Prevention of Corneal Ulceration

in the Developing World

John P. Whitcher, M.D., M.P.H.

M. Srinivasan, M.D.
Madan P. Upadhyay, M.D.

Corneal blindness in the developing world has traditionally been at-

tributed to trachoma, xerophthalmia, measles, neonatal ophthalmia, and
leprosy. The importance of superficial corneal trauma in agricultural
work, which frequently leads to rapidly progressing corneal ulceration and
visual loss, has been largely overlooked as a worldwide cause of unilateral
blindness. However, Thylefors1 estimated that up to 5% of all blinding
conditions are directly related to ocular trauma and that children may be
at greater risk than adults. A recent study in Uganda by Waddell2 indi-
cated that corneal ulceration was second only to cataract as the main cause
of blindness in the younger age group. Examination of 1,135 children
with subnormal vision revealed that 30.7% had visual impairment second-
ary to cataracts or poor surgical outcome, whereas 22.0% had visual loss
after corneal ulceration.
The social and economic impact of corneal ulceration is insidious,
because it causes bilateral blindness infrequently. The individuals most
commonly affected are farmers or laborers; men are at slightly more risk
than women; and the ulcers occur predominantly in middle-aged indi-
viduals who are in their most productive years.3,4 Because it affects pre-
dominantly the working poor in the developing world, microbial keratitis
is underreported and often neglected. A corneal ulcer can cause eco-
nomic disaster for a family on a subsistence income. Farmers and laborers,
who are not covered by any kind of health insurance, may have to spend
all their meager wages on medical treatment and be out of work for weeks
to months, ultimately driving their families into utter poverty. By conser-
vative estimates, at least 1.5 million new cases of unilateral blindness occur
worldwide every year owing to microbial keratitis. The affected individu-
als, who are truly victims of a “silent epidemic,”5 return to their previous
71
72 䡲 Whitcher et al.

jobs where they remain exposed to the same risk factors for developing
ulceration in the other eye.
The medical costs for treating microbial keratitis are almost always
prohibitively expensive, especially in the case of fungal ulceration, for
which medications are costly and the visual outcome is usually disappoint-
ing. In South India, approximately one-half of eyes with fungal ulceration
that receive appropriate treatment still develop blinding sequellae sec-
ondary to perforation, phthisis, and severe scarring. Bacterial ulcers fare
somewhat better, but central corneal scarring effectively means that an
individual is unilaterally blind for life because of the prohibitive cost of
corneal transplantation in most developing countries, the lack of facilities
and trained surgeons, and the scarcity of donor tissue for such transplan-
tation. The true economic costs of unilateral blindness secondary to cor-
neal ulceration are not known. Affected individuals are undoubtedly at
greater risk for injury to the fellow eye and are more prone to accidents
in general. In the case of bilateral blindness in children, the social and
economic impact over a lifetime is incalculable.

䡲 Epidemiological Features

Most corneal ulcers in the developing world occur after relatively

minor corneal trauma.3,4 Microbial pathogens then are introduced into
the corneal stroma by contamination of the object producing the abra-
sion, by the presence of pathogens in the environment, or by the patient’s
own conjunctiva or eyelids. Immediately after the corneal abrasion occurs,
there is a window of opportunity during which one can interfere with
microbial invasion before keratitis develops. If an infection becomes es-
tablished in the corneal stroma, the rapid growth of the microbial patho-
gens and the resulting tissue necrosis that occurs make medical reversal of
the process more difficult. The inflammatory mechanisms called into play
by the human body invariably produce rapid necrosis of the corneal
stroma, which then heals slowly, with the development of severe scarring
over weeks to months.
Few surveys have investigated the incidence of corneal ulceration,5
and the spectrum of microbial pathogens producing ulceration varies
from population to population, as shown by large studies in Asia and
Africa (table). Significantly, the most common bacterial pathogen causing
corneal ulceration in the majority of these studies was Streptococcus pneu-
moniae. In a series from South India, half of all the ulcers were caused by
fungal pathogens, with Fusarium species being the most commonly iso-
lated organisms.4 Only one population-based retrospective incidence sur-
vey has been reported from a developing country. Gonzales and col-
leagues6 found that the incidence of corneal ulceration in Madurai
District, South India, was 113 per 100,000 per year or ten times the inci-
 Corneal Ulceration Prevention 䡲 73

