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Vitamin A and the eye: An old tale for modern times

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Clinical presentations associated with vitamin A deficiency persist in poor regions globally with the same clinical features as those described centuries ago. However, new forms of vitamin A deficiency affecting the eyes, which have become widespread, as a result of modern societal habits are of increasing concern. Ophthalmic conditions related to vitamin A deficiency require the combined attention of ophthalmologists, pediatricians, internists, dermatologists, and nutritionists due to their potential severity and the diversity of causes. As the eyes and their adnexa are particularly sensitive to vitamin A deficiency and excess, ocular disturbances are often early indicators of vitamin A imbalance. The present review describes the clinical manifestations of hypovitaminosis A with an emphasis on so-called modern dietary disorders and multidisciplinary treatment approaches. The present review also discusses the relationship between retinoic acid therapy and dry eye disease.
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56  http://dx.doi.org/10.5935/0004-2749.20160018
INTRODUCTION
Night blindness, xerophthalmia, Bitot’s spot, keratitis, and kera-
tomalacia are well-known clinical manifestations of hypovitaminosis
A(1). However, this condition is classically related to food deprivation
associated with malabsorption syndrome resulting from poverty
and/or chronic disease(1-3).
The present review aims to inform health professionals of the
modern presentations, causes, associated systemic diseases, and risk
factors of hypovitaminosis A. The utility of retinoic acid application
for the treatment of skin diseases and dry eye is also discussed(4).
Herein, we present the clinical presentation of hypovitaminosis A
and discuss strategies for the investigation and treatment of the
causes and consequences of hypovitaminosis A and side effects of
the use of retinoic acid (a form of vitamin A) in dermatological and
oncological therapies.
HIsTORy
The classical clinical presentation of the disease currently known
as vitamin A deficiency was first described in antique medical docu-
ments of the ancient Egyptian civilization, although underlying me-
ABsTRACT
Clinical presentations associated with vitamin A deficiency persist in poor regions
globally with the same clinical features as those described centuries ago. However,
new forms of vitamin A deficiency affecting the eyes, which have become wides-
pread, as a result of modern societal habits are of increasing concern. Ophthalmic
conditions related to vitamin A deficiency require the combined attention of
ophthalmologists, pediatricians, internists, dermatologists, and nutritionists due
to their potential severity and the diversity of causes. As the eyes and their adnexa
are particularly sensitive to vitamin A deficiency and excess, ocular disturbances
are often early indicators of vitamin A imbalance. The present review describes the
clinical manifestations of hypovitaminosis A with an emphasis on so-called modern
dietary disorders and multidisciplinary treatment approaches. The present review
also discusses the relationship between retinoic acid therapy and dry eye disease.
Keywords: Vitamin A deficiency/complications; Eye manifestations; Bariatric surgery;
Blepharoplasty; Refractive surgical procedures; Xerophthalmia
RESUMO
As apresentações clínicas associadas à deficiência de vitamina A persistem em regiões
pobres ao redor do mundo com os mesmos achados clínicos descritos há séculos.
No entanto, novas formas de problemas causados pela vitamina A afetam os olhos,
estão associados com os hábitos da sociedade moderna e tem causado preocupação.
Eles exigem a atenção dos oftalmologistas, pediatras, internistas, dermatologistas e
nutricionistas, devido à sua gravidade e diversidade de causas. Uma vez que os olhos
e seus anexos são órgãos muito sensíveis à deficiência e excesso de vitamina A, mani-
festações oculares podem ser indicadores precoces do desequilíbrio de vitamina A. Essa
revisão traz as manifestações clínicas de hipovitaminose A enfatizando os chamados
distúrbios dietéticos modernos e formas de abordagem multidisciplinar. E também traz
evidências sobre a relação entre a terapia com ácido retinóico e doença do olho seco.
Descritores: Deficiência de vitamina A/complicações; Manifestações oculares; Cirurgia
bariátrica; Blefaroplastia; Procedimentos cirúrgicos refrativos; Xeroftalmia
chanisms were elucidated more recently. The causes of deficiencies
in the micronutrient vitamin A, the biochemical vitamin A pathway,
food sources of retinol (vitamin A) and its metabolites, and the phy-
siological roles of vitamin A have only begun to be understood since
the 20th century(5-9) (Figure 1; Table 1).
