Coniochaeta mutabilis keratitis with an unusual mode of transmission treated with penetrating keratoplasty and systemic antifungals

Abstract

Purpose

To report a case of fungal keratitis caused by Coniochaeta mutabilis along with its treatment and discuss the possibility of an unusual mode of transmission. Only a few cases of ocular C. mutabilis infection have been reported, and this is the first presenting domestic fowl as a potential source of infection.

Observations

A 52-year-old woman presented with a corneal ulcer following a week of increasing eye pain. Five months prior, she had a corneal abrasion in the same eye that resulted from trauma during yard work. Two weeks before presentation, she cared for a chicken with ocular infection. Culture of the corneal scraping identified Coniochaeta mutabilis, a rarely described fungal pathogen. After multiple treatment modalities were attempted, the patient ultimately underwent penetrating keratoplasty. No signs of infection recurrence were present during follow-up after the procedure.

Conclusions and Importance

C. mutabilis keratitis is a rare condition that typically presents with an aggressive nature and requires multiple forms of treatment. Here, we report direct contact with an infected chicken cornea as a possible mode through which the disease was acquired. Early suspicion of fungal etiology in cases of keratitis allows directed treatment, which may improve visual outcomes. Acknowledging unusual modes of transmission may help bring this differential diagnosis into consideration. Furthermore, given the scarcity of literature about this disease, individual case reports are informative for guiding future treatment and research.

1. Introduction

Ocular infections with Coniochaeta mutabilis (previously known as Lecythophora mutabilis) have been described only a few times in literature: one case of endophthalmitis,¹ one case of blebitis² and one case of keratitis-endophthalmitis,³ along with another report of keratitis caused by an unspecified organism belonging to the Lecythophora genus.⁴ Very recently, one case of keratitis initially attributed to Kabatiella zeae was found to be caused by C. mutabilis upon further molecular diagnostic analysis.⁵ All reported cases were aggressive in nature and one of them showed recurrence after deep anterior lamellar keratoplasty (DALK).³ We report a case of C. mutabilis keratitis that possibly derived from an unusual mode of transmission and demonstrated complete remission after penetrating keratoplasty (PKP) with adjunctive intracameral voriconazole and systemic antifungal medications.

2. Case report

An otherwise healthy 52-year-old caucasian woman with well-controlled hypertension presented to the clinic with a new corneal opacity in the OS that appeared after a week of increasing eye pain, along with irritation and decrease in vision of the same eye. The patient was a single-day contact lens user and occasionally reported prolonged use for more than a day. She had a history of corneal abrasion in the OS resulting from trauma while doing yard work five months prior to presentation, which had fully resolved within two weeks of treatment with topical tobramycin and dexamethasone drops. The patient claimed that her latest symptoms started after her chicken had an eye infection and she cleaned it using no protective equipment.

On examination, her best corrected visual acuity (BCVA) 20/60 in the affected eye and 20/20 in the OD, intraocular pressure was within normal limits for OU, and a 1.4 by 1.6 mm white heaped ulcer could be seen paracentrally in the OS, along with mild conjunctival injection (Fig. 1). Cultures were obtained and the patient was started on topical cyclopentolate every 8 h, and fortified vancomycin and tobramycin hourly, all in the OS only.

Fig. 1.

Baseline evaluation showing a 1.4 by 1.6 mm white heaped ulcer paracentrally located in the OS, along with mild conjunctival injection.

One week later, even though the patient had perceived a mild improvement in symptoms, small crystalline infiltrates started to appear at the edge of the ulcer, and cultures demonstrated the growth of a narrow septate hyaline mold, still unspecified. We opted to start topical natamycin every 2 h in the OS while keeping fortified vancomycin and tobramycin every 6 h. About ten days later, symptoms were stable and the crystalline infiltrates radiating from the edge of the ulcer appeared to be more consolidated, with an irregular epithelium covering the entire surface of the lesion. Aiming to enhance antifungal drug penetration, we debrided the lesion twice within an interval of one week and added voriconazole drops four times a day to the drug regimen.

Approximately 40 days after the cultures were obtained, an outside laboratory identified the fungus Coniochaeta mutabilis (formerly known as Lecytophora mutabilis). Based on speciation, we adjusted the drug regimen to voriconazole every 2 hours and natamycin every 6 hours, in the OS. Once the laboratory determined the antifungal sensitivity profile (Table 1), natamycin was promptly switched to amphotericin B. The patient maintained blurry vision, eye irritation and pain along with frequent headaches. She also reported seeing a mirrored image in the bottom of her visual field, likely a visual aberration from her infiltrate. On reevaluation after one month of antifungal therapy, her cornea demonstrated mild thinning with a less dense underlying opacity, and the radiating endothelial infiltrates were mostly resolved. However, despite the quiet-appearing eye, the patient reported severe discomfort, photophobia, and headaches. Given the stalled progress of treatment, we opted to perform two intrastromal injections of voriconazole under monitored anesthesia care, with a period of three days between each injection. Within an hour of each procedure, the patient experienced worsening eye inflammation and pain. She refused corneal transplant. We initiated a therapeutic trial of topical prednisolone to determine if the infection cleared while she continued amphotericin B and voriconazole drops. Her pain quickly resolved, but within three days the infiltrate was larger and prednisolone was stopped. Seven days after the injections, high-dose oral posaconazole (500 mg extended release daily) was started with monitoring of liver function. She discontinued the posaconazole after one week due to muscle aches and fatigue.

Table 1.

