Aspergillus terreus Endogenous Endophthalmitis in a Nonimmunocompromised Patient with a History of Bronchiectasis

Abstract

To present the first case of Aspergillus terreus endophthalmitis in a patient without previous ocular surgery or immunocompromised status with a review of literature.

• Aspergillus
• bronchiectasis
• endophthalmitis
• immunocompetent
• vitrectomy

Aspergillus is a rare pathogen and typically occurs with a background of immunosuppression including malignancies and diabetes. The species commonly associated with disease are Aspergillus flavus and Aspergillus fumigatus.1 Infections caused by A. terreus infections are uncommon and A. terreus endophthalmitis is uncommonly reported in the literature. We report a case of A. terreus endophthalmitis in a patient with bronchiectasis, but without prior intraocular eye surgery or history of immunosuppression.

A 35-year-old Chinese woman, who was a nonsmoker and not clinically immunocompromised, presented with swelling of the right eye with rapid deterioration of vision over 5 days. She had been investigated by her internist over the prior 5 months for an exacerbation of her longstanding bronchiectasis. However, all systemic and radiologic investigations for an underlying etiology were inconclusive. Systems review revealed that she had been experiencing flu-like symptoms for 1 week prior to presentation. There was no significant family medical or ocular history.

On examination, her best-corrected vision was hand movements in the right eye. Anterior segment evaluation revealed conjunctival injection, anterior chamber cells 3+ with fibrin but no hypopyon. There were focal areas of posterior synechiae with medium-sized keratic precipitates. Intraocular pressure was 10 mmHg on Goldmann applanation tonometry. No fundal view was possible on binocular indirect ophthalmoscopy due to a grade 4 severity vitritis. B-scan ultrasonography corroborated moderate-to-dense dispersed clumps of vitreous opacities and posterior ocular coat thickening with focal areas of vitreoretinal adhesions. There was no retinal detachment. The clinical presentation was consistent with severe right panuveitis. Her left eye was normal with a visual acuity of 6/9. Systemically she was apyrexial.

Blood investigations showed raised erythrocyte sedimentation rate (ESR) 67 mm/h and total white cell count 10.9 × 10⁹cells/L (polymorphs 73.0%, lymphocytes 20.8%). Infective screen was negative for syphilis, toxoplasma, human immune deficiency virus (HIV), and tuberculosis (TB). Autoimmune screen was negative for antinuclear antibody (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA). A presumptive diagnosis of endogenous endophthalmitis was made. A vitreous needle biopsy was performed with presumptive injections of intravitreal vancomycin, ceftazidime, and ganciclovir. Intravenous acyclovir was also commenced as empirical treatment for acute retinal necrosis. Biopsy samples sent for tetraplex polymerase chain reaction (PCR) detection were negative for Toxoplasma gondii, herpes simplex virus, varicella zoster virus, and Cytomegalovirus. Microbiological cultures, including fungal and TB cultures, were also negative. A repeat biopsy and antibiotic injection was performed 3 days later with similar negative findings and there was no clinical improvement. A trial of intravenous methylprednisolone 1 g daily for 3 days resulted only in mildly decreased vitritis with a mild subjective improvement of vision.

In view of her lack of clinical improvement, a diagnostic and therapeutic vitrectomy was performed. Vitreous biopsy samples showed fungal elements on 10% KOH wet mount examination and fungal cultures yielded filamentous fungi from two separate samples; this velvety, cinnamon brown fungus was subsequently identified as Aspergillus terreus (Figure 1) by matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS), and sequence analysis of the internal transcribed spacer (ITS) region. Postoperatively, the patient was commenced on intravenous voriconazole 400 mg twice daily (12.6 mg/kg/day) for 2 days and maintained on oral voriconazole 200 mg twice daily (6.8 mg/kg/day) for a total of 5 months. After 10 days of anti-fungal treatment, her cough resolved with improvement corroborated on serial chest CT scans. The ocular inflammation quietened and stabilized without further recurrences. Vision in her right eye improved to counting fingers, but improvement was limited by the presence of a thick epiretinal membrane.

FIGURE 1.  Lactophenol cotton blue mount showing filamentous fungi with biseriate phialides covering upper surface of the vesicle typical of Aspergillus terreus. Magnification × 400 863 × 647 mm (96 × 96 DPI).

