Saudi Journal of Ophthalmology (2012) 26, 191–197

Ophthalmic Pathology Update

Non-viral microbial keratitis in children

Abdullah G. Al-Otaibi, MD ⇑

Abstract

Microbial (non-viral) keratitis is a serious vision-threatening condition. The management of microbial keratitis in children is partic-
ularly complicated by the children’s inability to cooperate during examinations and the lack of information prior to presentation.
Predisposing factors vary according to geographical location and age. Corneal trauma is the leading cause for microbial keratitis in
children, followed by systemic and ocular disease. Etiologic agents are most frequently Gram-positive and Gram-negative bacteria
commonly found in contact lens-related microbial keratitis. Mycotic keratitis is a major risk factor in tropical weather conditions,
particularly when associated with agricultural trauma. Early diagnosis, intensive drug treatment, and timely planned surgical inter-
vention may effectively improve the outcome of pediatric microbial keratitis.

Keywords: Pediatric microbial keratitis, Children, Predisposing factor, Microbiology

Ó 2011 Saudi Ophthalmological Society, King Saud University. All rights reserved.
doi:10.1016/j.sjopt.2011.10.002

Introduction This review outlines the demographics, predisposing fac-

tors, laboratory and clinical findings, treatment, and outcome
Corneal infection is a major cause of ocular morbidity and of microbial keratitis in children.
blindness worldwide, both in developed and developing
countries.1 In developing countries, it is estimated that 1.5– Incidence of microbial keratitis
8 million of corneal ulcers occur each year.2,3,5 Srinivasan
et al.3 reported that ulceration of the cornea in South India Despite the improvements in treatment options, infectious
‘‘is a blinding disease of epidemic proportions.’’ Children microbial keratitis remains a significant cause of blindness
presenting with microbial keratitis are at risk of developing worldwide.4 The incidence of microbial keratitis is higher in
irreversible ocular deficits, such as those resulting from developing countries than in developed countries.5–7 Maurin
amblyopia.2,15 Therefore, the diagnosis and treatment of et al.58 found that the incidence of corneal related blindness
microbial keratitis in children is of utmost importance. How- in children in tropical countries is 20 times higher than that in
ever, studies pertaining to microbial keratitis in children are children from developed countries. In a study supervised by
scarce. Nonetheless, it is known that the microbial etiology the World Health Organization (WHO) South-East Asia Re-
and predisposing factors vary with geographic location and gional Office in New Delhi, it has been estimated that 6 mil-
age.4–8 In addition to the lack of knowledge, management lion cases of corneal ulcer occur every year in South-East
of microbial keratitis in children is hampered by the children’s Asia.5 The incidence of microbial keratitis ranges from 113
inability to provide complete medical history and to cooper- per 100,000 in India5 to as high as 799 per 100,000 in Nepal.6
ate during examination and treatment. Delay in management On the other hand, the incidence of microbial keratitis in the
may cause severe visual impairment. United States was estimated to be 2–11 per 100,000.7

Received 11 July 2011; received in revised form 18 September 2011; accepted 6 October 2011; available online 13 October 2011.

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

⇑ Address: King Abdul-Aziz University Hospital, King Abdul Aziz Road, P.O. Box 245, Riyadh 11411, Saudi Arabia. Tel.: +966 1 4775723; fax: +966 1
4775724.
e-mail addresses: [email protected], [email protected]

Peer review under responsibility

of Saudi Ophthalmological Society,
King Saud University
j Production and hosting by Elsevier
Access this article online: www.saudiophthaljournal.com
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192 A.G. Al-Otaibi

