Table of Contents

1. INTRODUCTION.............................................................................................................................1
1.1. Vitamin A Metabolism..............................................................................................................1
1.2. Clinical Classification and Diagnosis........................................................................................2
2. XN. NIGHT BLINDNESS.................................................................................................................3
3. EPIDEMIOLOGY.............................................................................................................................4
3.1. Age..............................................................................................................................................4
3.2. Sex...............................................................................................................................................5
3.3. Season.........................................................................................................................................5
3.4. Clustering...................................................................................................................................6
3.5. General pattern of disease.........................................................................................................6
4. ASSESSMENT AND CHARACTERIZATION OF THE PROBLEM.........................................6
4.1. Preliminary assessment and case-finding.................................................................................6
4.2. Prevalence surveys.....................................................................................................................8
4.3. Clinical Parameters...................................................................................................................9
4.4. Biochemical parameters............................................................................................................9
4.5. Dietary parameters..................................................................................................................10
5. TREATMENT.................................................................................................................................11
5.1. Medical status and diet............................................................................................................12
5.2. Eye care....................................................................................................................................12
5.3. Preventing recurrence.............................................................................................................12
5.4. Logistics....................................................................................................................................13
6. PREVENTION................................................................................................................................13
6.1. Periodic dosing.........................................................................................................................14
6.2. Fortification of items in the diet..............................................................................................16
6.3. Increased intake of dietary sources of vitamin A..................................................................16
7. EVALUATION................................................................................................................................18
BIBLIOGRAPHY.....................................................................................................................................20
APPENDIX ONE......................................................................................................................................21
 1. INTRODUCTION
Xerophthalmia remains the most important cause of childhood blindness in many developing
countries. Xerophthalmia is the general term applied to all the ocular manifestations of impaired
vitamin A metabolism, from night blindness through complete corneal destruction
(keratomalacia). It is among the oldest recorded afflictions of mankind, having been recognized
by both the ancient Egyptians and the Greeks. As recently as the late nineteenth and early
twentieth centuries numerous cases still occurred among malnourished individuals in such
widely scattered parts of the globe as Brazil, China, England, Japan, Denmark, and Russia.
Today blinding xerophthalmia is largely limited to developing countries, especially those in
Africa, Asia, and the Western Pacific. Isolated foci also exist in the Caribbean, Latin America,
and the Eastern Mediterranean. (1, 2) Recent data indicate that at least 5 million children in Asia
develop xerophthalmia every year, 250 000 of whom go blind. (3)
Modem concepts of the disease date from the early 1800s, when dogs that were "starved" on
sugar and distilled water developed perforating corneal ulcers resembling those in "ill-nourished
infants."4 It took one hundred years before investigators realized that these changes were due to
lack of a specific nutrient, (5-7) "fat-soluble A", present in the lipid fraction of milk, eggs, butter
and cod-liver oil, or as pro-vitamin A carotenoids in dark-green leafy vegetables and certain
coloured fruits. Histophathological observations soon demonstrated the importance of vitamin A
for the maintenance of normal epithelial integrity. (8)
1.1. Vitamin A Metabolism
VITAMIN A, or retinol, is a fat-soluble substance found in liver, particularly fish liver, and in
poultry, meat, and dairy products. Carotenes-potential precursors present in green leafy
vegetables, red palm oil, yellow fruits, and the like-can be converted to retinol in the wall of the
gut. The relative biological values of these various substances were formerly expressed in
international units (IV) of vitamin A activity, I IU being equivalent to 0.3 µ of retinol, 0.55 µ of
retinol palmitate, 0.6 µg of f3-carotene, and 1.2 µ of other pro-vitamin A carotenoids. Not only
are carotenes biologically less active than retinol, but their dietary sources are less efficiently
processed and absorbed from the gut. One must therefore ingest up to six times as much pro-
vitamin A f3-carotene (by weight) as retinol for a similar degree of effect.
Some 50-90% of ingested retinol is absorbed in the small intestine and transported, in association
with chylomicron, to the liver, where it is stored primarily as retinol palmitate. When needed, it

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is released into the bloodstream in combination with retinol-binding protein (RBP), a specific
carrier protein elaborated by the liver. The retinol is then removed from the serum and utilized
by epithelial cells throughout the body. The diagram overleaf gives a simplified schematic
outline of these metabolic pathways.
The liver stores form an important buffer for variations in vitamin A and f3-carotene intake.
When vitamin A intake surpasses 300-1200 µg/day of retinol, or its equivalent, the excess is
stored and liver reserves are increased. When vitamin A intake is less than this amount, liver
stores are drained to maintain serum retinol (vitamin A) at a normal level (above 200µg/1 or 0.7
µmol/I). When intake remains low for prolonged periods of time the liver stores become
depleted, serum retinol levels drop, epithelial function is impaired, and xerophthalmia appears.
The duration of inadequate intake required for this to occur depends upon the amount of vitamin
A (or precursor) ingested, the extent of pre-existing liver stores, and the rate at which vitamin A
is being utilized by the body.
A child with borderline, marginal intake to begin with will have very limited stores. Any sudden
drop in intake, either from a change in diet or interference with absorption (as in gastroenteritis)
or a sudden increase in metabolic demand (febrile state or growth spurt), will quickly deplete the
limited reserves and may precipitate frank corneal destruction, even in eyes that had previously
appeared entirely normal. Where liver stores have been very high, however, an individual may
go for months without vitamin A and not suffer serious consequences. The availability of stored
vitamin A will also depend upon the child's general nutritional status. Severely malnourished,
protein-deficient children synthesize RBP at a much reduced rate. Serum retinol levels will
therefore be subnormal, even if liver stores are high. Finally, a diseased liver cannot store as
much vitamin, or make as much RBP, as a normal one.
1.2. Clinical Classification and Diagnosis
Vitamin A deficiency is a systemic disease affecting epithelial structures in a variety of organs,
the eye being the most obvious and dramatic example. Keratinizing metaplasia of the respiratory
and intestinal epithelia is thought to be responsible for the pulmonary and gastrointestinal
symptoms found in the most severely affected children. But the classic clinical expression is
xerophthalmia, or "dry eye".
Uncomplicated, gradual depletion of vitamin A stores results in xerophthalmia of increasing
severity: night blindness, conjunctiva xerosis and Bitot's spot, corneal xerosis, and corneal

