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Synonym - xerotic keratitis

Xerophthalmia is the term used for deficient tear production leading to dry eye (particularly affecting the cornea) associated with vitamin A (retinol) deficiency. There may be insufficient absorption, or poor metabolism, of the vitamin. If left untreated, xerophthalmia progresses to keratomalacia: the cornea becomes thin and soft, eventually ulcerating. At worst, there may be perforation with secondary extrusion of the globe contents; however, other sequelae include corneal scarring, a permanent fibrotic deformity of the eyeball (phthisis bulbi) and blindness.[1]

  • It is a common cause of acquired paediatric blindness worldwide.
  • In western societies, it can occur amongst those with a poor nutritional status, due to a variety of factors (see below).

Risk factors[2]

  • Night blindness (nyctalopia or poor dark adaptation) tends to be the earliest ocular symptom of vitamin A deficiency.
  • Eyes become dry (cornea, lacrimal glands and conjunctiva are all affected) - known as xerosis.
  • Keratomalacia presents with bilateral central grey, indolent corneal ulcers surrounded by a dull, hazy cornea, sometimes with photophobia.
  • The cornea becomes soft and necrotic, usually progressing to perforation.
  • Bitot's spots[8] are areas of abnormal squamous cell proliferation and keratinisation of the conjunctiva, which look like foamy, wedge-shaped areas in the conjunctiva. They are usually temporal and are strongly associated with vitamin A deficiency, especially in young children.
  • White spots on the retina have been reported in one case.[18]
  • Plasma retinol and retinol binding proteins are suppressed in advanced vitamin A deficiency.
  • Iron and zinc levels may be relevant.[2]
  • Electroretinography[10, 17]

Addressing the ocular problems

  • Treatment will be on the aggressive end of the treatment spectrum of dry eye with intensive lubrication ± a bandage contact lens, depending on how far the condition has progressed.
  • Topical antibiotics will be required to prevent secondary keratitis.
  • Once the acute situation has settled, there will inevitably be some degree of corneal scarring. Depending on the extent and the individual's circumstances, keratoplasty may be considered. Success of this procedure for this condition has been limited[3] but there are occasional case studies suggesting that this line of treatment may have a future as techniques improve.[16, 19]

Addressing the systemic problems

  • Dietician advice for a vitamin A and protein-rich diet.
  • Vitamin A supplements may be used (intramuscular or oral).[12] Caution is needed in pregnant women because high vitamin A doses may be teratogenic.
  • Underlying problems need to be addressed, eg alcohol abuse, an eating disorder, gastrointestinal disease.
  • Other micronutrients (iron and zinc) may be important.[2] Addressing zinc deficiency may be helpful.[20]
  • The prognosis for xerophthalmia is good if treated in the early stages (subclinical deficiency or early eye changes).[3] However, as the condition progresses and keratomalacia develops, corneal changes may be irreversible.[2]
  • Xerophthalmia and keratomalacia are associated with increased mortality in children. An Indonesian study showed mortality rates increased with night blindness (x 2.7), Bitot's spots (x 6.6) and both features(x 8.6) reflecting the severity of the underlying vitamin A deficiency.[21]

An adequate and varied diet - good sources of vitamin A are liver, beef, chicken, eggs, fruit and vegetables (especially orange and green vegetables).[2] Other prevention strategies are:

  • Where there is vitamin A deficiency in a community, intervention is important, both to prevent blindness and to reduce child mortality.[21, 22]
  • Where early symptoms and signs of keratomalacia are present, they should be considered a 'red flag' in identifying children in need of urgent medical attention.[21]
  • High-dose oral vitamin A supplementation for children with measles in developing countries[1, 23] and high measles immunisation coverage.
  • Vitamin A supplementation in areas of high risk. There is a need for studies comparing different doses and delivery mechanisms.[24] Indiscriminate high-dose supplementation in India has been criticised.[25]
  • In areas with endemic vitamin A deficiency, vitamin A supplementation during pregnancy reduced the risk of maternal night blindness.[26]
  • Vitamin A supplements for individuals at risk, eg with cystic fibrosis.[27]
  • Follow-up for at-risk patients, eg those with malabsorption, liver disease or bariatric surgery.[11, 12]
  • Neonates who are very low birthweight have low vitamin A status, and a Cochrane review has questioned whether they require additional vitamin A supplementation.[28]

