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To review the clinical characteristics, diagnosis, and visual outcome in patients with non-contact lens related Acanthamoeba keratitis and compare the findings with reported series of contact lens associated Acanthamoeba keratitis. Medical and microbiology records of 39 consecutive patients with a diagnosis of Acanthamoeba keratitis, at a tertiary eyecare centre in India between January 1996 and June 1998, were analysed retrospectively. A majority of the patients presented with poor visual acuity and large corneal stromal infiltrates (mean size 38.20 (SD 26. 18) mm). A predisposing factor was elicited in 19/39 (48.7%) patients (trauma 15, dirty water splash three, leaf juice one). None of the patients had worn contact lenses. Most patients (26/39 (66. 6%)) came from a low socioeconomic background. Complaint of severe pain was not a significant feature and radial keratoneuritis was seen in 1/39 (2.5%) patients. A ring infiltrate was present in 41.1% of cases. A clinical diagnosis of fungal keratitis was made in 45% of the patients before they were seen by us. However, all patients were diagnosed microbiologically at our institute based on demonstration of Acanthamoeba cysts in corneal scrapings (34/39) and/or culture of Acanthamoeba (34/39). Treatment with biguanides (PHMB, 15/38 (39.4%), PHMB with CHx, 23/38 (60.5%), one patient did not return for treatment) resulted in healing with scar formation in 27 out of 31(87.0%) followed up patients (mean time to healing 106.9 days). Overall visual outcome was poor with no statistical difference between cases diagnosed within 30 days (early) or 30 days after (late) start of symptoms. The visual outcome in cases requiring tissue adhesive (five) and keratoplasty (three) was also poor. This is thought to be the largest series of cases of Acanthamoeba keratitis in non-contact lens wearers. In such cases, the disease is advanced at presentation in most patients, pathognomonic clinical features are often not seen, disease progression is rapid, and visual outcome is usually poor. Possible existence of Acanthamoeba pathotypes specifically associated with non-contact lens keratitis and unique to certain geographical areas is suggested.
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Patient characteristics, diagnosis, and treatment of
non-contact lens related Acanthamoeba keratitis
Savitri Sharma, Prashant Garg, Gullapalli N Rao
Abstract
Aim—To review the clinical characteris-
tics, diagnosis, and visual outcome in
patients with non-contact lens related
Acanthamoeba keratitis and compare the
findings with reported series of contact
lens associated Acanthamoeba keratitis.
Methods—Medical and microbiology
records of 39 consecutive patients with a
diagnosis of Acanthamoeba keratitis, at a
tertiary eyecare centre in India between
January 1996 and June 1998, were analysed
retrospectively.
Results—A majority of the patients pre-
sented with poor visual acuity and large
corneal stromal infiltrates (mean size 38.20
(SD 26.18) mm). A predisposing factor
was elicited in 19/39 (48.7%) patients
(trauma 15, dirty water splash three, leaf
juice one). None of the patients had worn
contact lenses. Most patients (26/39
(66.6%)) came from a low socioeconomic
background. Complaint of severe pain was
not a significant feature and radial kera-
toneuritis was seen in 1/39 (2.5%) patients.
A ring infiltrate was present in 41.1% of
cases. A clinical diagnosis of fungal kerati-
tis was made in 45% of the patients before
they were seen by us. However, all patients
were diagnosed microbiologically at our
institute based on demonstration of Acan-
thamoeba cysts in corneal scrapings (34/
39) and/or culture of Acanthamoeba (34/
39). Treatment with biguanides (PHMB,
15/38 (39.4%), PHMB with CHx, 23/38
(60.5%), one patient did not return for
treatment) resulted in healing with scar
formation in 27 out of 31(87.0%) followed
up patients (mean time to healing 106.9
days). Overall visual outcome was poor
with no statistical diVerence between cases
diagnosed within 30 days (early) or 30 days
after (late) start of symptoms. The visual
outcome in cases requiring tissue adhesive
(five) and keratoplasty (three) was also
poor.
Conclusions—This is thought to be the
largest series of cases of Acanthamoeba
keratitis in non-contact lens wearers. In
such cases, the disease is advanced at
presentation in most patients, pathogno-
monic clinical features are often not seen,
disease progression is rapid, and visual
outcome is usually poor. Possible exist-
ence of Acanthamoeba pathotypes specifi-
cally associated with non-contact lens
keratitis and unique to certain geographi-
cal areas is suggested.
(Br J Ophthalmol 2000;84:1103–1108)
From a historical perspective Acanthamoeba
keratitis has been described as a recent
epidemic.1It has been recognised in almost all
parts of the world.2–6 Evidence from several
studies has suggested soft contact lens wear as
the greatest risk factor78although some studies
have reported the development of Acan-
thamoeba keratitis in patients with no apparent
predisposing factor.49With most of the litera-
ture focusing on contact lens related Acan-
thamoeba keratitis, ophthalmologists may hesi-
tate to diagnose this entity in patients without
lenses. Chynn et al10 reported some of the
diVerences between contact lens and non-
contact lens related Acanthamoeba keratitis in a
small number of patients. Mean time to
diagnosis was significantly longer and visual
outcome was significantly lower in non-contact
lens users compared with those who wore con-
tact lenses. The study recommended the need
for increased suspicion of Acanthamoeba kerati-
tis in patients who did not present with the
obvious risk factor of contact lenses. On the
basis of our experience, on a much larger scale,
with Acanthamoeba keratitis unrelated to con-
tact lens wear, we support the above conten-
tion and report in this study 39 cases of Acan-
thamoeba keratitis in non-contact lens users.
We present the clinical characteristics, diagnos-
tic methods, treatment schedules, and out-
come in these cases and discuss our findings in
the context of reported series of Acanthamoeba
keratitis in patients using contact lenses.
Patients and methods
All patients treated for Acanthamoeba keratitis
between January 1996 and June 1998 were
included in the study. The clinical and
microbiology records were reviewed retrospec-
tively. Information obtained from the clinical
records included age, sex, socioeconomic
status, medical history including predisposing
risk factors, duration and type of symptoms,
prior diagnosis and treatment, presenting ocu-
lar findings, ocular treatment, and final visual
outcome.
