Fact-checked by Grok 2 weeks ago

Bitot's spots

Bitot's spots, named after French physician Pierre Bitot who first described them in 1863, are foamy, whitish or grayish triangular patches composed of keratinized, desquamated epithelial cells that form on the bulbar or palpebral conjunctiva, most commonly in the interpalpebral fissure near the temporal limbus.^[1] They represent an early clinical sign of vitamin A deficiency (VAD), classified as stage X1B in the World Health Organization's xerophthalmia grading system, which encompasses the spectrum of ocular manifestations from night blindness to severe corneal damage.^[2] These spots are typically asymptomatic but indicate underlying nutritional deficiency that can progress to irreversible blindness if untreated.^[1] VAD leading to Bitot's spots arises primarily from inadequate dietary intake of preformed vitamin A from animal products or its precursors like beta-carotene from plant sources and fortified foods, compounded by malabsorption issues like those following bariatric surgery^[3] or in populations with high rates of infections and diarrhea.^[2] Globally, Bitot's spots signal a major public health concern, with prevalence exceeding 0.5% in children under six years indicating a VAD public health problem, particularly in regions of Africa and South-East Asia where VAD affects populations in over half of countries.^[2] Although rare in developed nations, Bitot's spots underscore the reversible yet critical nature of addressing micronutrient deficiencies to safeguard vision.^[4]

Overview and History

Definition and Characteristics

Bitot's spots are foamy, greyish-white, or slightly yellowish triangular patches composed of keratinized epithelium on the bulbar conjunctiva, classified by the World Health Organization as stage X1B in the xerophthalmia spectrum, representing a preclinical sign of ocular involvement in vitamin A deficiency.^[5] These spots typically measure 2-3 mm in size and exhibit a raised, dry appearance with a superficial layer of frothy, silvery-gray material, resulting from the accumulation of desquamated, keratinized epithelial cells due to squamous metaplasia of the conjunctival epithelium.^[6]^[7] The lesions are often bilateral and located on the temporal bulbar conjunctiva adjacent to the cornea, though they may occasionally appear unilaterally or in irregular, oval shapes.^[8] Histologically, Bitot's spots consist of irregular epithelial maturation, keratin tangles, inflammatory infiltration, and masses of gram-positive bacilli mixed with fatty debris and edema, without involvement of goblet cells.^[6] In isolation, these spots are non-painful and asymptomatic, serving as a distinctive marker of conjunctival xerosis.^[8] This condition primarily arises from vitamin A deficiency, which impairs normal epithelial differentiation and leads to the characteristic keratinization observed in the ocular surface.^[5]

Historical Background

Bitot's spots were first described in 1863 by the French physician and anatomist Pierre Bitot (1822–1888), who observed these distinctive conjunctival lesions in malnourished children suffering from night blindness.^[9] In his seminal paper published in the Gazette Hebdomadaire de Médecine et de Chirurgie, Bitot detailed the spots as triangular, foamy, pearly or silvery patches on the bulbar conjunctiva, often located temporally to the cornea, with a rough, punctate surface that could be displaced by pressure from the eyelid.^[9] Working as a professor of anatomy at the Bordeaux School of Medicine and an honorary surgeon at the local hospital, Bitot's observations marked the first comprehensive clinical documentation of these lesions, linking them to conditions of nutritional deprivation in pediatric populations.^[9] The eponym "Bitot's spots" honors Pierre Bitot's pioneering work, as his precise depiction of the lesions' morphology and association with hemeralopia (night blindness) distinguished them from other conjunctival abnormalities.^[10] Prior to Bitot's description, similar ocular manifestations of malnutrition were not systematically characterized in Western medicine, though ancient civilizations had noted related eye conditions.^[11] Bitot's contributions elevated awareness of these signs as indicators of underlying nutritional deficits, paving the way for later connections to specific dietary deficiencies. Evidence of early recognition and treatment of eye disorders resembling those later identified as vitamin A deficiency dates back to ancient Egypt around 1500 BCE, where the Ebers Papyrus records remedies involving animal liver—a rich source of vitamin A—for night blindness.^[11] These treatments, which included squeezing juices from grilled or roasted ox or pig liver directly onto the eyes, empirically addressed symptoms like impaired dark adaptation, predating scientific understanding of the nutrient's role by millennia.^[11] By the late 20th century, Bitot's spots gained formal medical significance when integrated into the World Health Organization's (WHO) classification of xerophthalmia in the 1980s, designating them (as X1B) as a key clinical marker of vitamin A deficiency in global public health assessments.^[12] This standardization, refined through the Joint WHO/USAID meeting in Jakarta in 1974 and the Joint WHO/USAID/UNICEF/Hellen Keller International/IVACG meeting in Jakarta in 1980, emphasized their role in identifying at-risk populations and guiding intervention programs, building on Bitot's foundational observations.^[12]