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ulcerationl keratomalacia. All usually respond rapidly to vitamin A therapy, the milder
manifestations usually clearing without significant sequelae. The loss of deep corneal tissue,
however, from ulceration/- keratomalacia generally results in scarring and residual opacification.
The major signs and symptoms of xerophthalmia were recently reclassified (Table 1).2
Experiences has shown that, in the appropriate setting, a history of night blindness and
characteristic retinal specks are both highly specific for xerophthalmia, eliminating the need to
distinguish between "primary" and "secondary" signs. All Bitot's spots are accompanied by
underlying xerosis; hence the presence of xerosis does not distinguish new, active lesions from
old, residual ones. And the extent of active corneal destruction (ulceration/keratomalacia) is a
better index of visual prognosis than is its appearance, and therefore a better basis for sub
classifying the severity of involvement.
Table 1: Classification of xerophthalmia (1982 revision)
XN Night blindness
X1A Conjunctival xerosis
X1B Bitot's spot
X2 Corneal xerosis
X3A Corneal ulceration/keratomalacia < 1/3 corneal surface
X3B Corneal ulceration/keratomalacia;;" 1/3 corneal surface
XS Corneal sca
XF Xerophthalmic fundus

2. XN. NIGHT BLINDNESS

Retinol is essential for the elaboration of rhodopsin (visual purple) by the rods, the sensory
receptors of the retina responsible for vision under low levels of illumination. Vitamin A
deficiency can interfere with rhodopsin production, impair rod function, and result in night
blindness.
Night blindness is generally the earliest manifestation of vitamin A deficiency. When mild, it
may become apparent only after a photic stress, such as flying a kite on a sunny day. Affected
children no longer move about the house or village after dusk, but prefer to sit in a secure corner,
often unable to find their food or toys.
Night blindness of recent onset in a preschool child is practically pathognomonic of vitamin A
deficiency. Other causes of night blindness are relatively rare and almost never present in this
fashion. Among some societies or cultures, particularly those in which vitamin A deficiency is

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endemic, specific terms exist to describe the condition, such as "chicken eyes" (lacking rods,
chickens are night-blind).
Mothers do not always recognize the presence of night blindness, especially among children who
have not yet begun to crawl or toddle. When a mother does complain that it is present, however,
she is almost certainly correct, (1, 2) and this makes objective assessment unnecessary in most
routine clinical situations. Night blindness responds rapidly, usually within 24--48 hours, to
vitamin A therapy.
All children suspected, or at risk, of having xerophthalmia must have both eyes examined in
open shade or with the aid of a flashlight and loupe, if available. Unfortunately, because of the
pain and reflex blepharospasm accompanying corneal involvement, these children tend to keep
their eyes tightly shut. When necessary, the child's head can be stabilized by a parent or
attendant, while a physician carefully separates the lids with a sterile Desmarres retractor, lid
speculum, or bent paper-clip (as seen in most of the illustrations). The leading edge of the clip
should be held parallel to the lid. Once it has passed behind the lid margin it should be gently
angled forward, to avoid abrading the cornea or placing undue pressure on the globe.

3. EPIDEMIOLOGY
XEROPHTHALMIA results from an insufficient supply of vitamin A to the eye. The cause of
such a deficiency can be quite complex, and depends upon the type and amount of vitamin and
provitamin (primarily ~-carotene) ingested, the absorptive, transport, and storage capacities of
the individual, and his metabolic needs. Seemingly unrelated disease states can dramatically alter
each of these factors and, in turn, the individual's vitamin A balance. For example, gastroenteritis
will change the types and amounts of food offered to a child and his appetite, while the shortened
transit time will decrease absorption of what vitamin A is ingested. If he is already protein-
deficient, transport and storage may be decreased and the fever will increase his metabolic needs.
The cause and contribution of each of these factors may vary from one community to another,
resulting in different epidemiological patterns in respect of age, sex, season, magnitude, and
relative proportion of cases with and without corneal involvement. In general, however,
xerophthalmia is predominantly a disease of young children from depressed rural communities.
3.1. Age

