Vitamin A deficiency and xerophthalmia
David Livingstone first suggested that eye lesions were caused by nutritional deficiency. The antixerophthalmia factor was the first of the vitamins to be isolated.
Xerophthalmia is a late manifestation of vitamin A deficiency.
Vitamin A is not only the antixerophthalmia vitamin. It has also been called the “anti-infective vitamin” because rats with experimental deficiency had multiple infections. Children with
full-blown xerophthalmia have high mortality.
Children of 1-5 years given vitamin A capsules (one single capsule of 200 000 IU, repeated after
six months) had a 34% lower mortality than untreated children in adjacent villages. Subsequently similar prevention trials have been completed in several developing countries.
There is a strong synergistic association of measles and vitamin A deficiency. Measles can precipitate xerophthalmia and leads to low plasma vitamin A even in developed countries.
Vitamin A should be given to any child with severe measles or from a deprived background.
Stages of xerophthalmia
Severe xerophthalmia is virtually confined to infants and young children and usually associated with protein-energy malnutrition. The stages are classified as follows.
Night blindness (XIN)
is the earliest symptom but not elicited in infants.
In conjunctival xerosis (XIA)
one or more patches of dry non-wettable conjunctiva emerge “like sand banks at receding tide” when the child ceases to cry. It is caused by keratinising squamous metaphasia of the conjunctiva.
Bitot’s spots (XIB)
are glistening white plaques formed of desquamated thickened epithelium, usually triangular and firmly adherent to the underlying conjunctiva.
Corneal xerosis (X2)
is a haziness or a granular pebbly dryness of the cornea on routine light examination, beginning in the inferior cornea.
Corneal ulceration (X3A) or keratomalacia (X3B).
A punched out ulcer may occur or, in a severe case, colliquative necrosis of the cornea (keratomalacia). If promptly treated a small ulcer usually heals, leaving some vision. Large ulcers and keratomalacia usually result in an opaque cornea (X5) or perforation and phthisis bulbae.
Pathogenesis of xerophthalmia
If xerophthalmia occurs, adults have much lower vitamin A stores in their livers than in well-fed people.
Women start with low stores and throughout pregnancy have low intakes of vitamin A and carotene. Newborn babies have only one-fifth the liver vitamin A concentration of their mothers, even in well-fed communities, because vitamin A transport across the placenta is limited. Since the mother has low intakes and stores, her breast milk contains low concentrations of vitamin A and carotene. If the child has protein-energy malnutrition this impairs absorption and transport of vitamin A. Then a severe infection can precipitate clinical deficiency by increasing urinary loss of the vitamin and reducing hepatic synthesis of retinol binding protein.
The symptomatology of vitamin A deficiency can be explained by several functions of the vitamin. Retinaldehyde (retinal) is needed for the response of rods in the retina to light. Retinoic acid is needed to maintain differentiation of epithelia (for example, conjunctiva, respiratory), secretion of mucus, and tear production. In vitamin A deficiency cell-mediated immunity is impaired.
Diagnosis and treatment
Xerophthalmia is seen occasionally in patients with chronic jaundice or small bowel resection or
very restricted diets.
Treatment of xerophthalmia is urgent. The differential diagnosis includes smoke exposure, trauma, bacterial infections, measles, and trachoma. The child often has some other illness at
the time like gastroenteritis, kwashiorkor, measles, or respiratory infection, which can distract attention from the eyes unless they are examined systematically. If in doubt a dose of vitamin A
should be given. It can do no harm. The immediate treatment is 110 mg retinol palmitate or 66 mg retinol acetate (200 000 IU) orally or (if there is repeated vomiting or severe diarrhoea) 55 mg retinol palmitate (100 000 IU) water soluble preparation intramuscularly. For the next few days repeat the oral dose.
There are four strategies for prevention. In some countries two or more are being used side by side.
This emphasises regular consumption of locally grown plant sources of beta-carotene (pro-vitamin A). The best sources include mango, papaya, pumpkin, yellow sweet potatoes, carrots and palm oil, as well as eggs and liver. Dark green leafy vegetables, formerly encouraged, contain
useful amounts of beta-carotene but this was found to be poorly absorbed (and converted to vitamin A) with traditional cooking methods. Beta-Carotene in plant leaves is mostly in the
chloroplasts, which are not well digested. The carotene in fruits that contain it are more available and absorption of beta-carotene is improved if there is oil or fat in the meal.
(2) Vitamin A for mothers
The vitamin may be given to pregnant women, but it must not exceed 3300 IU (1 mg retinol) per day (or 23 300 IU once a week) because more vitamin A can be teratogenic. After delivery large single oral doses (200 000 IU) can be given to them in the first month. It should not be given
later in case they become pregnant again.
(3) Periodic dosing of young children
This should be done in areas of high incidence with capsules of 110 mg retinol palmitate or 66 mg retinol acetate (200000 IU) at six monthly intervals. Doses must be smaller in infancy.