Interestingly, one of the most complete and objective des-
criptions of the clinical manifestations of hypovitaminosis A was
published decades before the specific underlying cause was known
by the Brazilian ophthalmologist, Manoel da Gama Lobo, in 1865(10).
Dr. Gama Lobo reported four cases of children, all descendants of
slaves, with ocular disease who subsequently developed lung and
digestive disorders before ultimately dying. In this report, the disea-
se was termed Ophthalmia Braziliana, and the clinical progression
was comprehensively detailed. Food deprivation was identified
and credited to the practice of extensive monoculture in the farms
of Southeast Brazil, in that century dedicated to the production of
coffee and sugar.
Dr. Gama Lobo attributed the signs and symptoms observed
in his patients to the poor diet of slaves and their descendants, a
problem that he never saw in his homeland to north of the country
Vitamin A and the eye: an old tale for modern times
A vitamina A e o olho: uma velha história em tempos modernos
Jacqueline Ferreira Faustino1, alFredo ribeiro-silva2, rodrigo Faeda dalto1, Marcelo Martins de souza1, João Marcello Fortes Furtado1,
guteMberg de Melo rocha3, Monica alves4, eduardo Melani rocha1
Submitted for publication: September 8, 2015
Accepted for publication: October 20, 2015
1 Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Faculdade de
Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
2 Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade
de São Paulo, Ribeirão Preto, SP, Brazil.
3 Depar tamento de Medicina Social, Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo, Ribeirão Preto, SP, Brazil.
4 Departamento de Oftalmologia e Otorrinolaringologia da Faculdade de Ciências Médicas, Univer-
sidade Estadual de Campinas, Campinas, SP, Brazil.
Funding: This study was supported by CAPES, CNPq, FAPESP, FAEPA, and NAP-FTO-USP.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Eduardo Melani Rocha. Department of Ophthalmology, Otorhinolaryngology
and Head & Neck Surgery, School of Medicine at Ribeirao Preto, University of Sao Paulo. Av.
Bandeirantes, 3.900 - Ribeirão Preto, SP - 14049-900 - Brazil - E-mail: emrocha@fmrp.usp.br
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where agriculture production was dedicated to local consumption
and therefore more variable and abundant. At the end of his report,
Dr. Gama Lobo called the attention of legislators to the need for
laws aimed at preventing the sequence of problems he outlined. His
paper was published in Portuguese and in German but is relatively
unknown to the majority of the medical community, although it is
now freely available online(11,12).
Recent epidemiologic data from Brazil in a study population of
3,499 children aged between 6 and 59 months and 5,698 women
aged between 15 and 49 years revealed that hypovitaminosis A is
present in all five regions of Brazil with a prevalence of 17.4% and
12.3% among children and women, respectively(13). The highest
prevalence was found to be in urban areas and the northeastern and
southeastern regions of the country.
ClAssIC DIseAse
The typical medical scenarios leading to hypovitaminosis A are
low food intake, intestinal parasitosis, malabsorption syndromes, and
diets containing low amounts of vitamin A (Figure 2).
Hypovitaminosis A is classically caused by food deprivation. It is
present in rural areas and the peripheries of large cities in South Asia,
Africa, and Latin America, and the poor communities of large cities
of developed countries(14-17). The most vulnerable individuals are chil-
dren and pregnant women. The prevalence of hypovitaminosis A can
reach 50% in children under 6 years of age in certain areas(18). Labo-
ratory confirmation of the diagnosis of hypovitaminosis A is defined
as a serum retinol level <0.3 mg/l or 0.7 µM(19).
In addition to ocular problems, hypovitaminosis A also predispo-
ses individuals to retarded growth, infertility, congenital malforma-
tions, infections, and early mortality(18,20). The issue of vitamin A defi-
ciency in these populations, distributed in more than 45 countries,
has been the target of international preventive programs of vitamin
A supplementation and periodic evaluation(16,18,19).
