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Year : 2013  |  Volume : 2  |  Issue : 1  |  Page : 41-45

Vitamin A deficiency: An eye sore

Department of Ophthalmology, Christian Medical College and Hospital, Ludhiana, Punjab, India

Date of Web Publication1-Jan-2013

Correspondence Address:
Rupali Chopra
Department of Ophthalmology, Christian Medical College and Hospital, Ludhiana, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-019X.105329

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Vitamin A deficiency is a major cause of childhood mortality and morbidity in India and other developing countries. The ocular manifestations of vitamin A are collectively called xerophthalmia and range from conjunctival xerosis to severe blinding complications such as keratomalacia. Vitamin A deficiency exists as a major public health nutrition problem among preschool-aged children, especially in the South East Asian region, as well as among the pregnant and lactating women. Deficiency can be diagnosed by the ocular manifestations such as Bitot's spots, serum retinol levels, and conjunctival impression cytology (CIC). Improving vitamin A status in the diet or by periodic administration of vitamin A to children can reduce both mortality and blindness. This review is an attempt to highlight the ocular manifestations of vitamin A deficiency, its prevalence, treatment, and preventive strategies.

Keywords: Impression cytology, retinol, vitamin A deficiency, xerophthalmia

How to cite this article:
Chander A, Chopra R, Batra N. Vitamin A deficiency: An eye sore. J Med Nutr Nutraceut 2013;2:41-5

How to cite this URL:
Chander A, Chopra R, Batra N. Vitamin A deficiency: An eye sore. J Med Nutr Nutraceut [serial online] 2013 [cited 2024 Mar 3];2:41-5. Available from: http://www.jmnn.org/text.asp?2013/2/1/41/105329

  Introduction Top

Vitamin A is a fat-soluble vitamin ingested in the diet in two forms-as retinol itself from animal sources, such as milk, meat, fish, liver, and eggs, or as provitamin carotene from plant sources such as green leafy vegetables, yellow fruits, and red palm oil. [1],[2] Vitamin A deficiency is a major cause of childhood blindness in India and other developing countries. [3],[4] Vitamin A deficiency exists as a public health nutrition problem among preschool-aged children in 118 developing countries around the globe, with the South East Asian region harboring the maximum number of cases. [5] The consequences of vitamin A deficiency include all active clinical stages of xerophthalmia, impaired mechanisms of host resistance, increased severity of infection, anemia, poor growth, and mortality. Certain systemic illnesses are associated with vitamin A deficiency, such as measles, pneumonia, diarrhea, malabsorption due to cystic disease, liver disease, pancreatic disease, or inflammatory bowel disease. Various studies have shown that mortality rate can be decreased if Vitamin A is taken prophylactically. Vitamin A is necessary for preserving integrity and maintaining the functions of several organs in the body. This review is an attempt to highlight the ocular manifestations and prevalence of vitamin A deficiency and to discuss the physiological indicators available for its early diagnosis and prevention strategies.

Prevalence of Vitamin A deficiency

The ocular manifestations of vitamin A deficiency are collectively called xerophthalmia. It can affect any age group, but its most severe blinding complications affect children aged 6 months to 3 years. It was estimated that 127 million preschool children under 5 years of age are vitamin A deficient, of whom 4.4 million have xerophthalmia. [5] There are also an estimated 7.2 million pregnant women with Vitamin A deficiency (serum retinol < 0.7 μmol/l) at any one time in the developing world, of whom around 6 million are night blind, a condition attributed to vitamin A deficiency. [6] Even amongst school-aged children, the prevalence of vitamin A deficiency was found to be 23.4% in a study done in the countries within World Health Organization (WHO) South East Asian region.[7]


Vitamin A is a fat-soluble vitamin absorbed from the small intestine. Within the intestinal mucosal cells, carotene is converted to retinol and, along with the directly ingested retinol, is esterified to palmitic acid.

Retinyl palmitate then travels through the lymphatic system to the liver, where it is stored. In the presence of a metabolic requirement for vitamin A, retinyl palmitate is hydrolyzed, and the reconstituted retinol travels via the blood stream, attached to retinol-binding protein (RBP), to the tissue where it is needed. Adequate body stores of zinc and protein are necessary for the formation of RBP, without which vitamin A cannot be transported to its target tissues. [8],[9] In the eye, vitamin A has a pivotal role in the functioning of the retina and the conjunctiva.

