Anophthalmos 

Updated: Mar 25, 2016
Author: Nick Mamalis, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Practice Essentials

Anophthalmia can be challenging to treat. Patients with anophthalmia often require a team of specialists for proper care. Considerations include identifying associated abnormalities (eg, microcephalia) that may present additional risks to the patient. Aesthetics and cosmesis are important to the self-esteem of the patient. Oculofacial surgery may be costly and may be beyond the reach of many families. Long-term follow-up of the patient is necessary for maximizing his or her function and self-esteem.

Background

True or primary anophthalmos is very rare. Only when there is a complete absence of the ocular tissue within the orbit can a diagnosis of true anophthalmos be made. Extreme microphthalmos is seen more commonly. In this condition, a very small globe is present within the orbital soft tissue, which is not visible on initial examination.

Anophthalmia and microphthalmia may occur secondary to the arrest of development of the eye at various stages of growth of the optic vesicle. It is important to recognize microphthalmia because the development of the orbital region, as well as the lids and the fornices, is dependent on the presence of a normal-sized eye in utero.

Anophthalmia may lead to serious problems in a child due to not only the absence of a seeing eye but also the secondary disfigurement of the orbit, the lids, and the eye socket. Early treatment with various expanders or surgery, when necessary, will help decrease the orbital asymmetry and cosmetic deformities in these children.

See the clinical images below:

Anophthalmic socket (left eye). Anophthalmic socket (left eye).
Close-up view of anophthalmic socket (left eye). Close-up view of anophthalmic socket (left eye).

Pathophysiology

Anophthalmia occurs when the neuroectoderm of the primary optic vesicle fails to develop properly from the anterior neural plate of the neural tube during embryological development. The more commonly seen microphthalmia can result from a problem in development of the globe at any stage of growth of the optic vesicle.

The most common genetic disturbance associated with anophthalmia and microphthalmia is de novo loss of function mutations in the SOX2 gene.[1] In consanguineous families, the gene ALDH1A3 may also play an important role.[2]

Proper growth of the orbital region is dependent on the presence of an eye, which stimulates growth of the orbit and proper formation of the lids and the ocular fornices. Commonly, a child born with anophthalmia has a small orbit with narrow palpebral fissure and shrunken fornices.

Epidemiology

Frequency

United States

Congenital anophthalmos is a very rare condition that has a reported prevalence rate of 0.18 per 10,000 births.[3]

International

European rates are similar to those seen in the United States and have been reported as 0.19 case per 10,000 births.[4]

Australian rates are reported as 0.06-0.42 case per 10,000 births and 0.2-1.7 cases per 10,000 births for anophthalmia and microphthalmia, respectively.[5]

Mortality/Morbidity

Growth and development of the bony orbit is directly dependent on outgrowth of the globe.

Lack of an eye or a microphthalmic eye causes improper development of the orbit.

A small bony orbit results in hemifacial hypoplasia and will not allow a prosthesis to be fit. The cosmetic deformity can be quite significant.

Race

Classically, racial predilection for anophthalmos has not been reported; however, recent studies have shown an elevated prevalence in some ethnic groups. These groups include Pakistani and Scottish children. Genetic, environmental, and possible classification issues may explain these high rates of disease and need to be explored further.[6]

Sex

Sexual predilection for congenital anophthalmos has not been reported.

Age

Anophthalmos occurs in utero and is a congenital anomaly that is present at birth.

 

Presentation

History

The defect occurs in utero and is congenital. Children with anophthalmos are born with a unilaterally small orbit and no visible ocular tissue within the orbit.[7]

Physical

Physical findings are as follows.[8, 9, 5, 10]

Orbital findings may include the following:

  • Small orbital rim and entrance

  • Reduced size of the bony orbital cavity

  • Extraocular muscles are usually absent.

  • Lacrimal gland and ducts may be absent.

  • Small and maldeveloped optic foramen

Eyelid findings may include the following:

  • Foreshortening of the lids in all directions

  • Absent or decreased levator function with decreased lid folds

  • Contraction of orbicularis oculi muscle

  • Shallow conjunctival fornix, especially inferiorly

Globe findings may include the following:

  • Globe is completely absent in primary anophthalmos.

  • Extremely small and malformed globe is seen in microphthalmos.