Clinical Presentation

Appearance and Location

Bitot's spots present as well-defined, foamy white plaques on the ocular surface.^[10] These lesions are typically triangular or oval in shape, with the base situated at the limbus and the apex directed toward the lateral canthus.^[13] They consist of superficially accumulated keratin debris, imparting a dry, elevated, and bubbly texture.^[7] The spots are predominantly located on the temporal aspect of the bulbar conjunctiva, adjacent to the corneal limbus within the interpalpebral fissure.^[10] Less commonly, they may extend to the nasal conjunctiva or appear bilaterally.^[7] Variations in presentation include irregular shapes and a whitish coloration, with lesions generally measuring a few millimeters in extent.^[14] While typically associated with vitamin A deficiency, Bitot-like spots can rarely occur in other conditions such as chronic exposure to irritants or certain anterior segment pathologies.^[10] Under slit-lamp examination, Bitot's spots appear as slightly elevated, foamy areas of keratinization on the conjunctiva, lacking vascularization or signs of active inflammation.^[7] This biomicroscopic view highlights the superficial nature of the debris without deeper tissue involvement.^[10]

Associated Symptoms and Complications

Bitot's spots are often asymptomatic, presenting without noticeable discomfort to the patient, though some individuals may experience mild ocular irritation, photophobia, or a foreign body sensation attributable to underlying conjunctival dryness in the context of xerophthalmia.^[15] These symptoms arise from the squamous metaplasia and keratinization of the conjunctival epithelium, which can lead to subtle surface irregularities.^[1] In the progression of xerophthalmia due to vitamin A deficiency, Bitot's spots (classified as stage X1B) may advance to more severe corneal involvement, including corneal xerosis (X2), where the cornea becomes dry and hazy, followed by ulceration (X3A or X3B) or keratomalacia (X3C), characterized by corneal softening and melting.^[16] This stepwise deterioration reflects ongoing epithelial damage and can result in corneal scarring if the deficiency persists untreated.^[1] Untreated progression heightens the risk of complications such as bacterial keratitis, corneal perforation, and permanent vision impairment or blindness, with xerophthalmia-related changes contributing to an estimated 250,000 to 500,000 cases of childhood blindness annually worldwide, half of which lead to death within 12 months.^[2] Children with both Bitot's spots and night blindness face nearly nine times higher mortality risk compared to those without these signs, often exacerbated by concurrent infections like measles or diarrhea that further deplete vitamin A stores.^[15] Systemically, Bitot's spots frequently accompany night blindness (XN), an early indicator of vitamin A deficiency marked by impaired dark adaptation, as well as extraocular manifestations such as follicular hyperkeratosis of the skin.^[16] These associations underscore the broader impact of severe vitamin A deficiency on multiple tissues reliant on retinol for epithelial integrity and immune function.^[15]

Etiology and Pathophysiology

Role of Vitamin A Deficiency

Vitamin A, primarily in the form of retinol and its active derivatives retinal and retinoic acid, plays a critical role in maintaining the health of ocular tissues, particularly the conjunctiva. These compounds are essential for the differentiation and maintenance of epithelial cells, including the conjunctival goblet cells responsible for mucin production, which contributes to the tear film's protective mucin layer. In vitamin A deficiency (VAD), the lack of retinoic acid disrupts gene expression pathways involved in epithelial integrity, leading to impaired goblet cell function and reduced mucin secretion.^[16] The pathogenic process begins with progressive depletion of vitamin A stores, resulting in squamous metaplasia of the conjunctival epithelium. This metaplasia transforms the normally non-keratinized, mucin-secreting epithelium into a stratified, keratinized layer, which reduces tear film stability and promotes the accumulation of desquamated keratin debris. The foamy appearance of Bitot's spots arises from this keratin buildup, often colonized by bacteria such as Corynebacterium xerosis, forming triangular, white plaques typically on the bulbar conjunctiva. Bitot's spots represent an early, reversible manifestation of xerophthalmia, occurring when plasma retinol levels fall below 0.70 μmol/L, indicating subclinical deficiency.^[2]^[1]^[8] If dietary intake remains inadequate, liver stores—which normally contain 80-90% of the body's vitamin A reserves and can sustain physiological needs for up to several months—become depleted, allowing the condition to progress. At the cellular level, VAD impairs rhodopsin synthesis in the retina by limiting retinal availability, contributing to associated night blindness, while the absence of retinoic acid signaling in epithelial cells exacerbates hyperkeratinization and further compromises ocular surface protection. These mechanisms highlight Bitot's spots as a hallmark of VAD's impact on epithelial homeostasis.^[17]^[16]^[8]

Other Contributing Factors

While vitamin A deficiency remains the primary etiology of Bitot's spots, malabsorption syndromes can secondarily impair the uptake of this fat-soluble vitamin, leading to similar ocular manifestations. Conditions such as celiac disease disrupt intestinal absorption, resulting in vitamin A deficiency and the appearance of Bitot's spots, as documented in case reports of affected adults.^[18] Post-bariatric surgery, particularly Roux-en-Y gastric bypass, induces malabsorption of fat-soluble vitamins, with reported instances of xerophthalmia including Bitot's spots in patients following such procedures.^[19] Similarly, inflammatory bowel diseases like Crohn's disease can cause chronic malabsorption, contributing to vitamin A deficiency and associated Bitot's spots through reduced nutrient uptake in the small intestine.^[20] Iatrogenic factors may also precipitate Bitot's spots by interfering with vitamin A absorption or storage. Chronic liver disease, including alcoholic cirrhosis, impairs hepatic storage of vitamin A, leading to deficiency states that manifest as Bitot's spots and conjunctival xerosis.^[21] Long-term use of bile acid sequestrants like cholestyramine reduces fat-soluble vitamin absorption by binding bile acids in the gut, potentially resulting in vitamin A deficiency, though direct ocular cases are less commonly reported.^[22] Nutritional overlaps with other deficiencies occasionally contribute to Bitot's spots in contexts of broader malnutrition. A rare association exists with pellagra, caused by niacin (vitamin B3) deficiency, where shared dietary inadequacies may lead to overlapping vitamin A depletion and the development of these conjunctival lesions.^[23] Idiopathic cases of Bitot's spots, though uncommon, have been noted in elderly individuals without evident vitamin A deficiency, potentially exacerbated by age-related dry eye or conjunctival changes such as pinguecula.^[8] In such instances, evaluation for malabsorption or subclinical nutritional issues is recommended to rule out underlying contributors.^[23]