Antifungal susceptibility profile.

Drug	Minimal Inhibitory Concentration (mcg/mL)
Amphotericin B (AMB)	0.125
Natamycin (NAT)	8
Micafungin (MICA)	>8
Fluconazole (FLU)	16
Posaconazole (POS)	0.125
Voriconazole (VORI)	0.5

Two weeks later, we performed an intrastromal injection of amphotericin B along with cryotherapy. The patient again developed severe pain that began within an hour of the procedure. We discussed corneal transplant again, but she refused. We agreed on another therapeutic trial of prednisolone if she agreed to penetrating keratoplasty in the case of persistent infection. In two weeks, the deep radiating filaments on the corneal endothelium appeared larger (Fig. 2), so the patient agreed to schedule a penetrating keratoplasty. Adjunctive intracameral voriconazole rinse of the corneal bed and high-dose oral posaconazole 7 days before and 7 days after procedure were added. The procedure was performed without complications, and culture from the excised cornea grew a filamentous-appearing yeast after one week. Cyclosporine 1% drops were used for the first week, however, the patient developed intolerance to the medication. As a result, we switched to prednisolone acetate 1% four times daily. Amphotericin B drops were continued for three weeks post-operatively until the patient developed severe burning sensation. No more antifungal medications were used thereafter. At 8 months post-transplant, the patient demonstrated a well-adapted graft with no signs of infection recurrence.

Fig. 2.

Slit-lamp examination on PKP preoperative evaluation demonstrating consolidated crystalline infiltrates radiating from the edge of the original lesion.

3. Discussion

C. mutabilis ocular infections have scarcely been reported in literature, which adds difficulty to the choice of treatment modalities. In all reported cases, the course of disease tended to be very aggressive in nature, and in one case the infection recurred after transplantation with a partial-thickness graft.³ Antifungal susceptibility profiles varied in each case, showing that the species does not carry a consistent antifungal response.

Fungal keratitis may require multiple treatments to achieve favorable outcomes. Natamycin drops are the first-line treatment for the condition and are the most effective medication against the filamentous fungi Fusarium and Aspergillus.⁶ While the initial microbiology indicated a "narrow septate hyaline mold," speciation took about six weeks, determining that the organism was in fact a yeast (Coniochaeta mutabilis). When the antifungal sensitivity profile (Table 1) became available, it showed an increased susceptibility to amphotericin, and the drug regimen was promptly switched. The delay in identifying the organism may be attributed to the challenges in its molecular characterization, as also highlighted by Oremosu et al.⁵ Corneal scrapings were performed because previous consensus considered that they would increase antifungal drug penetration; however, a recent randomized control trial suggested that repeatedly performing this procedure may result in worse visual outcomes, and thus it should be limited to the purpose of obtaining samples.⁶ When further surgical interventions are needed, lamellar keratoplasty should be considered only if the patient has been pretreated intensively with antifungal medications and the infection has not yet progressed into deeper layers of the cornea.⁶ In late stages of disease, PKP is the preferred surgical approach since it has lower rates of infection recurrence overall and appears to result in better visual outcomes when compared to DALK.^6,7 In this case, the corneal filaments growing around the original lesion appeared to be endothelial. A similar pattern might have been the reason why DALK failed in the case reported by Fintelmann et al.³ As an alternative, conjunctival flaps have proven to be a prominent procedure in the management of severe fungal keratitis, offering a transitional opportunity in situations where a transplant is not readily available.^8,9

Globally, fungal keratitis affects over a million eyes each year, most of which will suffer significant damage to vision.¹⁰ These infections are particularly prone to derive from trauma with vegetable matter.¹⁰ However, although the patient had a history of ocular trauma while mowing the lawn with a string trimmer five months before, symptoms of infection only began after she had contact with her chicken's ocular condition. In addition, prevalent fungi such as Fusarium and Aspergillus have been reported as a cause of keratitis in chicken.^11,12 Accumulation of organic matter in henneries, either from animal excrements or feeds, creates an optimal environment for the growth of these organisms.¹¹ A study published in 1999 analyzed 158 samples of poultry feeds from a factory in Argentina and isolated different naturally occurring virulent strains of Fusarium spp.¹² During a remarkable outbreak in the twentieth century, almost 100 out of 1000 chicks at a poultry farm in Brazil were found to be suffering from Aspergillus fumigatus keratitis.¹³ Another study published in 2011 isolated filamentous fungi from poultry barns and determined that most of the specimens expressed virulence factors allowing them to cause opportunistic illnesses in humans. Among the isolates were species of Aspergillus and Paecilomyces genera, which are known to cause ophthalmic infections.¹¹

4. Conclusions

Although we cannot confirm that the patient's infection derived from the episode with her chicken, there is enough evidence to consider it a possible mode of transmission in this case. The patient reported to have poor contact lens hygiene and used daily lenses for multiple days, which is another well-known risk factor; however, Candida spp is normally the causative organism in these cases.⁶ Fungal keratitis often has morbid outcomes and delayed diagnosis increases the likelihood of surgical interventions.⁶ In that sense, acknowledging all possible modes of transmission may facilitate clinical suspicion and favor early directioning of treatment, which results in better visual outcomes.

Patient consent

The patient consented to publication of the case in writing. Still, this report does not contain any personal information that could lead to her identification.

Funding

This work received no funding or grant support.

Authorship

We attest that all authors contributed significantly to the creation of this manuscript, each having fulfilled criteria as established by the ICMJE.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.