Microbial keratitis occurs more frequently in adults than in studies analyzing the risk factors for microbial keratitis in In-
children. In agreement, in an epidemiological study of micro- dian children, which highlighted the association of protein-
bial keratitis in Southern California, only 11% of the cases in- energy malnutrition, immunization profile, and low socioeco-
volved children.8 nomic background with the development of microbial
keratitis.12,16
Predisposing factors Ocular conditions such as exposure keratopathy (Fig. 2),
trichiasis, and dry eye are major contributors to microbial ker-
atitis.2–4 Table 1 summarizes the risk factors reported in dif-
Trauma
ferent studies.
The most common predisposing factor for microbial kera-
titis in children is trauma.8–14,42 Corneal trauma disrupts the Clinical features of microbial keratitis
protective mechanism of the corneal epithelium, thereby
facilitating bacterial adhesion and accelerating subsequent Microbial keratitis presents a wide range of clinical
microbial penetration and replication.15,16 Different studies signs and symptoms. They include moderate to severe
showed a decrease of corneal ulcers following traumas in pain of rapid onset, severe redness of the conjunctiva,
adults59,60 which is a far more common predisposing factor hazy vision, photophobia, discharge, and swollen lids.
in rural areas where it accounts for up to 77.5% of cases.61 Signs usually include corneal infiltrate (either central or
Children are less cautious than adults, and they do not under- paracentral), epithelial defects over the infiltrate, inflam-
stand the inherent dangers associated with hazardous ob- matory cells in the anterior chamber with or without
jects during their activities of daily life.52 Objects of trauma hypopyon, folds in Descemet’s membrane, and sometimes
include plant, metal, or plastic pieces, firecrackers, and pen- endothelial inflammatory plaques. The wide spectrum of
cils. The history of trauma in childhood microbial keratitis was clinical manifestations can result in the incorrect selection
reported in 26% to 58.8%.8,9,13 of antimicrobial agents and a prolonged period of
resolution.28,46
Contact lens
Pathogenesis of microbial keratitis
Contact lens wear is a common predisposing factor in
many developed countries.9,10 In fact, it has been considered To establish a corneal infection, micro-organisms have
the leading cause of microbial keratitis in Taiwan.15 This can to overcome the natural barriers present at the ocular sur-
be explained by the relatively high prevalence of refractive face. The defense mechanisms include an intact epithelial
errors and the popularity of contact lens use in these areas. layer at the corneal surface and a tear film with antibacte-
In particular, overnight orthokeratology (OK) was reported rial properties. Physical trauma usually precedes invasion of
to be associated with infectious keratitis in myopic teenagers. micro-organisms. Many bacteria display several adhesins on
Watt and Swarbrick56 have provided an analysis of the first 50 fimbriated and nonfimbriated structures that may aid in
cases of microbial keratitis in overnight OK. Their findings their adherence to the host corneal cells. After the success-
showed that 60% of the affected OK patients were 15 years ful invasion of the corneal surface, bacteria can proliferate
old or younger. Of interest, 30% of these OK-related cases and penetrate into the corneal stroma.47 The host re-
were caused by Acanthamoeba, as opposed to only 5% of sponse is crucial for protecting the cornea, but, at the
infections reported in regular contact lens wearers. However, same time, it can produce some of the pathology that is
contact lens-related microbial keratitis cases are usually asso- associated with infectious keratitis. Polymorphonuclear neu-
ciated with Pseudomonas micro-organisms. At all ages, Pseu- trophils (PMNs) are found at the inflammatory site soon
domonas-mediated keratitis accounts for the largest mean after the infection. Their migration is associated with cor-
diameter of corneal ulcers, highest number of outpatient vis- neal damage and ultimately scarring or perforation in se-
its, and poorest visual acuity outcome.55 Hence, potential vi- vere cases.48 Degranulation of PMNs releases host
sual complications should be considered when prescribing enzymes and toxins that kill the invading bacteria and de-
overnight lenses.15 grade the corneal stroma. Influx of PMNs is mediated, on
the one hand, by chemokines and cytokines that are pro-
Systemic and ocular diseases duced by the host soon after the infection49 and, on the
other, by chemotactic bacterial peptides and endotoxins.50
Systemic infections and malignancies are the main causes The host inflammatory response is regulated by a different
in patients with severe systemic illness, especially in children network of chemokines and cytokines that are released
below the age of 4.8–10 Systemic diseases and malnutrition soon after infection to prevent further stromal damage
reduce the wound healing process that may be an important and to stimulate wound healing.51
reason for an increased risk for childhood microbial Kerati-
tis.62 A wide range of systemic diseases, including hypoxic Microbiology analysis
encephalopathy, pulmonary stenosis, malnutrition, multiple
congenital abnormalities, and severe prematurity, was found Normal flora of the conjunctiva
to be associated with microbial keratitis in children.8–11,13
Health-impaired infants should receive additional medical The normal ocular flora of newborns is acquired mainly
attention to prevent microbial keratitis, to which they are from the birth canal during normal delivery. It includes Lacto-
more susceptible.15 The relationship between the health sta- bacillus, Bifidobacterium, Corynebacterium, Peptostrepto-
tus and microbial keratitis in children was supported by two coccus, coagulase-negative Staphylococcus, and
Non-viral microbial keratitis in children 193

Table 1. Comparative analysis of reported case series of childhood microbial keratitis.

