Microphthalmia (Greek: , ), also referred as microphthalmos, is a developmental disorder of the

eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...

in which one (unilateral microphthalmia) or both (bilateral microphthalmia) eyes are abnormally small and have anatomic malformations. Microphthalmia is a distinct condition from

anophthalmia Anophthalmia (Greek: ἀνόφθαλμος, "without eye") is the medical term for the absence of one or both eyes. Both the globe and the ocular tissue are missing from the orbit. The absence of the eye will cause a small bony orbit, a constricte ...

and nanophthalmia. Although sometimes referred to as 'simple microphthalmia', nanophthalmia is a condition in which the size of the eye is small but no anatomical alterations are present.

Presentation

Microphthalmia is a

congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

disorder in which the globe of the eye is unusually small and structurally disorganized. While the axis of an adult human eye has an average length of about , a diagnosis of microphthalmia generally corresponds to an axial length below in adults. Additionally, the diameter of the

cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...

is about in affected newborns and in adults with the condition. The presence of a small eye within the orbit can be a normal incidental finding but in many cases it is atypical and results in visual impairment. The

prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

of this condition is around 1 in 10,000 births, and it affects roughly 3–11% of blind children.

Causes

It has been postulated that microphthalmia arises as a result of interference with postnatal eye growth, in contrast to

which originates much earlier during fetal development. Genetic causes of microphthalmia include chromosomal abnormalities (e.g.

Patau syndrome Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some or all of the cells of the body contain extra genetic material from chromosome 13. The extra genetic material disrupts normal development, causing multiple and co ...

mosaic A mosaic () is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/Mortar (masonry), mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and ...

trisomy 9 Full trisomy 9 is a rare and fatal chromosomal disorder caused by having three copies ( trisomy) of chromosome number 9. It can be a viable condition if the trisomic component affects only part of the cells of the body ( mosaicism) or in cases ...

13q deletion syndrome 13q deletion syndrome is a rare genetic disease caused by the deletion of some or all of the large arm of human chromosome 13. Depending upon the size and location of the deletion on chromosome 13, the physical and mental manifestations will vary ...

Wolf–Hirschhorn syndrome Wolf–Hirschhorn syndrome (WHS) is a chromosomal deletion syndrome resulting from a partial deletion on the short arm of chromosome 4 el(4)(p16.3) Features include a distinct craniofacial phenotype and intellectual disability. Signs and sympt ...

) or monogenetic Mendelian disorders (e.g.

CHARGE syndrome CHARGE syndrome (formerly known as CHARGE association) is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart ...

, Fraser syndrome, oculofaciocardiodental syndrome, Lenz microphthalmia syndrome). Microphthalmia in newborns is sometimes associated with

fetal alcohol spectrum disorder Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person who is exposed to alcohol during gestation. FASD affects 1 in 20 Americans, but is highly misdiagnosed and underdiagnosed. The several forms of the ...

or infections during pregnancy, particularly

herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two members of the Herpesviridae#Human herpesvirus types, human ''Herpesviridae'' family, a set of viruses that produce Viral disease, viral infections in the majority of humans. Both HSV-1 a ...

rubella Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and ...

and

cytomegalovirus ''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...

(CMV), but the evidence is inconclusive. The following genes, many of which are transcription and regulatory factors, have been implicated in microphthalmia, anophthalmia, and coloboma: ''SOX2'' has been implicated in a substantial number (10–15%) of cases and in many other cases failure to develop the ocular lens often results in microphthalmia.

Microphthalmia-associated transcription factor Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...

(MITF), located on chromosome 14q32, is associated with one form of isolated microphthalmia (MCOP1). In

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s, the failure of expression of MITF in the

retinal pigment epithelium The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), ...

prevents this structure from fully differentiating, causing a malformation of the

choroid fissure The tela choroidea (or tela chorioidea) is a region of meninges, meningeal pia mater that adheres to the underlying ependyma, and gives rise to the choroid plexus in each of the brain’s Ventricular system, four ventricles. ''Tela'' is Latin for ...

of the eye and drainage of

vitreous body The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the Lens (vision), lens and the retina of the eye, eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as ...

fluid. Without this fluid, the eye fails to enlarge, resulting in microphthalmia.

Waardenburg syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...

type 2 in humans may also be caused by mutations in MITF The human MITF gene is homologous to the mouse microphthalmia gene (gene symbol mi);

mouse A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...

with mutations in this gene are hypopigmented in their fur. The identification of the genetics of WS type 2 owes a lot to observations of

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

s of MITF-mutant mice.