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Children are born with limited vitamin A reserves and are dependent for the first 6-12 months of
life on vitamin A provided in the breast milk. When the mother is deficient in vitamin A the
newborn child's reserves are even smaller, and the amount of vitamin A provided in the breast
milk is reduced. Bottle-fed children are often at even greater disadvantage, receiving skimmed
milk (already low in vitamin A) that has been over diluted with water (frequently contaminated).
After 6 months of life the child requires supplementary feedings with foods rich in vitamin or
pro-vitamin A. For a variety of reasons, principally ignorance, cost, or unavailability, these may
not be consumed in adequate amounts.
It is also children who are at greatest risk from intestinal infestations and infections, which
impair vitamin A absorption; respiratory infections, tuberculosis, and measles (and other
childhood exanthems) that increase metabolic demands; and protein-energy malnutrition, which
interferes with the storage, transport and utilization of the vitamin. As children grow older, they
forage more widely (providing a more varied, nutritionally balanced diet) and suffer fewer
infections; general nutritional status and vitamin A status improve; and the risk of blinding
xerophthalmia declines.
Occasionally, factors responsible for vitamin A deficiency are prevalent among older
individuals, particularly prisoners, students and army recruits, who are then at risk of blinding
xerophthalmia.
3.2. Sex
Boys are frequently at greater risk of night blindness and Bitot's spot than are girls. In most
societies or cultures, however, the two sexes are at equal risk of severe blinding xerophthalmia
(corneal ulceration and keratomalacia).
3.3. Season
Xerophthalmia may be more prevalent at certain times of the year, the pattern being determined
by the severity and concurrence of the various factors that impair vitamin A status. In many areas
of the world this is the hot, dry season, when sources of vitamin A (and of food in general) are in
short supply and measles and diarrhoea are common. Measles is a particularly important factor,
precipitating as much as a quarter to a half of the cases of blinding xerophthalmia in Asia, and
perhaps even more in Africa. In many parts of Africa measles is said to be the commonest cause
of childhood blindness. The relative importance of xerophthalmia in such cases is as yet
uncertain.

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 3.4. Clustering
Since the dietary and health practices responsible for vitamin A deficiency are often shared by
other members of the community, xerophthalmia cases tend to cluster within specific families
and neighborhoods. Children living in the immediate vicinity of an active case of xerophtbalmia
are more likely to be deficient in vitamin A, and at higher risk of xerophthalmia, than children of
the same age, sex and socioeconomic status living in a different neighbourhood of the same
village or town.
3.5. General pattern of disease
The prevalence of milder manifestations (night blindness and vitamin A-responsive Bitot's spot
and conjunctival xerosis) usually increases from the age of about 2 years up to the early school
years. Malnutrition, if present, is usually mild. These signs may persist for months, tend to be
seasonal, and usually disappear spontaneously, probably with increased availability and
consumption of foods containing vitamin A (and carotene). They probably represent relatively
mild, isolated vitamin A deficiency and do little lasting damage, but they identify children and
communities at increased risk of developing destructive corneal lesions.
Children suffering from forms of the disease destructive to the cornea are usually younger (often
less than 1 year of age), more severely malnourished, and more deficient in vitamin A. History of
a recent precipitating event (pneumonia, measles, gastroenteritis, tuberculosis, etc.) is common,
and the mortality is often quite high (20-50%).

4. ASSESSMENT AND CHARACTERIZATION OF THE PROBLEM

THE formulation of an effective intervention program begins with the characterization of the
problem. Although costly and time-consuming, assessment is far less expensive than intervention
itself, may indicate that the problem is much more limited than originally anticipated, and may
suggest where and how prevention activities can best be applied. When clinicians, nutritionists,
or public health officials suspect the existence of a xerophthalmia problem, case-finding by local
or outside experts will determine whether or not the disease actually occurs in the community in
question. If it does, prevalence surveys are needed to determine its nature, magnitude, severity,
and geographical distribution.
4.1. Preliminary assessment and case-finding

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The search for active or healed cases of xerophthalmia should be directed by someone
experienced in the clinical recognition of the disease and knowledgeable about its
pathophysiology and nutritional determinants. Ideally, this should be someone from outside the
area concerned. Local specialists may mistakenly believe that xerophthalmia is not a significant
problem: they may not encounter the disease, because it occurs in areas or socioeconomic groups
not making use of their services; or they may misdiagnose it. On the other hand, misdiagnosis or
a biased referral pattern may lead them to believe it is a serious problem, when in fact it is not.
The outside expert provides a fresh, impartial viewpoint backed by experience in similar
situations elsewhere.
Cases should be sought in those areas where they are most likely to occur: slums and
impoverished villages; ophthalmic, malnutrition, and infectious-disease wards of pediatric
services; rehabilitation and feeding centers; and refugee camps, orphanages, and the like.
Careful, written records are more likely to be accurate than verbal «guesstimates", and direct
observation of active cases is the surest means of documenting the occurrence of the disease and
the validity of past diagnosis and historical data.
Where examination, chart review, or interviews are positive, data should be collected on age,
sex, seasonality, geographical distribution, and presence of antecedent or concomitant illnesses.
This will be useful in designing the definitive prevalence survey.
An orderly, comprehensive, preliminary investigation should include the following:
a) Interviews, preferably by structured questionnaire, with individuals likely to be
aware of the problem: central and provincial public health officials; clinicians,
nutritionists, and community health workers; directors and the staffs of hospitals,
feeding and rehabilitation centers, and schools for the blind.
b) Chart reviews at institutions where the disease is recognized or children are
known or suspected to suffer from corneal destruction: clinics and rehabilitation centers,
schools for the blind, and hospitals, where one may review all charts on children coded,
according to the International Classification of Diseases, for diseases likely to be
accompanied by, or mistaken for, xerophthalmia (conjunctivitis, keratitis, blindness,
malnutrition, measles, gastroenteritis) or, where coded charts do not exist, records from
the malnutrition, infectious disease, pediatric, and ophthalmic services. The conduct and