Source Location Risk factors (%) Rate of
Surgery (%)
8
Ormerod et al. Southern California Trauma; ocular disease 28
Cruz et al. 9 Florida Trauma (44); prior corneal surgery (24); systemic disease (14); 14
contact lens wear (12)
10
Clinch et al. New Orleans, LA and Trauma (34); systemic disease (27); contact lens wear (24) 21
Philadelphia, PA
11
Kunimoto et al. India Trauma (21); ocular disease (18); systemic disease (16); 16
contact lens wear (0)
12
Vajpayee et al. India Trauma (38); systemic disease (24); ocular disease (12); 6
contact lens wear (0)
14
Singh et al. India Trauma (69); unknown (29.8); contact lens wear (1) 2
15
Hsiao et al. Taiwan Contact lens wear (40.7); Trauma (21); Ocular disease (14.8); 14.8
Systemic disease (11.1)
13
Song et al. China Trauma (58.8); ocular disease (10); 74
previous corneal refractive surgery (5)

propionibacterium species.37 Streptococci mainly dominate United States, China, and India has been reported. This can
the normal conjunctival flora of older children, and coryne- be attributed to the relation between fungal infection and
bacteria are more abundant toward adulthood. tropical climate. Keratomycosis tends to increase in humid
environment. Regardless of the geographical location, the
Microbiology spectrum major predisposing factor for fungal keratitis is trauma in
the agricultural environment.13,14 The agricultural environ-
ment is rich in bacteria and fungi. Upon trauma caused by
Bacteria
plants or vegetable materials, micro-organisms penetrate
Non-viral microbial keratitis in children is caused mainly by
the cornea leading to keratitis.37
bacteria and, to a lesser extent, by fungi or parasites. Amoe-
Several studies from different parts of the world show var-
bae such as Acanthamoeba sp. are more related to contact
iable incidence of fungal keratitis. Cruz et al.9 reported an
lens-associated keratitis but are rarely reported in childhood
incidence rate of 18% of fungal microbial keratitis in children
microbial keratitis.17,18
in the United States. Song et al.13 reported that 48.7% of the
The rate of culture-positive specimens varies between re-
cases of childhood microbial keratitis in China is caused by
ports and is in the range of 48–87%. This wide range can
fungal micro-organisms. A large (213 children) retrospective
be explained by different laboratory facilities and previous
analysis of mycotic keratitis in India showed that Aspergillus,
use of topical antibiotics prior to scraping.
followed by Fusarium species, were the major causative fungi
Of the reported culture-positive groups, Staphylococcus
in childhood keratomycosis.21
species were among the most common isolated organisms.
Staphylococcus aureus and Streptococcus pneumoniae are
the predominant Gram-positive bacteria and Pseudomonas
aeuroginosa is the main Gram-negative bacterium associated
with microbial keratitis in children.10–14 Diagnosis of microbial keratitis in children
Coagulase-negative staphylococci, including S. epidermi-
dis, are the most common bacteria comprising the normal Clinical examination
conjunctival flora.19,20 These bacteria have been reported
to be associated with high incidence of microbial keratitis in A complete medical history and thorough eye examination
children.10–14 focusing on characteristic clinical features are essential for an
Like in adults, the microbial keratitis spectrum in children etiological diagnosis.22,23 Despite the fact that it is not always
varies according to the geographical location. Studies from easy to obtain a detailed history and to perform a thorough
South California, Florida, and Taiwan reported a high rate clinical exam on younger children, these measures should
of isolates of P. aeuroginosa.8,11,15 Other studies conducted not be compromised. Full eye examination and scraping of
in New Orleans, LA, Philadelphia, PA, and India have re- the infected cornea are required under sedation or general
ported a markedly lower prevalence of P. aeruginosa.10,12 anesthesia when dealing with children who are suspected
In the United States and Taiwan, P. aeruginosa isolates were to have microbial keratitis (Fig. 1). However, Thomas
associated with high number of contact lens-related corneal et al.26 in a study investigating a possible correlation be-
ulcers. Poor contact lens hygiene in contact lens-related tween clinical examination and the specific infecting agent
keratitis was noted in two studies.10,15 Table 2 highlights in microbial keratitis, concluded that the clinical features of
the incidence of different micro-organisms isolated in studies microbial keratitis may vary significantly and that no clinical
on childhood microbial keratitis. feature can be considered absolutely pathognomonic of a
particular type of infectious agent. Similar results were ob-
Fungi served in another study.25 Both studies concluded that clini-
Fungal microbial keratitis in children has been reported in cal examination alone cannot be taken as a basis for
several studies.9,10,12–14 A significant incidence of filamentous deciding the therapeutic regimen that should be followed
fungi in childhood microbial keratitis in Southern cities of the for a specific microbial organism.24,25
194 A.G. Al-Otaibi