The retina contains two distinct photoreceptor systems, the rods and the cones. The rods are responsible for vision in dim or low light and the cones are responsible for color vision and vision in bright light. Vitamin A is the backbone of the visual pigments for the rods and the cones, the major difference being the type of protein that is bound to the retinol. In rod cells, the aldehyde form of vitamin A (retinal) and the protein opsin combine to create rhodopsin, which is the photosensitive pigment. When light hits the rod cells, the pigment isomerizes, which leads to the nerve impulse and results in the visual signal. The pigment is broken down to opsin and the stereoisomer of retinal (all-trans configuration). The correct geometrical form of retinal has to be reconstituted to combine with opsin to reform the pigment. However, in this process, some of the retinal is always lost, so a constant source of vitamin A must be available for adequate levels of rhodopsin and optimal rod function. The mechanisms of stimulation, breakdown, and regeneration of visual pigments are thought to be similar in rod and cone cells. [10]

In the conjunctiva, vitamin A is necessary for the maintenance of the specialized epithelial surface. A lack of vitamin A leads to atrophic changes in the normal mucosal surface, with loss of goblet cells, and replacement of the normal epithelium by an inappropriate keratinized stratified squamous epithelium. In addition, the substantia propria of the cornea breaks down and liquefies (colliquative necrosis), resulting in keratomalacia. [11]

Ocular manifestations of Vitamin A deficiency

Vitamin A deficiency affects the retina, conjunctiva, and cornea, and the signs and symptoms tend to occur in a reliable sequence. The WHO classification of vitamin A deficiency is as follows: [12]

XNNight blindness
X1A Conjunctival xerosis
XIB Bitot's spot
X2 Corneal xerosis
X3A Corneal ulceration/keratomalacia involving one-third or less of the cornea
X3B Corneal ulceration/keratomalacia involving one-half or more of the cornea
XS Corneal scar

Night blindness

Because of the essential role of vitamin A in photoreceptor function, defective dark adaptation is the most characteristic early clinical feature, resulting in night blindness. Night blindness is the earliest clinical symptom and in children it presents as inability to find their way in dim light. Its occurrence reflects a failure of rod cells in the retina to maintain peripheral vision under dim light. Patient cannot read or drive a car in poor light. Electroretinography and dark adaptation can help in diagnosis of retinal function in early stage even if the person is asymptomatic.

Conjunctival manifestations

Xerosis (X1A) is the term used to describe dryness. Vitamin A deficiency leads to a loss of mucus-secreting goblet cells and eventually to squamous cell metaplasia of the conjunctival epithelial cells. Conjunctiva becomes dry, thick, and wrinkled. It gets keratinized, loses its normal transparency, and acquires a smoky appearance [Figure 1]. Conjunctival xerosis typically is found on the temporal and interpalpebral bulbar conjunctiva. Bitot's spots appear as grayish-white triangular plaques, firmly adherent to the conjunctiva due to increased thickness of conjunctiva in certain areas. They stain intensely with Rose Bengal dye. Conjunctival xerosis including Bitot's spots respond favorably to vitamin A and could be a marker to identify those communities with severe and longstanding vitamin A deficiency. [12],[13]
Figure 1: Conjunctival xerosis

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Corneal manifestations

The earliest corneal manifestation of xerophthalmia is instability of the precorneal tear film, which can lead to a dull and lusterless corneal appearance. The disorder is present in a majority of people who exhibit night blindness and Bitot's spots. The condition is almost always bilateral. If treatment is initiated at this point, healing usually takes place over the course of perhaps 1 week. If xerophthalmia persists for a long time, it progresses to keratomalacia (a full-thickness liquefactive necrosis of the cornea). Characteristically, these ulcers are small, partial, or of full thickness, located in the periphery in the early stages. With progression, they can extend to obscure the pupillary axis and develop secondary bacterial infection. [14]

The corneal stroma can slough, either leaving a descemetocele (herniation of Descemet's membrane, through a corneal wound or deep ulceration) or, in severe cases, causing perforation and loss of the anterior chamber. Vitamin A supplementation speeds healing. Often, keratomalacia is associated with a preceding systemic stressor, such as measles, diarrhea, or respiratory infection, or with concurrent severe protein-energy malnutrition. [15]

Corneal scar resulting from corneal ulceration due to vitamin A deficiency could potentially lead to blindness. In severe cases, there can be total loss of vision due to formation of anterior staphyloma (weakening and bulging of cornea lined anteriorly by epithelium and posteriorly by iris) [Figure 2].
Figure 2: Child with keratomalacia right eye

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Xerophthalmic fundus

Xerophthalmic fundus is uncommon, but it represents structural damage to the fundus in the form of yellow and white dots in the retinal periphery. Fluorescein angiogram reveals these dots to be focal retinal pigment epithelium defects. [16] Rarely, patients can present with scotomas corresponding to the area of retinal involvement. [17] These changes can respond to vitamin A therapy, with the scotoma disappearing in 1-2 weeks and retinal lesions fading in 1-4 months. [18]