Laboratory data of all patients were sought
from microbiology records. Results of smear
examinations of corneal scrapings which in-
cluded Gram stain, Giemsa stain, and potas-
sium hydroxide with calcofluor white
(KOH+CFW) stain were noted. Culture re-
sults indicating any significant growth of bacte-
ria, fungus, or Acanthamoeba were recorded
along with the in vitro sensitivity test results.
Cultures in all cases had included a variety of
media, such as sheep blood agar (aerobic,
anaerobic), chocolate agar, brain-heart infu-
sion broth, thioglycollate broth, Sabouraud’s
Br J Ophthalmol 2000;84:1103–1108 1103
Jhaveri Microbiology
Centre, LV Prasad Eye
Institute, LV Prasad
Marg, Banjara Hills,
Hyderabad-500 034,
India
S Sharma
Cornea Service
P Garg
G N Rao
Correspondence to:
Dr Sharma
savitri@lvpeye.stph.net
Accepted for publication
26 April 2000
www.bjophthalmol.com
dextrose agar, and non-nutrient agar with
Escherichia coli overlay, allowing for the growth
of bacteria, fungus, or Acanthamoeba. Signifi-
cance was assigned to the bacterial or fungal
growth if the same organism had grown in
more than one medium or a similar organism
was seen in the smears of corneal scrapings. All
organisms including Acanthamoeba were iden-
tified using standard procedures.11
Once the diagnosis was established by
microbiological investigation the treatment was
started with polyhexamethylene biguanide
0.02% (PHMB, Baquasil, ICI, USA) and/or
chlorhexidine digluconate 0.02% (CHx,
Sigma, C-9394) instilled half hourly to the
aVected eye day and night for 2–3 days (usually
as an inpatient) and then 1 hourly for a week.
The frequency of instillation of the biguanides
was reduced to 3 or 4 hourly per day according
to clinical response over subsequent weeks and
continued after resolution of inflammatory
signs for 2–3 weeks. In 18 (46.1%) cases
Neosporin ointment (neomycin, Dominion)
was added at night. Concomitant bacterial
infection was treated with ciprofloxacin 0.3%
eye drops and modified if required according
to the sensitivity results from the laboratory.
Topical cycloplegics and oral analgesics were
used in most cases. Steroids were not used in
any case.
For analysis, the patients were divided into
two groups according to the time between the
onset of symptoms and diagnosis of Acan-
thamoeba keratitis (initiation of antiamoebic
treatment). The “early” category consisted of
patients who were diagnosed within 1 month of
onset of symptoms and the remaining were
labelled as “late”.
Results
Over a span of 2
1
2
years, we treated 39 eyes of
39 patients with Acanthamoeba keratitis. Table
1 shows the demographic data of these
patients. The laboratory data are listed in
Table 2.
More males than females (23:16) were
aVected, though the diVerence was not signifi-
cant (p = 0.2945). Mean age of patients was
36.8 years with a range of 18–70 years.
All except six patients had received ophthal-
mic attention before reporting to our cornea
service and were being treated for presumed
bacterial, fungal, or viral keratitis based on
clinical features. None had been investigated
microbiologically. The most common clinical
suspicion was of fungal keratitis (15/33,
45.4%). Viral keratitis was suspected in only
four cases. One patient was clinically suspected
to have Acanthamoeba keratitis and was receiv-
ing PHMB.
None of the patients in our series wore con-
tact lenses. While 15 patients gave a history of
definite trauma with either vegetative matter,
stone, or dust, three patients reported splash-
ing unclean water into the eyes along with
trauma. In one patient, a suspected foreign
body on the cornea was removed with the
tongue. The same patient used extract of some
herbs in the eye before seeing a doctor who
treated her for bacterial keratitis. In 20
(51.2%) patients no definite risk factor could
be elicited from the history.
SIGNS AND SYMPTOMS
All patients presented to us with redness,
watering, and decrease in vision. Ocular pain
disproportionate to the degree of keratitis was
not noted for any of the patients. Various clini-
cal signs noted in our patients are shown in
Table 3. Radial keratoneuritis, which has been
described as specific for the diagnosis of Acan-
thamoeba keratitis, was seen in only one
patient. Anterior stromal infiltrates were
present in all patients except one in the late
group who had a corneal scar with oedema. A
ring infiltrate was present in 41.1% of the
patients and was the presenting feature more
often (45.8%) in the early than the late group
(33.3%). The diVerence was not statistically
significant (p = 0.6617). Less specific signs
Table 1 Age and sex distribution of patients with
laboratory confirmed Acanthamoeba keratitis
Patients
Category
TotalEarly Late
Sex
Male 15 8 23
Female 9 7 16
Age (years)
0–20 1 0 1
21–40 14 11 25
41–60 8 4 12
>61 101
Mean age (years) 36.75 37.00 36.8
No of patients 24 15 39
Early = cases diagnosed within 30 days of start of symptoms.
Late = cases diagnosed 30 days after start of symptoms.
Table 2 Laboratory data of early and late cases of
Acanthamoeba keratitis
Tests
Category
Total (39)
Early cases
(n=24)
Late cases
(n=15)
Acanthamoeba
Cysts in smears
Gram 15 (62.5%) 11 (73.3%) 26 (66.6%)
Giemsa 14 (58.3%) 9 (60.0%) 23 (58.9%)
KOH+CFW 21 (87.5%) 13 (86.6%) 34 (87.1%)*
Culture
Acanthamoeba 21 (87.5%) 13 (86.6%) 34 (87.1%)†
Gram +ve
bacteria
5 (20.8%) 4 (26.6%) 9 (23.0%)
*Smear −ve culture +ve - (5).
†Smear +ve culture −ve - (5).
Early = cases diagnosed within 30 days of start of symptoms.
Late = cases diagnosed 30 days after start of symptoms.
Table 3 Clinical signs in early and late cases of
Acanthamoeba keratitis at presentation
Clinical signs
Category
Total
(n=39)
Early cases
(n=24)
Late cases
(n=15)
Ring infiltrate 11 (45.8%)* 5 (33.3%) 16 (41.0%)
Satellite infiltrate 9 (37.5%) 2 (13.3%) 11 (28.2%)
DiVuse infiltrate 11 (45.8%) 10 (66.6%) 21 (53.8%)
Endothelial plaque 4 (16.6%) 1 (6.6%) 5 (12.8%)
Hypopyon 14 (58.3%) 7 (46.6%) 21 (53.8%)
Dendritic lesion 1 (4.1%) 0 1 (2.5%)
Radial
keratoneuritis
0 1 (6.6%) 1 (2.5%)
*In two cases the ring infiltrate was partial.