Microbiology workup

23
Stapathy and Vishalakashi
Corneal scrapings in children require sedation or general

36
anesthesia, especially if they are less than 2 years of age.12

Liesgang and Forster

Kunimoto et al. 11
Corneal scraping smears are inoculated in blood, chocolate,

Ormerod et al. 38

Vajpayee et al. 12
8
Ormerod et al.

Sabouraud agar, Lowenstein–Jensen agar, and thioglycolate

Clinch et al. 10

Singh et al. 14

Hsiao et al. 15
Song et al. 13
Cruz et al. 9 broth. Cultures for Acanthamoeba are performed if indicated
Reference

by clinical appearance or history. In general, corneal scrap-

ings and microbiological examination yield positive cultures
in only 52–65% of cases.38–41 Microscopic slides are used
for stained smears with Gram, Giemsa, and acid-fast
streptococci
a-Hemolytic

staining/acridine orange/calcofluor white (if fungi or Acantha-

moeba are suspected).41
4.5 (2)

1 (2.1)
17 (7)

2 (13)
9 (17)
NR

NR
NR

NR

NR

NR
0

Treatment
Streptococcus
pneumoniae

Antibacterial
5 (10.6)
15 (27)

6 (5.9)
20 (8)

19 (2)

13 (4)
3 (18)

1 (13)
9 (2)

7 (3)

Current therapeutic strategies to treating microbial kerati-

NR
0

tis aim at eradicating the microbial agent and moderating the

Pseudomonas

host immune response with corticosteroids to reduce the

aeroginosa

scarring while minimizing potential visual impairments. Topi-

18 (17.8)

21 (44.7)
16 (312)

cal application of the antimicrobial agents will lead to high

24 (10)

34 (15)
11 (74)
19 (35)

1 (2.6)
10 (9)
7 (14)
9 (2)

9 (6)

concentration of the drug at the infection site. Treatment of

microbial keratitis needs aggressive and frequent administra-
tion of the antimicrobial agents, which can be difficult when
Staphylococcus

treating children. At present, the standard treatment consists

of either fortified antibiotics – in the form of concentrated
% Of culture positive (No.)

9 (19.1)
22 (41)

20 (13)
aureus

aminoglycoside and cefazolin (e.g., tobramycin 1.3% and

17 (7)

21 (9)

30 (9)
8 (51)

5 (98)

7(6.9)

1(2.6)
5 (1)

3 (8)

cefazolin 5%) – or monotherapy with second-generation fluo-

roquinolone eye drops.26–29 In a 2003 review published in the
Staphylococcus

British Journal of Ophthalmology, about 75% of the corneal

epidermidis

ulcers were treated with fluoroquinolone monotherapy.57

Table 2. Incidence of micro-organisms isolated from adults and children with microbial keratitis.

16 (15.8)

14 (35.9)

The fourth-generation ophthalmic fluoroquinolones include

23 (15)

21 (60)

1 (2.1)
17 (7)
23 (5)

23 (7)
3 (19)

moxifloxacin and gatifloxacin are being used for the treat-

2 (1)

NR

NR

ment of bacterial conjunctivitis. Both antibiotics have better

in vitro activity against Gram-positive bacteria than ciproflox-
fungal sp.
% No. of

37 (38.1)

19 (48.7)
20 (133)

24 (857)

acin or ofloxacin. Moxifloxacin penetrates better into ocular

11 (20)

10 (11)

3 (6.4)
14 (4)

16 (8)

5 (14)
cases

tissues than gatifloxacin against gram-negative bacteria is

4 (2)
with

similar to that of older fluoroquinolones.63,64

0

These findings suggest that, moxifloxacin or gatifloxacin

% With >
1 species
isolated

may ba a preferred alternative to ciprofloxacin as the first-line

27 (11)

33 (62)

18 (18)

2 (4.2)
7 (21)

4 (15)
12 (6)

4(4.1)

1(2.6)
(No.)

