What is Heterochromia?
Heterochromia, or heterochromia iridum, refers to a condition where the two irises (the colored part of your eyes) are different colors. This can affect the entire iris or just a part of it.
Knowing the anatomy of the iris helps to understand what determines its color. The iris and a part known as the ciliary body form the front part of the uveal coat, which is the middle layer of the eye. The iris has two layers, both containing pigment. The front layer, called the iris stroma, is made of loose connective tissue and melanocytes, which are cells that produce the pigment. This pigment, along with other cells, is contained in a structure known as melanosomes. The color of your eyes is determined by the number of these structures and the amount of pigment they contain.
The type of pigment also affects eye color. There are two main types, eumelanin (brown to black pigment) and pheomelanin (red to yellow pigment). The specific type and amount of these pigments in the iris determines eye color. As we age, a yellow pigment called lipofuscin can accumulate in the iris.
Genetics also plays a big role in determining eye color, with as many as 150 genes involved. Two genes, OCA2 and HERC2, on chromosome 15, have a significant impact. OCA2 produces a protein that aids the maturation of melanosomes, and HERC2 controls OCA2. Eye color is largely determined by two more genes, EYCL1 and EYCL3. However, as many other genes also play a role, this can sometimes result in unexpected eye colors. Heterochromia can be inherited in certain cases, but often it occurs when genetic changes take place during cell division, creating an organism with genetically different cells.
The color of the eyes can change during a baby’s first year, especially between 3 and 6 months. Sometimes, certain conditions and injuries can cause changes in eye color or create the impression of different eye colors. Other factors, like light conditions, can also affect the appearance of the iris.
Finally, in addition to color, the iris tissue forms distinct patterns, much like fingerprints. These patterns can be used for automatic personal identification.
What Causes Heterochromia?
Most of the time, heterochromia, which is when a person has two different colored eyes, doesn’t have any real impact on a person’s health or well-being.
However, in some cases, heterochromia can be an indication of other health conditions present from birth. One of these is a condition called congenital Horner syndrome. This condition can cause other symptoms too, such as a small pupil, drooping eyelid, and decreased sweating on one side of the face. But these symptoms don’t have to be present for someone to be diagnosed with congenital Horner syndrome.
The color of our eyes comes from cells called iris stromal melanocytes, which develop from neurocrest cells in the womb. These cells are also responsible for the neurons that control our response to stress. Sometimes, if the path of these neurons is disrupted to the melanocytes in the eye, particularly early in life, it can result in having less brown pigment in one eye causing heterochromia.
Conditions that interrupts the development and migration of neurocrest cells, like Waardenburg syndrome and Parry-Romberg syndrome, can also contribute to heterochromia. Other health conditions related to birth that can cause heterochromia include ocular melanosis and certain neurocutaneous syndromes like Sturge-Weber syndrome.
Additionally, there are several other health conditions that are linked to heterochromia. For example, Waardenburg syndrome can cause hearing loss and abnormalities in facial features besides heterochromia. Parry-Romberg syndrome is associated with changes in the skin and tissues on one side of the face.
Sturge-Weber syndrome may cause a facial birthmark and complications in the brain lining. People with this syndrome may experience one-sided neurological issues, seizures, and a large facial birthmark. The eye on the same side of the face may exhibit unusual pigmentation, and glaucoma, which is a group of eye conditions that damage the optic nerve, isn’t uncommon.
Neurofibromatosis type I, or von Recklinghausen disease, can cause unusual growths in the iris and other clinical features and increase the risk of tumors in the optic nerve, which can be detected through an eye exam if a red reflection cannot be seen in one eye. Oculodermal melanocytosis refers to an unusual amount of pigmentation in the skin and eyes.
There are other causes of heterochromia that aren’t present at birth and can develop later in life, these include: acquired Horner syndrome, tumors such as neuroblastoma or neurilemmoma, eye injuries, inflammation of the iris and ciliary body (Fuchs heterochromic iridocyclitis), objects stuck in the eye including colored contact lenses, iron deposition in the eye, infiltration of melanocytes in the eye which can suggest a benign mole or skin cancer, local iris tumors, and certain types of eye drops.
Risk Factors and Frequency for Heterochromia
Heterochromia, which is not common, is a condition for which no widely accepted prevalence rate has been reported.
Signs and Symptoms of Heterochromia
The process of diagnosing eye issues revolves around two critical aspects: patient history and a physical examination.
When it comes to history, doctors look to categorize the onset of symptoms as either sudden (acute), slowly developing (subacute), or long-term (chronic). This helps in distinguishing between localized eye diseases and conditions caused by genetic factors. For instance, progressive facial hemiatrophy often indicates Parry-Romberg syndrome. Doctors will also inquire about symptoms like eye pain, redness, or visual problems, which could indicate local eye diseases. Besides, the history of trauma and eye drops use, particularly in one eye, can be relevant. Family history, such as a family member having neurofibromatosis type I is also informative.
