View source for Heterochromia iridum

{{short description|Difference in coloration, usually of the iris but also of hair or skin}}
{{distinguish|Heterochromatin|Dichromatic (disambiguation)}}
{{Infobox medical condition
| name = Heterochromia
| image = Cuando el color llama la atención.JPG
| alt = 
| caption = Complete heterochromia iridum
| symptoms = Different or partially different eye color
| complications = 
| onset = 
| duration = Lifelong
| causes = 
| risks = 
| diagnosis = 
| differential = 
| prevention = 
| treatment = Iris implant surgery (controversial for cosmetic purposes)
| medication = 
| prognosis = 
| frequency = 
| deaths = 
}}

'''Heterochromia''' is a variation in [[color]]ation most often used to describe color differences of the [[Iris (anatomy)|iris]], but can also be applied to color variation of [[hair]]<ref>{{cite journal | doi = 10.18295/squmj.2016.17.01.022 | volume=17 | title=Focal Scalp Hair Heterochromia in an Infant | year=2017 | journal=Sultan Qaboos University Medical Journal | pages=e116–118 | author=Kumar P| issue=1 | pmc = 5380409 | pmid=28417041 }}</ref> or [[skin]]. Heterochromia is determined by the production, delivery, and concentration of [[melanin]] (a [[pigment]]). It may be [[Biological inheritance|inherited]], or caused by genetic [[mosaicism]], [[chimerism]], [[disease]], or [[injury]].<ref name="Imesch">{{cite journal |vauthors=Imesch PD, Wallow IH, Albert DM |title=The color of the human eye: a review of morphologic correlates and of some conditions that affect iridial pigmentation throughout life.|journal=Survey of Ophthalmology|volume=41 |issue=Suppl 2 |pages=S117–23 |date=February 1997 |pmid=9154287 |doi=10.1016/S0039-6257(97)80018-5}}</ref> It occurs in humans and certain breeds of domesticated animals.

Heterochromia of the [[eye]] is called '''heterochromia iridum''' (heterochromia between the two eyes) or '''heterochromia iridis''' (heterochromia within one eye). It can be complete, sectoral, or central. In complete heterochromia, one iris is a different color from the other. In sectoral heterochromia, part of one iris is a different color from its remainder. In central heterochromia, there is a ring around the pupil or possibly spikes of different colors radiating from the pupil.

Though multiple causes have been posited, the scientific consensus is that a lack of [[genetic diversity]] is the primary reason behind heterochromia, at least in domestic animals. This is due to a mutation of the genes that determine melanin distribution at the 8-HTP pathway, which usually only become corrupted due to chromosomal homogeneity.<ref name="Loewenstein">{{cite book |author1=Loewenstein, John |author2=Scott Lee |title=Ophthalmology: Just the Facts |publisher=McGraw-Hill |location=New York |year=2004 |isbn=0-07-140332-9 }}</ref> Though common in some breeds of cats, dogs, cattle and horses due to inbreeding, heterochromia is uncommon in humans, affecting fewer than 200,000 people in the United States, and is not associated with lack of genetic diversity.<ref>{{cite journal | author = Konovalova EN, Gladyr EA, Kostiunina OV, Zinovieva LK | year = 2017 | title = Congenital Defects of Beef Cattle and General Principles of their Prevention | journal = Journal of Agriculture and Environment | volume = 2 | issue = 3 | doi = 10.23649/jae.2017.2.3.1 }}</ref><ref>{{cite journal | author = Ur Rehman H | year = 2008 | title = Heterochromia | journal = CMAJ | volume = 179 | issue = 5| pages = 447–448 | doi = 10.1503/cmaj.070497 | pmid = 18725617 | pmc = 2518194 | doi-access = free }}</ref>

The affected eye may be hyperpigmented (hyperchromic) or hypopigmented (hypochromic).<ref name="Loewenstein"/> In humans, an increase of melanin production in the eyes indicates [[hyperplasia]] of the iris tissues, whereas a lack of melanin indicates [[hypoplasia]].