Early = cases diagnosed within 30 days of start of symptoms.
Late = cases diagnosed 30 days after start of symptoms.
1104 Sharma, Garg, Rao
www.bjophthalmol.com
such as satellite stromal infiltrates, diVuse
stromal infiltrates, and endothelial plaques
were seen in many of the patients with no sig-
nificant diVerence between the early and late
groups. One patient in the early group
presented with dendritiform epithelial lesion
mimicking viral keratitis. More than half of the
patients (53.8%) had anterior chamber reac-
tion with hypopyon ranging from trace to 3.5
mm.
DIAGNOSIS
Diagnosis in all cases was based on the demon-
stration of Acanthamoeba cysts or trophozoites
in corneal scrapings by smear examination
and/or culture. Twenty four of 39 (61.5%)
patients were diagnosed within a month (early)
and 15 (38.5%) cases were diagnosed 1 month
(late) after start of symptoms. Twenty nine
(74.3%) cases were positive for Acanthamoeba
both on smear examination and culture where
as five each were detected either by culture or
smear (Table 2). Among 34 smear positive
cases, KOH+CFW stain detected cysts in all
cases. Fewer cases showed cysts in corneal
scrapings by Gram and Giemsa stain (26/34
(76.4%) and 23/34 (67.6%) respectively). Bac-
terial growth along with Acanthamoeba was
seen in five cases in the early group and four
cases in late group. The bacterial co-isolates
were mainly low virulence organisms such as
Staphylococcus epidermidis (6/9) and Corynebac-
terium species (2/9). Staphylococcus aureus was
isolated in one case.
TREATMENT OUTCOME
Anti-Acanthamoeba treatment with cationic
antiseptics (PHMB and/or CHx) was initiated
in all cases as soon as the microbiological
diagnosis was made. The therapeutic strategy
and outcome in all patients is shown in Figure
1. In 27 out of 31 patients followed up
(87.0%) the corneal infiltrate resolved follow-
ing medical treatment in a mean time of 106.9
(9–281) days. Seven patients were lost to
follow up, four of whom were refused
admission for financial reasons, and three
patients left against medical advice after being
treated for 5–7 days. Post-treatment visual
acuity was recorded in 14 early and 13 late
cases. Visual acuity before and after treatment
in early and late cases is shown in Figure 2.
Improvement in visual acuity following treat-
ment was seen in 35.7% (5/14) of early and
30.7% (4/13) of late cases (p=0.891). Applica-
tion of tissue adhesive (n-butyl cynoacrylate
tissue adhesive) with bandage contact lens was
performed in five cases (four in late, one in
early) for extreme thinning or perforation less
than 2 mm in size. After prolonged medical
therapy with PHMB and CHx (mean 88 days)
the infiltrates resolved with scarring and
Figure 1 Therapeutic strategy and treatment outcome in 39 patients with non-contact lens related Acanthamoeba
keratitis.
Total no of patients 39
Early 24 Late 15
Medical Mx
19
Non-specific Mx
(LTFU)
1
Surgical Mx
4
• PK 3
• Evisceration 1
• PHMB and/or CHx
• PHMB and CHx
+
+
• PHMB and CHx
tissue adhesive
tarsorrhaphy
• PHMB and/or CHx
• PHMB and CHx
+
tissue adhesive
12
1
1
9
4
Medical Mx
15
Surgical Mx
0
Healed scar
14
LTFU
5
Healed scar
13
LTFU
2
Figure 2 Pretreatment and post-treatment visual acuity in
non-contact lens related Acanthamoeba keratitis patients
diagnosed within 30 days (early, 14 cases) and 30 days
after (late, 13 cases) start of symptoms.
PLPR
Early
Late
CF
CF
HM
HM
6/60
6/60
6/36
6/36
6/30
6/30
6/18
6/18
6/12
PLPR
Post-treatment visual acuity
Pretreatment visual acuity
6/12
Patient characteristics, diagnosis, and treatment of non-contact lens related Acanthamoeba keratitis 1105
www.bjophthalmol.com
vascularisation in all. However, the final visual
acuity remained poor (PL/PR three, HM one,
and 6/36 one). Paramedian tarsorrhaphy was
performed for associated lagophthalmos in
one patient. Therapeutic penetrating kerato-
plasty (PK) was performed in three cases in
the early group owing to large infiltrate at the
time of presentation which failed to respond
even on intensive medical therapy. The
outcome of surgical excision however, was not
encouraging. One patient required limbus to
limbus graft 7 days after presentation. The
graft developed an infiltrate in the immediate
postoperative period followed by corneal
perforation and pseudocornea formation. The
graft failed in the second patient, and in the
third patient there was choroidal detachment
with vitreous opacities resulting ultimately in
phthisis. Development of vitreous opacities
and scleral involvement was noted in one
patient who ultimately required evisceration.
Discussion
Corneal ulceration is a major cause of mo-
nocular blindness in developing countries. A
recent report from this centre, in a well
conducted survey of an urban population in
south India, listed corneal blindness as the
third major cause of visual disability and
blindness.12 Incidence of corneal ulcers in
south India has been estimated to be 11.3 per
10 000 population and has been referred to as
a blinding disease of epidemic proportions.13
Epidemiology and aetiology of corneal ulcera-
tion in south India has already been
published14 wherein 1% of culture positive
cases were caused by Acanthamoeba. The
reported incidence of Acanthamoeba keratitis in
India varies from 1–3% in various
published14 15 and unpublished series. Of note,
barring single case reports in contact lens
wearers,16 17 all reported cases are predomi-
nantly seen in non-contact lens wearers.41415
While Sharma et al4reported complete healing
in four out of five adequately followed up
cases (treated with neosporin/miconazole/
ketoconazole) they did not comment on visual
outcome. Likewise, none of the other
studies14 15 has dwelt on clinical features, treat-
ment schedule, or visual outcome. Conse-
quently, such data are severely lacking from
this part of the world.
