Transcript A Case of Beauveria Bassiana Keratitis Confirmed by Gene

Phialemonium obovatum keratitis
after penetration injury of the cornea
Kwon-Ho Hong, M.D., Sung-Dong Chang, M.D.
Department of Ophthalmology, School of Medicine,
Dongsan Medical Center,
Keimyung University, Daegu, Korea
INTRODUCTION
The incidence of fungal keratitis has been considerably increased for the past 20-30 years.
The causative fungi include filamentous fungi in ocular trauma and nonfilamentous fungi
in chronic ocular surface disease. With the expanded use of antibiotic eye drops, the
increased use of steroid eye drop and the advancement of laboratory diagnostic tools, the
incidence of fungal keratitis has been greatly increased compared to the past.
Phialemonium genus is dematiaceous fungi, which is known as the causative fungus for
opportunistic infection in immunocompromised hosts. It is isolated from soil, air, water or
sewage. In very rare cases, it has been reported to be a cause of invasive disease.
We experienced a case in which the keratitis was developed during a monitoring of
clinical course after the primary closure of corneal laceration. In cultures of samples
obtained from the corresponding patient, Phialemonium obovatum was identified although
it has not ever been reported to be the causative fungus for infectious ocular disease.
CASE
•
A 54-year-old man suffered injury during road
construction when a nail fragment was stuck in his
left eye. He was referred to us from a local clinic for
further evaluation and treatment. At the time of
admission, his visual acuity was 0.8 in the right eye
and hand motion (HM) in the left eye. Slit lamp
examination revealed a full-thickness corneal laceration
6.5 mm in size spanning from the 4 o’clock to the 7
o’clock position in the vicinity of the corneal limbus.
A part of swollen lens was anteriorly displaced and a
hyphema was present. The patient was treated with
primary closure of the lacerated cornea. He had a oneyear history of hypertension and was taking oral
antihypertensives. He had no history of diabetes.
However, at the time of admission, his serum glucose
was 491 mg/dL, and viral markers were all negative.
There was no history of other systemic disease.
On postoperative day 1, the patient’s visual acuity was
HM, and the suture site was clear. A small amount of
viscoelastics remained in the anterior chamber.
(Figure A)
A
CASE
•
Approximately two weeks after surgery, the patient
was noted to have an epithelial defect and subepithelial
and stromal cell infiltrates at the suture site. However
KOH smear and Gram stain were negative. We subjected
the sample to bacterial and fungal culture. Meanwhile,
The corneal cellular infiltrate and the corneal epithelial
defect progressed. The cellular infiltrate was ring-shape
d, which was suggestive of various possible causes of
keratitis: fungus, pseudomonas, acanthameba, immune
reaction, or toxic keratitis. The smear tests were negative
for bacteria and fungi, so the patient was thought to
have toxic keratitis. The Pred-Forte ® (prednisolone
acetate 1%, Allergan, Waco, TX, USA) dose was therefore
increased and was applied to the eye in combination
with Vigamox® (moxifloxacin hydrochloride 0.5%, Alcon
Laboratory, Fort Worth, TX, USA) at two-hour intervals.
Nevertheless, the patient’s symptoms did not improve.
(Figure A)
A
CASE
•
By approximately three weeks after surgery, the
infiltration involved an extensive area of the cornea, the
symptoms had worsened, and stromal melting had
developed. The anterior chamber was no longer visible due
to corneal haze.
Approximately ten days after culture specimen inoculation,
P. obovatum was identified (Figure A , B). Natacin ®
(natamycin, Alcon Laboratory, Fort Worth, TX, USA) was
A
applied to the eye every two hours.
Thereafter, the corneal inflammation remained stable, and
the cornea itself underwent minimal change. However,
corneal thinning and a persistent epithelial defect were
noted in the central cornea. This led to permanent amniotic
membrane transplantation (P-AMT) and temporary amniotic
membrane transplantation (T-AMT).
