Ординатура / Офтальмология / Английские материалы / Handbook of Nutrition and Ophthalmology_Semba_2007

Fig. 19. Seasonality of xerophthalmia in Tianjin, China. (Reprinted from ref. 897.)

(369). In Tunisia, cases of xerophthalmia were also reportedly more common at the end of the hot summer and were associated with chronic diarrhea (872). The seasonal incidence of more than 15,000 cases of xerophthalmia among children was examined in four ophthalmic hospitals in India, Indonesia, and Vietnam (898). In Bangalore, India, there were more cases of xerophthalmia seen from April to June, and this coincided with a relative scarcity of green vegetables and milk and with a higher prevalence of summer diarrhea. In Surabaya and Bandung, Indonesia, the incidence of xerophthalmia was highest from about March to September. In Hanoi, Vietnam, there were two periods in which xerophthalmia was highest, from April to June and from October to December (898). In a longitudinal study of 312 children, aged 0–4 yr, in rural West Bengal, the incidence of night blindness and/or Bitot spots had a small peak in November–December and in a larger peak in May–June (899). The prevalence of Bitot spots was highest in the pre-monsoon season in West Bengal (899). In longitudinal field studies in Indonesia, the number of children with corneal involvement in xerophthalmia was highest in March through August (285). Among children admitted to Cicendo Eye Hospital in Bandung, Indonesia, the peak month of admissions was in March, which corresponds to the dry season (623). The periodicity of xerophthalmia in some populations needs to be taken in account when conducting epidemiological surveys of vitamin A deficiency. Xerophthalmia was also reported to increase after crop failure in Russia (900).

5.3.12. MALABSORPTION

Cystic fibrosis. Cystic fibrosis is an autosomal recessive disease that affects primarily Caucasian populations and is characterized by exocrine pancreatic insufficiency, altered pulmonary mucosal immunity, and other abnormalities affecting the liver, sweat glands, and genitourinary tract (901). Exocrine pancreatic insufficiency causes malabsorption of

fat and fat-soluble vitamins such as vitamin A, and problems such as steatorrhea and poor weight gain. Cystic fibrosis is caused by a mutation in the FES1 gene that encodes the cystic fibrosis transmembrane conductance regulator. Individuals with cystic fibrosis are at a high risk of developing vitamin A deficiency because of malabsorption of vitamin A (902). One study of 36 infants less than 2 mo of age in Colorado showed that vitamin A deficiency was present among 21% of those diagnosed with cystic fibrosis by newborn screening (903). There have been many case reports of xerophthalmia associated with cystic fibrosis (904–913). Low plasma vitamin A concentrations and impaired dark adaptation appear to occur frequently in cystic fibrosis, even among clinically stable, eutrophic, and retinol-supplemented adolescents (914). Night blindness and conjunctival xerosis may still occur despite vitamin A-supplementation among adolescents with cystic fibrosis, especially if they have liver disease (909).

Pulmonary exacerbations of cystic fibrosis are associated with an increase in inflammation and a decrease in plasma retinol concentrations (915). Xerophthalmic fundus has been reported in an 18-yr-old girl with cystic fibrosis who developed night blindness (908). Regular monitoring of serum retinol concentrations in individuals with cystic fibrosis has been recommended because vitamin A deficiency may still occur despite vitamin A supplementation (902). Low serum retinol concentrations were reported to have no correlation with pancreatic sufficiency in cystic fibrosis (916). Regular monitoring of serum retinol concentrations and adherence to vitamin A supplementation may help patients with cystic fibrosis avoid problems with night blindness (917,918). A study of vitamin A concentrations in the liver among fifteen patients with cystic fibrosis from 8 to 34 yr of age show that hepatic retinol concentrations decrease with age (919). These findings are suggestive that long-term vitamin A supplementation is unlikely to increase the risk of hypervitaminosis A in patients with cystic fibrosis (919). A transient increase in intracranial pressure, as manifested by a bulging anterior fontanelle, was reported in two 9-mo-old infants with cystic fibrosis and xerophthalmia after receiving high-dose vitamin A (913).