Epidemiology

Global Prevalence

Bitot's spots, a clinical manifestation of vitamin A deficiency (VAD), occur in approximately 0.5-2% of preschool-age children in VAD-endemic regions, serving as a key indicator for public health interventions. Globally, VAD affects about 11% (95% UI: 10-13%) of children under five years as of 2023, equivalent to roughly 70-80 million preschool children, with Bitot's spots representing a subset of overt clinical cases.^[24] The World Health Organization (WHO) classifies VAD as a public health problem in more than half of all countries, where the prevalence of Bitot's spots exceeding 0.5% in this age group signals severe risk.^[2]^[25]^[26] Regional variations highlight hotspots in South Asia, where prevalence reaches 1-3% in countries like India and Bangladesh, driven by dietary inadequacies and high population density. In sub-Saharan Africa, rates range from 0.5-1.5%, with studies in Ethiopia reporting 1.46% among preschool children, while Southeast Asia shows similar patterns. These areas account for the majority of cases, correlating closely with overall VAD burdens exceeding 20% in severely affected populations.^[27]^[28] Temporal trends indicate substantial progress, with VAD prevalence declining from 39% in 1991 to 29% by 2013 and further to 11% by 2023 across low- and middle-income countries, reflecting a roughly 61% reduction since 1990 attributable to global supplementation efforts.^[24]^[25] Clinical signs like Bitot's spots have similarly decreased, contributing to fewer cases of severe outcomes such as childhood blindness, which VAD still accounts for in about 5% of instances in low-income settings despite these gains. This decline is most pronounced in South Asia and Southeast Asia, where targeted programs have halved rates in some locales.^[2]^[29] Prevalence data are derived from clinical surveys employing WHO standardized indicators for xerophthalmia, including direct ophthalmologic examination for Bitot's spots and correlation with undernutrition metrics like low serum retinol levels. These assessments, often conducted in community-based studies, provide the foundation for monitoring and underscore the link to broader at-risk groups such as those in low-income households.^[2]^[26]

At-Risk Populations

Children under five years of age in low- and middle-income countries represent the primary at-risk group for developing Bitot's spots, as they experience the highest rates of clinical vitamin A deficiency (VAD) due to inadequate intake during weaning and early childhood diets lacking in preformed vitamin A sources.^[16] This vulnerability is particularly pronounced in regions of sub-Saharan Africa and South Asia, where preschool children account for the majority of xerophthalmia cases, including Bitot's spots.^[16] Pregnant and lactating women also face elevated risk, driven by heightened physiological demands for vitamin A that often exceed dietary availability in nutrient-poor settings, potentially leading to maternal VAD manifestations such as Bitot's spots.^[16] In rural areas of countries like Ethiopia, up to 76% of lactating mothers have been found deficient, exacerbating intergenerational transmission of VAD to offspring.^[16] Socioeconomic factors significantly amplify susceptibility, with rural poverty and food insecurity limiting access to diverse, vitamin A-rich foods like animal products, vegetables, and fortified staples.^[16] Populations reliant on monotonous, cereal-based diets—such as rice or maize without animal sources or supplementation—are especially prone, as these provide insufficient provitamin A carotenoids or retinol.^[30] Comorbid conditions further heighten risk by impairing absorption or increasing requirements; for instance, HIV/AIDS, measles, and recurrent diarrhea reduce serum retinol levels and exacerbate VAD in affected individuals.^[16] Refugee and disaster-affected populations, often displaced to resource-scarce environments, experience compounded vulnerabilities due to disrupted food systems and heightened infection rates.^[31] Gender disparities exist in certain regions, with some studies indicating slightly higher VAD prevalence among males.^[32]