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 interpretation of such reviews, however, are often hampered by vagaries and
inconsistencies in recordkeeping and retrieval.
c) Search for clinically active cases among children at high risk: those attending
clinics and feeding centers; admitted to ophthalmic, nutrition, infectious disease, and
general pediatric wards; or residing in urban slums or impoverished rural communities.
This can be carried out during a brief "expert" visit. Preferably doctors and nurses
should be carefully trained and motivated to examine the eyes of high risk children and
to recognize and record evidence of xerophthalmia in systematic fashion (see
xerophthalmia case reporting form, Appendix 1). This has the advantage of yielding
larger, more representative numbers of cases and data on seasonal variation. It also
promotes routine case-detection and treatment and establishes a relatively simple,
inexpensive basis for long-term surveillance.
d) Search for old healed disease, with histories compatible with prior
xerophthalmia (X2, X3) in schools for the blind, low-income urban areas, and in the
countryside.
e) Collection of existing data on dietary intake and serum vitamin A levels for the
population and presumed active cases. Where available, such data provide strong
corroborative support for this diagnosis of active disease and the potential presence of
the problem in the population as a whole.
4.2. Prevalence surveys
Prevalence surveys determine the proportion of individuals in the sample with a particular
attribute or abnormality at the time of examination-prevalence-and provide a basis for estimating
the frequency with which new, irreversible lesions are likely to occur over a given period of
time-incidence--{see section on interpretation, page 33). When the sample is carefully chosen to
be representative of the population under consideration, prevalence rates within the sample are
representative of those within the population as well.
Prevalence surveys are complex, expensive, and time-consuming. In general, they need be
undertaken only where preliminary investigations indicate the presence of a potentially
significant problem. Surveys containing clinical, biochemical, and dietary components are the
most efficient and definitive (unbiased) means of:

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 (a) establishing the nature, magnitude, severity, and geographical distribution of
xerophthalmia;
(b) determining whether it constitutes a significant public health problem;
(c) selecting suitable strategies for intervention;
(d) providing a baseline for evaluating the effectiveness of future intervention programs.
4.3. Clinical Parameters
A history of night blindness-often the most prevalent of the signs and symptoms of vitamin A
deficiency-is easily collected. Care must be taken, however, in accepting a positive history: it
should come from a responsible adult who recognizes that the child's behavior after dusk or in a
darkened room is distinctly different from that of other, normal children. The history is most
reliable when described with a local term specific for the condition. It is imperative the survey
team should make every effort to learn of such terms before conducting their interviews. Being a
mild sign of xerophthalmia, night blindness has the same significance and limitations as those
described for Bitot's spot, below.
Bitot's spot (XIB)
This is an easily recognized and relatively specific marker of active vitamin A deficiency, at least
among preschool children, and it is more prevalent than corneal disease. But it does not provide
any information on the magnitude or extent of ocular destruction and blindness. Areas with
similar Bitot's spot prevalence’s may have widely varying levels of corneal destruction, and vice
versa.
Although the diagnosis of xerophthalmia-related corneal destruction is retrospective, few if any
other conditions produce significant numbers of cases with a similar clinical and historical
pattern. Since only survivors are examined, the observed prevalence (frequency of cases in the
population at any one time) of sequel gives an inadequate idea of the incidence (number of new
cases in the community over a given period of time) of active disease.
4.4. Biochemical parameters
Despite the fact that active xerophthalmia is usually associated with low serum retinol (vitamin
A) levels, the relationship is insufficiently fixed and precise to permit the level of clinical disease
to be estimated from biochemical data alone. As part of a clinical prevalence survey, however,
serum retinol levels for "abnormal", "controls", and a random or a systematic subsample of the
study population (every twentieth child) can provide important insights into the distribution of