Individuals suffering from food deprivation and malabsorption
are often infected with intestinal parasite diseases, such as Ascaris
lumbricoides and Ancilostomides, Giardia lamblia, which may aggra-
vate the inflammatory background and the signs and symptoms of
hypovitaminosis A(21-24).
Other well-known causes of vitamin A deficiency can be grouped
into conditions associated with malabsorption syndrome. The treat-
ments of several diseases that cause digestive disturbances and/or
absorption of lipids and vitamin A have improved in recent decades
leading to increased life expectancy and improved the clinical con-
trol of hypovitaminosis A allowing the majority of patients to lead
a normal life. However, the majority of these patients will develop
xerophthalmia (the specific term for hypovitaminosis A-related dry
eye), which may progress to more severe ocular damage and other
clinical manifestations of vitamin A depletion(25-27).
Acquired diseases associated with malabsorption syndrome known
to cause hypovitaminosis A include chronic pancreatitis caused by
chronic alcoholism, liver and pancreas autoimmunity, Crohn’s disease,
and ulcerative colitis, among other diseases affecting the digestive
system(28).
Congenital diseases associated with malabsorption syndrome and
hypovitaminosis A include cystic fibrosis and short bowel syndrome,
among other genetic diseases that may impair intestinal vitamin A
absorption in individuals with normal or high oral intake of retinoid
and carotenoids(2,29,30).
The fourth group of conditions that classically cause hypovitami-
nosis A is those that may initially lead to malabsorption syndrome but
later progresses to impaired hepatic storage of vitamin A. Biliary cir-
rhosis, chronic hepatitis, and chronic cirrhosis caused by toxic agents,
viruses, and other causes may lead to hypovitaminosis A and should
be screened for and treated by parenteral vitamin A supplementation
according to body mass index and level of vitamin A deficiency(31).
MODeRN DIseAses AssOCIATeD wITH HypOvITAMINOsIs A
In recent decades, the conditions known to induce hypovitami-
nosis A have been classified into four groups. Despite their varying
prevalence, such conditions should be carefully considered by
ophthalmologists during routine clinical practice.
Modern causes of hypovitaminosis A that may also lead to xe-
rophthalmia and other eye diseases and cause blindness are shown
in (Figure 2 and Table 2) and comprising voluntary ingestion of low
vitamin A diets or restrictive diets (e.g., vegetarian or cafeteria diets),
psychiatric eating disorders (e.g., anorexia and bulimia), bariatric
Figure 1. Metabolic steps underlying vitamin A deciency from the dietary level to tar-
get cells.
Table 1. Vitamin A nomenclature
Name Group Characteristics
Retinoids Vitamin A and natural or synthetic derivate Similar chemical polyenes and polar end groups
Carotenes α-Carotene, β-carotene, g-carotene, and the xanthophyll β-cryptoxanthin Β-ionine rings
Vitamin A Group of lipophilic nutritional compounds Essential and broad effects on chordate animal bodies
Provitamin A Carotenes and retinyl esters Dietary and pharmaceutical sources of vitamin A
Retinoic acid Metabolite of vitamin A Transcription factor binding to cell nuclear receptors
Retinal Form of vitamin A Essential for vision function
Retinol Form of vitamin A Growth and development functions
Tretinoin All trans retinoic acid Pharmaceutical formulas
1 IU of vitamin A = 0.3 μg retinol = 0.34 μg retinil acetate = 0.6 μg β-carotene.
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surgeries mimicking malabsorption syndrome, and chronic diseases
that affect organs involved in vitamin A digestion or clearance (e.g.,
Sjögren’s syndrome and kidney failure).
Restrictive diets resulting from dietary behaviors may lead to
a status of hypovitaminosis A and the consequences mentioned
above. Diets adopted in conjunction with drugs to reduce appetite,
diets with monotonous ingredients, and diets with limited sources of
animal ingredients containing retinol and beta carotene (meat and
dairy products such as milk, eggs, and their derivatives) are typically
followed in the belief they will offer better control or prevention of
certain diseases or improve general health(32-35).