Diagnosis

Clinical Assessment

Clinical assessment of Bitot's spots primarily involves a targeted ocular examination to identify characteristic foamy, triangular patches on the bulbar conjunctiva, typically located temporally to the cornea in the interpalpebral fissure. These lesions are often visible without eversion but may require upper eyelid eversion using gentle pressure on the lid margin while asking the patient to look downward for complete inspection of the palpebral and bulbar conjunctiva.^[8]^[1] A penlight or hand-held light source is used for initial screening to highlight the whitish, opaque, foam-like deposits composed of desquamated epithelial cells and debris, distinguishing them from surrounding dry conjunctiva.^[33] In settings with access to advanced equipment, slit-lamp biomicroscopy provides magnified visualization, confirming the absence of active inflammation, vascular injection, or scarring that might suggest alternative pathologies.^[6] According to the World Health Organization (WHO) classification of xerophthalmia, Bitot's spots are graded as stage X1B, indicating a longstanding but non-blinding manifestation of vitamin A deficiency, following conjunctival xerosis (X1A) and preceding corneal involvement.^[1] This staging relies on clinical observation rather than quantitative metrics, with diagnosis confirmed by the lesions' foamy texture and lack of vascular changes or inflammatory signs.^[34] Supporting tests augment the clinical findings but are not always essential for initial diagnosis. The Schirmer test measures tear production by placing a filter paper strip in the lower conjunctival fornix for 5 minutes, with wetting less than 10 mm indicating reduced tear secretion consistent with xerophthalmia.^[8] Conjunctival impression cytology, involving the collection of epithelial sheets from the conjunctiva for microscopic analysis, reveals reduced goblet cells and squamous metaplasia, providing objective evidence of vitamin A deficiency-related changes.^[8]^[6] Serum retinol levels, assessed via high-performance liquid chromatography, provide biochemical confirmation, with concentrations below 0.70 μmol/L signaling vitamin A deficiency, though this test is often deferred in resource-limited environments due to cost and logistics.^[34] In field settings, particularly in endemic areas, diagnosis emphasizes simple visual inspection by trained community health workers using natural or ambient light, enabling rapid identification without specialized tools.^[33] These workers are trained to recognize the pathognomonic foamy patches through basic eyelid eversion and referral of suspected cases for supplementation, facilitating early intervention in public health programs.^[34]

Differential Diagnosis

Bitot's spots, characterized by foamy, triangular patches of keratinized conjunctiva typically located temporally to the limbus, require differentiation from other conjunctival abnormalities to ensure accurate diagnosis. Common mimics include degenerative conditions such as pinguecula, which present as yellowish, slightly elevated, and often vascularized nodules at the corneal limbus due to chronic sun exposure and aging, lacking the distinctive foam-like debris and association with nutritional deficiency seen in Bitot's spots.^[6] Similarly, simple conjunctival xerosis may appear as dry, wrinkled conjunctiva without the superficial keratin accumulation that defines Bitot's spots, often stemming from environmental dryness rather than vitamin A deficiency.^[1] Malignant lesions like ocular surface squamous neoplasia (including conjunctival squamous cell carcinoma) can resemble Bitot's spots with white, opaque, irregular plaques on the conjunctiva, but they are typically raised, friable, vascularized, and may cause pain or irritation, necessitating biopsy for confirmation.^[35] Nutritional deficiencies beyond vitamin A, such as pellagra from niacin (vitamin B3) deficiency, may produce pellagra-related conjunctivitis with red, inflamed, scaly changes around the eyes, accompanied by systemic features like dermatitis, diarrhea, and dementia, unlike the isolated, asymptomatic ocular findings in Bitot's spots.^[10] Riboflavin (vitamin B2) deficiency often manifests as angular blepharitis with fissured, inflamed lid margins and photophobia, differing from the non-inflammatory, foam-covered nature of Bitot's spots.^[36] Infectious etiologies like trachoma, caused by Chlamydia trachomatis, feature follicular conjunctivitis, tarsal scarring, and pannus formation, usually in endemic settings with a history of poor hygiene, contrasting with the non-follicular, reversible xerosis of Bitot's spots.^[6] Allergic conjunctivitis presents with bilateral itching, redness, watery discharge, and papillary reaction, without the dryness or keratinization typical of Bitot's spots.^[6] Overwear of contact lenses can induce superficial keratitis or conjunctival deposits that mimic foamy changes due to hypoxia and irritation, but these resolve upon lens discontinuation and lack nutritional context.^[37] A key differentiator for Bitot's spots is their nontender, foam-encased appearance on the bulbar conjunctiva, which typically resolves within weeks of vitamin A supplementation, confirming the diagnosis without invasive testing in most cases.^[8] Biopsy, rarely required, reveals hyperkeratosis, parakeratosis, acanthosis, and goblet cell loss, distinguishing it from neoplastic or inflammatory mimics.^[38]

Management and Treatment

Vitamin A Supplementation

Vitamin A supplementation serves as the cornerstone of treatment for Bitot's spots, directly addressing the underlying vitamin A deficiency that leads to their development.^[39] As a key component of the visual cycle and epithelial maintenance, replenishing vitamin A stores reverses the conjunctival keratinization characteristic of these lesions.^[6] The World Health Organization recommends high-dose oral vitamin A therapy for children with clinical signs of deficiency, including Bitot's spots. For children aged 12 months and older, the protocol involves 200,000 IU of retinol on day 1, repeated on day 2, and a third dose 1–4 weeks later; a similar regimen of 200,000 IU applies to adults. For infants aged 6–12 months, the dose is halved to 100,000 IU per administration following the same schedule; doses for those under 6 months are further adjusted to 50,000 IU.^[39] These regimens utilize oil-based preparations to enhance bioavailability and are administered as a medical emergency to prevent progression to more severe xerophthalmia. However, a 2024 study has raised concerns about potential hypervitaminosis A from repeated high doses, recommending monitoring for toxicity and possible dose adjustments.^[40] Administration is preferably oral via capsules or an oily solution to ensure absorption in the gastrointestinal tract. In cases of impaired absorption, such as severe malnutrition or malabsorption syndromes, intramuscular injection of a water-miscible formulation may be used as an alternative.^[6] Clinical improvement, including regression of the foamy, white plaques, typically becomes visible within 1–2 weeks of initiating therapy, with faster resolution observed in early-stage lesions.^[8] Efficacy is high, with studies reporting 94–97% improvement or cure rates within 6–8 days following high-dose supplementation in children with Bitot's spots.^[41] Overall resolution approaches 90% in uncomplicated vitamin A deficiency cases when treatment is prompt, though persistent spots may indicate ongoing deficiency or other factors requiring further evaluation.^[41] Monitoring involves clinical follow-up examinations at 1 month to assess lesion resolution and prevent recurrence. Serum retinol levels should be checked to confirm adequacy, with concentrations above 0.70 μmol/L indicating sufficient stores post-treatment.^[42]