  • Congenital cataract associated with microphthalmos

Systemic findings may include the following:

  • Hypoplasia of the optic nerve

  • Absence or dysplasia of septum pellucidum

  • Pituitary gland dysfunction and male genital abnormalities (if in conjunction with mutations of SOX2 gene)

  • Sensorineural hearing loss

  • Cleft lip/palate

  • Cardiac anomalies: Hemitruncus arteriosum, vetricular septal defects, and pulmonary hypertension.

Causes

Causes of anophthalmos include the following:

  • Idiopathic/sporadic

  • Inherited as dominant, recessive, or sex linked

  • Chromosome deletion in band 14q22-23 with associated polydactyly,[11] as well as a deletion in 7 p15.1-21.1 associated with cryptophthalmos/anophthalmos[12]

  • Trisomy 13-15

  • Genetic deletions involving SOX2 (10-20% of anophthalmia)[13, 5] ; SIX6; and STRA6; with many new microdeletions being reported, including within PAX6, RAX, and SMOC1[14] ; OTX2 (3% of anophthalmia); VSX2; FOXE3; BMP4; GDF6; and ALDH1A3 (involved in cellular retinoic acid synthesis).[15]

  • Maternal infections during pregnancy (ie, rubella, toxoplasmosis)

  • Often associated with syndromes with craniofacial malformation (ie, Goldenhar syndrome, Hallermann-Streiff syndrome)

 

DDx

Diagnostic Considerations

Congenital anophthalmia is a developmental disorder in which the eye does not develop or is underdeveloped. The diagnosis can be made based on observation. Many causes lead to congenital anophthalmia, including hereditary genetic conditions and de novo genetic conditions. While laboratory analysis can elucidate the genetic sequence that leads to this condition, the results are academic; the identification of the genes may not improve the treatment and outcome of the patient. The diagnostic and therapeutic strategy in congenital anophthalmia is mainly to identify and treat associated abnormalities and to maximize the patient's function without vision.

 

Workup

Imaging Studies

Imaging studies in anophthalmos are as follows.[16]

CT scan or MRI

CT scan or MRI of the head and the orbits is used to assess the presence of an extremely microphthalmic globe

Bilateral anophthalmos may have an associated absence of the optic chiasma, a diminished size of the posterior pathways, as well as agenesis or dysgenesis of the corpus callosum.[16]

Patients with unilateral anophthalmos may have severe craniofacial anomalies that need to be evaluated by scanning.

Ultrasound imaging

B-scan ultrasound will show a complete absence of ocular tissue in anophthalmos.

A-scan ultrasound will show a decreased axial length in microphthalmos.

Transvaginal ultrasound can detect eye malformations after 22 weeks’ gestation; however, its sensitivity for use in the detection of anophthalmia is not known.

Histologic Findings

Primary anophthalmos is characterized by a complete absence of ocular tissue within the orbit. Extreme microphthalmos is seen more commonly. Histopathological evaluation of orbital contents reveals an extremely small or malformed globe with only rudimentary ocular contents. Overall, extraocular muscles often are absent or markedly decreased in anophthalmia.

 

Treatment

Medical Care

Medical care in anophthalmos focuses on treating the soft tissue hypoplasia as well as asymmetric bony growth and is as follows.[17, 18, 19]

Ocular/orbital[20]

A solid conformer may be placed in the orbit to stimulate bony orbital growth and to enlarge the orbital cavity in an attempt to attain normal proportions.

Progressively increasing the size of conformers will often help to increase the size of the orbit.

Solid conformers require multiple procedures and are generally unable to keep pace with bony growth of the contralateral normal orbit.

An ocular prosthesis may be fitted over the conformer to improve the appearance.

In patients with unilateral anophthalmos, they and their families should be aware that the target proportions of a reconstructed orbit are not planned to exactly mirror that of a healthy orbit. In all likelihood, a perfectly normal-looking orbit will not be achieved.

Surgical Care

Surgical care in anophthalmos is as follows.[21]

Inflatable expander[22]

If conformers are not tolerated or are unsuccessful, an inflatable expander may be placed surgically.

The expander works best if placed relatively early in life, especially within the first year.

The inflatable silicone expander is placed surgically deep into the orbit and is accessible by a tube placed in the lateral orbital rim.