B
CASE
•
Approximately three weeks af ter the AMT was
performed, the P-AMT was peeled off, except for the
periphery. The corneal epithelium was almost completely
replaced with conjunctival epithelium. However, a small
epithelial defect remained in the periphery, corneal haze
was still present,and neovascularization was seen in the
peripheral cornea.
The patient was subjected to a single subconjunctival
injection of bevacizumab (2.5 mg/0.1mL) (Avastin ® ,
Genentech, Inc., San Francisco, CA, USA). Approximately
seven weeks after the AMT, the visual acuity was HM, and
the corneal epithelium was completely conjunctivalized. In
the periphery, however, a greater ingrowth of blood vessels
was obser ved. The corneal transplantation was
recommended due to persistent diffuse corneal opacity
(Figure A), but the patient refused it due to financial reason.
A
DISCUSSION
•
Fungal keratitis may be occurred secondary to trauma, and its incidence is increased by the use of
steroids and broad-spectrum antibiotics. It commonly occurs in subtropical rural areas in persons
engaged in agriculture or in those with immune compromise. Nevertheless, the epidemiologic
distribution and source organisms are variable, and the epidemiology is dependent on the
geographic area. The most common causative organism worldwide is Aspergillus. There is one report
that Aspergillus genus was also the most common causative strain (27.2%) in Korea. This was
followed in frequency by Cephalosporium (Acremonium) (18.2%), Chloridium glaucum (10.4%), and
Candida albicans (9.1%).
•
Phialemonium genus is intermediate in form between Acremonium and Phialophora. It was first
described by Gams and McGinnis in 1983. Based on the degree of pigmentation and its conidial
shape, it is classified into three types. P. obovatum forms white to pale yellow or greenish colonies
that initially produce green diffusible pigment and later produce black pigment at the colony center.
On light microscopy, the conidial shape has an obovate form. During a recent 20-year period, 15
reports of 16 cases of Phialemonium genus-induced infections were reported. Three of these
infections were intraocular P. curvatum infections. No ocular P. obovatum infections have been
reported.
DISCUSSION
•
In the current case, keratitis became progressively worse starting approximately two weeks after surgery. The
smear tests showed negative result despite of intrastromal cell infiltration showed a ring-shaped pattern. This
pattern was assumed to be due to the immune-mediated response. The frequency of steroid eye drop
inoculation was increased, and the clinical course was followed closely. However, the patient’s symptoms did
not improve. Under the assumption that the persistent epithelial defect and progression of inflammation were
due to the toxic effects of the eye drops, the frequency of eye drop inoculation was reduced to four times a
day except steroid. The bizarre clinical course led to a delayed diagnosis. After the culture results were
revealed, natamycin inoculation was initiated for the treatment of fungal keratitis. However, corneal thinning
developed as a result of delayed treatment, and AMT was required.
•
Fungal keratitis is an incurable corneal infection. Because the fungus invades the deep stroma, it cannot be
easily cultured in many cases. Furthermore, fungus identification is often difficult to perform on KOH smear
or culture. There are also instances in which the toxic effects of eye drops cannot be differentiated from the
inflammatory process seen during keratitis recovery.
•
Fungal keratitis may develop in immune compromised hosts, including those with diabetes. The current
patient had a blood glucose level of 491mg/dL at the time of admission. The patient was not aware that his
blood glucose level was high, and he had not been taking any medications for blood glucose control. It is
probable that his hyperglycemia had been present for a long period of time. This might have increased his
risk for developing fungal keratitis.
Conclusion
•
Negative cultures are seen in many patients with fungal keratitis. Early diagnosis
allows for administration of appropriate eye drops and surgical treatment, if
necessary. Delayed diagnosis can lead to a poor prognosis.
•
Phialemonium infections have been rarely reported. To date, two reports have
described three cases of endogenous endophthalmitis due to P. curvatum
inoculated through intrapenile injection. Our patient denied a history of such
injection.
•
To our knowledge, no case of ocular P. obovatum infection has been reported in
the literature. Therefore, we reported a case of fungal keratitis due to P. obovatum,
along with a review of the literature