Main

Sir,

Candida retinitis is a sight-threatening ocular infection that frequently occurs as a complication of candidemia. Voriconazole is a recently introduced broad-spectrum antifungal drug. To the best of our knowledge, its use in candida retinitis and candida endophthalmitis has not been reported before.

Case report

A 39-year-old ‘terminally ill’ woman with known systemic candidiasis secondary to central venous line infection was referred to the ophthalmic ‘on call team’. She complained of bilateral simultaneous visual deterioration of 1-week duration. Her past medical history included hyperactive thyroid associated with paroxysmal atrial fibrillation. She had recently undergone major gastrointestinal surgery for extensive small bowel infarction and developed postoperative sepsis. Ocular examination included bedside visual acuity (VA), intraocular pressure measurement using Perkins tonometer, direct ophthalmoscopy, and indirect ophthalmoscopy. Slit-lamp examination was not possible. Her corrected VA was 5/60 in the right eye and 6/60 in the left eye. Anterior segment examination was unremarkable with absence of a relative afferent pupillary defect and normal intraocular pressures. Fundus examination of both eyes revealed multiple, creamy white retinal lesions at the posterior pole (Figures 1 and 2). The overlying vitreous appeared clear, although detailed slit-lamp evaluation was not possible. A diagnosis of bilateral candida retinitis was made. Candida had been cultured from her blood, urine and sputum samples; however, information on drug sensitivities was not available at the time of treatment. Over the next few days, both general and ocular condition deteriorated despite high doses of intravenous fluconazole (800 mg daily for 2 weeks), therefore it was decided to use oral Voriconazole (4 mg/kg bodyweight) instead.

Figure 1
figure 1

Right eye fundus photograph showing multiple areas of candida retinitis with associated haemorrhages at posterior pole.

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Figure 2
figure 2

Left eye fundus photograph.

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After 2 days, the retinal lesions were seen to decrease in size. The patient was reviewed daily and 2 weeks later the lesions were significantly smaller in size. The same consultant ophthalmologist who had examined the patient prior to treatment with voriconazole noted the post-treatment clinical improvement. Unfortunately, the patient demised due to cardio-respiratory arrest and further follow-up including photographic documentation of clinical improvement following use of voriconazole was not possible.

Comment

Candidiasis is an opportunistic infection of intravenous drug users and debilitated patients. Ocular candidiasis can result from either haematogenous spread or direct inoculation and is characterised by anterior and/or posterior segment inflammation. Candida retinitis is characterised by small, round, white slightly elevated lesions that enlarge and extend into the vitreous cavity-forming floating white colonies. Endophthalmitis and severe retinal necrosis are seen in the advanced stage.1 Predisposing factors for endogenous candida endophthalmitis (ECE) include indwelling catheters, bacterial sepsis, prolonged broad-spectrum antibiotic use, and gastrointestinal surgery.2 In patients with candidaemia, the reported incidence of ECE is 28–37%. In spite of modern antibacterial, antimycotic, and operative therapies, ECE has a very poor prognosis and is associated with high mortality.

While use of amphotericin B and fluconazole in invasive fungal infections is well documented, the optimal management of candidal retinitis has not been determined.3 Amphotericin penetrates poorly into ocular fluids, is toxic, and must be given intravenously. Fluconazole is a bis-triazole derivative proven highly effective against candida. However, it is more effective in preventive use than in therapeutic use against ECE. In the treatment of patients with marked vitreous infiltrates from ECE, pars plana vitrectomy, appropriate systemic, and intravitreal antifungal medication are generally recommended.

Voriconazole, a member of second-generation antifungal triazoles, is a broad-spectrum antifungal agent with demonstrated in vitro activity against azole resistant species of Candida and Aspergillus.4 Voriconazole has good oral and parenteral bioavailability.5, 6 Voriconazole exhibits nonlinear pharmacokinetics. An apparent low volume of distribution (2 l/kg) suggests widespread distribution of the drug throughout the body tissues and fluids. Voriconazole levels in the cerebrospinal fluid appear to be the same as in serum. Information on penetration to sites such as eye is limited. The chief adverse effects reported are transient visual disturbances, hepatotoxicity, and skin reactions. Visual disturbances include enhanced light perception, blurred vision, photophobia, and colour vision changes.5, 7 These have been reported in 23–35% of patients. They generally occur within 30 min of dosing and most frequently during the first week of therapy.7 The majority of these events are mild and resolve even if treatment is continued.

Lewis et al8 studied antifungal activity in an in vitro model of Candidia catheter-related bloodstream infection. They ranked overall antifungal activity as amphotericin B > voriconazole > fluconazole.

Garbino et al4 reported successful treatment of Paecilomyces lilacinus endophthalmitis with oral voriconazole. Treatment with voriconazole was considered when the patient failed to improve on systemic fluconazole and oral itraconazole.

In our patient, the treatment was switched to oral voriconazole following deterioration on intravenous fluconazole.

Conclusion

Candida endophthalmitis can be the only manifestation of disseminated candidiasis. Early recognition is essential to prevent irreversible loss of vision. This case report suggests that voriconazole may have a role as primary treatment of endogenous candida endophthalmitis or in patients resistant to fluconazole.