Celiac sprue. Celiac sprue, also known as celiac disease and gluten-sensitive enteropathy, is a condition of the proximal small intestine that is characterized by malabsorption (920,921). The condition is associated with injury to the small intestine after the ingestion of wheat gluten or related rye and barley proteins and improves on treatment with a gluten-free diet. The condition has a genetic predisposition and may occur in one of every 120–300 persons in both Europe and the United States (921). It mostly occurs in Caucasians but has been reported occasionally in other ethnic groups. Abnormal T-cell mediated immune responses against ingested gluten may occur in those that are genetically predisposed together the disease (921). Common clinical manifestations include diarrhea, failure to thrive, and abdominal distention in children, and diarrhea and iron deficiency anemia in adults. Children and adults with celiac disease may have abnormal absorption of oral vitamin A (922). During active sprue, vitamin A absorption is severely impaired, but during remission of disease, the absorption of vitamin A may be satisfactory (923). Plasma retinol concentrations are reduced in patients with sprue compared with normal individuals (924). Keratomalacia was reported in a 64-yr-old man with a history of celiac sprue after he developed persistent diarrhea in spite of adherence to a gluten-free diet (925).

Other conditions. Night blindness associated with vitamin A deficiency has been reported with intestinal bypass surgery for morbid obesity (926–930). In addition to night

blindness, conjunctival xerosis (926) and Bitot spots (927) have also been reported after intestinal bypass surgery. Xerophthalmia and keratomalacia have been described in an infant with obstructive biliary cirrhosis (931). Night blindness has been associated with alcoholic liver disease (932–934). Severe protein energy malnutrition is associated with impaired intestinal absorption of vitamin A (935).

5.3.13. PREGNANCY

Night blindness has long been recognized among pregnant women, with hundreds of cases reported in the literature (936–961). The requirement for vitamin A increases during pregnancy, and many women may not have adequate intake of vitamin A and subsequently develop night blindness. In general, night blindness is more common in pregnant women from poor families and in association with complications of pregnancy such as hyperemesis, anorexia, diarrhea, and other concomitant infections. In a study conducted in 1889–1892 in Nishne Tagilsk in the Urals, O. Walter noted that night blindness among pregnant women seemed to peak in February through April, and a large proportion indicated that they had repeatedly been night blind during pregnancy (941). At a time when vitamin A deficiency was prevalent in Europe, Theodor Birnbacher and Emanuel Klaften noted that night blindness was more common among pregnant women than nonpregnant women of childbearing age (944), and Birnbacher attributed the night blindness to lack of vitamin A (946). Carsten Edmund (b. 1897) and Svend Clemmesen (b. 1901) in Copenhagen concluded that night blindness in pregnant women was due to vitamin A deficiency because the night blindness was promptly cured after treatment with parenteral vitamin A (947). After margarine was fortified with vitamin A in 1936–1937 in Denmark, they noted a decrease in the number of cases of pregnant women with night blindness (947). Parul Christian has recently brought attention to night blindness during pregnancy as an indicator of vitamin A deficiency (962).

5.3.14. NONPREGNANT WOMEN OF CHILDBEARING AGE

Night blindness has also been reported among nonpregnant women of childbearing age in India (963), Bangladesh (964), Nepal (965), and Cambodia (603). In the 1930s, Adalbert Fuchs reported that night blindness and keratomalacia occurred among lactating women in Mysore, India (966). A strong risk factor for night blindness among women of childbearing age is night blindness during the most recent pregnancy (603). However, it does not appear that vitamin A deficiency during the last pregnancy alone is the main determinant of night blindness, as one might expect that the point prevalence of night blindness would be highest immediately following pregnancy. Instead, the risk of night blindness appears to be consistently high and steady for many months following delivery (Fig. 20), which suggests that there are women who have greater risk overall of night blindness because of poor intake of vitamin A-rich foods (603). Among nonpregnant women in Cambodia, in a final multivariate analysis, risk factors for night blindness included materials of the wall of the house (OR 1.4, 95% CI 0.9–2.0), land ownership ≥0.5 hectares (OR 1.4, 95% CI 1.0–1.9), night blindness in the last pregnancy (OR 44.5, 95% CI 29.2–67.8), parity >3 (OR 1.5, 95% CI 1.0–2.1), diarrhea within the last 2 wk (OR 1.9, 95% CI 1.3–2.8), maternal body mass index (OR 1.8, 95% CI 1.2–2.7), and lack of consumption of vitamin A-rich animal foods in the last 24 h (1–60 REs, OR 1.1, 95% CI 0.7–1.6, ≥60 retinol equivalents, OR 0.7, 95% CI 0.4–1.0) (603).

