Why Does Jaundice Turn the Eyes Yellow? The Science Behind Bilirubin

Key Takeaways

• Jaundice turns the eyes and skin yellow because excess bilirubin, a byproduct of red blood cell breakdown, builds up and deposits in body tissues.

• The eyes yellow first because the elastin-rich, blood-vessel-rich tissue around them binds bilirubin more readily than skin does.

• What looks like a yellow sclera is more accurately yellowing of the conjunctiva, the thin membrane covering the sclera, based on decades of histological evidence.

• Visible eye yellowing typically appears once bilirubin crosses about 3 mg/dL.

• Carotenemia from beta-carotene-rich foods can yellow the skin but not the eyes, a useful clue that it is not jaundice.

Jaundice turns the eyes yellow because a pigment called bilirubin builds up in the blood and binds strongly to elastin, a stretchy protein found in the tissue around the eyes. Before it is processed by the liver, unconjugated bilirubin is fat soluble (lipophilic). Bilirubin has long been observed to preferentially accumulate in elastin-rich tissues such as the conjunctiva, although the exact molecular basis of this affinity has not been fully established. Because the conjunctiva is rich in elastin and has a dense blood supply, it picks up a yellow tint earlier and more visibly than the skin does.

This article breaks down how that happens, what it means when the eyes turn yellow, and a long-standing medical debate over which part of the eye is actually responsible.

What Is Bilirubin, and Where Does It Come From?

Bilirubin is a yellowish-orange compound produced daily as the body breaks down and recycles red blood cells. Red blood cells transport oxygen throughout the body with the help of a protein called hemoglobin.

When the red blood cells become old after about 120 days of functioning, the hemoglobin component of these cells breaks down into a green compound called biliverdin which is converted to bilirubin.

At this point, bilirubin is said to be in an “unconjugated” form meaning that it hasn’t yet been processed by the liver and therefore is insoluble in water and is transported through the blood stream bound to a protein carrier known as albumin.

Bilirubin is processed by the liver where it undergoes further metabolism to convert into a “conjugated” form (which is water soluble) and excreted via bile as digestive fluids and eliminated from the body through the intestines resulting in dark brown stool.

The buildup of bilirubin results in jaundice and happens when too much bilirubin is produced or when the processing capability of the liver or bile ducts is insufficient for the amount of bilirubin present. The bilirubin leaks from the blood to adjacent tissues, including the eyes and the skin.

Bilirubin is tested as a part of liver function tests as Total Bilirubin, Direct/ Conjugated Bilirubin and Indirect/ Unconjugated Bilirubin, along the AST and ALT to assess if any injury has occurred to the liver

Why Do the Eyes Turn Yellow Before the Skin in Jaundice?

The area often called the “white of the eye” turns yellow first because of a protein called elastin, which grabs onto bilirubin more readily than most other tissues do. Elastin is the protein that gives many tissues, including skin, blood vessels, and the tissue around the eyes, their stretch and recoil.

Bilirubin has a strong chemical attraction to elastin. Because unconjugated bilirubin is lipophilic before liver processing, it preferentially accumulates in tissues containing abundant elastin. The tissue covering the white of the eye is unusually rich in elastin and also has a denser blood supply than skin on most other parts of the body. That combination means it receives more bilirubin-carrying blood and stains faster and more visibly, often becoming noticeably yellow at bilirubin levels still too low to color the skin.

During a physical examination, clinicians often inspect the eyes first because subtle jaundice becomes visible there earlier than on the skin, particularly in people with darker skin tones or under variable lighting conditions.

Is It Really the Sclera that Changes Yellow? The “Scleral Icterus” Misnomer

Doctors have long called this sign “scleral icterus,” but Cleveland Clinic notes that the tougher white layer of the eye, called the sclera, barely absorbs bilirubin at all, even though the term remains the more commonly used one.⁶ The yellowing actually happens mainly in a different structure: a thin, clear, moist membrane called the conjunctiva.

The sclera is the tough, white outer wall of the eyeball itself, and it has relatively few blood vessels. The conjunctiva is the thin, transparent membrane that lies over the sclera and lines the inside of the eyelids. It is rich in both elastin and blood vessels, which is exactly the combination that attracts and holds onto bilirubin.

This distinction is not new. In 1979, ophthalmologists Tripathi and Sidrys examined eye tissue from jaundiced patients under the microscope and found almost no bilirubin staining within the sclera itself, even in a case where blood bilirubin was extremely high.¹

In 2001, physician John Kuiper published a case in the Annals of Internal Medicine showing a patient with localized eyelid swelling in whom the yellow tint appeared only over the swollen, blood-vessel-rich conjunctiva, with the surrounding sclera remaining unaffected.²

Some clinicians have since argued that “conjunctival icterus” is the more accurate term. In practice, “scleral icterus” remains the term used in textbooks and patient charts, largely because the visible sign looks the same to the examining eye either way.