On the other hand, some reports from the
USA10 and the UK18 have described the disease
in non-contact lens wearers. While contribut-
ing significantly to the understanding of Acan-
thamoeba keratitis in non-contact lens wearers,
both these studies were encumbered by rela-
tively small sample size. To the best of our
knowledge, the present study is the largest
series of patients with non-contact lens related
Acanthamoeba keratitis.
Diagnosis of Acanthamoeba keratitis, based
on clinical features, was made only in one out
of 33 patients by physicians who had treated
these patients before they were seen by us. The
majority of these patients (15/33(45.4%)) were
treated as fungal keratitis which is diVerent
from what has been reported for patients with
contact lens related Acanthamoeba keratitis
who generally undergo treatment for herpes
simplex keratitis before the microbiological
diagnosis is made.19 The presence of satellite
stromal infiltrates and endothelial exudates in
some of our patients points more towards fun-
gal aetiology. Additional reason for underdiag-
nosis of Acanthamoeba keratitis could have
been the relatively high incidence of fungal
keratitis in India (50%),14 and lack of enough
reports of Acanthamoeba keratitis in non-
contact lens wearers. Radial keratoneuritis,
described as typical for Acanthamoeba keratitis,
was also uncommon in our patients. Visual loss
in contrast with severe pain was the predomi-
nant symptom in our series. Absence of
complaints of pain disproportionate to clinical
features in our patients is probably related to
absence of keratoneuritis. Although predilec-
tion of Acanthamoeba to neural tissue has been
demonstrated,20 it is possible that the same is
not seen with all species and pathotypes of
Acanthamoeba.
Contact lens wear does not emerge as an
important risk factor for Acanthamoeba kerati-
tis in our population. This can probably be
attributed to the relatively few people who are
exposed to contact lens wear in this country.
In 20/39 (51.2%) of the patients in this series
a definite risk factor that led to Acanthamoeba
keratitis could not be elicited. In previously
published reports of this entity in non-contact
lens wearers from India4and elsewhere,10 18
trauma and exposure to contaminated water
have been identified as major risk factors. Use
of traditional eye medicine may be added as
another risk factor though this was reported in
just one patient in this series. A recent study
from south India reported use of traditional
eye medicine by 47.7% of patients with kerati-
tis in a rural setting.21 However, the lone
patient with Acanthamoeba keratitis in their
series had not used any traditional medicine. It
is possible that some of our patients experi-
enced events that were too trivial to remem-
ber. The low socioeconomic background of
our patients (26/39(66.6%)) may be a con-
tributory factor. The innocuous habit of
splashing water into the eye following dust fall
may not be remembered by the patients and
cannot be ruled out in our patients. On the
other hand, it is also possible that particularly
virulent strains of Acanthamoeba adhere to and
invade normal corneal epithelium, a possi-
bility suggested by the electron microscopy
study of Neiderkorn et al22 which showed rigid
host specificity of A castellanii to intact chinese
hamster, pig, and human corneas in vitro.
In this series the diagnosis and initiation of
treatment was delayed in 38.5% of patients by
more than 30 days. This is in contrast with
contact lens related Acanthamoeba keratitis.
Radford et al18 reported that diagnosis was
established within 1 month in 89% of contact
lens related cases. This delayed diagnosis
could have been because of lack of severe pain
and low socioeconomic status of most of our
patients. Compared with Acanthamoeba kerati-
tis in contact lens wearers, severe corneal fea-
tures were noted in our patients at presenta-
tion. The stromal infiltrates, even in early
1106 Sharma, Garg, Rao
www.bjophthalmol.com
cases, varied in size from 11.9–88 mm (mean
38.3 (SD 20.6) mm ). Large ulcer size and
central location in 22/24 (91.6%) patients in
the early group and 13/15 (86.6%) in late
group account for the overall poor visual out-
come in our patients. Though we found the
final visual outcome better in cases diagnosed
early than late, the diVerence was not
signifcant (p=0.891), which is in contrast to
other studies which have shown a significant
diVerence.10 18 23 While Radford et al18 related
the less assured visual outcome in patients
with no contact lens history to delayed
diagnosis we believe that this is also related to
the presence of more severe disease in these
patients. Wide variability in virulence among
the strains of Acanthamoeba in diVerent
geographical areas, as well as diVerences in
host immune responses, may contribute to the
variability in clinical presentation. In the
patients in this series, a rapid progression of
the corneal pathology leading to early and
severe damage to corneal tissues is seen. This
is in contrast with slow progress of the disease
in contact lens related keratitis where a
marked stromal involvement may not be obvi-
ous until 6 weeks or more.24 Though the host
factors may have an important part to play,
variability among diVerent strains can not be
ruled out. Co-infection with bacteria may be
another explanation in this setting; however, in
this series there were only nine (23%) cases
with mixed infection with bacteria.
Microbiological diagnosis in this series was
satisfactory in majority of the patients with the
organisms being demonstrated in smears and
cultures. In 32/34 cases the first scraping
yielded a positive result leaving only two
requiring rescrapes. As reported earlier,25
KOH+CFW staining of corneal scrapings
proved to be the most rewarding of all methods
for the diagnosis of Acanthamoeba keratitis.
With increased awareness and better diagnos-
tic facilities in this part of the world, the
incidence of Acanthamoeba keratitis is likely to
be reported more often in non-contact lens
wearers which may contrast with the decrease
in the number of cases reported from devel-
oped countries.18
The final visual outcome, as measured by
resolution of the infiltrate and healing of the
ulcer, was achieved in 27/31 (87.0%) patients
with no significant diVerence between early
and late cases. Use of cationic antiseptics
(PHMB and CHx) has resulted in a dramatic
improvement in the clinical management of
Acanthamoeba keratitis. We used PHMB in
15/38 (39.4%) and CHx with PHMB in 23/38
(60.5%) patients. Neosporin was used only
during sleeping hours in a limited number of
patients which may not have played a signifi-
cant part in control of infection. Although
combination therapy with PHMB and propa-
midine has been reported earlier23 the choice
of combination therapy with PHMB and CHx
was based on in vitro observation of low MCC
(minimum cysticidal concentration) of
PHMB and CHx and the reported synergistic
activity of both.26 The mean duration of treat-
ment in our patients was 106.9 days which is
comparable with the duration reported (135
days) for contact lens wearers,18 23 thereby sug-
gesting that though the clinical features were
severe time taken to respond to medical
therapy was not unduly long. This also
suggests that the susceptibility of Acan-
thamoeba to biguanides in our series is similar
to what has been reported from contact lens
wearers.