The term is derived from [[Ancient Greek]]: {{lang|grc|ἕτερος}}, {{lang|grc-Latn|héteros}} "different" and {{lang|grc|χρῶμα}}, {{lang|grc-Latn|chrôma}} "color".<ref>{{cite web|url=http://medical-dictionary.thefreedictionary.com/heterochromia+iridis |title=heterochromia iridis - definition of heterochromia iridis in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia |publisher=Medical-dictionary.thefreedictionary.com |access-date=2014-04-27}}</ref>
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==Background==
[[File:Khao Manee Lily (cropped 2).jpg|thumb|[[Khao Manee]] [[odd-eyed cat|cat with complete heterochromia]], and central heterochromia in both eyes.]]
[[Eye color]], specifically the color of the irises, is determined primarily by the concentration and distribution of melanin. Although the processes determining eye color are not fully understood, it is known that inherited eye color is determined by multiple [[genes]]. Environmental or acquired factors can alter these inherited traits.<ref name="Wielgus">{{cite journal |vauthors=Wielgus AR, Sarna T |title=Melanin in human irides of different color and age of donors |journal=Pigment Cell Research|volume=18 |issue=6 |pages=454–64 |date=December 2005 |pmid=16280011 |doi=10.1111/j.1600-0749.2005.00268.x}}</ref>

The color of the mammalian, including human, iris is very variable. However, there are only two pigments present, [[eumelanin]] and [[pheomelanin]]. The overall concentration of these pigments, the ratio between them, variation in the distribution of pigment in the layers of the stroma of the iris and the effects of light scattering all play a part in determining eye color.<ref name="Prota">{{cite journal |vauthors=Prota G, Hu DN, Vincensi MR, McCormick SA, Napolitano A |title=Characterization of melanins in human irides and cultured uveal melanocytes from eyes of different colors |journal=Experimental Eye Research|volume=67 |issue=3 |pages=293–9 |date=September 1998 |pmid=9778410 |doi=10.1006/exer.1998.0518}}</ref> In the United States, July 12 is observed by some as National Different Colored Eyes Day.<ref name="Different Colored Eyes Day">National Day Calendar [https://nationaldaycalendar.com/national-different-colored-eyes-day-july-12/ "National Different Colored Eyes Day - July 12"] {{webarchive|url=https://web.archive.org/web/20230331022026/https://nationaldaycalendar.com/national-different-colored-eyes-day-july-12/|date=2023-03-31}} ''National Day Calendar.'' November 8, 2022. Retrieved July 12, 2023.</ref>

==Classification==
<!--IMAGE-->[[File:Autosomal Dominant Pedigree Chart.svg|thumb|upright 1.3|Congenital heterochromia: inherited in [[autosomal dominant]] fashion (from men or women)]]<!--large enough to read legend-->

Heterochromia is classified primarily by onset: as either [[genetics|genetic]] or acquired. Although a distinction is frequently made between heterochromia that affects an eye completely or only partially (sectoral heterochromia), it is often classified as either genetic (due to [[mosaicism]] or [[congenital]]) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter.<ref name="Swann">Swann P. [http://www.optometry.co.uk/files/b9ef5756eeb28a9f1aca8872fd3f9c07_swann19990129.pdf "Heterochromia."] {{webarchive|url=https://web.archive.org/web/20060108225641/http://www.optometry.co.uk/files/b9ef5756eeb28a9f1aca8872fd3f9c07_swann19990129.pdf|date=2006-01-08}} ''Optometry Today.'' January 29, 1999. Retrieved November 1, 2006.</ref> Most cases of heterochromia are hereditary, or caused by genetic factors such as chimerism, and are entirely benign and unconnected to any pathology, but some are associated with certain diseases and syndromes. Sometimes one eye may change color following disease or injury.<ref>{{cite web|url=https://www.nlm.nih.gov/medlineplus/ency/article/003319.htm|title=Heterochromia: MedlinePlus Medical Encyclopedia|publisher=Nlm.nih.gov|access-date=2014-04-27}}</ref><ref name="Gladstone, R.M. 1969">{{cite journal|author=Gladstone RM|year=1969|title=Development and Significance of Heterochromia of the Iris|journal=Arch Neurol|volume=21|issue=2|pages=184–192|doi=10.1001/archneur.1969.00480140084008|pmid=5797351}}</ref><ref>{{cite journal|author=Guha M, Maity D|year=2014|title=Heterochromia iridis - a case study|journal=Explor Anim Med Res|volume=4|issue=2|pages=240–245}}</ref>

