What is the ocular differentiating factor between Osteogenesis Imperfecta (OI) and Ehlers-Danlos Syndrome (EDS)?

Ocular Differentiating Factor Between Osteogenesis Imperfecta and Ehlers-Danlos Syndrome

The key ocular differentiating feature is that blue sclerae are a characteristic and common finding in Osteogenesis Imperfecta (particularly types I, III, and VII), while Ehlers-Danlos Syndrome typically does NOT present with blue sclerae except rarely in the vascular type (type IV). 1, 2

Primary Distinguishing Features

Blue Sclerae in Osteogenesis Imperfecta

• Blue sclerae are present in all children with OI type I and can be dramatic in presentation 1
• OI type III shows variable scleral hue, while OI type VII characteristically presents with blue sclerae 1
• OI type IV typically has normal sclerae, which is an important distinguishing feature within OI subtypes 1
• The blue appearance results from decreased corneal and scleral thickness, allowing visualization of the underlying uveal tissue 3, 4

Scleral Appearance in Ehlers-Danlos Syndrome

• Blue sclerae are NOT a typical feature of most Ehlers-Danlos syndrome types 2
• Only the vascular form (type IV) of EDS has been associated with blue sclerae, and this is uncommon 2
• The primary ocular manifestations of EDS involve other structures, not scleral coloration 5

Additional Ocular Differences

Corneal Thickness

• OI patients have significantly reduced central corneal thickness (CCT), with 95.6% having CCT below 500 μm and 65.2% below 450 μm 4
• CCT is thinner and negatively correlated with the blueness of the sclera in OI patients 4
• This reduced thickness is not a characteristic feature of EDS 4

Other Ocular Findings in OI

• Decreased ocular rigidity leading to artificially low intraocular pressure measurements 4
• Increased risk of ruptures, lacerations, and trauma-related complications from minor injuries 3
• Myopia, keratoconus, and corneal opacity may occur 4
• Complications from standard surgical procedures due to structural weakness 3

Clinical Pitfalls to Avoid

Important caveat: Blue sclerae can occur in normal infants before 12 months of age, so this finding must be interpreted in context with other clinical features 1, 2

When evaluating a patient with suspected connective tissue disorder:

• Do not rely on blue sclerae alone for diagnosis, as overlap syndromes (OI/EDS) have been reported with mixed phenotypes 5, 6
• Consider that infants with OI types IV, V, and VI may have normal sclerae and present only with fractures 1
• Assess for the complete constellation of features: in OI, look for fractures, short stature, dentinogenesis imperfecta, and hearing loss; in EDS, look for joint hypermobility, skin hyperextensibility, and vascular fragility 1, 2, 6

Diagnostic Approach

When blue sclerae are present:

• Measure central corneal thickness via ultrasound pachymetry, as CCT <500 μm strongly suggests OI 4
• Evaluate for family history of fractures, hearing loss, and dental abnormalities characteristic of OI 1, 2
• Perform genetic testing for COL1A1/COL1A2 mutations to confirm OI diagnosis 1, 7

When blue sclerae are absent but connective tissue disorder suspected:

• Consider OI types IV, V, or VI which have normal sclerae 1
• Evaluate for EDS features: joint hypermobility, skin changes, and vascular fragility without blue sclerae 2, 6