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the disease. Low serum retinol levels for "abnormal" (children with active xerophthalmia, XN-
X3B) provide independent corroboration of the clinical diagnosis.
Serum retinol determinations on the random subsample establish the degree of subclinical
vitamin A deficiency in the community. Where retinol levels are generally low, approaching
those for “abnormal”, vitamin A deficiency are widespread and the community as a whole at risk
of clinical disease. Where they are high, however, the community as a whole is relatively
normal, and vitamin A deficiency and the potential for clinical disease are relatively infrequent.
How infrequent they are may be determined from the serum levels among controls. If these
approach the relatively normal levels of the random subsample, the potential for disease is
limited to those few individuals already having active xerophthalmia. On the other hand, if the
levels are more like those among the "abnormal", then the potential for disease is more
widespread, confined not to individual children but to neighborhoods or localities, especially
those in which the "abnormal" reside.
Biochemical components should be included only where adequate facilities exist for the
collection, storage, and transport of samples, and where equipment and expertise exist within the
country or arrangements have been made with a reference laboratory outside the country to carry
out the determinations.
4.5. Dietary parameters
Like serum retinol levels, dietary histories cannot determine the prevalence or severity of
xerophthalmia in the community. An understanding of food consumption patterns of children
with active xerophthalmia and their families is, however, indispensable for determining why
these children became deficient in vitamin A, selecting a vehicle for vitamin A fortification, and
designing appropriate messages for health education programs.
Three different sets of forms may be used: a family-based qualitative history to determine the
frequency with which different foods are eaten by the family as a whole, and where these foods
were procured; a similar form for individual children, which includes, in addition, questions on
breast-feeding and weaning practices; and a quantitative history which attempts to determine the
exact quantity of each food eaten by the child during the past 24 hours. For comparison, forms
are completed on all "abnormal" children, their matched controls, and a random or a systematic
subsample of all children (every twentieth child) examined, and their respective families. Where
children do not eat foods that constitute sources of vitamin or pro-vitamin A, it is important to

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enquire about the reasons (e.g., they are expensive, locally unavailable, not considered healthy
for children, the child does not like them, etc.).
The list of foods should include all locally available major sources of vitamin and provitamin A,
potentially fortifiable foodstuffs, staple foods, and major sources of protein. Qualitative data can
usually be collected by a suitably trained field worker, but quantitative data require a trained
nutritionist, samples of the foods under consideration, and scales to weigh the amounts the child
consumes, as indicated by the mother.

5. TREATMENT
Effective therapy requires prompt recognition of children with, or at high risk of developing,
active disease; immediate administration of massive doses of vitamin A with concomitant
treatment of underlying systemic illnesses and protein-energy malnutrition; and prevention of
any recurrence.
All children at risk of corneal destruction related to vitamin A deficiency must be promptly
identified. These include:
a) those who already have evidence of active xerophthalmia (XN-X3B);
b) Severely ill and malnourished children coming from communities where xerophthalmia is
known to occur, whether or not they themselves already have clinical evidence of vitamin
A deficiency.
Vitamin A Xerophthalmia is a medical emergency; requiring prompt administration of massive
amounts of vitamin A. Oral administration is just as effective as parenteral administration. As
oral dosing does not require sterile needles, syringes and special water-miscible preparations, it
is safe, cheap and increasingly available.1
Administer 110 mg oil- or water-miscible retinol palmitate or 66 mg retinol acetate (200000 IU
vitamin A) by mouth immediately upon diagnosis and repeat the dose the following day. An
additional dose should be given 1-2 weeks later to boost liver reserves. Because children with
severe protein-energy deficiency handle a massive dose poorly, they should receive an additional
dose, every 2 weeks, until protein status improves.
For children unable to swallow, or suffering from repeated vomiting or profuse diarrhoea, an
intramuscular injection of 55 mg water-miscible retinol palmitate (100 000 IU) should be

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substituted for the first oral dose. Oil-miscible preparations should never be given by injection
because they are poorly absorbed from the injection site.
For children less than 12 months of age the doses should be reduced by half. Where vitamin A
preparations are not yet available, treatment should be instituted with foods rich in vitamin A
(fish and animal livers, fish-liver oil, dairy products, etc.) or J3-carotene (lightly cooked, green
leafy vegetables, including leaves of the "drumstick" or "horseradish" tree (Moringa oieifera),
the various amaranths, cassava leaves, etc., red palm oil, and red, yellow, and orange colored
fruits, such as papaya and mango). Adding a small amount of edible oil will enhance the
absorption of the J3-carotene.
5.1. Medical status and diet
Children with xerophthalmia, particularly its blinding forms, are often severely ill, malnourished
and dehydrated. Proper treatment will help save their vision as well as their lives, and includes
general supportive care, rehydration, and frequent feedings (by nasogastric tube if necessary)
with easily digestible protein-rich foods. Respiratory and gastrointestinal infections, tuberculosis,
worm infestations, amoebiasis and the like should be treated with appropriate agents (antibiotics,
anthelmintic, etc.).
5.2. Eye care
In the presence of corneal involvement, apply broad-spectrum antibiotic eye ointment every 8
hours to reduce the risk of secondary bacterial infection. As always, established infections
require immediate, vigorous local and systemic therapy. Until such time as the responsible agent
is identified, antibiotics should be chosen to cover a wide range of organisms, especially
Staphylococcus and Pseudomonas (e.g., topical bacitracin and gentamicin, plus sub conjunctiva
and systemic gentamicin and methicillin). Every effort should be made to preserve the structural
integrity of the globe. Eyes with weakened corneas (active keratomalacia, ulceration, or
thinning) must be protected from undue pressure: examinations, applications of drugs, and
dressing changes should be done with the utmost care, and the eye covered, at all other times, by
a firm plastic or metal shield (one can easily be fashioned from discarded X-ray film). When
necessary, the child's hands can be restrained.
5.3. Preventing recurrence
The vulnerable children have already demonstrated that their home environment is deficient in
vitamin A. Their mothers need to be taught the necessity of providing diets rich in vitamin A and

