What causes bluish discoloration of the eyes (blue sclera)?

Bluish Discoloration of the Eyes (Blue Sclera)

Primary Cause

Blue sclera is primarily caused by osteogenesis imperfecta (OI), a genetic connective tissue disorder characterized by abnormal collagen type I production that results in thinning of the sclera, allowing the underlying uveal tissue to show through. 1

Major Etiologies

Genetic Syndromes

Osteogenesis Imperfecta (Most Common)

• OI Type I: Blue sclera remains intensely blue throughout life in all affected children 1, 2
• OI Types III and VII: Blue sclera present at birth but intensity fades by adolescence, with variable scleral hue in adulthood 1, 2
• OI Type IV: Typically has normal sclerae, which is an important distinguishing feature 1
• The blue discoloration results from decreased scleral thickness allowing visualization of the underlying choroidal pigment 3

Other Genetic Conditions

• Ehlers-Danlos syndrome (vascular type/Type IV): Characterized by thin skin, easy bruising, and blue sclera 1
• Loeys-Dietz syndrome: Features blue sclera along with arterial tortuosity and hypertelorism 1

Metabolic Bone Disorders

• Hypophosphatasia: Defective bone mineralization presenting with blue sclera 1
• Hypophosphatemic osteomalacia (rickets): Can present with blue sclera, osteomalacia, and poor growth 1

Physiologic Variants

• Normal infants before 12 months of age can have blue sclerae 1
• Preterm birth is associated with decreased bone mineralization that may contribute to blue sclera 1

Diagnostic Evaluation Algorithm

History Assessment

• Family history of multiple fractures, early-onset hearing loss, abnormal dentition, blue sclera, and short stature suggests OI 1
• Pregnancy and birth history, total parenteral nutrition, hepatobiliary disease, diuretic therapy, hypercalciuria, or corticosteroid use are relevant 1

Physical Examination

• Assess for signs of fractures, growth parameters, skin bruising, dental abnormalities (dentinogenesis imperfecta), and hair abnormalities 1
• Evaluate for other ocular abnormalities including corneal changes 1
• In OI, look for the complete constellation: fractures, short stature, dentinogenesis imperfecta, and hearing loss 1

Laboratory Studies

• Serum calcium, phosphorus, alkaline phosphatase levels, and urinary calcium excretion should be obtained 1
• Vitamin D levels can help rule out metabolic bone disorders 1

Imaging

• Radiographic studies to evaluate for fractures or bone abnormalities may be indicated 1

Genetic Testing

• COL1A1/COL1A2 mutation testing is recommended when OI is suspected 1

Critical Clinical Pitfalls

Distinguishing OI from Non-Accidental Injury

• In children with fractures and blue sclera, careful evaluation is needed to distinguish OI from non-accidental injury 1
• The presence of blue sclera in infants with unexplained fractures may suggest OI rather than abuse 1

Age-Related Changes

• Blue sclera intensity changes with age in certain OI types—what appears blue in infancy may normalize by adolescence in Types III and IV, but remains blue throughout life in Type I 2

Associated Ocular Complications

• Almost every component of the eye can be affected in OI, including decreased corneal and scleral thickness 3
• Patients are at risk for ruptures, lacerations, and other eye problems after minor trauma 3
• Keratoconus can occur as an associated finding in OI, though less commonly documented 4

Management Considerations

• Protective eyewear is recommended for OI patients to prevent accidental eye trauma 3
• When ocular surgery is required, it should be approached with caution due to structural abnormalities 3
• Corticosteroids may be used in treatment of non-infectious scleritis associated with blue sclera 1