor. Doses of 5- to 10-mg intravitreal amphotericin have been used. Retinal toxicity has been reported in animal models at these doses. Fluconazole and flucytosine have good intraocular penetration, but Candida species show high resistance to flucytosine.

A new systemic treatment is voriconazole; when administered orally or intravenously, it has good intravitreal concentrations. Intravitreal administration of voriconazole also seems safe without evidence of retinal toxicity with concentrations up to 25 mg/mL.

The echinocandins (caspofungin, micafungin, and anidulafungin) are newer agents that exert their antifungal activity by inhibiting D-glucan synthase, an enzyme involved in fungal cell wall synthesis. Because mammalian cells lack a cell wall, they also represent an ideal and specific target for antifungal therapy. Echinocandins exert antifungal activity against Candida and Aspergillus species.^[28]

In a double-blind multicenter trial of 239 patients, caspofungin was found to be as effective as amphotericin B in the treatment of candidemia. Patients were infused with either amphotericin B (0.6–1 mg/kg/d) or caspofungin as a single loading dose of 70 mg with a daily maintenance dose of 50 mg. In this cohort of patients, 7 patients with endophthalmitis were included and the endophthalmitis resolved in all 7 patients. Unfortunately, the authors failed to mention whether or not these 7 patients received caspofungin or amphotericin B. Significantly fewer drug-related adverse events occurred in the caspofungin group than in the amphotericin B group.^[29]

Gauthier et al reported a case of Candida endophthalmitis that failed treatment with caspofungin because of its poor penetration into the vitreous cavity.^[30]Given its limited vitreal penetration, the role of echinocandins remains to be determined in fungal endophthalmitis.

Surgical Care

The advent of pars plana vitrectomy has improved the treatment results of fungal endophthalmitis.

The advantages of pars plana vitrectomy are that it provides material for culture, removes viable organisms and inflammatory end products from the infected vitreous, and provides intravitreal access to antifungal agents (eg, amphotericin B).

Vitrectomy and intravitreal amphotericin B should be considered in those cases of endogenous fungal endophthalmitis where the disease is progressing despite initial therapy with an appropriate systemic antifungal agent.

As a general rule, moderate-to-severe vitreous involvement requires vitrectomy because most systemic antifungals have poor vitreous penetration.

Endogenous fungal endophthalmitis without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B.

Given the narrow therapeutic range of amphotericin B, it should not be given in a gas-filled eye.

Some authors have advocated the use of 400 µg of intravitreal dexamethasone as an adjuvant.

Consultations

Because endogenous fungal endophthalmitis frequently is an ocular manifestation of a systemic disease, the patient requires a multidisciplinary approach.

Prevention

Once a positive fungal culture is obtained, the patient should be started on systemic antifungals. At the same time, an ophthalmologic consultation should be obtained. In 2 different studies using this protocol, the incidence of endogenous fungal endophthalmitis was reported to be only 3-9%.

Long-Term Monitoring

Patients should receive follow-up care as needed. Optical coherence tomography (OCT) may assist in the follow-up of patients with fungal endophthalmitis. A small retrospective case series of 12 eyes of 7 patients showed 2 patterns of posterior segment involvement of fungal endophthalmitis. Fifteen eyes demonstrated chorioretinal infiltration on OCT imaging, whereas 5 eyes showed inner retinal/retinal vascular infiltration without choroidal involvement. The presence of optic nerve edema, epiretinal membranes, and subretinal fluid also was noted. Upon successful treatment, these OCT abnormalities resolved.^[31]

Further Inpatient Care

Many patients with fungal endophthalmitis are hospitalized. Patients may require intravenous medications.

Two dilated ophthalmic examinations still should be considered, even in asymptomatic patients with fungemia.^[32]

Guidelines

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Author

Lihteh Wu, MD Ophthalmologist, Costa Rica Vitreo and Retina Macular Associates

Lihteh Wu, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Club Jules Gonin, Macula Society, Pan-American Association of Ophthalmology, Retina Society

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Bayer; Quantel Medical, Roche; Iveric Bio<br/>Received income in an amount equal to or greater than $250 from: Bayer Health; Quantel Medical, Roche, Iveric Bio.

Coauthor(s)

Dhariana Acón, MD Ophthalmologist, Caja Costarricense Seguro Social, Hospital de Guapiles, Costa Rica

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

R Christopher Walton, MD Adjunct Professor, Department of Ophthalmology, University of Texas Health Science Center at San Antonio

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American Uveitis Society

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.