Exclusively vegetarian diets particularly put children and pregnant
woman at increased risk of hypovitaminosis A as the conversion of
beta carotenes present in vegetables to retinol is limited during di-
gestion and the availability of vitamin A for absorption and hepatic
storage is <20% of dietary vitamin A content(1).
The so-called cafeteria diet or competitive food, based on re-
freshing sodas and industrialized food, is predominantly composed
of carbohydrates and lipids of vegetal source and provides insuffi-
cient amounts of dietary vitamin A. Accordingly, such diets could be con-
sidered causes of hypovitaminosis A and associated ocular problems
in patients with excessive habits related to these diets(36).
The second group of causes of hypovitaminosis A includes the
psychiatric eating disorders, anorexia, and bulimia nervosa, recogni-
zed as major, growing health problems with severe clinical compli-
cations, and high mortality. Both can cause hypovitaminosis A due
to chronic dietary disturbances. The complexity of such conditions
must be recognized in the context of early signs of xerophthalmia
and should be managed in parallel with psychiatric specialists(37,38).
Bariatric techniques for the treatment of obesity include jejunoi-
leal bypass and stomach reduction to induce weight loss by malab-
sorbtive and restrictive mechanisms(39-41). Patients require vitamin su-
pplementation following these procedures; however, a recent study
in Brazil demonstrated that even before bariatric surgery a re lative
amount of patients already have hypovitaminosis A, and that this pre-
valence increases 30 and 180 days after the procedure(42). In patients
with no compliance for a period of weeks or months, ophthalmolo-
gists may evaluate the initial manifestations of hypovitaminosis A.
Special attention should be paid to patients undergoing oculoplastic
or refractive surgeries as their nutritional status may be subclinical
Figure 2. Classic and modern causes of hypovitaminosis A.
Table 2. Major causes of hypovitaminosis A and diagnosis guidelines
Major causes of deciency of vitamin A Description
Primary deficiency Low dietary intake of vitamin A
Food source: liver beef, damascus, spinach, cabbage, milk, carrot, and butter
Diagnosis: food intake history, liver function, and vitamin A serum levels
Restrictive and monotonous diets Restricted intake of sources of vitamin A and consumption of the same group of food for many months
Eating disorders: psychiatric, cafeteria diet, and vegetarian
Diagnosis: food intake history. Physical signs. Blood vitamin A levels
Malabsorption syndrome Reduction in uptake and mucosa transport of digested nutrients to the blood stream
Diagnosis: diarrhea, steatorrhea, weight loss, anemia, hyperkeratosis, and acrodermatitis. Blood examination to check
pancreas and liver function. Stool analysis (fat, parasites)
Bariatric surgery Surgery to treat obesity and associated diseases is divided into restrictive, disabsorptive, and mixed techniques and
often mimics malabsorption syndrome
Diagnosis: surgical history, use of vitamin supplements, bowel habits. Food intake history. Physical signs. Blood levels
of vitamin A. Stool analysis (fat)
Short bowel syndrome Mesenteric vascular disease typically caused by congenital obstruction, thrombosis, and other diseases requiring
bowel resection
Diagnosis: diarrhea, fatigue. Blood levels of vitamin A. Stool analysis (fat)
Liver failure Loss of liver digestive and storage functions due to alcohol toxicity, virus infection, or other causes. Malabsorption
mechanisms and signs may be present.
Diagnosis: blood levels of liver enzymes and vitamin A, virus serology. Stool analysis (fat)
Chronic pancreatitis Loss of pancreas exocrine function affecting digestion. Malabsorption mechanisms and signs may be present
Diagnosis: blood levels of pancreas enzymes and vitamin A. Stool analysis (fat)
Cystic fibrosis Inherited disease affecting chloride channels leading to exocrine gland dysfunction. Malabsorption mechanisms and
signs may be present
Diagnosis: low weight gain in infancy, progressive malnutrition, chronic cough with hypersecretion, chronic sinusitis,
biliary cirrhosis, diabetes, respiratory infections and infertility. Sodium and chloride levels in sweat
Salivary and deglutition diseases Swallowing problems due to xerostomia, tooth problems, and/or muscular deglutition dysfunction. Example: Sjögren’s
syndrome
Diagnosis: oral and dental examination and salivary flow rate
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and cause disturbances in ocular surface homeostasis and wound
healing leading to poor outcomes and serious ocular com plicat ions(40).
