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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.
- 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).
- Primary vitamin A deficiency is prevalent in much of the developing world, particularly endemic in South and East Asia where rice is the staple food.
- Children have much lower vitamin A stores than adults.
- Protein-energy malnutrition is associated with keratomalacia - the diet is likely to be deficient in vitamin A, due to reduced intake, but starvation also affects the metabolism of vitamin A. Zinc deficiency and iron deficiency may contribute.
- It may be precipitated by a systemic illness such as measles ('measles blindness'), pneumonia or diarrhoea.
- In the west, it is more likely to present in the context of:
- Severe mental illness or eating disorder, dietary limitation.[7, 8]
- Malabsorption of fat-soluble vitamins - eg from cystic fibrosis, coeliac disease, pancreatic disorders, liver disease, intestinal bypass surgery, bariatric surgery or inflammatory bowel disease. Biliopancreatic diversion may cause severe vitamin A deficiency. The onset of symptoms can occur many years after bowel surgery.
- Keratomalacia can occur in neonates due to maternal vitamin A deficiency.
- Old age can also put people at greater risk of vitamin A deficiency.
- Isotretinoin therapy may precipitate symptoms in those with low vitamin A levels.[14, 15]
- A case report describes keratomalacia resulting from uncontrolled phenylketonuria.
- 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 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.
- Plasma retinol and retinol binding proteins are suppressed in advanced vitamin A deficiency.
- Iron and zinc levels may be relevant.
- 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 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). 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. Addressing zinc deficiency may be helpful.
- The prognosis for xerophthalmia is good if treated in the early stages (subclinical deficiency or early eye changes). However, as the condition progresses and keratomalacia develops, corneal changes may be irreversible.
- 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.
An adequate and varied diet - good sources of vitamin A are liver, beef, chicken, eggs, fruit and vegetables (especially orange and green vegetables). 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.
- 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. Indiscriminate high-dose supplementation in India has been criticised.
- In areas with endemic vitamin A deficiency, vitamin A supplementation during pregnancy reduced the risk of maternal night blindness.
- Vitamin A supplements for individuals at risk, eg with cystic fibrosis.
- 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.
Further reading and references
; Chapter 29: historical aspects of the major neurological vitamin deficiency Handb Clin Neurol. 201095:435-44.
; Measles blindness. Surv Ophthalmol. 2004 Mar-Apr
; Keratoplasty for keratomalacia in preschool children. Br J Ophthalmol. 2003 May
; Xerophthalmia secondary to alcohol-induced malnutrition. Optometry. 2006 Mar
; Keratomalacia caused by psychiatric-induced dietary restrictions. Cornea. 2007 Sep26(8):995-7.
; Adult blindness secondary to vitamin A deficiency associated with an eating disorder. Nutrition. 2005 May
; Vitamin a deficiency. Cornea. 2008 Sep27(8):973
; Bitot's spots and vitamin A deficiency in a child from the UK. Br J Ophthalmol. 2001 Mar
; Vitamin A deficiency in coeliac disease. Br J Ophthalmol. 2000 Sep84(9):1079-80.
; Night blindness in primary biliary cirrhosis. CMAJ. 2010 Aug 10182(11):1212. Epub 2010 May 31.
; Vitamin A deficiency in a newborn resulting from maternal hypovitaminosis A after Am J Clin Nutr. 2002 Aug76(2):426-9.
; Vitamin A deficiency in patients with a remote history of intestinal surgery. Br J Ophthalmol. 2006 Aug90(8):955-6. Epub 2006 Jun 14.
; Keratomalacia in a neonate secondary to maternal vitamin A deficiency. Indian J Pediatr. 2005 Oct72(10):881-2.
; Night blindness precipitated by isotretinoin in the setting of hypovitaminosis A. Australas J Dermatol. 1999 Nov40(4):208-10.
; Night blindness, vitamin A deficiency, and isotretinoin psychotoxicity. Dermatol Online J. 2003 Dec9(5):30.
; Use of amniotic membrane graft and corneal transplantation in a patient with bilateral keratomalacia induced by uncontrolled phenylketonuria. Cornea. 2007 Jun26(5):629-31.
; Vitamin A deficiency in New York City. Lancet. 2010 Jul 24376(9737):267.
; Fundus white spots and acquired night blindness due to vitamin A deficiency. Doc Ophthalmol. 2009 Dec119(3):229-33. Epub 2009 Oct 7.
; Surgery of the cornea: corneal, limbal stem cell and amniotic membrane Dev Ophthalmol. 200841:159-70.
; Zinc therapy for night blindness in cystic fibrosis. J Cyst Fibros. 2008 Jul7(4):333-5. Epub 2008 Jan 8.
; Mortality associated with mild, untreated xerophthalmia. Trans Am Ophthalmol Soc. 1983
; The role of expanded coverage of the national vitamin A program in preventing J Nutr. 2010 Jan140(1):208S-12S. Epub 2009 Nov 25.
; Vitamin A for treating measles in children. Cochrane Database Syst Rev. 2005 Oct 19(4):CD001479.
; Vitamin A supplementation for preventing morbidity and mortality in children from Cochrane Database Syst Rev. 2010 Dec 812:CD008524.
; Time to stop giving indiscriminate massive doses of synthetic vitamin A to Indian Public Health Nutr. 2009 Feb12(2):285-6.
; Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database Syst Rev. 2010 Nov 1011:CD008666.
; Vitamin A supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2008 Jan 23(1):CD006751.
; Vitamin A supplementation to prevent mortality and short and long-term morbidity Cochrane Database Syst Rev. 2007 Oct 17(4):CD000501.
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