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shown how to prepare them from inexpensive, readily available sources (primarily mango,
papaya, carrots and dark-green leafy vegetables). As a rough estimate, 40 g of green or red
varieties of amaranth, 35 g of drumstick leaves, or 100 g of mango all provide the daily
requirements for toddlers and preschool children. Large, simple wall posters in clinic and
hospital waiting-rooms will alert mothers to the problem and its prevention. Nutritionists,
dietitians, and other specially trained personnel can instruct those with affected children in
greater depth. Periodic follow-up will ensure that xerophthalmia has not recurred and, where it
has, provide the opportunity for prompt treatment. Administration of a massive dose (appropriate
for age) at 4-6-monthly intervals will ensure that the child has adequate vitamin A stores.
5.4. Logistics
Prompt and effective therapy requires suitable vitamin A preparations to be available at all
hospitals, clinics, health units, and rehabilitation centers and to all primary health care workers
who are likely to encounter the disease. Standardized 100 000 and 200 000 IV capsules and
concentrated solution of vitamin A are cheap, increasingly available, and perfectly safe when
given in the recommended amounts. Larger doses or over frequent administration may be toxic,
however, resulting in headaches, vomiting, seizures, changes in mental activity, and other
evidence of increased intracranial pressure.
Prompt and effective therapy also requires doctors, nurses, and paramedical personnel trained in
the recognition and treatment of the disease. These last should be included in the basic curricula
of all schools of medicine, nursing, and paramedical training, and short courses should be held
for personnel already in practice. A series of simple, inexpensive teaching guides on the subject
have been produced for individuals of varying professional skills. Recognition and treatment
guides should be left at each center for future reference. Vitamin A therapy should be initiated by
the first member of the medical network who encounters the disease. Only then should cases of
corneal involvement, or of severe systemic infections or malnutrition, be referred for more
comprehensive treatment.

6. PREVENTION
Anything that improves the vitamin A status of high-risk individuals can have a dramatic impact
on the problem of blinding xerophthalmia. For example, environmental sanitation and better
housing, by reducing the prevalence and severity of respiratory tract infections, tuberculosis,

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diarrhea, and worm infestations, will increase absorption and reduce metabolic conversion and
loss of ingested vitamin A. Measles immunization will eliminate one of the commonest
precipitating factors of blinding xerophthalmia.
Only by ensuring that children receive adequate supplies of vitamin A, however, will the
underlying cause of the problem be removed. In general, such supplies must be greater than
"recommended daily allowances" (RDA) established for healthy children. They must be
adequate to overcome reduced absorption and increased requirements prevalent among
disadvantaged populations. They must also provide sufficient excess for the development of
vitamin A stores to protect high-risk children through seasonal fluctuations in the availability of
vitamin-A-rich foods.
The ultimate goal of any prevention program must be the regular, adequate dietary intake of
vitamin and pro-vitamin A by vulnerable children, and the elimination of all forms of vitamin A
deficiency. But this is a long-range task. In the interim, short-term, necessarily expensive
emergency measures are needed to prevent at least that degree of vitamin A deficiency
responsible for ocular destruction and blindness. How and to what extent this is accomplished
will depend upon the severity and nature of the deficiency, the resources available, and the
degree of dedication and desire to attack the problem. To be effective, all such programs must
reach the children at greatest risk.
An understanding of the dietary and socioeconomic determinants of xerophthalmia is necessary
in order to design appropriate intervention programs for each community. Where the necessary
data have not already been collected in the course of the original prevalence survey, limited
secondary investigations must be conducted in the areas of high prevalence. At least three
different forms of intervention are presently in use: periodic administration of large doses of
vitamin A; addition of vitamin A to one or more commonly consumed items (fortification); and
increasing the amount of vitamin and pro-vitamin A-rich foods in the diet.
6.1. Periodic dosing
Periodic dosing takes advantage of the fact that large quantities of vitamin A can be stored in the
liver for future use. Oral administration ofl10 mg retinol palmitate (66 mg of the acetate; i. e.,
200 000 IU), and half this dose for children below 12 months of age, every 4-6 months will
protect the vast majority of recipients from blinding xerophthalmia. The vitamin can be given as
a capsule or concentrated liquid. Except for children suffering from active xerophthalmia or

