Sclerocornea is an extremely rare
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 ...
anomaly 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 ...
, it is considered a form of
congenital corneal opacity (CCO) with no clear gender bias, in which 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 ...
blends with
sclera
The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective outer layer of the eye containing mainly collagen and some crucial elastic fiber.
In the development of t ...
, having no
clear-cut boundary.
The extent of the resulting opacity varies from peripheral to total (''sclerocornea totalis''). While the exact historical origins of its documentation are unclear, studies on sclerocornea has long been recognized in
ophthalmology
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 ...
as a rare but significant anomaly going as far back as the 1960's. The severe form is thought to be inherited in an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
manner, but there may be another, milder form that is expressed in a dominant fashion. In some cases the patients also have abnormalities beyond the eye (
systemic), such as limb deformities and craniofacial and genitourinary defects.
According to one tissue analysis performed after
corneal transplantation
Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue (the graft). When the entire cornea is replaced it is known as penetrating keratoplasty a ...
, the sulfation pattern of
keratan sulfate
Keratan sulfate (KS), also called keratosulfate, is any of several sulfated glycosaminoglycans (structural carbohydrates) that have been found especially in the cornea, cartilage, and bone. It is also synthesized in the central nervous system whe ...
proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to w ...
s in the affected area is typical for corneal rather than scleral tissue.
Sclerocornea may be concurrent with
cornea plana.
Signs and symptoms

Sclerocornea causes parts or all of the cornea to become cloudy. This cloudiness can be partial or complete. The more of the cornea that is affected, the worse a persons vision will be. The main area affected is the cornea, but the issue can also spread to nearby parts of the eye, like the
limbus
Limbus (Lat. "edge, boundary") may refer to:
* Corneal limbus, the border of the cornea and the sclera (the white of the eye)
* Limbus of fossa ovalis, in the heart
* Limbus 3 and Limbus 4, two line-ups of a German avant-garde musical group
* ...
and front eye structure, such as the
iris
Iris most often refers to:
*Iris (anatomy), part of the eye
* Iris (color), an ambiguous color term
*Iris (mythology), a Greek goddess
* ''Iris'' (plant), a genus of flowering plants
* Iris (given name), a feminine given name, and a list of peopl ...
. Since Sclerocornea is present from birth and does not develop later in life there are no short-term
symptoms
Signs and symptoms are diagnostic indications of an illness, injury, or condition.
Signs are objective and externally observable; symptoms are a person's reported subjective experiences.
A sign for example may be a higher or lower temperature ...
or
signs. The condition usually affects both eyes and it does not worsen overtime, the symptoms and severity are present from birth and generally remain stable.
As a result and depending on the variety, the patient may have poor vision from birth and in some cases problems with eye movement, such as
nystagmus
Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...
or
strabismus
Strabismus is an eye disorder in which the eyes do not properly align with each other when looking at an object. The eye that is pointed at an object can alternate. The condition may be present occasionally or constantly. If present during a ...
. Over time, people may develop severe
farsightedness
Far-sightedness, also known as long-sightedness, hypermetropia, and hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blur is due to incoming light being focused behind, instead o ...
,
glaucoma
Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
, and other eye issues.
Cause
The exact
cause
Causality is an influence by which one event, process, state, or object (''a'' ''cause'') contributes to the production of another event, process, state, or object (an ''effect'') where the cause is at least partly responsible for the effect, ...
of Sclerocornea is not fully understood, but it is believed to involve
genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
and developmental factors during
fetus
A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...
development. Sclerocornea can be
inherited genetically, as
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
or
recessive trait
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
, with the latter form often being more severe.
There are findings suggesting that a
genetic locus
In genetics, a locus (: loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total numb ...
at
chromosome
A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
22q11.2
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent ...
plays a crucial role in the formation and development of the eye during the early stages of
embryonic growth. This gene in some cases are associated with the genetic disorders like
Digeorge syndrome
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent ...
,
PHACES syndrome,
Dandy-walker malformation, and
Hurler syndrome
Hurler syndrome, also known as mucopolysaccharidosis Type IH (MPS-IH), Hurler's disease, and formerly gargoylism, is a genetic disorder that results in the buildup of large sugar molecules called glycosaminoglycans (GAGs) in lysosomes. The inabil ...
making genetic counseling important.
The condition is thought to occur because the
neural crest cells
The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, an ...
don't move or develop correctly between the 7th and 10th week of
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
. These cells are important for forming many parts of the eye structures, and abnormalities in their formation can lead to issues.
Recent research has highlighted the role of
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
/
deletion in the
RAD21
Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the ''RAD21'' gene. ''RAD21'' (also known as ''Mcd1'', ''Scc1'', ''KIAA0078'', ''NXP1'', ''HR21''), an essential gene, encodes a DNA repair#Double-strand b ...
gene. A 2019 study suggest that beyond its known role in
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
and chromosome organization, RAD21 may also contribute to the development of peripheral sclerocornea.
Pathophysiology or mechanism
The main problem affected in sclerocornea occurs in the cornea, which doesn’t develop correctly and starts to look more like the white part of the eye (the
sclera
The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective outer layer of the eye containing mainly collagen and some crucial elastic fiber.
In the development of t ...
). The condition is thought to occur because certain cells, called neural crest cells, don’t move or develop as they should during the 7th and 10th weeks of
gestation
Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregn ...
. When these cells do not migrate correctly, the cornea does not develop into a clear structure. Instead, it becomes
opaque
Opacity is the measure of impenetrability to electromagnetic or other kinds of radiation, especially visible light. In radiative transfer, it describes the absorption and scattering of radiation in a medium, such as a plasma, dielectric, shie ...
and the boundary of the cornea is found to be poorly defined.
