Blue Sclera (Bluish Eye Whites): Causes and Workup

Blue sclera is a bluish tint of the eye white that appears when uveal pigment shows through thin or translucent sclera.

Osteogenesis imperfecta is the classic association.

However, many patients with the sign have a different cause.

Therefore, the color alone never settles the diagnosis.

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Why Blue Sclera Looks Blue

Dense, irregular collagen fibers normally make the sclera opaque.

When the stroma thins or its fibers change, more light passes through.

The dark choroid then shows through, and scattered short wavelengths give a blue cast.

As a result, the tint reflects tissue structure, and no blue pigment is present.

Blue Sclera in Normal Infants

Many healthy newborns have faintly blue sclerae because their sclera is thin.

The tint usually fades in early childhood.

Therefore, an isolated blue hue in a thriving infant needs no workup.

However, persistence, fractures or a positive family history change that judgment.

Blue Sclera in Osteogenesis Imperfecta

Type I osteogenesis imperfecta classically produces a distinct, persistent blue tint.

Patients also report fractures after minor trauma, early hearing loss and sometimes fragile teeth.

In addition, central corneal thickness is often low (see osteogenesis imperfecta and the eye).

Most cases involve variants in COL1A1 or COL1A2.

Blue Sclera in Ehlers-Danlos Syndrome

Several Ehlers-Danlos types can thin the sclera.

The kyphoscoliotic type and brittle cornea syndrome carry the highest ocular risk.

In brittle cornea syndrome, a very thin cornea may rupture after trivial trauma.

Therefore, globe fragility matters more than the color (see Ehlers-Danlos syndrome and the eye).

Also, keratoglobus with blue sclera should prompt testing for this syndrome.

Iron Deficiency and Blue Sclera

Iron deficiency anemia is a common and easily missed cause.

Kalra and colleagues reported blue sclerae as a frequent sign in iron-deficient patients.

One proposed mechanism involves impaired collagen synthesis, because iron is a cofactor for prolyl hydroxylase.

Therefore, ask about heavy menses, diet and gastrointestinal blood loss.

Medications That Tint the Sclera

Long-term minocycline can deposit blue-gray pigment within the sclera.

Here the color comes from deposited pigment, while the scleral thickness stays normal.

In addition, some reports link chronic systemic corticosteroids to a bluish hue.

Then, a full drug history belongs in every assessment.

Myopia and Scleral Thinning

High axial myopia stretches and thins the sclera.

As a result, some highly myopic eyes show a mild bluish cast.

Refraction and axial length usually explain the finding.

Blue Sclera After Inflammation

Previous necrotizing scleritis can leave thin, gray-blue patches.

Scleromalacia perforans in long-standing rheumatoid arthritis looks similar.

These areas are focal, which separates them from diffuse congenital thinning.

Next, look for active inflammation and systemic disease (see scleritis workup).

Mimics With True Pigment

Ocular melanocytosis causes slate-gray scleral patches, often in one eye.

It raises the long-term risk of glaucoma and uveal melanoma.

Alkaptonuria and argyria can also discolor the sclera.

Therefore, separate deposited pigment from translucency before ordering tests.

Examining Blue Sclera at the Slit Lamp

First, note whether the tint is diffuse or focal and whether both eyes are involved.

Next, inspect the cornea for thinning, ectasia or a keratoglobus profile.

Then measure central corneal thickness with pachymetry.

Finally, record axial length when myopia seems likely.

History Clues

• Fractures after minor trauma
• Hearing loss or dental fragility
• Joint hypermobility, easy bruising or fragile skin
• Heavy menses, restricted diet or bowel symptoms
• Minocycline or long-term steroid use
• Family history of similar findings

Laboratory and Genetic Tests for Blue Sclera

A complete blood count and ferritin are sensible first tests in a well adult.

When syndromic features exist, refer to clinical genetics.

Panels may include COL1A1, COL1A2, PLOD1, ZNF469 and PRDM5.

Also consider cardiovascular evaluation when Marfan or Loeys-Dietz features appear.

Managing Blue Sclera

The tint itself needs no treatment.

However, iron replacement may lessen it in iron deficiency.

Patients with thin corneas need polycarbonate protective eyewear for sports and daily risk.

In addition, explain that minor blunt trauma can rupture a fragile globe.

Remember that thin corneas can make applanation readings falsely low at follow-up.

Pitfalls to Avoid

• Do not label every blue sclera as osteogenesis imperfecta
• Never ignore blue sclera combined with keratoglobus
• Check iron status before genetic testing in an otherwise well adult
• Do not confuse melanocytosis with scleral thinning

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References

1. Kalra L, Hamlyn AN, Jones BJ. Blue sclerae: a common sign of iron deficiency? Lancet. 1986;2:1267-1269.
2. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16:101-116.
3. Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8-26.
4. Burkitt Wright EM, Spencer HL, Daly SB, et al. Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. Am J Hum Genet. 2011;88:767-777.
5. Fraunfelder FW, Randall JA. Minocycline-induced scleral pigmentation. Ophthalmology. 1997;104:936-938.
6. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8: External Disease and Cornea. San Francisco: AAO; 2023.