Clinical Trial of 0.02% Polyhexamethylene
Biguanide Versus Placebo in the Treatment of
Microsporidial Keratoconjunctivitis
SUJATA DAS, SRIKANT K. SAHU, SAVITRI SHARMA, SHYAM SUNDAR NAYAK, AND SARITA KAR
●
PURPOSE: To evaluate the efficacy of 0.02% polyhexa-
methylene biguanide (PHMB) in the treatment of kera-
toconjunctivitis caused by microsporidia.
●
DESIGN: Prospective, double-masked, randomized, pla-
cebo-controlled clinical trial.
●
METHODS: One hundred forty-five patients in a single-
center, institutional setting were recruited. Patients with
superficial keratoconjunctivitis and corneal scrapings
with positive results for microsporidial spores were in-
cluded. Patients with any known allergy to PHMB, and
clinically suspected bacterial, viral, or fungal infection
were excluded from the study. One hundred forty-five
patients were treated at 4-hour intervals with either
topical 0.02% PHMB (n 72) or placebo (n 73). The
patients were followed-up on day 3 1, day 7 1, and
weekly thereafter, until complete resolution of the cor-
neal lesions. Patients with deterioration of clinical symp-
toms and signs were removed from the study and were
treated with PHMB. Main outcome measures included
resolution time, cure time, and final visual outcome.
●
RESULTS: Resolution time was defined as the amount
of time until disappearance of corneal epithelial infil-
trates. Cure time was defined as the interval until absence
of conjunctival congestion, corneal epithelial lesion, and
superficial punctate keratitis. Baseline characteristics
showed no relevant difference between the groups. The
mean resolution time was 4.9 2.2 days and 4.6 2.3
days in the PHMB and placebo groups, respectively (P
.49). The mean time for cure was 13.5 6.6 days and
9.4 5.1 days in PHMB and placebo groups, respec-
tively (P .004). There was no significant difference in
the final visual outcome between the groups (P .10).
No serious adverse effects were noted.
●
CONCLUSIONS: Treatment of microsporidial kerato-
conjunctivitis with PHMB does not offer any significant
advantage over placebo, suggesting self-limiting nature of
the disease. (Am J Ophthalmol 2010;150:110 –115.
© 2010 by Elsevier Inc. All rights reserved.)
M
ICROSPORIDIA ARE SMALL, OBLIGATE, SPORE-
forming, intracellular living eukaryotes that
infect a broad range of vertebrates and inver-
tebrates.
1
In humans, microsporidia are opportunistic
pathogens that are reported to cause gastrointestinal, sinus,
pulmonary, muscular, renal, and ocular disease. The ocular
manifestations include superficial keratoconjunctivitis and
stromal keratitis.
2
The early reports of microsporidial
keratoconjunctivitis involved immunocompromised pa-
tients.
3–6
However, these pathogens seem to be increas-
ingly prevalent in immunocompetent patients.
7–10
We
have reported an epidemic of keratoconjunctivitis caused
by microsporidia.
9
The management of microsporidial keratoconjuncti-
vitis is challenging because no definitive treatment
exists. Anecdotal reports of specific treatment include
the use of albendazole,
8,11
broad-spectrum antibiotics,
7,8
itraconazole,
10,12
propamidine isoethionate,
6,13
fumagil-
lin,
3,5,14
chlorhexidine,
7
polyhexameththylene biguanide,
7
and lubricants.
3
In all studies, epithelial keratoconjuncti-
vitis has been reported to resolve in a varying period
without significantly affecting visual acuity. The present
study was designed to determine the clinical efficacy of
0.02% polyhexameththylene biguanide (PHMB) in the
treatment of keratoconjunctivitis caused by microsporidia.
METHODS
THIS SINGLE-CENTER, DOUBLE-MASKED, RANDOMIZED, PLA-
cebo-controlled clinical trial examined 145 patients. In-
formed written consent was obtained from each participant
before inclusion in the study.
●
INCLUSION AND EXCLUSION CRITERIA: Patients with
superficial epithelial keratitis or keratoconjunctivitis and
whose corneal scrapings showed positive results for micros-
poridia spores were included in the study. The patients
needed to have the ability to understand and sign an
informed consent form. For patients younger than 18 years,
the informed consent was required to be understood and
signed by the parent or guardian. The exclusion criteria
included known allergy to PHMB and clinically suspected
bacterial, viral, or fungal infection of the cornea.
Accepted for publication Jan 29, 2010.
From the Cornea and Anterior Segment Service (S.D., S.K.S., S.S.N.)
and the Ocular Microbiology Service (S.S., S.K.), L. V. Prasad Eye
Institute, Bhubaneswar, Orissa, India.
Inquiries to Savitri Sharma, Ocular Microbiology Service, L. V. Prasad
Eye Institute, Bhubaneswar, Orissa, India 751024; e-mail: savitri@
lvpei.org
© 2010 BY ELSEVIER INC.ALL RIGHTS RESERVED. 110 0002-9394/$36.00
doi:10.1016/j.ajo.2010.01.038