Yellow eyes

Yellow eyes, medically referred to as scleral icterus, are characterized by a yellowish discoloration of the sclera. This condition often indicates an underlying disturbance in bilirubin metabolism or liver function. Recognizing yellow eyes early is important for diagnosing potentially serious systemic disorders.

Anatomy and Physiology of the Eye and Liver Interaction

The appearance of yellow eyes is closely linked to both ocular anatomy and liver physiology. Understanding these structures and functions helps explain why bilirubin deposition occurs in the sclera.

• Sclera and conjunctiva: The white part of the eye is thin and vascular, making it sensitive to changes in bilirubin levels.
• Bilirubin metabolism: Bilirubin is produced from the breakdown of hemoglobin, conjugated in the liver, and excreted via bile. Disruption in any step can lead to accumulation in tissues.
• Relationship between hepatic function and ocular signs: Elevated bilirubin levels in the blood are deposited in scleral tissue, causing visible yellowing.

Etiology of Yellow Eyes

Hepatocellular Causes

Diseases affecting liver cells can impair bilirubin processing, resulting in yellow eyes.

• Hepatitis (viral, autoimmune, or drug-induced)
• Cirrhosis and chronic liver disease
• Non-alcoholic fatty liver disease

Obstructive Causes

Blockage of bile flow can prevent bilirubin excretion and cause its accumulation.

• Gallstones and biliary obstruction
• Cholangiocarcinoma or pancreatic tumors
• Post-surgical or congenital bile duct abnormalities

Hemolytic Causes

Excessive breakdown of red blood cells increases bilirubin production beyond the liver’s capacity to process it.

• Hemolytic anemia
• Transfusion reactions
• Inherited disorders such as sickle cell disease or thalassemia

Other Causes

Some conditions can cause yellow eyes without primary liver or hemolytic pathology.

• Neonatal jaundice
• Drug or toxin-induced jaundice
• Rare metabolic disorders like Gilbert’s syndrome

Pathophysiology

The yellow discoloration of the eyes occurs due to elevated levels of bilirubin in the blood, a condition known as hyperbilirubinemia. The mechanisms vary depending on the underlying cause.

• Bilirubin production, conjugation, and excretion: Bilirubin is formed from heme breakdown, conjugated in the liver, and excreted in bile. Impairment at any stage leads to accumulation.
• Mechanisms leading to hyperbilirubinemia: Increased production (hemolysis), decreased conjugation (hepatocellular disease), or obstruction of excretion (bile duct blockage).
• Deposition in scleral tissue: Bilirubin binds to elastin in the sclera, causing the characteristic yellow appearance.

Clinical Presentation

Patients with yellow eyes often present with visible scleral icterus along with other systemic symptoms depending on the underlying condition.

• Visual identification: Yellowing of the sclera and sometimes the skin, usually first noticed in the eyes.
• Associated systemic symptoms: Fatigue, dark urine, pale stools, nausea, pruritus, abdominal pain.
• Patterns of onset: Acute onset may indicate hepatitis or obstruction, whereas gradual yellowing is often seen in chronic liver disease.

Diagnostic Evaluation

Proper evaluation of yellow eyes involves a combination of history, physical examination, laboratory tests, and imaging studies to identify the underlying cause.

• History taking: Assess onset, duration, progression, associated symptoms such as fatigue, abdominal pain, pruritus, and medication use.
• Physical examination: Inspection of sclera and skin, palpation for hepatomegaly, splenomegaly, or tenderness in the abdomen.
• Laboratory investigations: Liver function tests (AST, ALT, ALP, bilirubin), complete blood count, coagulation profile, and viral serologies.
• Imaging studies: Ultrasound, CT, or MRCP to evaluate liver, bile ducts, and pancreas for obstruction or structural abnormalities.
• Special tests: Hemolysis markers, autoimmune panels, or metabolic studies as indicated by the clinical scenario.

Management Strategies

General Measures

Initial management includes supportive care aimed at reducing symptoms and preventing further liver damage.

• Hydration and nutritional support
• Avoidance of alcohol and hepatotoxic medications
• Rest and monitoring of vital signs and liver function

Medical Treatment

Treatment is tailored to the specific underlying cause of yellow eyes.

• Management of liver disease with antivirals, immunosuppressants, or medications for non-alcoholic fatty liver disease
• Treatment of hemolytic conditions with transfusions, steroids, or disease-specific therapy
• Use of medications to alleviate pruritus or cholestasis, such as cholestyramine

Surgical and Procedural Interventions

In cases of obstructive jaundice, procedural interventions may be required.

• Biliary drainage or stenting for obstruction due to stones or tumors
• Cholecystectomy or tumor resection when indicated

Complications

Yellow eyes can indicate serious underlying pathology, and if left untreated, complications may arise depending on the cause.

• Progression to liver failure: Advanced hepatocellular disease can result in hepatic insufficiency and multi-organ dysfunction.
• Hepatic encephalopathy: Accumulation of toxins in the blood due to liver dysfunction may lead to cognitive impairment and altered consciousness.
• Coagulopathy and bleeding disorders: Impaired liver function affects clotting factor synthesis, increasing the risk of hemorrhage.
• Chronic complications: Recurrent biliary obstruction or hemolysis can lead to gallstones, cholangitis, or persistent anemia.

Prevention

Preventive strategies aim to reduce the risk of developing yellow eyes by addressing modifiable risk factors and monitoring chronic conditions.

• Vaccination: Immunization against hepatitis A and B to prevent viral liver disease.
• Avoidance of hepatotoxic substances: Limiting alcohol intake and avoiding unnecessary medications that can damage the liver.
• Monitoring chronic liver conditions: Regular follow-up with liver function tests and imaging in patients with known liver disease.
• Healthy lifestyle: Balanced diet, regular exercise, and maintaining a healthy weight to reduce the risk of non-alcoholic fatty liver disease.

References

1. Schiff ER, Maddrey WC, Sorrell MF. Schiff’s diseases of the liver. 12th ed. Hoboken: Wiley-Blackwell; 2017.
2. Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s gastrointestinal and liver disease. 11th ed. Philadelphia: Elsevier; 2021.
3. Boyd AS, Goldsmith LA. Clinical dermatology. 5th ed. Philadelphia: Elsevier; 2020.
4. Friedman LS. Approach to the patient with jaundice. N Engl J Med. 2018;379(17):1642–1652.
5. Runyon BA. Management of adult patients with jaundice and liver disease. Lancet. 2019;394(10214):875–888.
6. Berger J, Berger S. Hepatobiliary disorders: Diagnosis and treatment. 2nd ed. New York: Springer; 2016.
7. Neuschwander-Tetri BA. Jaundice: Clinical features and evaluation. Gastroenterol Clin North Am. 2020;49(2):197–214.
8. American Association for the Study of Liver Diseases. Evaluation of the patient with jaundice. Hepatology. 2021;73(5):1927–1945.
9. James WD, Berger TG, Elston DM. Andrews’ diseases of the skin: Clinical dermatology. 14th ed. Philadelphia: Elsevier; 2020.