Additional Interventions

In cases where Bitot's spots persist despite adequate vitamin A supplementation, surgical excision of the affected conjunctiva may be considered, particularly for symptomatic or non-responsive lesions. This procedure, often performed using techniques such as the Fugo blade under local or general anesthesia, involves puncturing and sweeping away the defective tissue, followed by post-operative antibiotic-steroid ointment application for about 10 days to prevent infection and promote healing. Such interventions are rarely required, as most spots resolve with vitamin A therapy, but they can be effective in restoring conjunctival integrity within days to weeks.^[43]^[7] Supportive care plays a key role in managing associated ocular surface dryness and discomfort. Artificial tears or lubricating eye drops, such as carboxymethylcellulose-based formulations, are recommended to alleviate xerosis and maintain corneal hydration, especially during the initial treatment phase. Additionally, underlying malabsorption issues contributing to vitamin A deficiency should be addressed; for instance, discontinuing medications like cholestyramine that inhibit gastrointestinal absorption of fat-soluble vitamins can help improve nutrient uptake.^[44]^[45]^[8] When Bitot's spots occur in the context of multiple nutritional deficiencies, multivitamin therapy may be warranted to target co-existing issues, such as zinc deficiency, which impairs retinol-binding protein synthesis and exacerbates vitamin A effects. For example, zinc supplementation alongside vitamin A has been shown to enhance resolution in deficient patients. In severe malnutrition scenarios, assessment for other B-vitamin shortages is essential to prevent complications like concurrent pellagra from niacin deficiency.^[8]^[46] Referral to an ophthalmologist is advised if spots progress to corneal involvement, such as keratomalacia, or if secondary bacterial infection develops, necessitating prompt evaluation with tests like Schirmer or rose bengal staining. In such instances, topical antibiotics may be prescribed to treat infection and prevent further damage, alongside monitoring for subconjunctival fibrosis or symblepharon.^[47]^[44]^[8]

Prevention

Nutritional Strategies

Nutritional strategies to prevent Bitot's spots focus on ensuring adequate vitamin A intake at the individual and household levels, primarily through dietary diversification, targeted supplementation, and fortification of common foods, as these approaches address the underlying vitamin A deficiency that manifests as the condition.^[48] A key component involves promoting the consumption of foods rich in preformed vitamin A, such as liver, eggs, and dairy products, alongside provitamin A carotenoids found in carrots, sweet potatoes, and dark leafy greens like spinach and kale, which the body converts to active vitamin A.^[49] These sources are particularly emphasized in regions with limited access to animal products, where plant-based options can effectively meet needs if consumed in sufficient quantities. For children, the recommended daily intake is 400–600 μg retinol activity equivalents (RAE), corresponding to ages 4–13 years, to support eye health and prevent deficiency signs like Bitot's spots.^[49] In non-emergency settings for at-risk children, low-dose oral vitamin A supplementation—such as 10,000 IU weekly—has been shown to protect against respiratory infections and maintain vitamin A status without the risks associated with high-dose regimens.^[50] This approach is suitable for subclinical deficiency areas, providing steady intake to complement diet and reduce the incidence of ocular manifestations.^[50] Food fortification enhances vitamin A delivery by adding the nutrient to household staples, including edible oils, refined sugar, wheat flour, and milk, which are widely consumed and stable vehicles for the vitamin.^[51] Programs fortifying these items at levels such as 10–18 mg retinol equivalents per kg have successfully boosted population intake in deficient areas, indirectly preventing conditions such as Bitot's spots by increasing bioavailability without requiring behavioral changes.^[52] Nutrition education plays a vital role, with counseling focused on balanced diets rich in vitamin A sources, particularly during critical periods like weaning—when infants transition to solid foods—and pregnancy, to safeguard maternal and fetal stores.^[48] Such guidance encourages incorporating diverse, affordable foods into meals, improving long-term adherence and reducing deficiency risks at the family level.^[53]

