color
Color (or colour in English in the Commonwealth of Nations, Commonwealth English; American and British English spelling differences#-our, -or, see spelling differences) is the visual perception based on the electromagnetic spectrum. Though co ...
ation most often used to describe color differences of the iris, but can also be applied to color variation of
hair
Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals.
The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and ...
or
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
. Heterochromia is determined by the production, delivery, and concentration of
melanin
Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes.
There are ...
(a
pigment
A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub ...
disease
A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
, or
injury
Injury is physiological damage to the living tissue of any organism, whether in humans, in other animals, or in plants.
Injuries can be caused in many ways, including mechanically with penetration by sharp objects such as teeth or with ...
. 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
Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species. It ranges widely, from the number of species to differences within species, and can be correlated to the span of survival for a species. It is d ...
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. 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.
The affected eye may be hyperpigmented (hyperchromic) or hypopigmented (hypochromic). In humans, an increase of melanin production in the eyes indicates
hyperplasia
Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of Tissue (biology), organic tissue that results from ...
of the iris tissues, whereas a lack of melanin indicates
hypoplasia
Hypoplasia (; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.Ancient Greek
Ancient Greek (, ; ) includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Greek ...
: , "different" and , "color".
Background
Eye color
Eye color is a polygene, polygenic phenotypic trait determined by two factors: the pigmentation of the eye's Iris (anatomy), iris and the frequency-dependence of the scattering of light by the Turbidity, turbid medium in the Stroma of iris, str ...
, 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
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. Environmental or acquired factors can alter these inherited traits.
The color of the mammalian, including human, iris is very variable. However, there are only two pigments present, eumelanin and
pheomelanin
Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the Biological pigment, pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melan ...
. 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. In the United States, July 12 is observed by some as National Different Colored Eyes Day.National Day Calenda "National Different Colored Eyes Day - July 12" ''National Day Calendar.'' November 8, 2022. Retrieved July 12, 2023.
Classification
Heterochromia is classified primarily by onset: as either 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
A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...
) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter.Swann P "Heterochromia." ''Optometry Today.'' January 29, 1999. Retrieved November 1, 2006. 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.
*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
Hypoplasia (; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.Congenital Horner's syndrome – sometimes inherited, although usually acquired.
*
Waardenburg syndrome
Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...
– 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.
* 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.
* Incontinentia pigmenti
* Parry–Romberg syndrome
Acquired
Acquired heterochromia is usually due to injury, inflammation, the use of certain eyedrops that damage the iris, or tumors, both benign and malignant.
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 analogues ( latanoprost, isopropyl unoprostone, travoprost, and bimatoprost) are used topically to lower intraocular pressure in
glaucoma
Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
patients. A concentric heterochromia has developed in some patients applying these drugs. A stimulation of melanin synthesis within iris melanocytes has been postulated.
*
Neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
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 with results suggesting that there is more difficulty recognizing iris color changes in dark-eyed individuals.
* Acquired Horner's syndrome – usually acquired, as in neuroblastoma, although sometimes inherited.
*
Neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
–
Melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
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.
Heterochromia has also been observed in those with Duane syndrome.
*Chronic iritis
*Juvenile xanthogranuloma
*
Leukemia
Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
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.
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.
It is unknown how rare sectoral heterochromia is in humans, but it is considered to be less common than complete heterochromia.
Central
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
Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes.
There are ...
.
In history and culture
Heterochromia of the eye was first described as a human condition by
Aristotle
Aristotle (; 384–322 BC) was an Ancient Greek philosophy, Ancient Greek philosopher and polymath. His writings cover a broad range of subjects spanning the natural sciences, philosophy, linguistics, economics, politics, psychology, a ...
, who termed it ''heteroglaucos''.
Notable historical figures thought to have heterochromia include the
Byzantine emperor
The foundation of Constantinople in 330 AD marks the conventional start of the Eastern Roman Empire, which Fall of Constantinople, fell to the Ottoman Empire in 1453 AD. Only the emperors who were recognized as legitimate rulers and exercised s ...
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. A more recent example is the German poet, playwright, novelist, scientist, statesman, theatre director, and critic, Johann Wolfgang Goethe.
The '' Alexander Romance'', an early literary treatment of the life of
Alexander the Great
Alexander III of Macedon (; 20/21 July 356 BC – 10/11 June 323 BC), most commonly known as Alexander the Great, was a king of the Ancient Greece, ancient Greek kingdom of Macedonia (ancient kingdom), Macedon. He succeeded his father Philip ...
, 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.
In the Ars Amatoria, the Roman poet
Ovid
Publius Ovidius Naso (; 20 March 43 BC – AD 17/18), known in English as Ovid ( ), was a Augustan literature (ancient Rome), Roman poet who lived during the reign of Augustus. He was a younger contemporary of Virgil and Horace, with whom he i ...
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
Marcus Tullius Cicero ( ; ; 3 January 106 BC – 7 December 43 BC) was a Roman statesman, lawyer, scholar, philosopher, orator, writer and Academic skeptic, who tried to uphold optimate principles during the political crises tha ...
also mentions the same feature of 'double pupils' as being found in some Italic women.
Pliny the Elder
Gaius Plinius Secundus (AD 23/24 79), known in English as Pliny the Elder ( ), was a Roman Empire, Roman author, Natural history, naturalist, and naval and army commander of the early Roman Empire, and a friend of the Roman emperor, emperor Vesp ...
related this feature to the concept of 'the
evil eye
The evil eye is a supernatural belief in a curse brought about by a malevolent glaring, glare, usually inspired by envy. Amulets to Apotropaic, protect against it have been found dating to around 5,000 years ago.
It is found in many cultures i ...
'.
The twelfth-century scholar Eustathius, in his commentary on the Iliad, reports a tradition in which the
Thracian
The Thracians (; ; ) were an Indo-European speaking people who inhabited large parts of Southeast Europe in ancient history.. "The Thracians were an Indo-European people who occupied the area that today is shared between north-eastern Greece, ...
Thamyris
In Greek mythology, Thamyris (Ancient Greek: Θάμυρις, ''Thámuris'') was a Thrace, Thracian singer. He is notable in Greek mythology for reportedly being a lover of Hyacinth (mythology), Hyacinth and thus to have been the first male to hav ...
(son of the nymph 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.
In other animals
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 cats are white, or mostly white, with one normal eye (copper, orange, yellow, green), and one blue eye. Among dogs, complete heterochromia is seen often in the Siberian Husky and few other breeds, usually Australian Shepherd and 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 coloring. Complete heterochromia occurs also in
cattle
Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
and even
water buffalo
The water buffalo (''Bubalus bubalis''), also called domestic water buffalo, Asian water buffalo and Asiatic water buffalo, is a large bovid originating in the Indian subcontinent and Southeast Asia. Today, it is also kept in Italy, the Balkans ...
. It can also be seen in ferrets with
Waardenburg syndrome
Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...
Dachshund
The dachshund ( or ; German: 'badger dog'), also known as the wiener dog or sausage dog, badger dog, doxen and doxie, is a short-legged, long-bodied, hound-type dog breed. The dog may be smooth-haired, wire-haired, or long-haired, with varie ...
and Chihuahua. It also occurs in certain breeds that do not carry the merle trait, such as the Siberian Husky, Dalmatian, and rarely, Shih Tzu. There are examples of cat breeds that have the condition such as Van cat.