7 (2)

monotherapy in bacterial keratitis. A more recent study33 did

NR
NR

not show any difference in the efficacy of monotherapy with

fourth-generation fluoroquinolones in the treatment of bac-
55 (1931)

39 (48.8)
56 (371)
82 (186)

97(31.2)
positive
Culture

87 (41)
76 (22)

86 (44)

57 (64)

35 (70)

63 (30)
47 (58)

terial corneal ulcers when compared with combination ther-

(No.)

apy of fortified antibiotics, which could reduce the

%

frequency of application of antimicrobial drugs in uncooper-

Children (0–16)
Children (0–16)

Children (0–16)

Children (0–16)

Children (0–16)
Children (0–16)

Children (0–16)
Children (0–16)
All ages (0–95)
All ages (0–95)

All ages (5–89)

ative children.
In crying uncooperative children, regular topical adminis-
tration of the topical antibiotics is not feasible, which has
All ages
Age (y)

led some investigators to advocate repeated subconjuctival

injection under sedation and papoose restraint.8,31
No. of
cases

3528
663
227

113

310

Antifungal
47
29

51

50

48
81
80
New Orleans

Unlike antibiotics for bacteria, the spectrum of antifungal

NR = not reported.
South Florida
Philadelphia/
Los Angeles

Los Angeles

medications is limited and more often associated with poor

Hyderabad
New Delhi

Göteborg

corneal penetration and less antifungal activity against infect-

Location

Sweden

Taiwan
Miami

ing fungi, which make mycotic keratitis more prone to cor-

China
India

India
India
US

neal perforation and ocular complications, such as

endophthalmitis, in comparison to bacterial keratitis.30 None-
Non-viral microbial keratitis in children 195

theless, topical natamycin (5%), fluconazole (0.5%), and

amphotericin B (0.25%) are known to be effective antifungal
drugs in treating childhood microbial keratitis.10,11,13

Corticosteroids

The action of corticosteroids is known to slow down the

host inflammatory response and may hinder the eradication
of invading micro-organisms.53 The role of corticosteroid re-
mains controversial; however, when they are used, close fol-
low-up and strict guidelines are mandatory to ensure the best
outcome for these patients. In general, corticosteroids are
recommended for less severe cases of corneal ulceration that
are small in size and peripheral in location.38 They should not
be used until specific antimicrobial therapy has controlled
microbial proliferation, and clear clinical improvement is
evident.54

Outcome
Figure 2. Bilateral cryptophalmous with exposure keratopathy and
Most ulcers, including those occurring in children below microbial keratitis in left eye.
the age of 3 years, are successfully treated with topical ther-
apy alone.9–11
The rate of surgical intervention (in the form of therapeutic
penetrating keratoplasty and conjunctival flaps, therapeutic nutrition were 36% less likely to have a poor outcome.16 On
lamellar keratoplasty, and debridement, alone or in combina- the other hand, the visual prognosis for fungal keratitis in chil-
tion with amniotic membrane transplantation) is less than dren has been associated with poor outcome.32–35
20% in treated children with microbial keratitis in most of Parmar et al. compared microbial keratitis in three differ-
the reports8–15 (Table 1). ent groups: a pediatric group, an elderly group, and a control
One study from China13 reported high incidence of surgi- group between 17 and 64 years of age. They found that
cal intervention (74%). This figure is probably attributed to microbial keratitis in children was more likely to be associated
the fact that majority of the patients lived in rural areas in Chi- with bacterial infection, non severe ulcers, and more likely to
na and were exposed to agricultural activities, leading to a resolve with medical therapy alone when compared with
high fungal infection rate (48.7%). microbial keratitis in adults.36 A study published by Hsiao
Severe protein-energy malnutrition and bilateral keratitis et al.15 concluded that poor vision outcome was associated
cases have been associated with a higher rate of surgical with polymicrobial infection, fungal infection, systemic dis-
intervention. In general, patients without protein-energy mal- ease, and ocular disease.

Summary

Pediatric microbial keratitis is an uncommon but poten-

tially serious condition. The causative micro-organisms of
(non-viral) microbial keratitis in children are predominantly
bacteria and to a lesser extent, fungi. Of the bacteria patho-
gens, Staphylococcus sp., S. pneumonia, and P. aeruginosa
are the most common. The risk factors for microbial keratitis
in children include trauma, severe systemic and ocular dis-
ease, and contact lens wear. Treatment for pediatric micro-
bial keratitis usually starts with application of fortified
topical antimicrobial drugs, followed by anti-inflammatory
agents. Children suffering from microbial keratitis are at risk
of amblyopia.15 Thus, early diagnosis and treatment is neces-
sary to minimize any vision-threatening complications.

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