Table 1. Central Corneal Ulcers in the Developing World: Geographical Comparison

South South Bangla- West South
Africa8 Africa9 Nepal3 desh10 Africa11 India4
Date of study 1985 1987 1991 1994 1995 1997
No. of ulcers 91 131 405 142 199 434
Culture positive (%) 68 65 80 82 57 68
Organisms cultured
Bacteria (%)
Most frequent pathogens* 90 96 79 66 49 47
Streptococcus pneumoniae 40 16 31 32 13 44
Staphylococcus species 13 61 22 3 29 16
Pseudomonas species 17 6 11 48 25 14
Other bacteria (%) 30 17 36 17 33 26
Fungi (%) 10 4 21 44 51 53
*Each species as a percentage of the total number of bacteria cultured.

dence in the United States. Generalizing these findings to all of India, an

estimated 840,000 people develop a corneal ulcer annually in that coun-
try.
A number of risk factors may predispose an individual in a developing
country to microbial keratitis. Geographical environmental, social, and
ethnic differences are usually of great importance. Undoubtedly, however,
the most important risk factor is a history of corneal trauma. Unlike in the
industrialized world, where contact lens wear is the main risk factor for
developing corneal ulceration, in the developing world contact lenses are
worn by a relatively small portion of the population. In contrast, the
majority of the population is involved in agricultural labor, and the op-
portunities for repeated incidences of corneal trauma are numerous. Geo-
graphical areas that are consistently warm and humid, such as South
India, tend to have a greater number of fungal ulcers, whereas regions
with more temperate climates, such as the mountainous areas of Nepal,
have a preponderance of bacterial ulcers. Individuals such as farmers, day
laborers, and brick or stone workers are prone to frequent corneal abra-
sions. Often, the poorest people in any given community tend to have a
higher risk for microbial keratitis because of their occupational exposure
and their lack of ready access to the health care system.

䡲 Diagnosis and Treatment

Microbial keratitis, by definition, is a suppurative infection of the

corneal stroma with an associated epithelial defect and signs of inflam-
mation. The pathogens usually responsible are bacterial, fungal, or para-
sitic. The herpesviruses and other viral pathogens usually are excluded
74 䡲 Whitcher et al.

from this definition. Even though good epidemiological evidence does

not exist, it is usually assumed that herpes simplex virus is an uncommon
cause of corneal blindness in developing countries. Patients who develop
a corneal ulcer usually give a history of redness, pain, and sensitivity to
light, with an associated decrease in visual acuity. Although the distinction
between central corneal ulcers and peripheral ulcers is somewhat arbi-
trary, microbial keratitis does not have to occupy the visual axis to be
included in the corneal ulceration category.
Corneal ulcers are characterized by the presence of a white or yellow-
ish stromal infiltrate or infiltrates with an associated epithelial defect. The
eye exhibits signs of inflammation: injection, an anterior chamber reac-
tion and, possibly, a hypopyon. The patient is in pain and usually presents
as an acute emergency. If there is a delay in receiving treatment, as was
seen frequently in a study in Nepal where patients sometimes had to walk
for weeks to get to a hospital,3 total corneal necrosis may be seen on
presentation, with corneal perforation and endophthalmitis. Because of
the delay in diagnosis and treatment, microbial keratitis in developing
countries is often much more severe on initial presentation. Both bacte-
rial and fungal ulcers may present with a large area of central necrosis and
a significant hypopyon. Satellite lesions with soft feathery edges are a
prominent sign of fungal keratitis in developing countries but, in general,
the ulcers seen under these circumstances are much more aggressive than
those seen in industrialized countries and quickly perforate. Likewise,
bacterial ulcers progress rapidly to involve the entire cornea. Medical
treatment then becomes problematic because, even if the ulcer is steril-
ized, necrosis is usually so extensive that surgical intervention may be
necessary to maintain the integrity of the eye.
If culture facilities are not available, corneal scrapings can be of great
help in making a tentative etiological diagnosis. Staining a bacterial ulcer
smear with Gram’s or Giemsa stain can be performed with minimal equip-
ment. Examining corneal scrapings from fungal ulcers is greatly facilitated
by using a KOH wet mount. Fortunately, Acanthamoeba is a rare cause of
corneal ulceration in the developing world, but the organisms can still be
identified from direct corneal scrapings stained with Giemsa stain.
In general, physicians and health care workers in developing coun-
tries are incredibly dedicated. However, they often lack training and even
the simplest material resources. Equipment and instruments often are
antiquated and in need of repair, and medications are limited and pro-
hibitively expensive. Successful treatment of microbial keratitis is prob-
lematic under the best of circumstances. In the setting of a developing
country where everything is in short supply, the odds are stacked against
successful therapy. Because laboratory facilities often are inadequate or
unavailable, the treatment of corneal ulcers is frequently empirical.
The choice of antibiotics for the treatment of bacterial ulcers must
cover S. pneumoniae, as this is the most common corneal pathogen in many
 Corneal Ulceration Prevention 䡲 75