Public Health Measures

Public health measures to address Bitot's spots, a clinical sign of vitamin A deficiency (VAD), emphasize large-scale interventions aimed at preventing and reducing incidence in vulnerable populations. Supplementation campaigns, led by organizations such as UNICEF and WHO, deliver high-dose vitamin A capsules during Child Health Days in endemic areas, targeting children aged 6-59 months with biannual dosing of 100,000-200,000 IU every 4-6 months.^[54] These events integrate multiple health services and have achieved coverage rates exceeding 80% in regions like South Asia and parts of sub-Saharan Africa, though global two-dose coverage among priority countries has declined to approximately 52% as of 2022.^[55]^[56] By reaching over 290 million children at peak in 2009, such campaigns have significantly lowered VAD-related morbidity, though coverage has fluctuated due to funding and logistical issues.^[56] Food fortification programs form another cornerstone, with national policies mandating vitamin A addition to staple foods in high-burden countries. In India, government recommendations since 2017 have promoted fortification of edible oils (6-9.9 µg retinol equivalents per gram) and milk (270-450 µg per liter), targeting preschool children and women to avert substantial disability-adjusted life years from VAD complications like night blindness.^[57] In Indonesia, mandatory fortification of cooking oil since 2011 has markedly reduced VAD prevalence from 12.2% to 2.9% in evaluated populations, including a 96% drop among children aged 24-59 months, by boosting serum retinol levels and contributing 26-40% of daily vitamin A needs.^[58] These initiatives have collectively lowered VAD by 20-40% in targeted regions through sustained consumption of fortified products. In October 2025, WHO issued updated guidelines on fortification of edible oils and fats with vitamins A and D to further support such public health interventions.^[59]^[60] Surveillance and screening efforts are embedded in routine health systems to enable early detection and response. Vitamin A supplementation is often integrated into immunization visits, such as measles vaccinations, allowing health workers to assess and deliver doses during the same contact, thereby improving coverage among children aged 6-23 months.^[54] Community-based growth monitoring programs, involving regular anthropometric checks and nutritional education, help identify early VAD signs like Bitot's spots in preschoolers, particularly in rural settings where facility access is limited. These approaches facilitate targeted interventions and data collection for national VAD surveys. Policy impacts demonstrate both successes and hurdles in scaling these measures. Nepal's national vitamin A program, launched in the 1990s, achieved over 80% coverage across all districts by 2002 and reduced subclinical VAD prevalence by more than 60%, from 32.3% in 1998 to 12.5% in 2016, saving an estimated 45,000 young lives between 2002 and 2017.^[61] This success persisted through the 1996-2006 civil conflict via female community health volunteers and biannual campaigns.^[61] However, in other conflict zones, such as parts of sub-Saharan Africa and South Sudan, programs face challenges including disrupted supply chains, security risks, and low health worker retention, resulting in coverage below 50% and persistent high VAD burdens.^[62]^[63]

