Evaluation and Treatment Approach for Bluish Sclera
Blue sclera is primarily caused by osteogenesis imperfecta (OI), but can also be associated with other genetic syndromes, metabolic disorders, and certain systemic diseases. A thorough evaluation is essential to determine the underlying cause and guide appropriate management. 1
Causes of Blue Sclera
- Osteogenesis imperfecta (OI) - particularly in types I, III, IV, and VII; type I has distinctly blue sclerae that remain intensely blue throughout life, while in types III and IV, the blue color may fade with age 1, 2
- Ehlers-Danlos syndrome (vascular form/type IV) 1
- Loeys-Dietz syndrome 1
- Hypophosphatasia 1
- Hypophosphatemic osteomalacia ("rickets") 1
- Normal finding in infants under 12 months of age 1
- Preterm birth (associated with decreased bone mineralization) 1
- Various other genetic syndromes and disorders (over 66 genetic syndromes have been associated with blue sclera) 3
Diagnostic Evaluation
History
- Family history of multiple fractures, early-onset hearing loss, abnormally developed dentition, blue sclera, and short stature (suggests OI) 4
- Past medical history including:
- Pregnancy and birth history (preterm birth may increase risk) 4, 1
- History of total parental nutrition, hepatobiliary disease, diuretic therapy, hypercalciuria, or corticosteroids 4
- Chronic diseases affecting bone health (renal insufficiency, metabolic acidosis, malabsorption) 4
- Neurological disorders that limit mobility 4
- Dietary history and medications affecting bone health 4
Physical Examination
- Complete eye examination including:
- Comprehensive physical examination looking for:
- Signs of fractures (swelling, limitation of motion, point tenderness) 4
- Growth parameters (abnormal weight may suggest neglect or endocrine/metabolic disorders) 4
- Skin examination for bruising (particularly in unusual locations) 4
- Dental abnormalities (dentinogenesis imperfecta may be present in OI) 4, 1
- Hair abnormalities (sparse, kinky hair is associated with Menkes disease) 4
Laboratory and Imaging Studies
- Serum calcium, phosphorus, and alkaline phosphatase (alkaline phosphatase may be elevated with healing fractures) 4, 1
- Consider serum parathyroid hormone and 25-hydroxyvitamin D levels 4
- Urinary calcium excretion (random urinary calcium/creatinine ratio) 4
- Genetic testing for COL1A1/COL1A2 mutations when OI is suspected 1
- Radiographic studies to evaluate for fractures or bone abnormalities when indicated 4
Treatment Approach
For Osteogenesis Imperfecta
- Multidisciplinary management involving genetics, orthopedics, physical therapy, and ophthalmology 1
- Bisphosphonate therapy to increase bone density and reduce fracture risk 1
- Physical and occupational therapy to improve mobility and function 1
- Orthopedic interventions for fracture management and skeletal deformities 1
- Regular monitoring for hearing loss and dental issues 1
For Other Underlying Conditions
- Treatment directed at the specific underlying disorder:
For Scleritis (if present with blue discoloration)
- Treatment depends on whether the scleritis is infectious or non-infectious 6
- Non-infectious scleritis may require:
- Nonsteroidal anti-inflammatory drugs
- Corticosteroids
- Immunomodulatory therapy
- Biologic agents (anti-TNF alpha or anti-CD20) in severe cases 6
Special Considerations
- In children with fractures and blue sclera, careful evaluation is needed to distinguish OI from non-accidental injury 4, 1
- Blue sclera in OI type I persists throughout life, while in types III and IV it may fade with age 2
- The intensity of blue coloration can vary and may require objective assessment methods like the 'BLUES' procedure 5