Studies are taking place at our centre to
determine susceptibility of Acanthamoeba iso-
lates from non-contact lens wearers to various
antimicrobials and the results (unpublished)
support this hypothesis.
Although the visual outcome was poor, a
clinical resolution of infiltrate was obtained in
majority of the patients with a promise of good
vision following optical corneal graft at a later
stage. Increased awareness may enable early
and frequent recognition and proper manage-
ment of this devastating corneal disease in
patients other than contact lens wearers.
Financial support: Hyderabad Eye Research Foundation,
Hyderabad, India.
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1108 Sharma, Garg, Rao
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... Infective keratitis with acanthamoeba spp. is a serious eye disease. The disease is rare in non-contact lens wearers 1 and frequently remain undiagnosed in clinical practice leading to preventable loss of vision. To the best of our knowledge, the present case series is the first one in literature where diagnosis of acanthamoeba keratitis is based solely on detection of motile trophozoites in direct wet mount examination. ...
... Fibrosis and thinning of cornea is seen of our series were noncontact lens wearer. In Sharma et al. 1 series of 39 cases, 15 (38.46%) were diagnosed in more than 30 days and 24 (61.53%) within 30 days of initial symptoms. ...
... In our series, delayed presentations, presence of excruciating pain and blepharospasm with varying combinations of signs like ring infiltrate (complete ring in cases 1 and 3) and incomplete ring in case 2), hypopyon (in cases 2 and 3) and failure of antifungal, antibacterial, antiviral medications aroused the suspicion of Acanthamoeba keratitis. Radial perineural infiltrate was found in case 2. All these clinical features and their frequencies were in conformity with those of Sharma et al. 1 Treatment protocol and Visual recovery of our cases were in conformity with those reported by Lim 128 N et al.. ...
Article
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Acanthamoeba keratitis is diagnosed fairly late because of lack of early clinical suspicion and unavailability of simple and effective technique for detection of the protozoa in ordinary laboratory settings. The detection of motile trophozoites in wet mount preparation of corneal scraping is probably the best confirmatory test of Acanthamoeba keratitis in ordinary laboratory settings. However, it is not easy to demonstrate motile trophozoites given the fact that the trophozoites rapidly encyst outside living tissue. We employed a protocol of preparation and transport of the wet mount to the nearby laboratory within fifteen minutes whereby optimum chance of demonstration of motile trophozoites was possible. We had been successful to detect the typical amoeboid movement of acanthamoeba in three cases. Healing of ulcers were achieved by an appropriate therapy in all three cases. Visual recovery was good in two out of three cases. To the best of our knowledge, the present case series is the first one in English literature where diagnosis of acanthamoeba keratitis is based solely on detection of motile trophozoites in direct wet mount examination. A careful history and an incisive look into the corneal lesion revealed some clue to suspect the acanthamoeba etiology. Simple laboratory technic employing wet mount microscopy rapidly confirmed the diagnoses. Healing of ulcers were achieved in all three cases by instillation of 0.02% chlorhexidine eye drop. Visual recovery was good in two out of three cases.
... For example, a significant rise in AK was seen in the 1980s in the United States, when contact lens was first introduced [17], and the increased incidence in Iowa in 1994 was most likely caused by water contamination due to regional flooding [18]. In contrast, AK is more commonly caused by ocular trauma in developing countries with either stone, dust, mud, or vegetative materials and water contamination [19][20][21]. For example, less than 5% of AK cases were contact lens users in India [22,23] and 53.1% of patients were associated with trauma, and more than half (50.8%) of them were farmers from our study in China [24]. ...
... Early clinical suspicion of AK is an important issue. If a contact lens-related eye infection is not responding well to typical antimicrobial (bacteria, fungus, or viruses) agents, AK should be considered as a potential cause [20,78,79]. Additionally, a detailed medical history, including corneal trauma with exposure to contaminated water or soil, corticosteroid therapy, and ocular surface disease should be considered [25,78,[80][81][82]. ...
Article
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Acanthamoeba keratitis is a rare parasitic infection of the cornea that can lead to permanent blindness if not diagnosed and treated promptly. We collected data on the incidences of Acanthamoeba keratitis from 20 countries and calculated an annual incidence of 23,561 cases, with the lowest rates in Tunisia and Belgium, and the highest in India. We analyzed 3755 Acanthamoeba sequences from the GenBank database across Asia, Europe, North America, South America, and Oceania and genotyped them into T1, T2, T3, T4, T5, T10, T11, T12, and T15. Many genotypes possess different characteristics, yet T4 is the most prevalent genotype. As efficient treatment against Acanthamoeba remains lacking, prevention from early diagnosis via staining, PCR, or in vivo confocal microscopy (IVCM) becomes significant for the condition's prognosis. IVCM is the most recommended approach for the early detection of Acanthamoeba. If IVCM is unavailable, PCR should be used as an alternative.
... The uniqueness of our trial is that in all of the 14 patients from our study, PDAT was applied immediately after the confirmation of diagnosis in contrast to previously published series [18], where it was performed in very advanced stage of infection as a measure to avoid TPK. There is a significant improvement in visual acuity, probably explained by faster clinical response and less scarring [21,22]. ...
Article
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Purpose To report the outcome of Acanthamoeba keratitis, with early addition of Photo-dynamic antimicrobial therapy with Rose Bengal (PDAT-RB) to the medical treatment (combination of 0.02% Polyhexamethylene Biguanide (PH)and 0.02% chlorhexidine(CH)). Methods Patients were recruited based on the infiltrate size being < 8 mm and limited to the mid stroma, < 300µ, and confirmed microbiological diagnosis. Along with the continuation of PHMB + CH, patients were also treated with PDAT-RB twice with a gap of one week using 0.1% w/v RB and green LED (525 nm) array immediately after the confirmation of diagnosis. Results A total of 14 patients were enrolled. All the enrolled patients received adjuvant PDAT-RB within 5 (2.5 to 11) days of diagnosis. The average diameter and median depth of the infiltrate were 5.7 ± 1.56(V), 5.9 ± 1.38(H) mm, and 250 (250 to 300)µ, respectively. The mean LogMAR visual acuity at the time of presentation was 2.52 ± 0.95. Out of 14 enrolled patients, infection was resolved in 12 (85.7%) patients, whereas 2 (14.3%) patients needed TPK. The median days to resolve were 110 (67 to 150) days. The final mean LogMAR Visual acuity at the end of the follow-up was 1.60 ± 1.3. Conclusion The study demonstrates the effective resolution of Acanthamoeba keratitis when treated with early adjuvant photodynamic antimicrobial therapy using Rose Bengal (PDAT-RB).
