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  • Case report
  • Open Access
  • Open Peer Review

Candida glabrata endophthalmitis following penetrating keratoplasty in a patient with negative donor rim culture

  • 1,
  • 1,
  • 1 and
  • 1Email author
BMC Ophthalmology201010:18

https://doi.org/10.1186/1471-2415-10-18

  • Received: 10 February 2010
  • Accepted: 11 June 2010
  • Published:
Open Peer Review reports

Abstract

Background

Candida glabrata endophthalmitis following keratoplasty is rare and almost always associated with positive donor rim culture.

Case presentation

A 63-year-old patient, diagnosed Fuch's endothelial dystrophy in both eyes underwent a penetrating keratoplasty in his right eye. He had multiple underlying medical problems, which included diabetes mellitus, hypertension, hypoadrenalism on oral dexamethasone and fatty liver secondary to hypertrigliseridemia. He developed multiple suture abscesses, corneal haziness, retrocorneal white plaques and a level of hypopyon two weeks after an uneventful penetrating keratoplasty in his right eye. Cultures of the donor button and the transport media culture were negative. Candida glabrata was isolated successfully from the aqueous and vitreous taps. He was treated with a combination of topical, intracameral, intravitreal and intravenous Amphotericin B. His final visual acuity remained poor due to the haziness of the corneal button.

Conclusion

Candida glabrata endophthalmitis following penetrating keratoplasty can occur in negative donor rim and transport media cultures. The growth of the organism is facilitated by the patient's immunocompromised status. Awareness by the ophthalmologists and appropriate choice of antibiotics are mandatory in this challenging condition.

Keywords

  • Fluconazole
  • Endophthalmitis
  • Candida Glabrata
  • Final Visual Acuity
  • Bullous Keratopathy

Background

Candida glabrata is a very rare cause of endophthalmitis following penetrating keratoplasty. We reviewed 12 reported cases of Candida glabrata endophthalmitis following penetrating keratoplasty with varying onset from 1978 to 2010, in which most of them had positive donor rim culture.

We report on a case of Candida glabrata endophthalmitis following an uneventful penetrating keratoplasty in an immunocompromised patient. Cultures of the donor rim and transport media did not grow any microorganism. The organism was successfully isolated from both, the aqueous and vitreous taps. A prompt recognition and appropriate management are essential in this condition.

Case presentation

A 63-year-old gentleman with Fuch's endothelial dystrophy in both eyes underwent a penetrating keratoplasty in his right eye. He had multiple underlying medical problems, which included diabetes mellitus, hypertension, fatty liver secondary to hypertrigliseridemia and hypoadrenalism. He had been on oral dexamethasone 5 mg morning and 2.5 mg night dose since 3 years ago.

The donor cornea was harvested eleven hours postmortem from a 56-year-old gentleman who died from peritonitis secondary to perforated appendicitis, with underlying pulmonary hypertension, valvular heart disease and chronic obstructive pulmonary disease. Donor tissue was stored for nine days at 4°C in Optisol-GS culture solution.

The pre-op visual acuity was 6/60 with no improvement with pinhole in the right eye and hand movement with good projection of light in the left eye. There was evidence of bullous keratopathy and guttata at the endothelial layer of cornea in both eyes. The right eye was pseudophakic. There was a dense cataract in his left eye. The intraocular pressure was normal in both eyes. Pre-operative B-scan ultrasonography confirmed an intact retina with clear vitreous. Systemic evaluations included full blood picture and chest x-ray did not reveal foci of infection.

The penetrating keratoplasty was uneventful. On day one postoperatively, his visual acuity was counting fingers at 2 feet. There was a generalized epithelial defect over the whole corneal button. The epithelium healed completely after ten days.

At two weeks postoperative period, he complained of pain in the right eye and his visual acuity deteriorated to hand movement. The conjunctiva was congested and the corneal became hazy. There were multiple suture abscesses with retrocorneal plaques and a level of hypopyon (Figure 1). B-scan ultrasonography showed evidence of vitreous abscesses and a flat retina (Figure 2).
Figure 1
Figure 1

Anterior segment photograph showing multiple suture abscesses and retrocorneal white plaques at the donor host interface at 2 weeks postoperative period.