A deficiency are night blindness and Bitot spots. Although the earlier literature may refer to night blindness and Bitot spots as “mild” vitamin A deficiency, the presence of clinical vitamin A deficiency actually represents a later, more severe state of vitamin A deficiency. A simple history of night blindness can be used as a diagnostic indicator for vitamin A deficiency (972) and is especially useful in areas where vitamin A deficiency is endemic. As noted previously, Bitot spots are considered pathognomonic for vitamin A deficiency. Individuals who have had longstanding clinical vitamin A deficiency may develop irreversible squamous metaplasia of the conjunctiva, and Bitot spots in these individuals may not respond to vitamin A therapy. Thus, Bitot spots may not necessarily represent active vitamin A deficiency, especially among school-aged children. Infants or children with corneal xerosis, corneal ulceration, or keratomalacia are at an extremely high risk of dying, and great attention must be paid to treatment of vitamin A deficiency and supportive measures (see Subheading 7). Corneal scarring is sometimes used as a indicator of past vitamin A deficiency, however, other conditions such as trauma and bacterial ulceration can also leave a corneal scar after the corneal has healed, thus, corneal scarring may be relatively nonspecific. A history of measles associated with corneal scarring may improve the specificity of the diagnosis of vitamin A deficiency.

6.2. Assessment of Vitamin A Status

A wide variety of methods are available to assess vitamin A status, and the more commonly utilized techniques include serum retinol concentrations, breast milk retinol concentrations, conjunctival impression cytology, dark adaptometry, RDR test, and modified relative dose response (MRDR) test (973,974). Liver retinol concentrations are often considered the “gold standard” for vitamin A status, but liver biopsy is highly invasive and rarely used s. The methods for the assessment of “vitamin A status” are sometimes not directly comparable, as the endpoints of these measures are quite different, i.e., (1) intake of vitamin A (dietary assessment), (2) hepatic reserves of vitamin A (RDR, MRDR), (3) circulating vitamin A (serum retinol), (4) effect of vitamin A on function (dark adaptometry, pupillary threshold, conjunctival impression cytology), and

(5) total body vitamin A stores (deuterated retinol dilution technique). To give some examples, a child could have adequate intake of vitamin A, as demonstrated by dietary assessment, but show impaired dark adaptometry because of malabsorption of vitamin A as a result of intestinal parasites. A lactating woman could have high breast milk retinol concentrations but low serum levels of retinol because of inflammation.

6.2.1. SERUM RETINOL CONCENTRATIONS

Serum or plasma retinol concentrations are widely used to assess the vitamin A status of populations (see Subheading 4), but are considered less reliable for assessment of vitamin A status in individuals (973,974). Serum retinol can be measured using high performance liquid chromatography (973), and unless measurements are made immediately, serum or plasma samples should be stored at −70°C or less prior to analysis. In large surveys, the frequency distribution of serum retinol concentrations can provide useful information about the general vitamin A status in a population. The proportion of people with serum retinol concentration <0.70 μmol/L is used by WHO to determine whether vitamin A deficiency is a public health problem (975). Mild, moderate, and severe vitamin

A deficiency as a public health problem in a population is thought to be reflected by a prevalence of ≥2 to <10%, ≥10 to <20%, and ≥20%, respectively (975).

Although serum retinol concentrations are widely used as an indicator of vitamin A status, this assessment method may have some limitations. In the 1940s, longitudinal studies of vitamin A status in adults showed that upper respiratory infections and episodes of fever were associated with a depression in blood retinol concentrations (976). Decreased plasma vitamin A concentrations were observed during infections such as pneumonia (977), and autopsy studies showed normal hepatic vitamin A stores among children who had decreased plasma vitamin A concentrations prior to death (978).

RBP is a negative acute phase protein, and in the presence of inflammation or infection, retinol-binding protein and retinol concentrations may decrease (217,979).

In order to avoid overestimating the prevalence of vitamin A deficiency in populations with a high prevalence of infections, it has been proposed that individuals with elevated acute phase proteins be excluded or that serum retinol concentrations be “adjusted” (980). However, the approach to exclude individuals with infection or depend on “adjusted” retinol values may result in selection bias, as the remaining individuals without infection may be healthier and no longer representive of the population that is being surveyed (981). Because vitamin A deficiency is a syndrome characterized by immune suppression, increased susceptibility to infections, and elevated acute phase proteins (584,676,982), the exclusion of individuals with low plasma retinol concentrations and elevated acute phase proteins may also lead to an underestimation of the prevalence of vitamin A deficiency in some populations (981). Serum retinol concentrations could theoretically be affected by iron deficiency (983,984). Because serum retinol levels are thought to be under homeostatic regulation in the individual, some studies have not shown any response of serum retinol concentrations to vitamin A supplementation (974).