... The hallmarks of AK include ring infiltrate, radial keratoneuritis, and disproportionate pain. [31,[39][40][41] Patients usually present with unilateral disease; however, it may be bilateral in up to 7.5% of patients, especially in CL wearers associated with poor lens hygiene. [42] The disease classically starts as an epithelial lesion and progresses to involve the stroma. ...
Article
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Acanthamoeba keratitis (AK) generally displays a protracted course with significant morbidity. This is partly due to the fact that it is often misdiagnosed as viral or fungal keratitis. It is associated most with contact lens (CL) wear in developed countries, and exposure to soil or unsanitary water in the developing countries. The textbook description of AK includes the presence of ring infiltration, radial keratoneuritis, and disproportionate pain. Of the patients that presented to our tertiary care center, only 40% had a history of CL use, and 33% had a ring infiltrate. Corneal scraping for microbiological culture on non-nutrient agar serves as the gold standard for diagnosis. Corneal biopsy and confocal microscopy hold diagnostic value in deeper lesions, and polymerase chain reaction and newer molecular techniques are emerging as rapid and effective tools. Biguanides are the drug of choice for AK. But it is important to reconstitute these drugs in correct dosages; otherwise, corneal toxicity can take place. The use of corticosteroids in AK is a matter of debate. We have used corticosteroids in cases with persistent keratitis, severe pain, and extra-corneal manifestations under the cover of amoebicidal therapy. Surgical intervention in the acute phase is reserved for advanced AK with limbus encroachment, perforations, or fulminant corneal abscesses. AK is thus a severe, potentially blinding disease, where a prompt diagnosis ensuring the timely commencement of amoebicidal therapy is an essential component of improving the patient’s prognosis. In this article, we have discussed the presentation, challenges in diagnosis and management, and our experience in managing AK.
... The source and country of origin of the Acanthamoeba strains assessed in this study are given 126 in table S1, and figure S1. A total of 51 isolates were included with 33 isolates from Australia 127 (19 corneal, 9 water and 5 nasal mucosa isolates), 13 from India (all corneal isolates), and five Acanthamoeba genotypes were identified by PCR followed by sequencing of 18S rRNA. 155 Amoebal cells grown in PYG were harvested in 1 mL of 1X PBS (2.7 mM KCl, 1.4 mM NaCl, 156 10 mM Na2HPO4 and 1.8 mM KH2PO4, pH 6.9) and centrifuged for 10 mins at 500xg and 157 washed three times with 1X PBS to remove the medium. ...
Article
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Acanthamoeba, a free-living amoeba in water and soil, is an emerging pathogen causing severe eye infection known as Acanthamoeba keratitis. In its natural environment, Acanthamoeba performs a dual function as an environmental heterotrophic predator and host for a range of microorganisms that resist digestion. Our objective was to characterize the intracellular microorganisms of phylogenetically distinct Acanthamoeba spp. isolated in Australia and India through directly sequencing 16S rRNA amplicons from the amoebae. The presence of intracellular bacteria was further confirmed by in situ hybridization and electron microscopy. Among the 51 isolates assessed, 41% harboured intracellular bacteria which were clustered into four major phyla: Pseudomonadota (previously known as Proteobacteria), Bacteroidota (previously known as Bacteroidetes), Actinomycetota (previously known as Actinobacteria), and Bacillota (previously known as Firmicutes). The linear discriminate analysis effect size analysis identified distinct microbial abundance patterns among the sample types; Pseudomonas species was abundant in Australian corneal isolates (P < 0.007), Enterobacteriales showed higher abundance in Indian corneal isolates (P < 0.017), and Bacteroidota was abundant in Australian water isolates (P < 0.019). The bacterial beta diversity of Acanthamoeba isolates from keratitis patients in India and Australia significantly differed (P < 0.05), while alpha diversity did not vary based on the country of origin or source of isolation (P > 0.05). More diverse intracellular bacteria were identified in water isolates as compared with clinical isolates. Confocal and electron microscopy confirmed the bacterial cells undergoing binary fission within the amoebal host, indicating the presence of viable bacteria. This study sheds light on the possibility of a sympatric lifestyle within Acanthamoeba, thereby emphasizing its crucial role as a bunker and carrier of potential human pathogens.
... 2,3 Contact lens wear is the most common risk factor associated with the development of Acanthamoeba keratitis; however, ocular infection may also develop subsequent to corneal trauma with exposure to contaminated water or soil. 4,5 Acanthamoeba keratitis can be experimentally induced in pigs, rabbits, hamsters, rats, and mice; however, naturally acquired corneal Acanthamoeba infection is not reported in these host species. [6][7][8][9][10][11] To consistently induce keratitis, many of the previously described animal models of Acanthamoeba keratitis utilize methods that do not replicate natural infection pathogenesis in human patients, including techniques such as corneal stromal injection of amoebae, concurrent treatment with immunosuppressive medications, or delivery of amoebae to the cornea in wax films. ...