Figure 2
Figure 2

B-scan ultrasonography showing evidence of vitreous abscess with an intact retina in his right eye

There was no organism isolated from either the cultures of donor corneal rim or transport medium. However, both the aqueous and vitreous taps grew Candida glabrata. Conjunctiva swab from the fellow eye and blood culture were negative.

He was treated with a combination of treatment, which included topical Amphotericin B 0.15% hourly and 0.5 mg/kg/day of intravenous Amphotericin B daily for the duration of six weeks. An intravitreal injection of 5 μg Amphotericin B was given once while performing the aqueous and vitreous taps. 5 μg of Amphotericin B was injected intracamerally two weeks later. He was monitored closely for signs of Amphotericin B toxicity.

He did not develop any toxic effect or serious complication during the therapy except for a minimal elevation of liver enzymes. He showed an encouraging clinical improvement, though his final visual acuity remained poor due to the haziness of the corneal button.

Conclusions

Candida glabrata endophthalmitis following penetrating keratoplasty is very rare but has devastating effects. It typically occurs within the first and second week post penetrating keratoplasty [14]. In contrast, there were cases occurred as early as 10 hours post transplantation or as late as 5 months post surgery [57]. Our patient developed features of endophthalmitis at two weeks post penetrating keratoplasty.

Candida glabrata, formerly known as Torulopsis glabrata is a non-dimorphic/haploid yeast that has recently emerged as an important nosocomial pathogen [8]. It can be found in normal healthy skin, respiratory, genitourinary and gastrointestinal systems. It is a highly opportunistic pathogen of the urogenital tract and the blood stream.

The prevalence is high in HIV positive patients and the elderly, other risk factors include prolonged hospitalization and prior antibiotic use [8]. Infection with Candida glabrata can be mucosal or systemic, and occurs more commonly in an immunocompromised or a debilitated host.

Table 1 summarizes 12 reported cases of Candida glabrata endophthalmitis in the literature from 1998-2010. All of the cases had either positive cultures of donor rim or transport medium [17, 912]. Both negative donor rim and transport medium cultures in postkeratoplasty endophthalmitis caused by Candida glabrata has never been reported previously. To the best of our knowledge, this is the first reported case of Candida glabrata postkeratoplasty endophthalmitis with negative donor rim and transport medium cultures.
Table 1

Comparison between previously reported cases of Candida glabrata endophthalmitis following penetrating keratoplasty

Author/Year

Age/Gender

Indication for PK

Onset of endophthalmitis

Culture

Treatment

Side effects

Larsen PA et al, 1978

76/Female

Aphakic bullous keratopathy

48 days

Positive (donor rim and fluid)

Topical and intravenous amphotericin B, oral and topical flucytosine

Renal toxicity; death

Cameron JA et al, 1991

22/Male

Keratoconus

7 days

Positive (donor rim)

Intravitreal amphotericin B, subconjunctival miconazole, topical natamycin,oral flucytocine

Not stated

Antonios et al, 1991

30/Male

Cornea scar

11 days

Positive (donor rim)

Not stated

Not stated

Cameron JA et al, 1998

46/Male

Cornea scar

3 weeks

Positive (donor rim)

Not stated

Not stated

Chapman FM et al, 1998

43/Male

Keratoconus

4 days

Positive (transport medium)

Topical,intracameral and subconjunctival amphotericin B

Nil

Garcia-Valenzuela E et al, 2005

85/Female

Fuch's endothelial dystrophy, pseudophakia

5 months

Positive (donor rim)

Oral fluconazole, intravitreal and intrastromal amphotericin B,

Not stated

Keyhani et al, 2005

82/Female

Pseudophakia corneal oedema

1st to 2nd week

Positive (donor rim)

Not stated

Not stated

Grueb M et al, 2006

26/Male

Keratoconus

10 hours

Positive (transport medium)