Patients with the above-mentioned conditions may share a number
of characteristics including individual concern and anxiety regarding
body image, health, and satisfaction with food consumption.
The fourth class of modern causes of hypovitaminosis A that may
contribute to or worsen ocular surface diseases is the chronic disease
leading to chronic impairment of the organs involved in digestion
and clearance of vitamin A metabolites (Figure 1). Although the
ma jority of these diseases are not new, improvements in therapeutic
approach have allowed affected patients to lead longer and more acti-
ve lives. Similarly, vitamin A deficiency may be neglected in patients
receiving frequent healthcare.
Within this group, the diseases causing severe dry mouth, such
as head and neck radiotherapy and Sjögren’s syndrome, may limit
deglutition and digestion and impose dietary restrictions that may
lead to hypovitaminosis A(43,44). Therefore, dietary habits and vitamin
A levels should be evaluated in patients presenting the diseases des-
cribed above and ocular surface complications. Although patients
commonly present with dry eye disease associated with these con-
ditions, the clinical picture may be aggravated by hypovitaminosis A.
Renal failure and hemodialysis are associated with dry eye disease
and ocular surface changes in diabetic and nondiabetic patients(45,46).
There is currently controversy regarding lower vitamin A levels in
such patients as renal failure reduced the reliability of traditional me-
thods of measuring vitamin A levels. However, lower blood vitamin
A levels have been shown to be associated with higher morbidity and
mortality in these patient populations(47,48). Recently, a case of night
blindness and compatible retinal changes was described in a he-
modialysis patient with apparent normal levels of serum retinol that
were corrected with retinol palmitate treatment(49).
sIDe effeCTs Of vITAMIN A MeDICAl Use
The utility of vitamin A topical eye drop administration in treating
dry eye has been comprehensively investigated(50,51). Vitamin A topi-
cal eye drops may also have utility in the treatment of skin diseases
and specific types of cancer including ocular surface neoplasia(52,53).
However, excessive vitamin A intake is known to induce gastric and
neural side effects such as abdominal and head pain, nausea, and
irritability(54,55). These symptoms may be aggravated by chronic use of
vitamin A eye drops and lead to the development of blurred vision and
pseudotumor cerebri(56-58). A clinical history of dry skin and mucosa,
nausea, and retinoic acid intake in meals or pharmaceutical formu-
lations should inform suspicion of acute and chronic side effects or
consequences of excessive vitamin A dosing.
Recently, two publications reviewed the mechanisms underlying
the induction of meibomian gland dysfunction and dry eye symptoms
by systemic retinoic acid therapy for acne. The authors discussed
the effects of systemic and topical skin or ocular application of diffe-
rent forms and doses of vitamin A formulations. Moreover, it was
persistent meibomian gland dysfunction after systemic retinoic acid
discontinuation was reported(4,52).
CAse RepORTs
Case report 1: A 2-year-old boy presented with a history of con-
se cutive episodes of hordeola affecting the upper and lower lids of
both eyes over the preceding 12 months. The patient had a history
of photophobia and crying without tears. Previous ocular treatment
included lubricants and antiallergic eye drops. The patient was an
only child with no other personal or family antecedents. His dietary
habits were based on soft drinks and junk food between meals with
deficient intake of meat, milk derivatives, vegetables, and fruits.
Swollen lids and hordeola affecting both eyes were observed on exa-
mination. He was able to fix and follow light projection with both eyes
but was unable to perform visual acuity testing. Slit lamp examination
demonstrated mild punctate keratitis and an epithelial defect in the
right cornea. The rest of the ocular examination was normal. His
body weight matched the 50th percentile for age and sex (12.7 kg);
however, his height was in the tenth percentile (84 cm). Laboratory
testing was requested and identified hypochromic and microcytic
anemia with low blood levels of iron and retinol (32.7 μg/dl and
0.20 mg/l, where the normal levels for children are 50-150 μg/dl
and 0.30-0.80 mg/l, respectively).