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protein energy deficiency (kwashiorkor) or some other severe precipitating illness, proper
safeguards are needed to ensure that the massive dose is not repeated more frequently than once
every month.
A massive vitamin A dose is extremely inexpensive; the major cost is in distribution. Where
distribution can be accomplished through existing programs (by malaria, family planning or
primary village level health workers, midwives, etc.) the cost is not excessive; but where single-
purpose workers have to be newly employed it rises dramatically. Efficiency and even efficacy
can be increased by targeting the distribution to the children at greatest risk: those with diarrhea,
respiratory tract infection, generalized malnutrition, severe systemic illnesses, measles, etc.
wherever they are encountered in the medical network. It should be recognized, however, that
large numbers of children will remain unprotected. Characteristically, these children are from the
lowest socioeconomic strata; often reside in remote, inaccessible areas; rarely if ever make use of
existing health facilities; and are at the highest risk of disease. Advantage can be taken of the fact
that vitamin A deficiency and xerophthalmia cluster. Vitamin A distribution (as well as nutrition
education) can be targeted to regions, villages, neighborhoods and even families where the
prevalence of xerophthalmia is particularly high. Since children living in the same neighborhood
as an active case of xerophthalmia are at higher risk of disease than those living elsewhere, it
may prove more efficient for the village health worker (or field staff of the local dispensary) to
treat the entire neighborhood instead of just the child with known disease.
A variety of mechanisms are available for identifying active cases of xerophthalmia (and thereby
the high-risk communities in which they reside). In one innovative approach schoolchildren are
trained to screen their younger siblings for night blindness and report the results to their teachers.
Massive dosing can be usefully targeted to another "captive" group: newborn babies and their
mothers. Where births are commonly attended by health personnel (often traditional birth
attendants or community health workers), these can be instructed to administer 27.5 mg retinol
palmitate (50000 IU vitamin A) to the newborn and 165 mg (300000 IV) to the mother. Giving
the vitamin directly to the child ensures that he or she will have increased liver reserves, even if
breast-feeding is discontinued; giving it to the mother ensures that these reserves will continue to
be augmented during the first 6 months of breast-feeding. Specially calibrated spoons, droppers
or containers will be required for administering the appropriate dosage to newborn children.

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Because of the potential risk of teratogenicity from a massive dose, a woman of child-bearing
age should receive a massive dose only when it is absolutely certain she is not pregnant (i. e.,
within one month of giving birth). It is safe and advisable for lactating and pregnant women in
high-risk communities to receive frequent, low-dose vitamin A supplementation where feasible-
for instance, 2.75 mg retinol palmitate (5000 IV) once a day or 11 mg (20 000 IU) once a week.
Tablets, capsules and syrups containing these dosage levels are widely available.
6.2. Fortification of items in the diet
Addition of selected nutrients to common dietary constituents ("fortification") provides a method
of delivering vitamin A to high-risk children without having to seek them out individually. As
fortification provides supplementary vitamin A at a more regular rate and lower dosage than does
mass dosing, it can also increase vitamin A intake of pregnant and lactating women (and hence
of their newborn and breast-fed infants) without concern about a possible teratogenic effect.
A variety of items can be fortified with vitamin A. But, for fortification to be effective, the item
must be consumed by a significant proportion of the target population, and in amounts
comparable to (or greater than) that of wealthier, maximum-consuming segments of society.
Otherwise it will be difficult to deliver adequate supplementation to those who need it without
overdosing those who do not. For practical reasons the item must also be processed at a limited
number of central sites where the fortification process can be carefully monitored and controlled.
The choice of potential suitable vehicles is therefore extremely restricted, especially since
impoverished rural families, from which most xerophthalmia cases arise, consume few centrally
processed items. Carefully conducted dietary studies are required to identify items meeting these
minimal criteria.
6.3. Increased intake of dietary sources of vitamin A
Mass dosing and fortification are artificial means of compensating for inappropriate dietary
practices. For most communities, a more logical and less expensive long-range solution lies in
changing those practices. Socioeconomic and dietary data from the prevalence survey will help
to reveal which they are.
The problem commonly lies in early discontinuation of breastfeeding and late, inadequate
introduction of carotene-rich fruits, dark green leafy vegetables, and red palm oil. Prolongation
of breast-feeding and early supplementation (preferably by 6 months of age) with tasty, easily
digested pro-vitamin-A-rich fruits (e.g., mango and papaya) or appropriately prepared dark-green

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leafy vegetables are likely to have a significant impact. Dark-green leafy vegetables are often the
least expensive and most widely and consistently available source of vitamin A activity. The
same amount of vitamin A is obtained from 68 g of spinach as from 63 g of calf liver, 227 g of
hens' eggs, I. 7 liters of whole cow's milk, or 6 kg of beef or mutton. But mothers may not know
that dark-green leafy vegetables are appropriate for young children; and that they should be
moderately boiled to increase digestibility and remove toxic substances found in some varieties,
should be shredded (mashed or sieved for infants:) and mixed with the staple food to encourage
consumption, if necessary, and should be fed with a small amount of edible oil to improve
absorption.
Before embarking on an educational campaign, it is necessary to determine, through small but
intensive anthropologic/dietary studies, exactly why xerophthalmic children are not presently
consuming adequate amounts of foods rich in vitamin or pro-vitamin A. It makes little sense to
encourage the consumption of green leafy vegetables if they are not locally available. It makes
equally little sense to encourage home gardening if they are locally plentiful.
Knowing which vitamin- and pro-vitamin-A-rich foods are available and the reasons why they
are not being consumed provides a solid basis for designing intervention strategies. For example,
if parents of children with active xerophthalmia are found to consume large quantities of foods
rich in vitamin or pro-vitamin A, but do not feed them to the children, the appropriate message
will be quite different from the one that should be used if the families never consume such foods.
A finely focused approach, taking into account local cultural proclivities, will have the greatest
success.
In areas where green leafy vegetables and other sources of vitamin and pro-vitamin A are scarce
or expensive, home gardening or other horticultural activities may need to be promoted. Family
members, for instance, may need motivation and instruction in planting home gardens. This task
and similar ones-such as informing mothers about the importance of prolonging breast-feeding
and introducing early supplementation-have been carried out by primary health workers, village
level "extension" workers, and specially trained personnel addressing "captive" populations at
hospitals, clinics, and rehabilitation centers (where the mothers are often directly involved in
growing and preparing the foods). Mass media techniques, common in technologically advanced
countries, are proving surprisingly effective in rural, agrarian societies. But although health
education techniques are undergoing considerable development, educational programs tend to

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spread slowly. It is therefore important that they be actively developed and encouraged, along
locally appropriate lines, even while short-term emergency measures are in use.