A. terreus endophthalmitis has been described in the literature in association with immunocompromised states, including intravenous drug abuse, hematological malignancies, or after ocular surgery. Our patient neither was clinically immunocompromised nor had a history of prior ocular surgery. There have been 8 cases of A. terreus endophthalmitis described previously: 5 were endogenous in immunocompromised individuals associated with malignancy (especially hematological), chemotherapy, corticosteroid use, and iatrogenic immunosuppression, 2 in postcataract surgery, and 1 due to penetrating intraocular trauma.2–9

A. terreus endophthalmitis shares similar clinical characteristics with other cases of Aspergillus endophthalmitis. The patients typically present with unilateral mild ocular discomfort and gradual vision loss over a few days. Conjunctival injection with a severe anterior uveitis may occur. Posterior segment findings often reveal moderate-to-severe vitritis with large vitreous clumps, yellowish exudative retinal lesions frequently involving retinal vessels, associated pre- and intraretinal hemorrhages, and ischemic retinal vascular occlusions. Pseudohypopyon and exudative retinal detachments have also been described.10

Diagnosis is often difficult and delayed diagnosis is a common problem. Within the context of an appropriate clinical history, clinicians need to approach these cases with a high degree of clinical suspicion. It is important to establish an early diagnosis, as early treatment is correlated with better final visual acuity.11 Anterior and posterior chamber isolates should be taken for microbiological culture and PCR analysis. Corroborative isolates from other body sites may aid the diagnosis in disseminated cases. However, the sensitivities of vitreous needle biopsies and PCR analyses are reported to be only about 50 and 72%, respectively. Vitrectomy biopsies in these cases may have the highest yield, with sensitivity reported at 90%.12 Early vitrectomy should be considered in cases refractory to treatment, as larger volumes of sample can be obtained more safely for analysis. Multiple vitrectomies may sometimes be necessary before a positive growth is obtained due to the fastidious nature of fungus. Therapeutic vitrectomy has also been shown to improve outcomes.4,7,10

Diagnosis is complicated by the fact that A. terreus is commonly considered a laboratory contaminant. This assumption may further delay the diagnosis, as positive samples with A. terreus may be dismissed.3 As such, clinicians need to have a high index of suspicion of uncommon fungal infection based on the patient's clinical presentation of symptoms and signs.

Systemic and intravitreal amphotericin B has long been the standard treatment for endogenous Aspergillus endophthalmitis. However, A. terreus has been described to exhibit resistance to amphotericin B in up to 98% of isolates.13 Alternative systemic antifungals that have been advocated include itraconazole and voriconazole. Voriconazole has an oral bioavailability of 96% in patients with normal gastrointestinal absorption and achieves therapeutic aqueous and vitreous levels in noninflammed human eyes.14 The use of intravitreal voriconazole alone has been shown to be effective in case reports.7,11

Chronic pulmonary aspergillosis is a smouldering infection that is hard to diagnose and identify systemically. A. fumigatus is almost always the causative organism. In our case, although all medical tests supported that she was immunocompetent, her bronchiectasis could have been caused by a chronic A. terreus infection, which had then spread to her eye. Previously, our patient had been investigated extensively in Australia and Malaysia for bronchiectasis, but she was not keen on more invasive tests for this episode and her CT scans did not suggest any active or previous disease characteristic of Aspergillus involvement. We acknowledge that chronic bronchiectasis is a form of immunocompromise. However, given the time sequence of her illness, it was likely that the cause of her bronchiectasis was A. terreus, which eventually resulted in endophthalmitis through hematogenous spread.

To conclude, A. terreus is typically an opportunistic pathogen in susceptible individuals but we have demonstrated that it can also occur in relatively healthy individuals, possibly if they have been exposed to a high level of environmental Aspergillus. Early diagnostic and therapeutic vitrectomy is useful for obtaining sufficient samples for organism identification and also to reduce organism load and inflammatory mediators in the eye. Voriconazole has emerged as an effective antifungal agent with good bioavailability and efficacy against A. terreus. A high index of suspicion for fungal endophthalmitis is necessary in posterior uveitides not responding to standard microbial antibiotics or steroid treatment.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.