===Genetic===
====Abnormal iris darker====
*[[Lisch nodules]] – iris [[hamartoma]]s seen in [[neurofibromatosis]].
*[[Ocular melanosis]] – a condition characterized by increased pigmentation of the [[uvea (anatomy)|uveal tract]], [[episclera]], and anterior chamber angle.
*[[Oculodermal melanocytosis]] (nevus of Ota)<ref name="Loewenstein"/>
*[[Pigment dispersion syndrome]] – a condition characterized by loss of pigmentation from the posterior iris surface which is disseminated intraocularly and deposited on various intraocular structures, including the anterior surface of the iris.{{medical citation needed|date=January 2016}}
*[[Sturge–Weber syndrome]] – a syndrome characterized by a [[port-wine stain]] nevus in the distribution of the trigeminal nerve, [[ipsilateral]] leptomeningeal angiomas with intracranial calcification and neurologic signs, and angioma of the choroid, often with [[secondary glaucoma]].<ref>{{cite journal |vauthors=van Emelen C, Goethals M, Dralands L, Casteels I |title=Treatment of glaucoma in children with Sturge-Weber syndrome |journal=Journal of Pediatric Ophthalmology and Strabismus|volume=37 |issue=1 |pages=29–34 |date=Jan–Feb 2000 |doi=10.3928/0191-3913-20000101-08 |pmid=10714693}}</ref><ref>{{cite web |url=http://www.answers.com/sturge-weber+syndrome%26r%3D67 |title=Sturge-Weber syndrome: Definition and Much More from Answers.com |publisher=Answers.com<! |access-date=2009-11-19 |archive-date=2011-06-28 |archive-url=https://web.archive.org/web/20110628183610/http://www.answers.com/sturge-weber+syndrome%26r%3D67 |url-status=dead }}</ref>

====Abnormal iris lighter====
[[File:Heterochromia plos.png|thumb|right|Individual with [[Waardenburg syndrome|Waardenburg Syndrome]] Type II exhibiting complete heterochromia iridum]]

*Simple heterochromia – a rare condition characterized by the absence of other ocular or systemic problems. The lighter eye is typically regarded as the affected eye as it usually shows iris [[hypoplasia]]. It may affect an iris completely or only partially.
*[[Horner's syndrome|Congenital Horner's syndrome]]<ref name="Wallis">{{cite journal |vauthors=Wallis DH, Granet DB, Levi L |title=When the darker eye has the smaller pupil |journal=Journal of American Association for Pediatric Ophthalmology and Strabismus|volume=7 |issue=3 |pages=215–6 |date=June 2003 |pmid=12825064 |doi=10.1016/S1091-8531(02)42020-4}}</ref> – sometimes inherited, although usually acquired.
*[[Waardenburg syndrome]]<ref name="Wallis"/> – a syndrome in which heterochromia is expressed as a bilateral iris hypochromia in some cases. A Japanese review of 11 children with albinism found that the condition was present. All had sectoral/partial heterochromia.<ref>{{cite journal |vauthors=Ohno N, Kiyosawa M, Mori H, Wang WF, Takase H, Mochizuki M |title=Clinical findings in Japanese patients with Waardenburg syndrome type 2 |journal=Japanese Journal of Ophthalmology|volume=47 |issue=1 |pages=77–84 |date=Jan–Feb 2003 |pmid=12586183 |doi=10.1016/S0021-5155(02)00629-9}}</ref>
*[[Piebaldism]] – similar to Waardenburg's syndrome, a rare disorder of melanocyte development characterized by a white forelock and multiple symmetrical hypopigmented or depigmented [[macules]].
*[[Hirschsprung's disease]] – a bowel disorder associated with heterochromia in the form of a sector hypochromia. The affected sectors have been shown to have reduced numbers of melanocytes and decreased stromal pigmentation.<ref name="Brazel">{{cite journal |vauthors=Brazel SM, Sullivan TJ, Thorner PS, Clarke MP, Hunter WS, Morin JD |title=Iris sector heterochromia as a marker for neural crest disease |journal=Archives of Ophthalmology|volume=110 |issue=2 |pages=233–5 |date=February 1992 |pmid=1736874 |doi=10.1001/archopht.1992.01080140089033}}</ref>
*[[Incontinentia pigmenti]]<ref name="Loewenstein"/>
*[[Parry–Romberg syndrome]]<ref name="Loewenstein"/>

===Acquired===
[[File:Sled dog on Svalbard with heterochromia.jpg|thumb|right|upright=1.4|An [[Alaskan husky]] sled dog with heterochromia. Huskies are a breed known to have a high incidence of heterochromia.]]

