2020–2021 BCSC Basic and Clinical Science Course™
8 External Disease and Cornea
Chapter 8: Systemic Disorders With Corneal and Other Anterior Segment Manifestations
Inherited Metabolic Diseases
Disorders of Lipoprotein Metabolism
Hyperlipoproteinemias are common conditions associated with premature coronary artery and peripheral vascular disease. Recognition of the ocular hallmarks of these diseases, such as xanthelasma and corneal arcus, can result in early intervention and reduced morbidity.
Schnyder corneal dystrophy, a dominantly inherited category 1 corneal dystrophy, can be associated with hyperlipoproteinemia. Corneal dystrophies are discussed in Chapter 7.
See BCSC Section 1, Update on General Medicine, for additional information about hyperlipoproteinemias.
Extracellular deposits consist of cholesterol, cholesterol esters, phospholipids, and triglycerides.
Corneal arcus is a very common degenerative change in older patients and does not require systemic evaluation (see Chapter 6 for further discussion of corneal arcus). However, corneal arcus in individuals younger than 40 years or asymmetric corneal arcus may be associated with a hyperlipoproteinemia with elevated serum cholesterol level. These patients should have a systemic workup. Unilateral or asymmetric corneal arcus may be secondary to carotid atherosclerotic disease on the less affected side.
A fasting and alcohol-restricted lipid profile that includes cholesterol, triglycerides, and high-density and low-density lipoproteins (HDL and LDL, respectively) is typically considered. The clinician can then classify these patients phenotypically to assess their risk for atherosclerotic disease.
Early detection of a hyperlipoproteinemia by the ophthalmologist allows time for the patient to be referred for dietary or drug treatment.
Abnormal reductions in serum lipoprotein levels occur in 5 disorders:
lecithin–cholesterol acyltransferase (LCAT) deficiency
fish eye disease
The last 2 disorders do not result in corneal disease; the discussion in this section focuses on the other 3 disorders.
LCAT promotes transfer of excess cholesterol from peripheral tissues to the liver, and a deficiency of this enzyme results in accumulation of unesterified cholesterol in the plasma and tissues. This, in turn, leads to atherosclerosis, renal insufficiency, early corneal arcus, and nebular corneal clouding composed of minute focal lipid deposits.
LCAT deficiency and fish eye disease are allelic variants of the same genetic locus on band 16q22.1. In fish eye disease, LCAT levels are normal, but the enzyme does not function properly. Tangier disease is characterized by a complete absence of serum high-density α-lipoproteins. The gene responsible for this disease maps to 9q22–q31.
LCAT deficiency, fish eye disease, and Tangier disease are rare autosomal recessive conditions. Familial LCAT deficiency is characterized by peripheral arcus and nebular stromal haze made up of myriad minute focal deposits of lipid that appear early in childhood but do not interfere with vision (Fig 8-3). Fish eye disease features obvious corneal clouding from minute gray-white-yellow dots that progress from the periphery to the central cornea to decrease vision. Tangier disease features very large orange tonsils; enlarged liver, spleen, and lymph nodes; hypocholesterolemia; and abnormal chylomicron remnants. Affected corneas show diffuse clouding and posterior focal stromal opacities but no arcus. Neuropathy leads to lagophthalmos and corneal sequelae.
Figure 8-3 Clinical photograph from a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency, showing peripheral arcus and nebular stromal haze.
(Courtesy of Gerald Zaidman, MD.)
LABORATORY EVALUATION AND MANAGEMENT
The serum lipid profile shows characteristic low levels of HDL (markedly low in Tangier disease). Recognition of hypolipoproteinemia can allow the clinician to make appropriate referrals and encourage the patient to seek genetic counseling.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.