Clinical findings and laboratory testing indicated the chronic pre-
sence of hordeola, syndrome sicca, growth retardation, and anemia
were all consequences of a diet deficient in essential elements such
as vitamin A and iron (Fe). The diet was reoriented, and the child was
maintained under close observation by his pediatrician until clinical
signs improved fully.
Case report 2: A 71-year-old woman presented with decreased
vision and pain in the left eye (OS) for 20 days and a diagnosis of
corneal ulcer. She was receiving antibiotic and corticosteroids eye
drops at the time of presentation. She had previously undergone
cataract surgery in both eyes 2 months prior to this presentation.
Her medical history was noncontributive except for inappetence and
weight loss of approximately 10 kg over the preceding year. Her visual
acuity was 0.5 in her right eye (OD) and counting fingers at 1 m OS.
Biomicroscopic examination revealed conjunctiva hyperemia and a
1.5 mm by 2.5 mm corneal ulcer without secretion or infiltration. A
diagnosis of microbial keratitis was made, and eye drops were chan-
ged accordingly. During follow-up, she developed a corneal ulcer OD
and the ulcer in the OS worsened. Severe corneal punctate fluores-
cein staining and conjunctival Rose Bengal staining were observed
in both eyes. The Schirmer test without anesthesia was zero in both
eyes. Her salivary flow was 0.06 ml/min (normal values >0.1 ml/min;
Figure 3). Laboratory tests were positive for SSa and SSb (anti-Ro and
anti-La antibodies, respectively), and blood levels of vitamin A were
0.2 mg/l. A minor salivary gland biopsy demonstrated leukocyte infil-
tration with focal organization, ductal dilation, and extensive fibrosis
replacing acinar structures. The focus score was graded 4. During eva-
luations, the patient developed corneal melting OD and underwent
penetrant keratoplasty. The present findings indicated a diagnosis of
Sjögren’s syndrome aggravated by hypovitaminosis A. After a period
of corticosteroids and vitamin A therapy, her general and ocular
symptoms improved. Her case illustrates a delicate combination of
causes of sicca syndrome (Sjögren’s syndrome and hypovitaminosis
A) leading to a severe presentation. The extensive fibrosis of salivary
gland structures, almost completely replaced by fibrosis, may be a
consequence of concurrent disease and ageing (Figure 3 D).
Case report 3: A 22-year-old woman presented with ocular pain,
lid edema, and thick tearing for 5 months not improved by lubricants,
cyclosporine eye drops, or bandage contact lenses. She reported a
habit of mucous fishing. Her previous medical history included myo-
pia, allergy, and acne vulgaris. She had been prescribed a 6-month
course of oral isotretinoin 6 years previously without side effects
and again 6 months prior to the current complaint. Examination
revealed skin scarring, meibomian gland dysfunction, and punctate
and filamentary keratitis that was worse OD (Figure 4). The tear film
breakup time was 3 s in both eyes and the tarsal conjunctiva presen-
ted papillary reaction. The Schirmer test without anesthesia was zero
in OD and 2 mm in OS, and her salivary flow rate was 0.033 ml/min.
Laboratory testing was negative for hormonal abnormalities, and
cystic fibrosis and her vitamin A blood levels were 0.4 mg/l. Tests for
autoimmune diseases were negative for SSa and SSb, rheumatoid
factor, and antinuclear antibody. Her condition was attributed to
a side effect of isotretinoin treatment that had persisted after an
18-month interruption of oral isotretinoin intake. Her case corrobo-
rates previous reports of vitamin A-induced dry eye and represents a
severe form of this condition that persisted after discontinuation of
the causative medication.