References

[1]
Xerophthalmia - StatPearls - NCBI Bookshelf - NIH
Apr 17, 2023 · Bitot Spots (X1B) Bitot's spots are whitish, opaque deposits on the palpebral conjunctiva, usually the interpalpebral area.
[2]
Vitamin A deficiency - World Health Organization (WHO)
Xerophthalmia is the clinical spectrum of ocular manifestations of vitamin A deficiency; these range from the milder stages of night blindness and Bitot spots ...
[3]
Bitot's Spots following Bariatric Surgery: An Ocular Manifestation of a ...
Dec 21, 2017 · These findings were highly suggestive of vitamin A deficiency, supported by the presence of severe ocular surface dryness, night blindness, and ...
[4]
Bitot's Spots: Look at the Gut - PMC - NIH
Bitot's spots represent an ocular manifestation of VAD.[1] VAD is an important cause of preventable blindness in the developing world.Missing: symptoms | Show results with:symptoms
[5]
Xerophthalmia and night blindness for the assessment of clinical vitamin A deficiency in individuals and populations
### Summary of Bitot's Spots from WHO Classification of Xerophthalmia
[6]
Xerophthalmia - EyeWiki
Jul 20, 2025 · Bitot spots (Grade X1B): Bitot spots are collections of desquamated, keratinized epithelial cells mixed with the gas-forming bacteria ...
[7]
Immunohistochemistry in an Adult Case of Bitot's Spots Caused by ...
Dec 15, 2023 · Bitot's spots (BS) are the buildup of superficially located keratin in the conjunctiva and are early indicators of vitamin A deficiency (VAD).Missing: definition | Show results with:definition
[8]
Management of Bitot's Spots - American Academy of Ophthalmology
Dec 1, 2016 · Bitot's spots are typically dry-appearing triangular patches of xerosed conjunctiva with a layer of foam on the surface, usually located temporal to the cornea.
[9]
[PDF] Historical eponyms of vitamin A (1863–1954) | AVESİS
Bitôt is credited for providing the first comprehensive clinical description of the ocular findings in nyctalopia (night blindness), the condition later known.
[10]
Bitot-like spots in children with normal vitamin A levels - PMC - NIH
Sep 16, 2021 · A Bitot spot is a conjunctival lesion, classically associated with severe vitamin A deficiency. In this paediatric series, we describe ...
[11]
A History of Vitamin A and Retinoids
This is a historical account of the recognition of human vitamin A deficiency from ancient Egypt to the present century, as well as a history of the discovery ...
[12]
Modified classification of xerophthalmia
5 Only those Bitot's spots accompanied by conjunctival xerosis, usually in the 0-5 years age group, are indicative of vitamin A deficiency. This xerosis may be ...
[13]
Bitot-like Spots and Congenital Aniridia: A Case Report - PMC
Feb 4, 2025 · Bitot's spots are white foamy triangular or round-shaped spots, with the base located at the temporal limbus and the apex towards the lateral ...
[14]
Cancer-Associated Retinopathy - StatPearls - NCBI Bookshelf
[155] Other early external ocular findings include Bitot spots (oval or triangular, foamy lesions of the conjunctiva) and conjunctival xerosis (wrinkling of ...
[15]
The eye signs of vitamin A deficiency - PMC - NIH
Bitot's spots (Figure 2) are characteristic of VAD and are not caused by any other condition. The slightly elevated, white foamy lesion is usually seen on the ...
[16]
Vitamin A Deficiency - StatPearls - NCBI Bookshelf
A well-performed history of a patient can raise suspicion for vitamin A deficiency. · As the severity of deficiency worsens, signs of xerophthalmia develop with ...
[17]
Vitamin A Deficiency: Background, Pathophysiology, Etiology
Feb 3, 2025 · An adult liver can store up to a year's reserve of vitamin A, whereas a child's liver may have enough stores to last only several weeks.
[18]
Bitot's Spots: Look at the Gut - PubMed
Although usually a result of malnutrition, VAD can accompany malabsorption syndrome. We report a case of VAD as manifested by Bitot's spots and eventually ...
[19]
Xerophthalmia secondary to bowel malabsorption after Roux-en-Y ...
Jan 24, 2024 · This is, to our knowledge, the first case report of xerophthalmia in a patient with Lynch syndrome. Keywords: Bitot's spots; Lynch syndrome; ...
[20]
Nyctalopia and Xerophthalmia in a Patient With Crohn's Induced ...
Aug 4, 2023 · This case illustrates the potential for VAD secondary to malabsorption from Crohn's disease and the importance of taking a full patient history ...Missing: syndromes | Show results with:syndromes<|control11|><|separator|>
[21]
Ocular manifestations of liver disease: an important diagnostic aid
Apr 15, 2024 · Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis.Missing: chronic | Show results with:chronic
[22]
The effect of cholestyramine on intestinal absorption - PubMed
With prolonged treatment folate deficiency occurred, as evidenced by a fall in the mean serum folate concentration from 7-7 ng/ml before treatment to 4-4 ng/ml ...
[23]
Bitot's Spot Overlying a Pinguecula | JAMA Ophthalmology
For example, Bitot's spots have been seen in patients with pellagra, a vitamin B deficiency state. In addition,. References. 1. Thygeson P: Thirteenth annual ...
[24]
Trends and mortality effects of vitamin A deficiency in children in 138 ...
In 1991, 39% of children were vitamin A deficient, declining to 29% in 2013. In 2013, 94,500 deaths from diarrhea and 11,200 from measles were attributable to ...
[25]
Prevalence and Associated Factors of Clinical Vitamin A Deficiency ...
Oct 20, 2020 · The prevalence of Bitot's spot and night blindness was 0.8% and 1.2%, respectively. Pre-school children who were from highland (AOR: 3.71; 95% ...
[26]
Prevalence and associated factors of clinical manifestations of ...
Mar 14, 2016 · The odds of Bitot's spots (1.46 %) and night blindness (1.22 %) were higher than the WHO Cut-off levels used to define a public health problem.
[27]
Vitamin A Deficiency in Schoolchildren in Urban Central India
The results suggest that in urban central India, the mean (SE) prevalence of xerophthalmia is about 6.5% (0.2%) based on Bitot spots and/or night blindness.
[28]
The prevalence of vitamin A deficiency and its public health ...
Aug 11, 2023 · In 2005, the WHO estimated that 33.3% of preschool-age children, equivalent to 190 million children, had VAD, with a majority of cases in SEAR ( ...
[29]
https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(15)00039-X/fulltext
[30]
Understanding Dietary Diversity, Dietary Practices and Changes in ...
Nov 13, 2020 · Most frequently, micronutrient malnutrition is experienced by the poorest households due to cereal-based, monotonous diets that lack dietary ...
[31]
[PDF] Vitamin A supplementation for refugees and famine victims - IRIS
Children aged at least 12 months and adults of either sex with corneal or milder xerophthalmia (Bitot's spots or night blindness) ... in populations at high risk ...
[32]
Prevalence of demographic factors associated with vitamin A ...