6.2.2. BREAST MILK RETINOL CONCENTRATIONS

Breast milk retinol concentrations are considered a good indicator of vitamin A deficiency among lactating women (985), and procurement of a milk sample is less invasive than taking a venous blood sample. Milk retinol concentrations can be measured using high-performance liquid chromatography (974). WHO utilizes a cut-off of breast milk retinol of ≤1.05 μmol/L (or ≤8 μg/g milk fat) to define the prevalence of vitamin A deficiency (975). Mild, moderate, and severe vitamin A deficiency as a public health problem in a population is thought to be reflected by a prevalence of <10%, ≥10 to <25%, and ≥25%, respectively (975). Breast milk retinol concentrations generally increase following vitamin A supplementation (985).

Unlike serum retinol concentrations, breast milk retinol concentrations do not appear to be affected by systemic inflammation (986). The two major sources of vitamin A in the circulation that are available for uptake by the mammary gland for secretion in breast milk are retinol carried by retinol-binding protein and retinyl esters carried by chylomicrons. Studies in animals suggest that chylomicrons provide at least one-third to one-half of vitamin A to mammary gland tissue during lactation for secretion into milk (181), and that in rats, milk retinol can vary with dietary vitamin A intake even when plasma retinol concentrations are relatively unaffected (182). Animal studies show that there may be a homeostatic mechanism by which the transfer of retinol from the circulation to breast

milk is protected within a fairly large range of liver vitamin A stores and serum retinol concentrations (180). In the rat, moderate restrictions of dietary fat or protein had little effect on transfer of vitamin A from dam to pup, but more severe dietary restrictions had a negative impact on milk volume (180). All of these observations suggest that breast milk retinol is shielded from changes in plasma retinol because the mammary gland utilizes a large proportion of retinyl esters that have entered the circulation after absorption in the gastrointestinal tract. A recent study of breast milk concentrations among women with a high prevalence of inflammation shows if defined by milk retinol concentrations, vitamin A deficiency would be a moderate public health problem in the study population (986). However, if serum retinol concentrations were used as the indicator of vitamin A status, and those with inflammation were excluded as advocated by Thurnham and colleagues (980), it would lead to the erroneous conclusion that vitamin A deficiency were not a public health problem in this study population (986).

The concentration of retinol can be expressed per gram of fat in milk if a creamatocrit is obtained, or can be expressed as concentration of retinol per volume of milk. In casual breast milk samples, the measurement of breast milk retinol per gram of fat was found to be the most accurate indicator of response to vitamin A supplementation (987), but another study found that breast milk vitamin A was most sensitive to changes in vitamin A status when expressed as retinol per volume of breast milk (988). Breast milk retinol concentrations decline over time following delivery (989), thus it may be necessary to adjust for time postpartum in comparing breast milk concentration between groups of women.

6.2.3. CONJUNCTIVAL IMPRESSION CYTOLOGY

Conjunctival impression cytology (CIC) is a method in which cells taken from the bulbar conjunctival surface are stained and examined microscopically (973). The basis for this technique dates to the early twentieth century, when scientists noted that keratinization and loss of goblet cells and mucus in the conjunctival epithelium occurred in experimental animals and in humans with vitamin A deficiency. The degree of keratinization in conjunctival smears was used as a method to diagnose vitamin A deficiency by Sweet and K’ang in the 1930s (369). John Youmans (1893–1979) and colleagues examined conjunctival smears that were stained with hematoxylin and eosin, and they noted keratinization of the conjunctival epithelium in adults suspected of having vitamin A deficiency (990). The investigators concluded that conjunctival smear cytology was inadequate for the assessment of vitamin A deficiency because of the great variability in keratinized cells and the lack of response after treatment with vitamin A (990). In another study of conjunctival smear cytology, histological changes were validated against another index of vitamin A status, and the percentage of keratinized cells had poor correlation with plasma retinol concentrations (991). In conjunctival smear cytology, the loss of goblet cells and mucus and loss of nuclei in epithelial cells were considered important indicators of xerosis due to vitamin A deficiency (992).