Acquired heterochromia is usually due to injury, inflammation, the use of certain eyedrops that damage the iris,<ref>{{cite journal |author=Liu CSC |title=A case of acquired iris depigmentation as a possible complication of levobunolol eye drops |journal=British Journal of Ophthalmology|volume=83 |issue=12 |pages=1405–6|date=August 1999 |pmid=10660314|doi=10.1136/bjo.83.12.1403c|pmc=1722884}}</ref> or tumors, both benign and malignant.<ref>{{Citation |last1=Lui |first1=Forshing |title=Heterochromia |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK574499/ |access-date=2024-07-22 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=34662013 |last2=Stokkermans |first2=Thomas J.}}</ref>

====Abnormal iris darker====
*Deposition of material
**[[Siderosis]] – iron deposition within ocular tissues due to a penetrating injury and a retained iron-containing, intraocular foreign body.
**[[Hemosiderosis]] – long standing hyphema (blood in the anterior chamber) following blunt trauma to the eye may lead to iron deposition from blood products.
*Certain eyedrops – [[prostaglandin|prostaglandin analogues]] ([[latanoprost]], isopropyl unoprostone, [[travoprost]], and [[bimatoprost]]) are used topically to lower [[intraocular pressure]] in [[glaucoma]] patients. A concentric heterochromia has developed in some patients applying these drugs. {{medical citation needed span|date=January 2016|The stroma around the iris sphincter muscle becomes darker than the peripheral stroma.}} A stimulation of melanin synthesis within iris melanocytes has been postulated.<ref>{{cite journal|title=Mechanism and Clinical Significance of Prostaglandin-Induced Iris Pigmentation|last1=Stjernschantz|first1=Johan W.|last2=Albert|first2=Daniel M.|author2-link=Daniel M. Albert|last3=Hu|first3=Dan-Ning|last4=Drago|first4=Filippo|author4-link=Filippo Drago (pharmacologist)|last5=Wistrand|first5=Per J.|journal=[[Survey of Ophthalmology]]|date=August 2002|volume=47|pages=S162–S175|doi=10.1016/S0039-6257(02)00292-8|pmid=12204714}}</ref>
*[[Neoplasm]] – Nevi and melanomatous tumors.
*Iridocorneal endothelium syndrome<ref name="Loewenstein"/>
*Iris ectropion syndrome<ref name="Loewenstein"/><ref>{{cite book |last1=Sridhar |first1=Uma |last2=Tripathy |first2=Koushik |title=StatPearls |date=January 2023  |publisher=StatPearls Publishing, Treasure Island, FL |url=https://www.ncbi.nlm.nih.gov/books/NBK580493/ |chapter=Iris Ectropion Syndrome|pmid=35593818 }}</ref>