Article
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Purpose: To develop a feline model of acute Acanthamoeba keratitis using methods that replicate natural routes of infection transmission. Methods: Corneal Acanthamoeba castellanii inoculation was performed by three methods: topical inoculation with Acanthamoeba solution following corneal abrasion, placement of a contaminated contact lens for 7 days, and placement of a contaminated contact lens for 7 days following corneal abrasion. Sham inoculations with parasite-free medium and sterile contact lenses were also performed. Cats were monitored by ocular examination and in vivo corneal confocal microscopy for 21 days post-inoculation. Corneal samples were collected at intervals for microbiologic assessment, histopathology, and immunohistochemistry. Results: All cats in the corneal abrasion groups developed clinical keratitis. Clinical ocular disease was inconsistently detected in cats from the contaminated contact lens only group. Initial corneal lesions were characterized by multifocal epithelial leukocyte infiltrates. Ocular lesions progressed to corneal epithelial ulceration and diffuse stromal inflammation. After 14 days, corneal ulcerations resolved, and stromal inflammation consolidated into multifocal subepithelial and stromal infiltrates. Corneal amoebae were detected by culture, in vivo confocal microscopy, histopathology, and immunohistochemistry in cats with keratitis. Neutrophilic and lymphocytic keratoconjunctivitis with lymphoplasmacytic anterior uveitis were identified by histopathology. Coinfection with aerobic bacteria was detected in some, but not all, cats with keratitis. Ocular disease was not detected in the sham inoculation groups. Conclusions: Feline Acanthamoeba keratitis is experimentally transmissible by contaminated contact lenses and topical inoculation following corneal epithelial trauma. Translational relevance: Experimentally induced acute Acanthamoeba keratitis in cats is clinically and histopathologically similar to its human counterpart.
... The disease occurs mainly in immunocompetent persons; nowadays, contact lens wearers are at the highest risk of this disease [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. AK can also occur in persons not using contact lenses: micro-injuries of corneal epithelium, ocular surgery, and exposure of the eye to natural water bodies containing Acanthamoeba forms are predisposing circumstances for this ocular amoebic infection in humans [27][28][29][30][31]. Usually, one eye is affected; however, bilateral infections have also been reported. ...
Article
Full-text available
Background: Amoebae of the genus Acanthamoeba cause a sight-threatening infection called Acanthamoeba keratitis. It is considered a rare disease in humans but poses an increasing threat to public health worldwide, including in Poland. We present successive isolates from serious keratitis preliminary examined in terms of the identification and monitoring of, among others, the in vitro dynamics of the detected strains. Methods: Clinical and combined laboratory methods were applied; causative agents of the keratitis were identified at the cellular and molecular levels; isolates were cultivated in an axenic liquid medium and regularly monitored. Results: In a phase-contrast microscope, Acanthamoeba sp. cysts and live trophozoites from corneal samples and in vitro cultures were assessed on the cellular level. Some isolates that were tested at the molecular level were found to correspond to A. mauritanensis, A. culbertsoni, A. castellanii, genotype T4. There was variability in the amoebic strain dynamics; high viability was expressed as trofozoites’ long duration ability to intense multiply. Conclusions: Some strains from keratitis under diagnosis verification and dynamics assessment showed enough adaptive capability to grow in an axenic medium, allowing them to exhibit significant thermal tolerance. In vitro monitoring that was suitable for verifying in vivo examinations, in particular, was useful to detect the strong viability and pathogenic potential of successive Acanthamoeba strains with a long duration of high dynamics.
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OBJETIVORevisar las características clínicas, diagnóstico, tratamiento y resultados visuales en pacientes con diagnostico de queratitis por Acanthamoeba (QA). Demostrar la importancia del diagnóstico precoz y de un tratamiento rápido y efectivo.MATERIAL Y MÉTODOEstudio retrospectivo de 14 ojos en igual número de pacientes con diagnóstico de QA, tratados en Centro Visión entre Julio 2008 a Junio 2012. Todos los casos fueron confirmados por frotis y/o cultivo. Se formaron dos grupos: precoz y tardío. La terapia se realizó con polihexametilén biguanida y propamidina. Luego de eliminar la infección se registró la agudeza visual final y la duración del tratamiento.RESULTADOSEl grupo más frecuentemente afectado fue entre 21 a 40 años (9 casos). Sólo dos ojos (14,3%) fueron correctamente diagnosticados inicialmente como QA. Once pacientes (78,6%) fueron usuarios de lentes de contacto. El signo más frecuente fue infiltrado difuso (62,3%); el infiltrado perineural sólo se vio en un caso. Cinco pacientes se diagnosticaron dentro de los primeros treinta días (precoz), y nueve casos posteriormente (tardío). La mediana de la agudeza visual postratamiento en el grupo precoz fue 20/40 y en el tardío 20/400. La mediana de la duración del tratamiento en el grupo precoz fue de seis meses y de diez meses en el tardío.CONCLUSIONESLa mayoría de ojos (85,7%) fueron inicialmente catalogados erróneamente como queratitis de otra etiología. Cuando la QA es diagnosticada precozmente, existe un mejor pronóstico visual, y además no será necesario un tratamiento muy prolongado
Article
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Acanthamoeba keratitis is a potentially sight-threatening infection of the cornea that can lead to blindness. Over the past few decades, there has been a rise in the reported cases worldwide, which is in line with the increase of contact lens wearers. Here, we present three cases of Acanthamoeba keratitis with different outcomes.
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Introduction: The eyes are the most precious human organ for the function of vision, expression and beauty. Good vision contributes to improved athletic ability, better driving skills, improved learning, comprehension and better quality of life. Eye helps to participate in occupation, hobbies, and even to perform most everyday tasks. Aim: To assess the practice of ocular hygiene and the risk for ocular disorders among undergraduate students in a selected college in Southern India. Materials and Methods: A cross-sectional study was conducted in Yenepoya Ayurvedic College, Mangaluru, Karnataka, India from October 2021 to September 2022. It was conducted among 178 subjects recruited by convenience sampling technique. Undergraduate students between the age group of 18-24 years were selected as study participants. Students who underwent special training in ocular hygiene were excluded from the study. One time data was collected using demographic proforma, ocular hygiene practice scale and risk assessment checklist for ocular disorders. Participants were required to take 30 minutes to complete the data collection questionnaires. The collected data was coded and transformed into a master data sheet for statistical analysis. Data was analysed by descriptive and inferential statistics. Results: The results of this study showed that 47 (26.4%) of the students had a very good practice and 124 (69.7%) of them had good practice of ocular hygiene. The results of risk assessment for ocular disorders showed that 146 (82%) had low-risk and a very less percentage 3 (1.7%) of them had a high-risk for the development of ocular disorders. There was a significant association between practice scores and demographic characteristics such as age (p-value=0.04) and using eye accessories (p-value=0.03). Conclusion: In this study, there was a negative correlation between practices of ocular hygiene and risk for ocular disorders among undergraduates. Vision impairment and eye conditions are associated with poor quality of life. An initiative can be taken to improve the practice of ocular hygiene to reduce the risks for ocular disorders among undergraduates.