In terms of physical examination, a look at old photographs, particularly those from childhood, might prove useful. The doctor will be searching for signs of heterochromia (differently colored eyes) or symptoms of Horner syndrome, like partial drooping of the eyelid (ptosis) and smaller pupil size (miosis). In addition, other signs related to specific syndromes, such as cutaneous neurofibromatosis, facial hemiatrophy, facial birthmarks (port-wine stains), hearing loss, and unusual facial features will be checked for. Lastly, a thorough examination of the eye itself, notably the iris, anterior chamber, pupil size and response, corneal conditions, and measurement of the pressure within the eye can provide key information.
- Differentiating the nature of symptom onset: acute, subacute, or chronic
- Noting the presence of eye symptoms like pain, redness, and visual disturbances
- History of trauma or use of eye drops
- Family history of neurofibromatosis type I
- Reviewing old photos to look for heterochromia or signs of Horner syndrome
- Observing signs of specific syndromes
- Careful examination of the eye itself
Testing for Heterochromia
If your doctor suspects you have Horner Syndrome, you might need an eye examination by an eye specialist, an ophthalmologist. They will use a tool called a slit lamp to examine your eyes. This examination is important as it helps the doctor look for other indicators of Horner Syndrome.
In addition to the eye exam, your doctor may also order specific urine tests such as catecholamines and VMA tests. These tests measure the activity of your sympathetic nervous system, which is often elevated in conditions like neuroblastoma (a type of cancer that mostly affects children) and various tumors originating from nerve tissue. These tests are helpful, especially in children, to rule out the likelihood of these types of cancers.
Computerized Tomography (CT) scans of the chest and abdomen can also be done to help find the cause of Horner syndrome or check for neuroblastoma or other tumors, especially in children and infants. Other types of CT scans, such as CT angiogram and CT skull base, can be done to check for underdevelopment of the internal carotid artery (a major blood vessel in the head and neck), which could indicate congenital Horner syndrome, or signs of a carotid dissection (a tear in the inner layer of the carotid artery), which could be a sign of chronic acquired Horner syndrome.
Most times, if your eyes are different colors (a condition known as heterochromia) but there are no other strange findings upon physical examination, you might just have harmless heterochromia. If that’s the case, you usually don’t need any further evaluation and can simply be reassured by your doctor that there’s nothing to worry about.
Treatment Options for Heterochromia
Heterochromia is a condition where the eyes have different colors, but it’s not a disease in itself. Instead, it’s a sign that there may be an underlying health issue, and that’s where treatment would typically be focused. For example, it could be related to other conditions affecting the eye.
If heterochromia comes with other symptoms like small pupils (miosis) and a slight drooping of the upper eyelid (partial ptosis), it may be due to a condition called Horner syndrome. When this condition is present from birth, it’s usually of no concern and doesn’t need any treatment. However, if it appears in early childhood it could be a sign of a tumor in the sympathetic nervous system, specifically a neuroblastoma. This would require immediate medical attention to make a diagnosis and start treatment.
In contrast, if heterochromia and Horner syndrome appear in adulthood, it usually indicates a long-term disease that’s not likely to be cancerous.
What else can Heterochromia be?
Heterochromia is a medical condition that can be a sign of various issues. When a doctor is trying to determine the cause of heterochromia, they’ll consider the following potential causes:
- Benign isolated heterochromia, which means the condition is harmless and not connected to any other issues
- Congenital Horner syndrome, a condition present from birth
- Horner syndrome that started before the two years of age
- Horner syndrome that has persisted for a long time
- Heterochromia that’s tied to other conditions that are present from birth
- Diseases affecting the eye and the colored part of the eye (the iris), such as Fuchs heterochromic iridocyclitis and melanoma
What to expect with Heterochromia
The future health impacts of heterochromia, or having two different colored eyes, really depends on why it’s happening. It’s crucial, especially in babies and children, to rule out certain serious conditions such as neoplasias (tumors) in the sympathetic chain—a part of the nervous system. One example is neuroblastoma, a type of cancer that can have severe outcomes if it’s diagnosed and treated late.
Another condition to think about is Fuchs heterochromic iridocyclitis, which can risk a person’s vision because it can lead to glaucoma, a condition that causes damage to your eye’s optic nerve and gets worse over time. Some people with heterochromia might have a melanoma, a type of skin cancer, in their iris—the colored part of the eye.
Most of the time, the cause of heterochromia isn’t anything to worry about—it’s simply a harmless difference in eye color. Another common cause is congenital Horner’s syndrome, a condition that a person is born with that usually doesn’t cause serious health problems.
Possible Complications When Diagnosed with Heterochromia
Heterochromia, a condition where the eyes are different colors, is not harmful. It is a clinical sign but does not cause any health issues on its own.