The expander can be gradually filled with liquid (eg, saline) on a weekly or biweekly basis.

The advantage of an inflatable expander is that it may allow more rapid and extensive orbital tissue expansion as compared with solid conformers.

Integrated orbital tissue expanders have been shown[23] to stimulate orbital bone growth in a feline model.[24]

Recent clinical reports have shown promising results in the stimulation of anophthalmic orbital growth.[25, 26]

Self-expanding hydrophilic, osmotic expanders[27]

A new possible treatment is the use of self-inflating expanders.

Hydrophilic expanders are placed in their dry, contracted state. The expanders then expand gradually to their full size via osmotic absorption of surrounding tissue fluid.

This method offers the benefit of controllable self-expansion, without the necessity of repeated fittings of solid conformers or surgical placement of external tubing required for inflatable expanders.

Long-term biocompatibility studies have not been completed, but early results are promising.

Injectable calcium hydroxylapatite

Volume augmentation in the anophthalmic socket with injectable hydroxylapatite (Radiesse) has been reported.[28]

Eyelid surgery

The increase in the size of a conformer is often limited by shortening of the eyelids in the palpebral fissure, which do not permit passage of a large conformer. The horizontal length of the palpebral fissure may be increased surgically by performing a lateral canthotomy or cantholysis.

An additional method to lengthen the eyelids can be accomplished by a combination of skin, mucosal, or cartilage grafts.

Eyelid reconstruction presents a challenge. In cases of anophthalmia, skin graft is required to construct eyelids. Since the area around the eye is cosmetically important, grafts from areas of the head covered by hairline may be advantageous.[29]

Orbital surgery

If conformers and expanders are unsuccessful, the bony orbit may be expanded surgically. This method is preferred in cases of late referral or insufficient orbital volume.

The orbit can be expanded in 3 different directions, as follows: laterally, inferiorly, and superiorly.

Surgical expansion of the orbit can be accomplished by dividing the bony orbital rim into 3 parts in a stepwise fashion.

Cranial bone grafts may be used to augment deficient orbital contours.

Lastly, a bicoronal approach through the scalp may be necessary when the orbital roof has to be elevated.

A survey of oculofacial surgeons found that silicone and acrylic were the most popular orbital implant materials in both adults and children, followed by porous polyethylene. The mean implant size was 20.2 ± 1.78 mm in adults and 17.2 ± 2.36 mm in the pediatric population.[30]

Consultations

Anophthalmos causes serious psychological problems due to not only the absence of an eye but also the disfigurement of the orbital socket and the eyelids. Psychological counseling or consultation may be warranted for these children.

 

Follow-up

Complications

Significant cosmetic deformities are often seen if the anophthalmic orbit is not treated early.

Even after proper treatment using conformers, expanders, or surgical treatment, results are often cosmetically disappointing.

Fitted prostheses are completely immobile.

The eyelids often show significant malformations and are shortened and immobile.

Phantom eye syndrome (PES) is defined as any sensation experienced by a patient with anophthalmia or enucleation and may include phantom pain, phantom sensation, and phantom vision.[31] These sensations may be painful and distressful and may lead to decreased quality of life.

Prognosis

True anophthalmos is considered a pediatric ocular emergency.

As the growth and development of the bony orbit are dependent on the growth of the globe, the absence of an eye or an extremely microphthalmic eye impedes the proper development of the orbit.

The small bony cavity not only is a cosmetic deformity but also does not allow proper fitting of a prosthesis.

Even with proper early treatment, results are often disappointing in patients with anophthalmos.

Recent neuroimaging studies found that a significant rewiring of the brain occurs in individuals with early-life blindness. In individuals with anophthalmia or early-life blindness, the superior colliculus is recruited for auditory processing.[32]

Patient Education

Inform the child with anophthalmos as well as the family that the treatment of this condition could be a long and complicated one.

Multiple conformers, expanders, and surgical treatments may be necessary to create an adequate-sized orbital cavity for placement of a proper-fitting prosthesis. In addition, multiple eyelid and conjunctival surgeries may be necessary throughout the child's life.

The National Eye Institute (NEI) maintains a Web page with answers to frequently asked questions and links to resources that patients may find helpful.