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  • Lanska DJ; Chapter 29: historical aspects of the major neurological vitamin deficiency Handb Clin Neurol. 2010 95:435-44.
  1. Semba RD, Bloem MW; Measles blindness. Surv Ophthalmol. 2004 Mar-Apr
  2. Ansstas G et al, Vitamin A Deficiency, eMedicine, Dec 2010
  3. Vajpayee RB, Vanathi M, Tandon R, et al; Keratoplasty for keratomalacia in preschool children. Br J Ophthalmol. 2003 May
  4. Roncone DP; Xerophthalmia secondary to alcohol-induced malnutrition. Optometry. 2006 Mar
  5. Cooney TM, Johnson CS, Elner VM; Keratomalacia caused by psychiatric-induced dietary restrictions. Cornea. 2007 Sep 26(8):995-7.
  6. Velasco Cruz AA, Attie-Castro FA, Fernandes SL, et al; Adult blindness secondary to vitamin A deficiency associated with an eating disorder. Nutrition. 2005 May
  7. Basti S, Schmidt C; Vitamin a deficiency. Cornea. 2008 Sep 27(8):973
  8. Ramsay A, Sabrosa NA, Pavesio CE; Bitot's spots and vitamin A deficiency in a child from the UK. Br J Ophthalmol. 2001 Mar
  9. Alwitry A; Vitamin A deficiency in coeliac disease. Br J Ophthalmol. 2000 Sep 84(9):1079-80.
  10. Waqar S, Kersey T, Byles D; Night blindness in primary biliary cirrhosis. CMAJ. 2010 Aug 10 182(11):1212. Epub 2010 May 31.
  11. Huerta S, Rogers LM, Li Z, et al; Vitamin A deficiency in a newborn resulting from maternal hypovitaminosis A after Am J Clin Nutr. 2002 Aug 76(2):426-9.
  12. Chae T, Foroozan R; Vitamin A deficiency in patients with a remote history of intestinal surgery. Br J Ophthalmol. 2006 Aug 90(8):955-6. Epub 2006 Jun 14.
  13. Gupta M, Jora R, Bhatia R, et al; Keratomalacia in a neonate secondary to maternal vitamin A deficiency. Indian J Pediatr. 2005 Oct 72(10):881-2.
  14. Welsh BM, Smith AL, Elder JE, et al; Night blindness precipitated by isotretinoin in the setting of hypovitaminosis A. Australas J Dermatol. 1999 Nov 40(4):208-10.
  15. Danby FW; Night blindness, vitamin A deficiency, and isotretinoin psychotoxicity. Dermatol Online J. 2003 Dec 9(5):30.
  16. Habot-Wilner Z, Spierer A, Barequet IS, et al; Use of amniotic membrane graft and corneal transplantation in a patient with bilateral keratomalacia induced by uncontrolled phenylketonuria. Cornea. 2007 Jun 26(5):629-31.
  17. Braunstein A, Trief D, Wang NK, et al; Vitamin A deficiency in New York City. Lancet. 2010 Jul 24 376(9737):267.
  18. Genead MA, Fishman GA, Lindeman M; Fundus white spots and acquired night blindness due to vitamin A deficiency. Doc Ophthalmol. 2009 Dec 119(3):229-33. Epub 2009 Oct 7.
  19. Kruse FE, Cursiefen C; Surgery of the cornea: corneal, limbal stem cell and amniotic membrane Dev Ophthalmol. 2008 41:159-70.
  20. Tinley CG, Withers NJ, Sheldon CD, et al; Zinc therapy for night blindness in cystic fibrosis. J Cyst Fibros. 2008 Jul 7(4):333-5. Epub 2008 Jan 8.
  21. Sommer A; Mortality associated with mild, untreated xerophthalmia. Trans Am Ophthalmol Soc. 1983
  22. Semba RD, de Pee S, Sun K, et al; The role of expanded coverage of the national vitamin A program in preventing J Nutr. 2010 Jan 140(1):208S-12S. Epub 2009 Nov 25.
  23. Huiming Y, Chaomin W, Meng M; Vitamin A for treating measles in children. Cochrane Database Syst Rev. 2005 Oct 19 (4):CD001479.
  24. Imdad A, Herzer K, Mayo-Wilson E, et al; Vitamin A supplementation for preventing morbidity and mortality in children from Cochrane Database Syst Rev. 2010 Dec 8 12:CD008524.
  25. Kapil U; Time to stop giving indiscriminate massive doses of synthetic vitamin A to Indian Public Health Nutr. 2009 Feb 12(2):285-6.
  26. van den Broek N, Dou L, Othman M, et al; Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database Syst Rev. 2010 Nov 10 11:CD008666.
  27. O'Neil C, Shevill E, Chang AB; Vitamin A supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2008 Jan 23 (1):CD006751.
  28. Darlow BA, Graham PJ; Vitamin A supplementation to prevent mortality and short and long-term morbidity Cochrane Database Syst Rev. 2007 Oct 17 (4):CD000501.
Dr Naomi Hartree
Document ID:
1323 (v22)
Last Checked:
18 February 2011
Next Review:
17 February 2016

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