====Abnormal iris lighter====
*[[Fuchs heterochromic iridocyclitis]] – a condition characterized by a low grade, asymptomatic [[uveitis]] in which the iris in the affected eye becomes hypochromic and has a washed-out, somewhat moth eaten appearance. The heterochromia can be very subtle, especially in patients with lighter colored irides. It is often most easily seen in daylight. The prevalence of heterochromia associated with Fuchs has been estimated in various studies<ref>{{cite journal |vauthors=Yang P, Fang W, Jin H, Li B, Chen X, Kijlstra A |title=Clinical features of Chinese patients with Fuchs' syndrome |journal=Ophthalmology|volume=113 |issue=3 |pages=473–80 |date=March 2006 |pmid=16458965 |doi=10.1016/j.ophtha.2005.10.028}}</ref><ref>{{cite journal |vauthors=Arellanes-Garcia L, del Carmen Preciado-Delgadillo M, Recillas-Gispert C |title=Fuchs' heterochromic iridocyclitis: clinical manifestations in dark-eyed Mexican patients |journal=Ocular Immunology and Inflammation|volume=10 |issue=2 |pages=125–31 |date=June 2002 |pmid=12778348 |doi=10.1076/ocii.10.2.125.13976|s2cid=21171244 }}</ref><ref name="Tabbut">{{cite journal |vauthors=Tabbut BR, Tessler HH, Williams D |title=Fuchs' heterochromic iridocyclitis in blacks |journal=Archives of Ophthalmology|volume=106 |issue=12 |pages=1688–90 |date=December 1988 |pmid=3196209 |doi=10.1001/archopht.1988.01060140860027}}</ref> with results suggesting that there is more difficulty recognizing iris color changes in dark-eyed individuals.<ref name="Tabbut"/><ref>{{cite journal |author=Bloch-Michel E |language=fr |title=Fuchs heterochromic cyclitis: current concepts |journal=Journal Français d'Ophtalmologie|volume=6 |issue=10 |pages=853–8 |year=1983 |pmid=6368659}}</ref>
*[[Horner's syndrome|Acquired Horner's syndrome]] – usually acquired, as in [[neuroblastoma]],<ref>{{cite journal |vauthors=Mehta K, Haller JO, Legasto AC |title=Imaging neuroblastoma in children |journal=Critical Reviews in Computed Tomography|volume=44 |issue=1 |pages=47–61 |year=2003 |pmid=12627783 |doi=10.1080/10408370390808469}}</ref> although sometimes inherited.
*[[Neoplasm]] – [[Melanoma]]s can also be very lightly pigmented, and a lighter colored iris may be a rare manifestation of metastatic disease to the eye.
*[[Parry–Romberg syndrome]] – due to tissue loss.<ref name=GARD>{{cite web |title= Heterochromia iridis |author=[[Genetic and Rare Diseases Information Center]] (GARD)|url=https://rarediseases.info.nih.gov/diseases/8590/heterochromia-iridis}}</ref>
Heterochromia has also been observed in those with [[Duane syndrome]].<ref>{{cite journal |vauthors=Khan AO, Aldamesh M |title=Bilateral Duane syndrome and bilateral aniridia |journal=Journal of American Association for Pediatric Ophthalmology and Strabismus|volume=10 |issue=3 |pages=273–4 |date=June 2006 |pmid=16814183 |doi=10.1016/j.jaapos.2006.02.002}}</ref><ref>{{cite journal |vauthors=Shauly Y, Weissman A, Meyer E |title=Ocular and systemic characteristics of Duane syndrome |journal=Journal of Pediatric Ophthalmology and Strabismus|volume=30 |issue=3 |pages=178–83 |date=May–Jun 1993 |doi=10.3928/0191-3913-19930501-12 |pmid=8350229}}</ref>
*Chronic [[iritis]]<ref name="Loewenstein"/>
*Juvenile [[xanthogranuloma]]<ref name="Loewenstein"/>
*[[Leukemia]] and [[lymphoma]]<ref name="Loewenstein"/>

===Partial heterochromia – different colors in the same iris===
Partial heterochromia is most often a benign trait of genetic origins, but, like complete heterochromia, can be acquired or be related to clinical syndromes.
[[File:Sectoral heterochromia in left eye.png|thumb|right|Sectoral heterochromia]]

====Sectoral====
In sectoral heterochromia, areas of the same iris contain two different colors, the contrasting colors being demarcated in a radial, or sectoral, manner. Sectoral heterochromia may affect one or both eyes.<ref>{{cite web |title=Heterochromia iridis |url=https://rarediseases.info.nih.gov/diseases/8590/heterochromia-iridis |website=Genetic and Rare Diseases Information Center (GARD) – an NCATS Program |publisher=NIH |access-date=9 February 2019 |date=8 April 2015}}</ref>
It is unknown how rare sectoral heterochromia is in humans, but it is considered to be less common than complete heterochromia.