Systemic fluconazole, Topical and intracameral amphotericin B

Nil

Al Assiri A et al, 2006

69/Male

Trachomatous scarring

5 months

Positive (donor rim)

Topical and intracameral amphotericin B, systemic fluconazole

Not stated

Caldwell MC et al, 2009

57/Male

Post LASIK keratectasia

10 days

Positive (donor rim)

Oral fluconazole, intravitreal and topical amphotericin B, topical and oral voriconazole

Liver toxicity

Tappeiner C et al, 2009

70/Female

Fuch's endothelial dystrophy

1 day

Positive (donor rim)

Oral fluconazole, topical and subconjunctival amphotericin B, intravenous liposomal amphotericin B and intravenous caspofungin

Not stated

Tappeiner C et al, 2009

53/not stated

Fuch's endothelial dystrophy

1 day

Positive (donor rim)

Oral fluconazole and voriconazole; intracameral and subconjunctival Amphotericin B, intravenous liposomal amphotericin B and intravenous caspofungin

Renal toxicity

Current study

63/Male

Fuch's endothelial dystrophy

2 weeks

Negative (donor rim and transport medium) Positive (recipient AC and vitreous tap culture)

Topical, intravenous, intravitreal and intracameral amphotericin B

Nil

Cultures of the donor rim and transport medium were negative in our patient. However, the organism was isolated successfully from the aqueous and vitreous cultures. It seems most likely that an unrecognized Candida glabrata infection was present in the affected eye of the recipient. It is less likely that the contamination occurred during keratoplasty as it was performed under strictly sterile condition. We believe that the patient's immunocompromised status facilitated the infection process.

Candida glabrata is resistant to fluconazole and the other azoles group of antifungal but sensitive to Amphotericin B [8]. Several mechanisms of azole resistance have been identified, that include increased P-450-dependent ergosterol and an energy-dependent efflux pump of fluconazole, possibly via a multidrug resistance-type transporter [13, 14]. Secondary in vitro resistance is the most common form of resistance in candida glabrata [15]. The reason for this rapid development of secondary antifungal resistance is unknown, but the haploid state of candida glabrata is thought to be a contributing factor [8].

In contrast, in vitro resistance of candida glabrata and candida albicans to ketoconazole and itraconazole accounts for only 15% but yet still significant [8]. Flucytosine resistance has been described extensively in candida albicans but not in candida glabrata. It has not been widely used in candida glabrata infections but may be useful in the future.

Fortunately, clinically significant amphotericin B resistance is still very uncommon among most Candida species and amphotericin B resistance has not been described in candida glabrata. In general, intracameral, intravitreal, intrastromal, subconjunctival, topical and systemic Amphotericin B have been used in the treatment of the Candida glabrata endophthalmitis [1, 47, 9, 10, 12].

Two patients developed renal toxicity after the treatment with intravenous Amphotericin, one of them subsequently died [10, 12]. Liver toxicity had been reported in a patient who was treated concurrently with oral fluconazole [4]. Beside the above mentioned side effects, there were no documented serious complications in Candida glabrata endophthalmitis patients treated with various methods of Amphotericin B delivery (Table 1).

Fortunately, our patient did not develop any side effect during the course of Amphotericin B treatment. We had monitored him closely soon after commencing the treatment. We did not encounter retinal toxicity being reported as a side effect in our literature review though it has been mentioned in rabbit eyes [16, 17].

Beside drugs resistance, relapse of Candida glabrata endophthalmitis is another challenging episode among the managing ophthalmologists. It had been reported months to years after primary eradication of the infection [4, 6, 18]. Thus, it is very essential to monitor closely these patients as the recurrence is common.

In conclusion, Candida glabrata endophthalmitis is uncommon but a potentially devastating complication following penetrating keratoplasty. A complete work-up is essential to identify the source of infection and prompt treatment is indicated. This case highlights that ophthalmologists should have a high index of suspicious especially when managing patients with immunocompromised status even with negative donor and transport media cultures.

Consent

Declarations

Authors’ Affiliations

(1)
Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

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  19. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/10/18/prepub

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