Some studies have shown that boys are more prone to subclinical vitamin A deficiency12 In this study, however, deficiency was similarly common in both sexes ...
[33]
[PDF] WORLD HEALTH ORGANIZATION • GENEVA
Methods of testing. Under field conditions the testing may be performed by auxiliary medical staff using natural light. Local health workers can be readily.
[34]
Serum retinol concentrations for determining the prevalence of ...
May 30, 2011 · Assessment of serum retinol permits both the monitoring of trends of vitamin A deficiency as well as the evaluation of the impact of ...
[35]
Ocular Surface Squamous Neoplasia - EyeWiki
Apr 21, 2025 · Bitot spots (xerophthalmia); Benign ... Human papillomaviruses in intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva.
[36]
Riboflavin Deficiency - Nutritional Disorders - Merck Manuals
The most common signs of riboflavin deficiency are pallor and maceration of the mucosa at the angles of the mouth (angular cheilitis) and vermilion surfaces of ...<|control11|><|separator|>
[37]
Contact Lens–Related Complications - StatPearls - NCBI Bookshelf
Jun 11, 2023 · CL worn over the eye may result in conjunctival and corneal complications secondary to hypoxic changes, chemical toxicity, hypersensitivity reactions, ...Missing: foam Bitot's
[38]
Bitot's spots following hemicolectomy | Eye - Nature
Jul 10, 2003 · Histologically, Bitot's spots show hyperkeratosis, parakeratosis, and loss of goblet cells. There are only two previously reported cases of ...
[39]
a guide to their use in the treatment of vitamin A deficiency and ...
Jun 16, 1997 · Provides concise, authoritative advice on the use of high-dose vitamin A supplements for the control of vitamin A deficiency and the emergency treatment of ...
[40]
Focusing on xerophthalmia, vitamin A deficiency
Jul 5, 2019 · Sommer noted. Another manifestation of xerophthalmia is the presence of Bitot's spots on conjunctiva, which are comprised of keratin. “Vitamin A ...<|control11|><|separator|>
[41]
Vitamin A - Principles of Nutritional Assessment
At a population level, WHO recommend a serum retinol cutoff of <0.70µmol/L to indicate whether vitamin A deficiency is likely to be a public health problem.
[42]
Bitot's Spots | Ento Key
Sep 11, 2016 · For patients who are nonresponsive to vitamin A therapy, the available treatment for Bitot's spots is excision of the defective conjunctiva.Missing: debridement | Show results with:debridement
[43]
Xerophthalmia: Symptoms, Causes & Treatment - Cleveland Clinic
Bitot spots: You have foamy silver-gray triangular spots that appear on the whites of your eyes. Corneal xerosis: Your cornea is dry and it shouldn't be ...
[44]
Retinol, Aquasol A (vitamin A) dosing, indications, interactions ...
... age: 200,000 units PO qDay for 2 days; repeat dose again after 2 weeks. Females of reproductive age with night blindness or Bitot's spots: 5000-10,000 units ...<|control11|><|separator|>
[45]
Bitot's spot without hypovitaminosis A | Eye - Nature
Apr 25, 2025 · Bitot's spot is a conjunctival lesion associated to vitamin A deficiency, in a xeroftalmia context, usually found in patients suffering from malnutrition or ...Missing: pathophysiology | Show results with:pathophysiology
[46]
Managing eye health in young children - PMC - PubMed Central - NIH
Bitot's spots are an indication of Vitamin A deficiency. Note the typical ... Refer to an ophthalmologist, preferably one trained in paediatric ophthalmology.
[47]
Prevention of Vitamin A Deficiency - NCBI - NIH
Vitamin A intervention approaches are commonly grouped into two main control strategies: (1) direct increase in vitamin A intake through dietary modification ...
[48]
Vitamin A and Carotenoids - Health Professional Fact Sheet
Mar 10, 2025 · ... months to 5 years had vitamin A deficiency in 2013 [27]. Deficiency ... Preterm infants have low liver stores of vitamin A at birth ...
[49]
The beneficial effects of weekly low-dose vitamin A supplementation ...
Conclusions: Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and ...
[50]
Vitamin A fortification of staple foods
Aug 9, 2023 · Foods such as edible oils and fats, cereal grains, condiments, refined sugar and milk have been successfully fortified with vitamin A and ...Missing: flour | Show results with:flour
[51]
Food Fortification to Reduce Vitamin A Deficiency - ScienceDirect.com
In practice, oils, hydrogenated oils, cereal flours and sugar should be fortified at no more than 20 mg/kg. Vitamin A losses during production, storage and ...
[52]
Culture, Environment, and Food to Prevent Vitamin A Deficiency
Lack of vitamin A in the diet is the root cause of vitamin A deficiency, and dietary modification is generally regarded as the ultimate goal for the prevention ...<|control11|><|separator|>
[53]
Children 6-59 months receiving vitamin A supplements
The recommended doses are 100 000 international units (IU) for children aged between 6 and 11 months, and 200 000 IU for children aged between 12 and 59 months.
[54]
Vitamin A Deficiency in Children - UNICEF DATA
Aug 25, 2025 · The World Health Organization classified vitamin A deficiency as a public health problem affecting about one third of children aged 6 to 59 ...Missing: Bitot's spots
[55]
[PDF] COVERAGE AT A CROSSROADS - Unicef
The global prevalence of vitamin A deficiency in children under age 5 has declined from about 39 per cent to about 30 per cent over the past two decades ...Missing: Bitot's | Show results with:Bitot's<|control11|><|separator|>
[56]
Cost-effectiveness of oil and milk fortification by scale for reducing ...
Sep 8, 2025 · To address the issue, the Government of India has recommended fortification of oil and milk to improve Vitamin A and Vitamin D consumption.
[57]
[PDF] evaluation-of-the-impact-of-vitamin-a-fortified-cooking-oil-indonesia ...
Apr 4, 2012 · The objective of this study was to measure the impact of vitamin A fortification of unbranded cooking oil on serum retinol concentrations and ...
[58]
Vitamin A-fortified cooking oil reduces vitamin A deficiency in infants ...
Vitamin A-fortified cooking oil reduces vitamin A deficiency in infants, young children and women: results from a programme evaluation in Indonesia - PMC.Missing: VAD | Show results with:VAD
[59]
To see, hear, and live: 25 years of the vitamin A programme in Nepal
Nepal's vitamin A supplementation programme has maintained coverage rates >80% for 25 years, despite geographical challenges and civil conflict. Central to this ...
[60]
A Review of Vitamin A Supplementation in South Sudan
Jun 29, 2022 · Vitamin A deficiency (VAD) is likely a severe public health problem among preschool-aged children in South Sudan based on a high under-5 mortality rate.<|control11|><|separator|>
[61]
Evaluation of Nutrition Interventions in Children in Conflict Zones
Sep 7, 2017 · The burden faced by children is evident from nutritional deficiencies reported in current conflict-affected areas.