parts of the world. However, the gram-negative pathogens, such as pseu-

domonads, cannot be overlooked because of the severity of the keratitis
that they produce. Any empirical therapy for a bacterial ulcer should
include cefazolin or the equivalent to cover gram-positive organisms and
a fluoroquinolone or an aminoglycoside to cover gram-negative patho-
gens. Antifungal medications are more problematic because they fre-
quently are unavailable. Pimaricin in a 5% suspension may sometimes be
in stock, and amphotericin B drops can be made up as a 0.15% topical
solution. These two medications are frequently used together to treat
filamentous fungi, but yeasts respond best to amphotericin B alone. Em-
pirical antibiotic treatment of any central ulcer without first ruling out the
possibility of a fungal infection invites disaster, especially in areas such as
South India where fungal pathogens cause half of all the ulcers seen.
Obtaining corneal scrapings and staining the smears with Gram’s or Gi-
emsa stain to make an etiological diagnosis prior to initiating therapy is
critical in avoiding treatment disasters.

䡲 Prevention

Because of the often prohibitive cost of treating microbial keratitis in

a developing country and the invariably blinding corneal scarring that
occurs, prevention is the ideal approach for reducing the epidemic num-
bers of corneal ulceration now occurring. Theoretically, the majority of
ulcers could be prevented if a combination antibiotic-antifungal ointment
were instilled into the eye immediately after an individual suffered a cor-
neal abrasion. A large-scale program could be implemented through the
existing village health care systems in many countries, and public aware-
ness of ulcer prevention could be increased using the eye health educa-
tion programs already in place. Unfortunately, a commercially available
antibiotic-antifungal eye ointment does not currently exist and, until re-
cently, no study had been done that proved that the incidence of corneal
ulceration could be significantly reduced by prophylactic treatment. Up-
adhyay and coworkers7 have recently reported the results of such a study
in Nepal, however. They demonstrated that the application of chloram-
phenicol ointment three times daily for 3 days in eyes of patients who had
suffered corneal abrasions dramatically reduced the rate of corneal infec-
tion after corneal abrasion. Moreover, none of the patients who presented
for treatment within the first 18 hours after injury developed an ulcer but,
as this time interval increased, more cases of ulceration occurred. Even
though ethical considerations prevented the use of a control group, the
large number of patients surveyed over the 2-year period of this prospec-
tive population-based study provides the strongest evidence thus far that
antibiotic prophylaxis may be effective in preventing corneal ulceration
after abrasion, if the treatment is administered in a timely fashion.
76 䡲 Whitcher et al.

䡲 Recommendation

The problem of microbial keratitis in the developing world should be

handled at the grass-roots level. Gonzales and associates6 found that many
of the ulcers in South India were treated by village healers and nonoph-
thalmologists who had little knowledge of disease pathogenesis or stan-
dard methods of therapy. Remedies used by traditional healers often en-
hance the development of microbial keratitis after corneal abrasion by
introducing bacterial or fungal pathogens in contaminated solutions or
organic materials.4 With simple training, most health care workers would
be able to administer prophylactic ointment after corneal abrasions, and
they could also be instructed in how to recognize corneal ulcers early
during the first stages of their development. In most cases, personnel are
already in place, but they require better training and specific instructions
for referring suspected cases of microbial keratitis to regional health cen-
ters for treatment.
Until recently, the enormity of the problem of microbial keratitis in
the developing world was not appreciated. Population-based studies spon-
sored by the World Health Organization are now under way in several
countries in Southeast Asia to define the true incidence of corneal ulcer-
ation, to examine the importance of risk factors, and to determine the
most common pathogens responsible for ulceration in each geographical
area. As the epidemiology of microbial keratitis in the developing world
becomes better understood, prevention and treatment programs that are
evidence-based can be implemented. It is hoped that by that time new
antifungal-antibiotic medications will be available for large-scale preven-
tion programs and that more effective and affordable antimicrobial agents
will be available for treating those ulcers that elude prevention.

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 Corneal Ulceration Prevention 䡲 77

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