  1. Clinical: Vitamin A deficiency can be diagnosed clinically by the above-mentioned corneal and conjunctival signs. Night blindness and xerosis are the initial signs of vitamin A deficiency, followed by formation of Bitot's spot.
  2. Serum levels of vitamin A: Serum retinol levels can also be assessed to determine vitamin A deficiency. The national prevalence of marginal vitamin A deficiency is defined by serum retinol <20 μg/dl or 0.7 μmol/l, and severe retinol deficiency as <10 μg/dl or 0.35 μmol/l. [12]
  3. CIC: The corneal and conjunctival epithelium undergoes keratinizing metaplasia in the vitamin A-deficient state, as do epithelial cells in other organs. [19] Histological abnormalities on the bulbar conjunctiva, including separation and distortion of epithelial cells and losses of mucin-secreting goblet cells, occur with mild vitamin A deficiency before the onset of clinically apparent surface changes. [20] CIC and impression cytology with transfer (ICT), a modification of the initial method, are based on well-described histopathologic changes due to vitamin A deficiency. Briefly, the method involves gently applying a strip or disk of cellulose acetate filter paper to the temporal bulbar conjunctiva for 2-3 seconds, which, after removal, is placed in fixative. In the laboratory, filter paper specimens are stained, clarified, and mounted for examination. The ICT method differs in that once collected, specimens are immediately transferred to a glass slide through finger pressure; they are then fixed and stained for viewing. [21] Specimens are microscopically examined for the presence and density of goblet cells or mucin spots, and the density, size, and shape of epithelial cells in relation to specimen area or number of microscopic fields. [22],[23],[24] Abnormal specimens are often devoid of goblet cells and mucin droplets and are often characterized by large, separated, or keratinized epithelial cells. [25],[26] The presence of a minimum density of goblet cells, with or without a normal epithelial sheet, typically defines a lower limit for a normal diagnosis.


Children with any stage of xerophthalmia should be treated with vitamin A, according to the WHO treatment guidelines. The goal of therapy is to replenish vitamin A stores.

Oral therapy: The oral regimen of vitamin A is 200,000 IU on day of presentation, next day, and 2-4 weeks later. [27],[28] Children less than 1 year of age or less than 8 kg should receive half the dose of the above dose. Repeat 200,000 IU every 6 months up to 6 years of age to prevent recurrence. An easy way of oral administration is by pinching the capsule of vitamin A and making the child to drink it.

Parenteral therapy: If the patient has severe disease, is unable to take oral feeds, or has malabsorption, the preferable dose is 100,000 IU of vitamin A given intramuscularly. [29] Supportive, nutritional, and antibiotic therapy should be considered, as indicated by the patient's condition, along with dietary counseling.

Children with severe measles should also receive vitamin A as they are very likely to be benefited from such therapy both in terms of saving sight and reducing case fatality. [15]


Prevention can be categorized into three groups:

  • Dietary diversification: Increasing vitamin A intake from available and accessible foods, achieved through nutritional education, social marketing, home or community garden programs, and other measures to improve food security.
  • Fortification: Taking advantage of the existing consumption patterns of fortifiable foods to carry vitamin A into the diets of populations.
  • upplementation: Providing supplementation to high-risk group, particularly to preschool-aged children, on a periodic basis and to mothers within 6-8 weeks after childbirth.

Improving vitamin A status in the diet or by periodic administration of vitamin A to children can reduce both mortality and blindness. For prophylaxis, newborn should receive 50,000 IU of vitamin A, children younger than 1 year should receive 100,000 IU every 4-6 months, and adults and children older than 1 year should receive 200,000 IU every 4-6 months. Under vitamin A supplementation program through Reproductive and Child Health (RCH) program and now National Rural Health Mission (NRHM), children between 9 and 36 months of age are to be provided with vitamin A solution every 6 months, starting with 100,000 IU at 9 months of age along with measles vaccination and subsequently 200,000 IU every 6 months till 36 months of age. [28],[29]

  Conclusion Top

Vitamin A deficiency is an important preventable cause of childhood blindness which can be prevented by timely detection and vitamin A supplementation. Xerophthalmia is the most readily recognized clinical manifestation of vitamin A deficiency and has been the most widely employed definitive criterion for assessing whether vitamin A deficiency poses a significance public health problem. Vitamin A supplementation should be routinely given in children with measles, diarrhea, and malnutrition. Many of the eye signs of vitamin A deficiency are pathognomonic for the condition, and so can be used to diagnose and screen patients for the same.

  References Top

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20.Keenum G, Semba D, Wirasasmita S, Natadisastra G, West K, Sommer A. Assessment of vitamin A status by a disk applicator for conjunctival impression cytology. Arch Ophthalmol 1990;108:1436-41.  Back to cited text no. 20
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