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INvesTIgATION
Hypovitaminosis A should be suspected in all cases of night blindness,
ocular surface foreign body sensation, and photophobia without other
evident causes. Crying without tearing is another relevant symptom of
hypovitaminosis A. Recurrent hordeolum, meibomian gland dysfunc-
tion identified by gland dropout or inflammation with thickened lipid
secretion, corneal epithelial defect, conjunctiva metaplasia (where
Bitot’s spot is an advanced form and a hallmark), and diffuse punctate
keratitis also represent signs suspicious for hypovitaminosis A.
In all patients suspected to have hypovitaminosis A, a dietary intake
and nutritional habits enquiry must be conducted, with previously
validated evaluation models available. In children, investigations of
height and weight gain during the management period may also
have utility.
The utility of blood vitamin A levels measurements is broadly
accepted, and a classification system established by the World Health
Organization has defined low vitamin A levels as serum retinol con-
centrations <0.3 mg/l or 0.7 µM. There have been concerns regarding
the reliability of blood concentration measurements as the liver is
able to sustain normal levels even in extremely vitamin A-deficient
states(19,59,60).
Other blood tests including complete blood count, protein, albu-
min, micronutrients, electrolyte concentrations, and stool fat micros-
copy have all demonstrated utility in assessing vitamin A deficiency
severity. In addition, liver function tests, serology for hepatitis, and
sweat sodium chloride test values >60 mM may aid in distinguishing
between liver diseases and cystic fibrosis, respectively.
Ocular surface assessments may be performed with vital staining
and tear secretion measurements (fluorescein dye and Schirmer’s
test). Corneal and conjunctival impression cytology allows documen-
tation of ocular surface epithelial metaplasia, square and speculate
cells morphology, reduced nuclear size, and the absence or paucity
of goblet cells on microscopy. Ocular surface assessments have de-
monstrated utility as simple and mildly invasive methods of recor-
ding and monitoring hypovitaminosis A in early xerophthalmia(61).
CONClUsION
The major aim of treatment is to restore vitamin A levels in cases
of hypovitaminosis and reduce exposure in conditions associated
with side effects of oral or skin topical vitamin A use. Details regarding
dosage and administration routes are outside the scope of the pre-
sent review, as they are dependent on the underlying cause, patient
characteristics, and severity of individual cases.
Healthcare professionals attending poor populations and pa-
tients with chronic malabsorption syndrome, hepatic, and other re-
lated diseases should be familiar with the classic causes of hypovita-
minosis A. The modern causes of hypovitaminosis A do not have the
same magnitude in terms of prevalence but should be considered
by ophthalmologists in daily clinical practice. Hypovitaminosis A can
cause blindness and corneal opacity, but it is also an important cause
of morbidity and mortality.
Increased suspicion of hypovitaminosis A due to ocular surfa ce
symptoms and signals should direct prompt investigation of nu tritional
and digestive problems followed by interdisciplinary management
allowing early diagnosis and treatment of the causes and effects of
the majority of diseases related to hypovitaminosis A.
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A
C
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Figure 3. A 71-year-old woman with bilateral corneal ulcers, weight loss, and features
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AB C


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... Although the body stores vitamin A as retinyl ester in liver and to a lesser extent in adipose, lung, and other tissues, these stores may become depleted over time if the diet is consistently deficient in vitamin A, or stores may never develop in children who are not adequately breastfed and/or do not receive an adequate diet after weaning (141). Food deprivation, unbalanced diet, and malabsorption syndromes are the most common causes of deficiency (142)(143)(144). Worldwide, dietary deficiency is by far the most common cause, epidemic in developing countries and particularly affecting young children (145,146). ...
... Worldwide, dietary deficiency is by far the most common cause, epidemic in developing countries and particularly affecting young children (145,146). Dietary deficiency may also be observed in individuals with low general food intake, such as in anorexia or bulimia nervosa (142). Fat malabsorption syndromes can result in hypovitaminosis A, such as due to chronic pancreatitis, inflammatory bowel disease, and liver disease (142,147). ...
... Dietary deficiency may also be observed in individuals with low general food intake, such as in anorexia or bulimia nervosa (142). Fat malabsorption syndromes can result in hypovitaminosis A, such as due to chronic pancreatitis, inflammatory bowel disease, and liver disease (142,147). ...
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