7. EVALUATION
Xerophthalmia prevention programs are still in their infancy, and no method, no matter how
successful in one country, is assured of success in another. To prevent the needless expenditure
and false sense of security engendered by theoretically useful but ineffective programs, every
new program should undergo evaluation. One should at least know whether or not it is having its
desired effect. A program launched to prevent ulceration keratomalacia (X3A, X3B) should in
fact be shown to reduce corneal destruction. Measuring changes in biochemical status or the
prevalence of night blindness and Bitot's spot (XN, XIB) in the community is not sufficient. If,
on the other hand, keratomalacia is not a significant problem and the intervention is intended to
improve the general vitamin A status of the population at large, such changes are legitimate
criteria for investigation.
New intervention programs should begin as pilot projects in limited, high-risk areas. Their
effectiveness can be assessed, the problems identified, and changes made before expending large
amounts of time, money, and effort in what might turn out to be a useless and inefficient
approach. The effectiveness of the program can best be determined from prevalence data, for
which the assessment phase will already have provided a baseline, and from clinical records. The
latter approach is simpler, but potentially biased, and requires a clinical unit that encounters and
accurately recognizes and records large numbers of cases. While these criteria are rarely
fulfilled, simple standardized xerophthalmia-reporting forms can easily be developed for
hospitals and clinics recognizing large numbers of cases (Appendix I). Repeated prevalence
surveys are more representative of the community at large, but provide less detailed information
on active corneal disease. Wherever possible, both techniques should be employed.
Comparisons are needed between populations covered and not covered by the program. Ideally,
there should be one group of participants in the pilot program and, at the same time, a control
group of non-participants. This system of concurrent controls ensures the most accurate
comparisons. The two groups should be as much alike as possible, at least as regards
socioeconomic conditions, dietary practices, ecological setting, age, sex, and prevalence of
clinical disease.

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Occasionally, countrywide programs are launched without pilot evaluations beforehand. In this
instance concurrent controls are not available. Comparisons must be made between conditions
prevailing before and after the institution of the program (historical controls). Such comparisons
are far less definitive. Variations in harvests, epidemic diseases (gastroenteritis, measles, etc.),
and the like can all influence the incidence and prevalence of xerophthalmia independently of the
intervention program itself. Nevertheless, where it is the only available basis for evaluation, it
should be utilized. Adequate baseline data must be accumulated before initiating the intervention
program, especially when utilizing historical controls. Sufficient numbers of control cases should
be chosen to demonstrate effectiveness at the lowest level considered to justify continuing the
program.
In addition to absolute levels of effectiveness, evaluation of the efficiency, strengths, and
weaknesses of a program may indicate how it could be improved.

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BIBLIOGRAPHY
1. SOMMER, A. Nutritional blindness: xerophthalmia and keratomalacia, New York.
Oxford University Press, 1982.
2. Control of vitamin A deficiency and xerophthalmia. Report of a jOint
WHOIUSAIDIUNICEFIHKlIlVACG Meeting, Geneva. World Health Organization.
1982 (WHO Technical Report Series. No. 672).
3. SOMMER, A. et al. lancet, 2; 1407 (1981)
4. MACKENZIE, W. A practical treatise of diseases of the eye, London, Longman, 1830.
5. GOLDSCHMIDT, M, Graeje's Arch. Ophthalmol., 90: 354 (1915)
6. McCoU.UM, E. V. & SIMMONDS, N. Bioi. Chem., 32: 181 (1917)
7. BLOCH, C. E. J. Hyg., HJ: 283 (1921).
8. WOLBACH, S. B. & HOWE, P. R. J. expo Med., 47: 753 (1925); Arch. Pathol. lAb.
Med., S: 239 {I 928).
9. WORLD HEALTH ORGANIZATION. Methods of assessment of avoidable blindness,
Geneva, 1980 (WHO Offset Publication No. 54).
10. The prevention of blindness: report of a WHO Study Group. Geneva, World Health
Organization, 1973 (WHO Technical Report Series, No. 518).
11. WORLD HEALTH ORGANIZATION. Guidelines for programmes for the prevention of
blindness, Geneva, 1979.
12. Epidemiology of onchocerciasis: report of a WHO Expert Committee. Geneva, World
Health Organization, 1976 (WHO Technical Report Series, No. 597).

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APPENDIX ONE
CLINIC-BASED CASE·REPORTING FORM
A simple line listing, as shown here, is sufficiently detailed to monitor the number, types, and
origin of cases presenting at treatment facilities. It has been kept short and simple to facilitate its
use by overworked clinic personnel.
Xerophthalmia case-reporting form
Clinical facility _________________
Case Date Patient' Village Age Sex Record all abnormalities present
Number s Name or XN X1B X2 X3
Locality OD OS OD OS OD OS
1
2
3
4
5
6
7
8
9
10
11
12
13
14

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