A 48-year-old white male presented for acute care, complaining of bilateral ocular irritation, blurry near vision and “yellow eyes.” He reported several prior years of alcohol and drug abuse––although he claimed that he was sober for the past four months. His medical history was reportedly unremarkable, but he admitted that he had not been to a physician in more than 10 years.

Upon examination, his corrected visual acuity was 20/20 OD and OS at distance and near. Slit lamp evaluation revealed notable bulbar hyperemia OU, with a distinct yellow hue in the conjunctival tissue. Otherwise, he exhibited clear corneas, normal intraocular pressure and unremarkable posterior segment structures OU. Upon further questioning, the patient denied any history of recent ocular trauma.

Conjunctival Icterus
The clinical finding of “yellow eyes” is relatively uncommon. The proper medical term for this condition is surprisingly not jaundice, but rather icterus. Both terms denote a discoloration of the skin or mucous membranes associated with excess bilirubin. But, while jaundice is indicative of multi-tissue involvement, icterus is defined as yellowing of a specific entity––such as the eye. Thus, a patient with icterus may subsequently be reclassified as being jaundiced upon further evaluation.

Historically, this ocular phenomenon has been described as scleral icterus––although there is evidence that the pigment deposition actually occurs in the overlying conjunctiva, rather than in the sclera.¹ Hence, the term conjunctival icterus is preferred today.^2,3

Associated Conditions
Numerous ocular and systemic conditions may be linked to conjunctival icterus:

• Subconjunctival hemorrhage is one of the more clinically significant causes of icterus. In this instance, as the blood pigment (heme) undergoes normal catabolism, bilirubin is produced––yielding the familiar yellow coloration that is also evident in bruises, bile and urine.⁴

• Hyperbilirubinemia, or increased levels of serum bilirubin, is more commonly associated with icterus than subconjunctival hemorrhage. Hence, the finding of conjunctival icterus––particularly when it is bilateral in nature––presents a diagnostic dilemma with a host of potential systemic implications.
Identifying the correct underlying etiology involves appropriate laboratory and physical testing.^5,6 Bilirubin is produced throughout the body, but is metabolized in the liver and excreted via the bile ducts into the small intestine.

Our patient presented with bilateral bulbar hyperemia and notable conjunctival yellowing (OD left, OS right).

Hepatic and biliary disorders are highly correlated with hyperbilirubinemia, and therefore, liver function tests must be a primary consideration in patient management (see “Common Liver Panel/Liver Function Tests,” right).

Elevated serum bilirubin levels will help confirm the clinician’s suspicions, and may point toward an initial diagnosis of hepatitis, alcoholic cirrhosis, hemolytic anemia or systemic infections, such as leptospirosis.

Abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels are suggestive of liver toxicity due to drugs or other toxic substances, chronic hepatitis, obstruction of bile ducts or cirrhosis. Very high ALT and AST levels are indicative of acute viral hepatitis. The AST/ALT ratio can be helpful in distinguishing between the various aforementioned conditions.

Abnormal alkaline phosphatase levels are characteristic of biliary obstruction and may occur as a possible result of bile duct cysts, gallstones or tumors, or pancreatic tumors. Serum albumin is also helpful in diagnosing liver and renal disease; low levels correlate with cirrhosis and nephritic syndrome, while high levels are associated with chronic dehydration.

• Leptospirosis, a rare and severe infection that occurs from contact with bacteria of the Leptospira genus, is another important consideration in cases of conjunctival icterus. Generally, the bacteria is encountered only in warm climates, and is associated with exposure to water that has been contaminated by animal urine.⁷

Common Liver Panel/Liver Function Tests8

• Bilirubin. There are two different bilirubin tests: total and direct. Direct bilirubin represents the conjugated form, which occurs after it has been processed by the liver. These tests are useful in cases of jaundice and, when used together, can help to isolate the lesion’s location. –Reference range: Total 0.3-1.9mg/dL; Direct 0.0-0.3mg/dL. • Alanine aminotransferase (ALT). An enzyme mainly found in the liver, ALT is one of the best tests for detecting hepatitis. –Reference range: 10-40IU/L. • Aspartate aminotransferase (AST). This enzyme is not specific to the liver (e.g., it is also present in the heart and skeletal muscle), but its concentration may increase following acute liver damage. The AST to ALT ratio is sometimes useful in differentiating between causes of liver damage. –Reference range: 10-34IU/L. • Alkaline phosphatase (ALP). This enzyme often increases following bile duct obstruction. –Reference range: 44-147IU/L. • Albumin. The main protein produced by the liver, albumin levels decrease in patients with chronic liver disease (e.g., cirrhosis) or renal disorders (e.g., nephrotic syndrome). –Reference range: 3.4-5.4g/dL. • Total protein (TP). This measurement includes albumin as well as globulin. Low values may implicate liver disease or acute infection, while high concentrations are found in patients with paraproteinaemia, Hodgkin’s lymphoma or leukemia. –Reference range: 6.0-8.3g/dL.

Additional non-specific signs and symptoms of leptospirosis may include cough, sore throat, headache, muscle or abdominal pain, conjunctivitis, swollen lymph glands and enlargement of the spleen and/or liver (hepatosplenomegaly). Fortunately, leptospirosis can be managed with broad-spectrum antibiotics, such as azithromycin, ceftriaxone, doxycycline or penicillin.

Patients with abnormal signs, symptoms and laboratory results warrant referral to an internist for additional serology, including a complete blood count with differential, prothrombin time, hepatitis-specific antibodies, iron and ferritin levels.

Urinalysis can be helpful in further evaluation of albumin or total protein abnormalities. Ultimately, a liver biopsy may be required for a definitive diagnosis of specific entities, such as hepatitis A, alcoholic liver disease, tuberculosis and liver cancer.

In our patient, his long history of drug and alcohol abuse prompted a presumptive diagnosis of liver disease, with a differential of cirrhosis and hepatitis. Leptospirosis was also considered, because the patient admitted to residing in generally poor living conditions throughout his recent life. We referred him for appropriate blood work and scheduled a consultation with an internist. The results of his evaluation are still pending.

1. Kuiper JJ. Conjunctival icterus. Ann Intern Med. 2001 Feb 20;134(4):345-6.
2. Beisel B. Use of the term conjunctival icterus instead of scleral icterus. Am Fam Physician. 2005 Jan 1;71(1):49.
3. Ng BJ, Alexander D, Robinson GM. Unilateral conjunctival icterus and no ‘glass eye’. Intern Med J. 2012 Jun;42(6):735-6.
4. Stafanous SN, Matthew M. An unusual case of recurrent subconjunctival haemorrhage causing yellow-brown discolouration due to haemosiderin deposition. Orbit. 2009;28(2-3):179-80.
5. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005 Feb 1;172(3):367-79.
6. Lee TH, Kim WR, Poterucha JJ. Evaluation of elevated liver enzymes. Clin Liver Dis. 2012 May;16(2):183-98.
7. Rathinam SR. Ocular manifestations of leptospirosis. J Postgrad Med. 2005 Jul-Sep;51(3):189-94.
8. National Institutes of Health. MedlinePlus. Available at: www.nlm.nih.gov/medlineplus/. Accessed March 28, 2013.