====Central====
[[File:Liv Agar central heterochromia.jpg|thumb|Central heterochromia, blue with brown]]
Central heterochromia is also an eye condition where there are two colors in the same iris; but the arrangement is concentric, rather than sectoral. The central (pupillary) zone of the iris is a different color than the mid-peripheral (ciliary) zone. Central heterochromia is more noticeable in irises containing low amounts of [[melanin]].<ref>{{cite journal|title=Iris pigmentation as a quantitative trait: variation in populations of European, East Asian and South Asian ancestry and association with candidate gene polymorphisms|last1=Edwards|first1=Melissa|last2=Cha|first2=David|last3=Krithika|first3=S.|last4=Johnson|first4=Monique|last5=Cook|first5=Gillian|last6=Parra|first6=Esteban J.|journal=[[Pigment Cell & Melanoma Research]]|date=2015-11-07|volume=29|issue=2|pages=156|doi=10.1111/pcmr.12435|pmid=26547379|doi-access=free}}</ref>

==In history and culture==
Heterochromia of the eye was first described as a human condition by [[Aristotle]], who termed it ''heteroglaucos''.<ref name="Gladstone, R.M. 1969" />

Notable historical figures thought to have heterochromia include the [[Byzantine emperor]] [[Anastasius I Dicorus|Anastasius the First]], dubbed ''dikoros'' (Greek for 'having two pupils'). "His right eye was light blue, while the left was black, nevertheless his eyes were most attractive", is the description of the historian [[John Malalas]].<ref>{{Cite journal|last=Baldwin|first=Barry|title=Physical Descriptions of Byzantine Emperors|date=1981|journal=Byzantion|volume=51|issue=1|pages=8–21|jstor=44170668|issn=0378-2506}}</ref><ref>{{Cite journal|last1=Fronimopoulos|first1=John|last2=Lascaratos|first2=John|date=1992-03-01|title=Some Byzantine chroniclers and historians on ophthalmological topics|journal=Documenta Ophthalmologica|language=en|volume=81|issue=1|pages=121–132|doi=10.1007/BF00155022|pmid=1473460|s2cid=26240821|issn=1573-2622}}</ref><ref>Head, C. (1980)"PHYSICAL DESCRIPTIONS OF THE EMPERORS IN BYZANTINE HISTORICAL WRITING", ''Byzantion'', Vol. 50, No. 1 (1980), pp. 226-24, Peeters Publishers, p. 229</ref> A more recent example is the German poet, playwright, novelist, scientist, statesman, theatre director, and critic, [[Johann Wolfgang Goethe]].<ref>Friedenthal, Richard (1963). [https://books.google.com/books?id=zK3q-R6RHYkC&pg=PA472&dq=%22blue+ring%22 ''Goethe: His Life and Times'']. Transaction Publishers. p. 472. {{ISBN|978-1-412-84321-8}}.</ref>

The ''[[Alexander Romance]]'', an early literary treatment of the life of [[Alexander the Great]], attributes heterochromia to him. In it he is described as having one eye light and one eye dark. However, no ancient historical source mentions this. It is used to emphasise the otherworldly and heroic qualities of Alexander.<ref>Nawotka, Krzysztof (2010) ''Alexander the Great'', Cambridge Scholarship Publishing, {{ISBN|9781443818117}}, p. 44</ref><ref>Boardman, J. (2019) ''Alexander the Great: From His Death to the Present Day'', Princeton University Press, Princeton N.J., p. 40</ref>

In the [[Ars Amatoria]], the Roman poet [[Ovid]] describes the witch Dipsas as having 'double pupils'. Kirby Flower Smith suggested that this could be understood as heterochromia, though other scholars have disagreed. The Roman jurist and writer [[Cicero]] also mentions the same feature of 'double pupils' as being found in some [[Italic peoples|Italic]] women. [[Pliny the Elder]] related this feature to the concept of 'the [[evil eye]]'.<ref>Alvar Nuño, A. (2012) "Ocular Pathologies and the Evil Eye in the Early Roman Principate", '' Numen'', Vol. 59, No. 4 (2012), pp. 295-321, pp. 299-301</ref>