In CIC, cells are sampled by applying cellulose acetate filter paper to the bulbar conjunctiva, and then the sample is stained using periodic acid-Schiff (PAS) to stain the mucin of goblet cells and hematoxylin to stain the nuclei of epithelial cells (993,994). Another variation of this method is to transfer the cells onto a glass slide before staining (995). The CIC technique is relatively inexpensive, does not require cold storage of samples, and requires a microscope and stains, but difficulties with CIC include problems with interpre-

tation of cytologic changes, confounding by conjunctivitis, and poor correlation of CIC with other measures of vitamin A status such as serum retinol levels and RDR testing (996, 997). Trachoma and conjunctivitis, which may be common in many populations, interferes with the interpretation of CIC (998).

The abnormal cytologic changes seen in CIC should theoretically return to normal following vitamin A supplementation. In a placebo-controlled clinical trial in Indonesia involving 236 preschool children with and without xerophthalmia, the abnormalities seen in CIC at the baseline exam (994) did not respond by five weeks following high-dose vitamin A supplementation (Semba, unpublished data). In the same children, most Bitot spots disappeared five weeks after vitamin A supplementation (257). In another study, abnormal CIC did not respond to vitamin A supplementation until 70–110 d after highdose vitamin A supplementation (999). It is unclear why large lesions such as Bitot spots would dramatically disappear within five weeks after high-dose vitamin A supplementation, but microscopic lesions of keratinization and goblet cell loss should require months to return to normal.

6.2.4. DARK ADAPTOMETRY

Dark adaptation is a process in which the rod photoreceptors fully regenerate rhodopsin in darkness after exposure to a bright light. The process takes approx 30–35 min. In vitamin A deficiency, rhodopsin levels in the retina decline, and dark adaptation is impaired. The relationship between impaired dark adaptation and vitamin A deficiency was investigated extensively in the 1930s and 1940s (1000,1001). The threshold for light perception progressively decreases during dark adaptation. A transient plateau is reached at 1–5 min in normal, vitamin A-sufficient people, and after several minutes, there is a transition from cones to rods, with a progressive decrease in threshold until about 30–35 min when the final rod threshold is reached. In vitamin A-deficient individuals, the threshold for dark adaptation is higher. Clinical dark adaptometers can be used to assess dark adaptation, but these instruments tend to be less suitable for field use and for use among children, who may not cooperate with the conditions of testing. Portable dark adaptometry has been used in the field for measuring the time it takes for children to identify letters illuminated by a dim light after the eye has been exposed to bright light (1002). Another procedure, termed rapid dark adaptation time, involves measuring the time it takes for a subject to sort white, blue, and red disks into three piles under lighting conditions consistent with rod illumination after the eyes have been exposed to bright light (1003).

6.2.5. RELATIVE DOSE RESPONSE AND MODIFIED RELATIVE DOSE RESPONSE

The RDR and MRDR tests are used to assess liver reserves of vitamin A. These tests rely on the principle that during vitamin A deficiency, apo-retinol-binding protein (unbound to retinol) accumulates in the liver. After a small oral dose of vitamin A is delivered, holo–- retinol-binding protein (bound to retinol) is released by the liver into the circulation. The RDR test involves taking a blood sample, giving a standard oral dose of vitamin A, and then drawing a second blood sample 5 h after administration of the vitamin A dose. The response is measured as a percentage: RDR = (A5 – A0)/A5, where A5 = serum retinol concentration 5 h after dosing, and A0 = serum retinol concentration before dosing (1004). An RDR of ≥20% is considered to indicate inadequate liver vitamin A reserves. Although the RDR test has been used successfully in some clinical and field studies, the obvious

drawback is the need to draw two successive blood samples on subjects and to have them wait for five hours between the two blood drawings. The RDR test may not be reliable among subjects who have infections and an acute phase response (1005). The MRDR test involves giving a single oral dose of 3,4-didehydroretinol, which will also combine with apo–retinol-binding protein in the liver to form holo-retinol-binding protein released into the circulation. A blood sample is drawn 4–6 h after dosing, an the molar ratio of 3,4- didehydroretinol/retinol (DR/R) is measured in the serum. A DR/R ratio of ≥0.06 is considered to be consistent with inadequate vitamin A status (1006).

