• Small eye, unilateral or bilateral, including axial length and corneal diameter

• With or without intraocular anomalies or systemic disease


1–2 per 10,000 newborns (1)[C]


• Ocular coloboma (1)[C]

• Congenital cataract

• Intrauterine infection (especially rubella)

• Wide range of chromosomal aberrations, syndromes, and congenital disorders

• Possibly some teratogens including ionizing radiation, alcohol, and isotretinoin


• Known genes for isolated ocular involvement include CHX0, SHH, OTX2, MAF, PAX6, CRYAA, GDF6, SIX6, CMIC, RX, CRYBA4, and FOXE3. Other loci known but gene not cloned.

• Known genes with syndrome associations include CHD7 (CHARGE syndrome), DPD (developmental delay), HESX1 (septo-optic dysplasia), SOX2 (multiple anomalies), BMP4 (multiple anomalies), STRA6 (multiple anomalies, Matthew Wood syndrome), HCCS (microphthalmia with linear skin defects syndrome), ANOP1 (Lenz microphthalmia), BCOR (oculofacialcardiodental). Multiple other genes and loci known.

• Isolated and syndromic forms may be autosomal dominant or autosomal recessive. Syndromic may also be X-linked dominant or X-linked recessive.

• Sporadic cases may or may not be heritable.

• Familial cases may have variable expression. Incomplete penetrance is rare.

• Unilateral cases may be genetic (2)[B].


• Genetic counseling and/or prenatal testing (if mutated gene known or syndrome recognized in family)

• Avoidance of in utero exposures if known risk for infection or teratogen

• Can be detected by prenatal ultrasound at 12–13 weeks (3)[C], (4)[C]


Incomplete ocular development during embryogenesis as a result of a variety of faulty processes of ocular growth, most often involving mutations in developmental genes acting as transcription factors for other downstream genes.


• Mutated or otherwise abnormal gene(s), especially when bilateral

• Infection or teratogen exposure in utero

• Coloboma or rarely primary aphakia

• Idiopathic


• Ocular coloboma

• Congenital cataract, especially if nuclear or persistent fetal vasculature (PFV, formerly known as PHPV), or other forms of anterior segment dysgenesis (5)

• Optic nerve abnormalities (e.g., hypoplasia)

• Retinal dysplasia (5)

• No consistent systemic associations except perhaps developmental delay when chromosomal aberration or other systemic syndromic findings

• Anterior chamber depth usually normal (shallow in nanophthalmia)



• Family history of microphthalmia or related congenital ocular disease

• Known exposure to infection or teratogen in utero

• Other known associated anomalies or developmental delay


• Full ocular examination including inferior nasal peripheral retinal examination for coloboma

• Systemic examination for other anomalies

• Nystagmus and strabismus may be present

• Refraction may range from high hyperopia to high myopia

• Assessment of visual function

• Clinical assessment of size of palpebral fissure and periocular tissue/bone size

• Assessment of anterior chamber depth



Initial lab tests

• None if no systemic involvement

• Karyotype if other congenital anomalies

• Specific genetic analysis based on diagnosis (e.g., FISH for microdeletion 22q11 if considering CHARGE syndrome, specific gene mutation analysis as directed by diagnosis)

Follow-up & special considerations

• Genetic consultation if systemic abnormalities or developmental delay and if family history or recognized genetic diagnosis

• Examine parents for ocular signs and peripheral asymptomatic coloboma if child has coloboma.


Initial approach

• B-scan to assess retina and optic nerve if no view. Will also rule out primary aphakia.

• B-scan or UBM may be used to assess scleral thickness.

• A scan for axial length

• Consider neuroimaging if bilateral optic nerve involvement

• Consider CT scan if evidence of small orbit (especially if severe)

Follow-up & special considerations

• If other findings, suggesting glaucoma risk (e.g., elevated risk in aphakia) requires ongoing monitoring every 6 months for glaucoma. Sedation/anesthesia as needed.

• If coloboma, examine every 6 months to screen for retinal detachment.

Diagnostic Procedures/Other

Genetic counseling and molecular genetic testing as appropriate and available.

Pathological Findings

Incomplete ocular development possibly including retina, optic nerve, iris, and choroid.


• Anophthalmia (no evidence of a globe on imaging or on postmortem dissection of orbit)

– Nanophthalmia

– Microcornea without microphthalmia (1)[C]

– Phthisis (e.g., following infection or trauma)



• None for the primary disorder but may need treatment for secondary concerns such as glaucoma

• Consider atropine (0.5% if <1 year old) if anterior chamber shallow as prophylaxis for angle closure and other complications or if glaucoma present and anterior chamber shallow/flat

• Avoid pilocarpine if anterior chamber shallow (nanophthalmia)


General Measures

Amblyopia therapy as indicated

Issues for Referral

• Genetic consultation if systemic signs or family history

• Low vision evaluation and support as indicated

• Retinal surgery for detachment due to coloboma. Surgery is not beneficial in cases of congenital retinal non-attachment/retinal dysplasia and usually not helpful in congenital retinal detachment

Additional Therapies

• If nonfunctional eye and small palpebral fissure/orbital opening, consider scleral shell to encourage periocular tissue growth. Severe cases may benefit from intraorbital balloon placement by craniofacial surgeon (6)[C].

• If nonfunctional eye and microphthalmia mild, consider plus lens in spectacle for enhancing appearance of eye (enlarging) to outside observer.


None proven or indicated.


Cataract, glaucoma, retina, and strabismus as needed.



• As needed for amblyopia monitoring and treatment

• As needed for secondary complications (cataract, glaucoma, retinal detachment, and strabismus). Every 6 months if glaucoma risk or coloboma

• Low vision

• Follow orbital and periocular tissue growth especially in the first 5 years of life

Patient Monitoring

• School performance and development

• Patient concerns about appearance


• Genetic counseling

• Low vision intervention

• International Children’s Anophthalmia and Microphthalmia Network www.anophthalmia.org/


• Variable acuity – depends in part on, presence of other ocular or non ocular abnormalities. Very poor prognosis if associated with primary aphakia, retinal dysplasia, congenital retinal detachment/non attachment.

• Risk for retinal detachment if coloboma may be in excess of 2%

• Risk for glaucoma depends on associated ocular anomalies


• Retinal detachment if coloboma

• Glaucoma if aphakia, persistent fetal vasculature (PFV), and anterior segment dysgenesis


1. Warburg M. Classification of microphthalmos and coloboma. J med Genet 1993;30:664–669.

2. Fleckenstein M, Maumenee IH. Unilateral isolated microphthalmia inherited as an autosomal recessive trait. Ophthalmic Genet 2005;26:163–168.

3. Wong HS, Parker S, Tait J, Pringle KC. Antenatal diagnosis of anophthalmia by three-dimensional ultrasound: A novel application of the reverse face view. Ultrasound Obstet Gynecol 2008;32:103–105.

4. Chitayat D, Sroka H, Keating S, et al. The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, Anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): Report of eight cases including a living child and further evidence for autosomal recessive inheritance. Am J Med Genet 2007;143A:1268–1281.

5. Weiss AH, Kousseff BG, Ross EA, Longbottom J. Complex microphthalmos. Arch Ophthalmol 1989;107:1619–1624.

6. Gossman MD, Mohay J, Roberts DM. Expansion of the human microphthalmic orbit. Ophthalmology 1999;106:2005–2009.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Microphthalmia
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