The twelfth-century scholar [[Eustathius of Thessalonica|Eustathius]], in his commentary on the Iliad, reports a tradition in which the [[Thracians|Thracian]] [[Thamyris]] (son of the nymph [[Argiope (mythology)|Argiope]]), who was famed for his musical abilities, had one eye that was grey, whilst the other was black. W. B. McDaniel suggests that this should be interpreted as heterochromia.<ref>McDaniel, W,B. (1918) "The Pupula Duplex and Other Tokens of an "Evil Eye" in the Light of Ophthalmology", ''Classical Philology'', Vol. 13, No. 4 (Oct., 1918), pp. 335-346, The University of Chicago Press, p.338</ref>

==In other animals==
{{see also|Odd-eyed cat}}
[[File:Angoraturco.jpg|thumb|A [[Turkish Angora]] cat with complete heterochromia.]]
Although infrequently seen in humans, complete heterochromia is more frequently observed in species of domesticated mammals. The blue eye occurs within a white spot, where melanin is absent from the skin and hair (see [[Leucism]]). These species include the [[cat]], particularly breeds such as [[Turkish Van]], [[Khao Manee]] and (rarely) [[Japanese Bobtail]]. These so-called [[odd-eyed cat]]s are white, or mostly white, with one normal eye (copper, orange, yellow, green), and one blue eye. Among [[dog]]s, complete heterochromia is seen often in the [[Siberian Husky]] and few other breeds, usually [[Australian Shepherd]] and [[Catahoula Cur|Catahoula Leopard Dog]] and rarely in [[Shih Tzu]]. Horses with complete heterochromia have one brown and one white, gray, or blue eye—complete heterochromia is more common in horses with [[pinto horse|pinto]] coloring. Complete heterochromia occurs also in [[cattle]] and even [[Domestic Asian Water Buffalo|water buffalo]].<ref>{{cite journal |vauthors=Misk NA, Semieka MA, Fathy A |title=Heterochromia iridis in water buffaloes (''Bubalus bubalis'') |journal=Veterinary Ophthalmology|volume=1 |issue=4 |pages=195–201 |year=1998 |pmid=11397231 |doi=10.1046/j.1463-5224.1998.00036.x}}</ref> It can also be seen in ferrets with [[Waardenburg syndrome]], although it can be very hard to tell at times as the eye color is often a midnight blue.

Sectoral heterochromia, usually sectoral hypochromia, is often seen in [[dog]]s, specifically in breeds with [[merle (coat color in dogs)|merle]] coats. These breeds include the [[Australian Shepherd]], [[Border Collie]], [[Collie]], [[Shetland Sheepdog]], [[Welsh Corgi]], [[Pyrenean Shepherd]], [[Mudi]], [[Beauceron]], [[Catahoula Cur]], [[Dunker]], [[Great Dane]], [[Dachshund]] and [[Chihuahua (dog)|Chihuahua]]. It also occurs in certain breeds that do not carry the merle trait, such as the [[Siberian Husky]], [[Dalmatian dog|Dalmatian]], and rarely, [[Shih Tzu]]. There are examples of cat breeds that have the condition such as [[Van cat]].<ref name="Turkish Van Cats">{{cite web |url= http://cats.animal-world.com/Natural-Breeds/TurkishVanCat.php |archive-url= https://web.archive.org/web/20130913063521/http://cats.animal-world.com/Natural-Breeds/TurkishVanCat.php |url-status= dead |archive-date= September 13, 2013 |title=Turkish Van Cats |access-date=8 April 2014}}{{tertiary}} </ref>

==See also==
<!-- Do NOT add fictional characters to this list, there are too many of them. -->
{{columns-list|colwidth=30em|
* [[Brushfield spots]]
* [[Coloboma]]
* [[Erythrism]]
* [[List of people with heterochromia]]
* [[List of systemic diseases with ocular manifestations]]
}}

==References==
{{reflist}}

==External links==
*{{commonscatinline}}
{{Medical resources
| ICD10       = {{ICD10|Q13.2}}, {{ICD10|H20.8}}, {{ICD10|L67.1}}
| ICD9        = {{ICD9|364.53}}
|DiseasesDB=31289
| OMIM        = 142500
| MedlinePlus = 003319
| MeSH        = C538115
}}
{{Eye pathology}}
{{Pigmentation disorders}}
{{Medicine}}

[[Category:Disturbances of pigmentation]]
[[Category:Eye color]]
[[Category:Eye diseases]]
[[Category:Genodermatoses]]
[[Category:Medical signs]]