6.2.6. PUPILLARY THRESHOLD

Pupillary threshold is a measure of pupil diameter in subjects that are exposed to low illumination. In people with vitamin A deficiency, the pupil does not constrict normally to light because the amount of rhodopsin in the retina is reduced. Measurement of pupil diameter during dark adaptation was proposed as an objective test for vitamin A deficiency as early as the 1930s, but initial testing in vitamin A-deficient rabbits was negative (1007). In the pupillary threshold test, a battery-powered, hand-held illuminator is placed over the eyes, with one eye exposed to a yellow-green, light-emitting diode (LED) that has 12 intensity settings and the contralateral eye illuminated obliquely with a red LED. The subject has both eyes exposed to a bright light and then undergoes dark adaptation for 10 min in a dark tent. Pupillary threshold is measured by having the right eye fix on a nonaccommodative target at two meters (to prevent pupillary constriction with accommodation) under conditions of increasing stimulus intensity. The left eye is observed using the red LED and a 2.5× loupe until a pupillary response is clearly visible (1008). Pupillary threshold has been tested among young children in Indonesia (1008) and India (1009), and among pregnant women in Nepal (1010). Pupillary threshold correlates with serum retinol concentrations and responds well following vitamin A supplementation (1009).

6.2.7. DIETARY ASSESSMENT

A simplified dietary assessment questionnaire was developed by the International Vitamin A Consultative Group to identify populations at risk for vitamin A deficiency (1011). The questionnaire is adapted for use in different populations, based on locally available sources of vitamin A-rich foods. Food composition tables are used to categorize local foods into high, moderate, and low, depending on vitamin A content of the food and usual portion sizes. Local workers administer the questionnaire to determine the intake and portion size in the last 24 h, and then the usual frequency of intake on a daily, weekly, and monthly basis (1011). A food frequency questionnaire has also been developed by Helen Keller International and uses 24-h recall (602).

6.2.8. OTHER TESTS

Serum –RBP. Serum RBP has been advocated as a surrogate measure for serum retinol (1012–1014). Serum RBP and retinol are highly correlated, and RBP can be measured using simple immunodiffusion assays (1012) or by enzyme-linked immunosorbent assay; however, as an indicator of vitamin A status, serum RBP has the same limitations of serum retinol under conditions of inflammation or infection.

RBP/TTR ratio. The ratio of RBP to TTR has been advocated as a method to measure vitamin A status in the presence of inflammation (1015). During the acute phase response, serum RBP and retinol decrease, but TTR may not decrease, thus, it is thought that a low

Table 5

Treatment Schedule and Vitamin A Dose

for All Age Groups Except Women of Reproductive Age

molar ratio of RBP/TTR can identify people with vitamin A deficiency in the presence of infection (1015). Despite these theoretical considerations, the RBP/TTR ratio has shown poor sensitivity and specificity as an indicator of vitamin A status when applied in studies among hospitalized children in Africa (1016) and among children with inflammation (1017).

Retinoyl β–glucuronide (RAG) hydrolysis test. The RAG hydrolysis test is based on the measurement of retinoic acid in serum (1018). After oral administration of RAG in vitamin A-sufficient animals, RAG is slowly hydrolyzed to retinoic acid, but in vitamin A-defi- cient animals, the hydrolysis of RAG to retinoic acid is more rapid, and higher retinoic acid concentrations are found in serum (1019). The RAG hydrolysis test is currently undergoing evaluation among children in India (A. Barua, personal communication).

Isotope dilution technique. An isotope dilution technique using deuterated retinol has been used to quantitatively estimate total body reserves of vitamin A in humans (1020, 1021). The technique can detect changes in total body stores of vitamin A in response to different daily vitamin A supplements (1022). The deuterated-retinol-dilution technique has been used to show that consumption of vitamin A-rich plant foods can improve totalbody vitamin A stores among men in Bangladesh (1023).

7. TREATMENT OF VITAMIN A DEFICIENCY

7.1. Vitamin A Capsules

High-dose vitamin A supplementation is recommended for immediate treatment of infants, children, and adults (except women of reproductive age) with xerophthalmia according to the treatment schedule shown in Table 5. Women of reproductive age who have night blindness or Bitot spots should be treated with ≤10,000 IU/day or weekly doses of ≤25,000 IU. If women of reproductive age have acute corneal lesions (corneal xerosis, corneal ulceration, keratomalacia), they should be treated as in Table 5. Retinyl palmitate in oily solution, as contained in capsules, is recommended to be taken by mouth. The oral route of administration should be used in almost all cases, and for infants and young children, the capsule can be cut with scissors and the oily solution squeezed into the mouth. Children with corneal xerosis, corneal ulceration, or keratomalacia are usually admitted to the hospital, and this also helps facilitate adjunct support and administration of the vitamin A dose on the following day. For children with night blindness and/or Bitot spots, the subsequent doses of vitamin A can be given to the parent or guardian for administration in the home. Parenteral therapy should be avoided unless the child cannot swallow