At What Bilirubin Level Do the Eyes Actually Turn Yellow?

Doctors can usually see yellowing of the eyes once blood bilirubin rises above roughly 3 mg/dL (milligrams per deciliter), about three times the normal upper limit.³ Below that threshold, elevated bilirubin may still show up on a blood test without being visible to the eye.

The greenish tinge seen in severe, longstanding jaundice comes from biliverdin, the same greenish pigment bilirubin is made from. This pigment is responsible for the green color of an old bruise as it heals.

What Causes the Bilirubin Buildup in the First Place?

Jaundice happens when bilirubin production outpaces the liver's ability to clear it, or when something blocks its exit from the body. Doctors group the causes into three categories based on where in the process the problem lies:

1. Prehepatic (before the liver): too much red blood cell breakdown overwhelms a normal liver, as can happen in certain types of anemia.

2. Hepatic (in the liver): the liver itself is damaged or inflamed and cannot process bilirubin normally, as in hepatitis or cirrhosis.

3. Posthepatic (after the liver): bile ducts that carry processed bilirubin out of the body become blocked, for example by gallstones or a tumor.

Yellow Eyes Without Jaundice: Carotenemia and Other Look-Alikes

Eating large amounts of beta-carotene-rich foods, such as carrots, pumpkin, or squash, can turn the skin yellow-orange without raising bilirubin at all. This harmless condition is called carotenemia, and importantly, it does not turn the eyes yellow.

The excess carotene pigment deposits in the outer, fatty layer of the skin rather than in the conjunctiva, so the eyes stay white. This makes eye color a genuinely useful way to tell carotenemia apart from true jaundice at a glance, though a blood test is still the reliable way to confirm either.

Is Bilirubin Only Bad? A Newer Layer to the Science

For decades, bilirubin was viewed only as a waste product the body needed to get rid of. Research over the past few decades has found it also acts as a natural antioxidant, a substance that helps protect cells from a type of ongoing chemical damage called oxidative stress, caused by unstable molecules known as free radicals.

In a landmark 1987 study published in Science, researchers showed that bilirubin efficiently neutralizes these damaging molecules in laboratory experiments, in some conditions performing better than vitamin E, a well-known antioxidant.⁴

A more recent study published in Scientific Reports, part of the Nature portfolio of journals, found that bilirubin also helps protect the cells lining human blood vessels from this same kind of oxidative damage.⁵

This research connects to a real-world observation: people with Gilbert syndrome, a common and harmless inherited condition in which bilirubin runs mildly elevated for life, appear to have somewhat lower rates of heart disease.

This does not mean higher bilirubin is generally desirable or something to aim for.

Jaundice itself, at the levels that turn the eyes and skin visibly yellow, always reflects an underlying problem and warrants medical evaluation.

If One Sees Yellowing of Eyes, When to Seek Medical Advice Immediately

• Yellowing of the eyes or skin that appears rapidly, over hours to a few days

• Yellowing accompanied by abdominal pain, fever, or confusion

• Dark urine together with pale, clay-colored stools

• Jaundice appearing in a newborn within the first 24 hours of life, or worsening after the first day

• New jaundice in someone with known liver disease, heavy alcohol use, or medications known to affect the liver

Frequently Asked Questions Regarding Jaundice

References

1. Tripathi, Ramesh Chandra, and Linas A. Sidrys. “‘Conjunctival Icterus,’ Not ‘Scleral Icterus.’” JAMA 242, no. 23 (1979): 2558. https://pubmed.ncbi.nlm.nih.gov/490877/

2. Kuiper, John J. “Conjunctival Icterus.” Annals of Internal Medicine 134, no. 4 (2001): 345–346. https://doi.org/10.7326/0003-4819-134-4-200102200-00029

3. Joseph, Abel, and Hrishikesh Samant. “Hyperbilirubinemia.” In StatPearls. Treasure Island, FL: StatPearls Publishing. Last updated August 8, 2023. https://www.ncbi.nlm.nih.gov/books/NBK544252/

4. Stocker, Roland, Yorihiro Yamamoto, Antony F. McDonagh, Alexander N. Glazer, and Bruce N. Ames. “Bilirubin Is an Antioxidant of Possible Physiological Importance.” Science 235, no. 4792 (1987): 1043–1046. https://doi.org/10.1126/science.3029864

5. Ziberna, Lovro, Mitja Martelanc, Mladen Franko, and Sabina Passamonti. “Bilirubin Is an Endogenous Antioxidant in Human Vascular Endothelial Cells.” Scientific Reports 6 (2016): 29240. https://www.nature.com/articles/srep29240

6. Cleveland Clinic. “Scleral Icterus: What It Is, Causes, Care & Treatment.” Last modified July 23, 2024. https://my.clevelandclinic.org/health/symptoms/scleral-icterus