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To determine the epidemiological characteristics and risk factors predisposing to corneal ulceration in Madurai, south India, and to identify the specific pathogenic organisms responsible for infection. All patients with suspected infectious central corneal ulceration presenting to the ocular microbiology and cornea service at Aravind Eye Hospital, Madurai, from 1 January to 31 March 1994 were evaluated. Sociodemographic data and information pertaining to risk factors were recorded, all patients were examined, and corneal cultures and scrapings were performed. In the 3 month period 434 patients with central corneal ulceration were evaluated. A history of previous corneal injury was present in 284 patients (65.4%). Cornea cultures were positive in 297 patients (68.4%). Of those individuals with positive cultures 140 (47.1%) had pure bacterial infections, 139 (46.8%) had pure fungal infections, 15 (5.1%) had mixed bacteria and fungi, and three (1.0%) grew pure cultures of Acanthamoeba. The most common bacterial pathogen isolated was Streptococcus pneumoniae, representing 44.3% of all positive bacterial cultures, followed by Pseudomonas spp (14.4%). The most common fungal pathogen isolated was Fusarium spp, representing 47.1% of all positive fungal cultures, followed by Aspergillus spp (16.1%). Central corneal ulceration is a common problem in south India and most often occurs after a superficial corneal injury with organic material. Bacterial and fungal infections occur in equal numbers with Streptococcus pneumoniae accounting for the majority of bacterial ulcers and Fusarium spp responsible for most of the fungal infections. These findings have important public health implications for the treatment and prevention of corneal ulceration in the developing world.
Article
Objective-To investigate reasons for an increase in cases of Acanthamoeba keratitis related to contact lenses. Design-Case-control study. Cases were contact lens related acanthamoeba keratitis patients treated between 1 September 1989 and 31 August 1992. Controls were lens users without lens related disease who presented as new patients to the casualty department from 1 March 1992 to 31 August 1992. All subjects completed a questionnaire detailing lens use and hygiene practices. Setting-Eye hospital. Subjects-35 cases with acanthamoeba keratitis and 378 controls. Main outcome measures-Relative risks comparing different contact lens types, socioeconomic classification, age, sex, lens use, lens wearing experience, hygiene compliance, and hygiene systems. Results-The crude relative risk for developing acanthamoeba keratitis with the use of daily wear disposable lenses was 49.45 (95% confidence interval 6.53 to 2227; P < 0.001) compared with conventional soft lenses (the referent). Multivariable analysis showed that this increased risk could be largely attributed to lack of disinfection (relative risk 55.86 (10 to 302); P < 0.001) and use of chlorine based disinfection (14.63 (2.8 to 76); P = 0.001) compared with other chemical systems (the referent). None of the other outcome measures showed a significant association. Conclusions-Both failure to disinfect daily wear soft contact lenses and the use of chlorine release lens disinfection systems, which have little protective effect against the organism, are major risk factors for acanthamoeba keratitis. These risks have been particularly common in disposable lens use. Over 80% of acanthamoeba keratitis could be avoided by the use of lens. disinfection systems that are effective against the organism.
Article
Acanthamoeba is a free-living ubiquitous ameba that is responsible for a small but increasing number of cases of keratitis. The infection is associated with minimal corneal trauma and soft contact lens wear. It typically presents as a unilateral central or paracentral corneal infiltrate, often with a ring-shaped peripheral infiltrate. The lesion is often confused with fungal, bacterial, or herpetic keratitis. Successful therapy hinges on early recognition and aggressive therapy with appropriate topical antiamebic medication, often in conjunction with penetrating keratoplasty. Thirty-five cases from the world literature are reviewed.
Article
Purpose. A multi-centre survey was conducted to monitor the frequency of Acanthamoeba keratitis (AK), and associated risk factors, during the last 4 years in England. Methods. A consultant in each of the 15 Regional Health Authorities (RHAs) was asked to complete a clinical data sheet for each patient in their region retrospectively identified as presenting with AK between 1. 10. 92 and 30. 9. 96. Clinical and postal patient questionnaire data were entered on to a central database. Results. A preliminary report from 8 RHAs is presented. 213 patients with a diagnosis of AK were identified: 114/213 (55%) were tissue culture / histolog) positive for AK, the remainder having a clinical diagnosis supported by perineural infiltrates (47/99, 47%), or other characteristic features including culture of Acanthamoeba from contact lens (CL) paraphernalia (21/99, 21%). 197213 (92%) patients were CL wearers, and at least 115 (58%) of these were using disposable CL. From CL users who had completed a questionnaire (120) it was possible to identify one or more previously established risk factors - swimming with CL (59), non-sterile water/saline use (14), omitted disinfection (69) and chlorine-based disinfection (49) - in all but 5 patients. The total numbers of patients for each year, excluding those from overseas (14), was 47, 60,64 and 28 respectively, Conclusions. Preliminary results from this survey emphasise the preventable nature of this disease: inadvisable CL practices accounted for i 92/213 (90%) of cases, and it is hypothesised that the reduction in cases during the last year may be the result of improved CL hygiene after widespread media attention to CL-related AK during November 1995.
Article
Previous controlled studies on contact lens-associated ulcerative keratitis were performed before the widespread use of disposable contact lenses. Therefore, a controlled study was undertaken to determine the relative risk of ulcerative keratitis among users of disposable soft contact lenses compared with the risk among users of other lens types. Forty-six consecutive cases of contact lens-associated ulcerative keratitis were identified between January 1990 and June 1992 at a corneal specialty practice in western Michigan. Five controls, matched to each case patient according to the dispensing data and prescribing practitioner, were obtained for 42 cases (91%). Users of daily-wear rigid gas-permeable lenses had the lowest risk of developing ulcerative keratitis. Relative to users of daily-wear soft contact lenses, users of extended-wear soft contact lens had an age-adjusted and sex-adjusted relative risk of 1.87 (95% confidence interval, 0.61 to 5.71). Disposable soft contact lens users had the highest risk of developing ulcerative keratitis, with an adjusted relative risk of 14.16 (95% confidence interval, 5.47 to 37.63) compared with daily-wear soft contact lens users and 7.66 (95% confidence interval, 2.27 to 25.83) compared with conventional extended-wear soft contact lens users.