Diagnosis

Microphthalmia is often diagnosed soon after birth. An initial diagnosis usually occurs after the eyes are inspected through the lids. In addition to visual examinations, measurements of the cornea are used in the diagnosis of this condition. An

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

may also be conducted to confirm whether the axial length of the eye is clinically below average (i.e. at least 2

standard deviation In statistics, the standard deviation is a measure of the amount of variation of the values of a variable about its Expected value, mean. A low standard Deviation (statistics), deviation indicates that the values tend to be close to the mean ( ...

s below the age-adjusted mean). When a case of microphthalmia is detected, the patient should visit an eye specialist as soon as possible. It is important for an

ophthalmologist Ophthalmology (, ) is the branch of medicine that deals with the diagnosis, treatment, and surgery of eye diseases and disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a ...

to conduct a thorough examination within 2 weeks after birth. The ophthalmologist will confirm the preliminary diagnosis and look for signs of other anomalies in both eyes. These abnormalities may include

coloboma A coloboma (from the Greek , meaning "defect") is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is ...

optic nerve hypoplasia Optic nerve hypoplasia (ONH) is a medical condition arising from the underdevelopment (hypoplasia) of the optic nerve(s). This condition is the most common congenital optic nerve anomaly. The optic disc appears abnormally small because not all t ...

, retinal dystrophy, and

cataract A cataract is a cloudy area in the lens (anatomy), lens of the eye that leads to a visual impairment, decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or ...

. Ultrasound may also be used to determine the presence of any internal eye issues, which may not otherwise be visible. It is possible for individuals with microphthalmia to have some vision in the affected eye(s). For this reason, the vision of infants with microphthalmia should be evaluated early on, even in severe cases. Pediatric vision tests along with electrodiagnostics are typically used to assess visual acuity. If no related symptoms are present, microphthalmia is defined as non-syndromic or isolated microphthalmia (MCOP). When occurring in conjunction with other developmental defects, it may be diagnosed as syndromic microphthalmia (MCOPS). Approximately 60 to 80% of microphthalmia cases are syndromic. Several types of MCOPS have been recognized based on their genetic causes:

Treatment

Microphthalmia cannot be cured. However, there are treatments options to manage the condition and its associated symptoms. When the affected eye(s) display some visual function, a patient's eyesight can be improved (sometimes up to good state) by plus lenses, as a small eye is usually far-sighted. When one of the eyes is unaffected, caution should be taken to guard this 'good' eye and preserve its vision. In these unilateral cases, eye

glasses Glasses, also known as eyeglasses (American English), spectacles (Commonwealth English), or colloquially as specs, are vision eyewear with clear or tinted lenses mounted in a frame that holds them in front of a person's eyes, typically u ...

may be worn to offer a measure of physical protection. A key aspect of managing this condition is accounting for the small volume of the eye. The small orbit size characteristic of microphthalmia can impact the growth and structural development of the face after birth. As a result, microphthalmia can cause hemifacial asymmetry. This possibility is a particular concern for individuals with unilateral cases of microphthalmia. With one eye of average size, the asymmetry often becomes much more severe as the child ages. An axial length of less than indicates that a microphthalmic eye's growth will not be sufficient, and intervention will be necessary to reduce the degree of facial asymmetry. Minimizing facial asymmetry is important for cosmetic and structural reasons. In order to address the size discrepancy of the affected eye(s), it is important to begin eye socket expansion early in life. The face reaches 70% of its adult size by roughly 2 years of age, and 90% of its adult size by about 5.5 years of age. Additionally, the symmetry fostered by early socket expansion allows for a better prosthetic fit later in life. Typically, an infant begins wearing a

conformer A conformer is a clear acrylic shell fitted after an enucleation of the eye Enucleation is the removal of the eye that leaves the eye muscles and remaining orbital contents intact. This type of ocular surgery is indicated for a number of oc ...

, or an unpainted

ocular prosthesis An ocular prosthesis, artificial eye or glass eye is a type of craniofacial prosthesis that replaces an absent natural eye following an enucleation, evisceration, or orbital exenteration. Someone with an ocular prosthesis is altogether blin ...

, in the first weeks of life. The conformer is repeatedly replaced with a prothesis of a slightly larger size. This process, which takes place during the first 5 years of life, gradually enlarges the eye socket. Socket expansion through the use of implants of increasing size is another effective strategy. After socket expansion is complete, a painted prosthetic eye can be worn for cosmetic reasons. If the microphthalmic eye has functional vision, an affected individual may opt against wearing a painted prothesis. Lenses are also sometimes used for cosmetic purposes, such as a plus lens to enlarge the microphthalmic eye.

Epidemiology

Microphthalmia and anophthalmia combined are estimated to occur in about 1 in 10,000 births, though estimates have varied from 2 and 23 in 100,000 births. Approximately 3–11% of all blind children born globally have microphthalmia.

References

External links

{{Congenital malformations and deformations of eye, ear, face and neck Congenital disorders of eyes Rare diseases