Under a
microscope
A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic ...
, the cornea’s layers, known as
stromal
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine muco ...
lamellae
Lamella (: lamellae) means a small plate or flake in Latin, and in English may refer to:
Biology
* Lamella (mycology), a papery rib beneath a mushroom cap
* Lamella (botany)
* Lamella (surface anatomy), a plate-like structure in an animal
* Lame ...
, are disorganized, have extra blood vessels, and the cornea’s structure is different from the usual structure of cornea's. Even though the cornea becomes more like the sclera, it still has some unique markers that show it retains some of its original characteristics.
Scientists don’t fully understand how all the changes happen, but they think it could be due to problems with certain genes such as 22q11.2. There are also studies coming out stating that a mutation or deletions in the gene RAD21 might be causing the bad development of neural crest cells.
Diagnosis
Diagnosis
Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...
typically involves a
pediatric
Pediatrics (American English) also spelled paediatrics (British English), is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, pediatrics covers many of their youth ...
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 ...
after a basic outpatient examination and might require a
geneticist
A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic process ...
for counseling if an inherited form is suspected. A
slit-lamp examination is used to evaluate the cornea.
Imaging techniques, such as
anterior segment optical coherence tomography (ASOCT), can help assess the depth of the opacity and the structure of the
anterior segment
The anterior segment or anterior cavity is the front third of the eye that includes the structures in front of the vitreous humour: the cornea, iris, ciliary body, and lens
A lens is a transmissive optical device that focuses or dispers ...
of the eye. Other evaluations include under anesthesia to get measurement of corneal thickness with ultrasound pachymetry.
Misdiagnosis
A medical error is a preventable adverse effect of care (" iatrogenesis"), whether or not it is evident or harmful to the patient. This might include an inaccurate or incomplete diagnosis or treatment of a disease, injury, syndrome, behavior, ...
can happen due to overlapping features with other congenital
corneal opacities
Corneal opacification is a term used when the human cornea loses its transparency. The term corneal opacity is used particularly for the loss of transparency of cornea due to scarring. Transparency of the cornea is dependent on the uniform diamete ...
. Diagnostic delays may happen if systemic associations are not immediately recognized.
Treatment or management

Primary treatment for Sclerocornea is
Penetrating keratoplasty (PK), it is only considered for severe cases although success rates are variable due to risks like
graft rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient ...
and
glaucoma
Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
. In a study, of eight patients with
Peters anomaly
Anterior segment mesenchymal dysgenesis, or simply anterior segment dysgenesis, is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, associa ...
and 10 with sclerocornea, underwent penetrating keratoplasty when they were 5 years or younger. The
graft
Graft or grafting may refer to:
*Graft (politics), a form of political corruption
*Graft, Netherlands, a village in the municipality of Graft-De Rijp
Science and technology
*Graft (surgery), a surgical procedure
*Grafting, the joining of plant ti ...
survival was poor in patients with sclerocornea compared to those with peters anomaly. Another study showed failure in 75% of the cases of PK (penetrating keratoplasty) in patients with sclerocornea. It is said that the presence of opacity or
vascularization
Vascularisation is the physiological process through which blood vessels form in tissues or organs. Vascularisation is crucial to supply the organs and tissues with an adequate supply of oxygen and nutrients and for removing waste products.
Bloo ...
in the limbus and in the
peripheral cornea and the diameter of the patients cornea were correlated with graft failure.
Non surgical options include refractive correction, such as glasses or contacts if possible or
optical iridotomy, this can be considered for milder cases.
Prognosis
The
prognosis
Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
depends on the extent of the condition. Visual outcomes depend on the timing and extend of intervention. Treatment of sclerocornea has a high rate of failing however those that succeed with treatment are likely to have favorable outcomes. The poor prognosis of corneal transplantation in sclerocornea is related to
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 ...
l vascularization, related to changes in the eye mostly
glaucoma
Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
, and the need for related surgeries such as lensectomy, a surgical procedure that removes the eye's natural lens and replaces it with an implant and
vitrectomy
Vitrectomy is a surgery to remove some or all of the vitreous humor from the Human eye, eye.
Anterior vitrectomy entails removing small portions of the vitreous humor from the front structures of the eye—often because these are tangled in an i ...
, among others. In patients with partial sclerocornea, optical correction, with glasses, should be performed early in order to avoid
amblyopia
Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to fully process input from one eye and over time favors the other eye. It results in decreased vision in an eye that typically appears normal in other aspects. Amb ...
due to high
hyperopia
Far-sightedness, also known as long-sightedness, hypermetropia, and hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blur is due to incoming light being focused behind, instead o ...
.
Epidemiology
Sclerocornea is a rare disorder, with no clear gender bias. In one study, 14 patients were diagnosed with a congenital corneal opacity over a 40-year study period, yielding a birth prevalence of 1 in 5188 live births. The mean age at diagnosis was 7.5 months (range 0–48 months) and 9 (64.3%) were males. Out of the 14 patients diagnosed only 2 of them had sclerocornea. This condition also often accompanies other
congenital disorders
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...
such as peters anaomly, affecting its distribution and manifestation.
Research directions
Recent research has focused on the genetic causes of sclerocornea and improving treatment options. Studies have identified that mutations in specific genes play a role in different forms of the condition.
GJA8 Mutations: Researchers found that mutations in the
GJA8
Gap junction alpha-8 protein is a protein that in humans is encoded by the ''GJA8'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA tha ...
gene can cause a severe form of sclerocornea, where the entire cornea is affected. This highlights the importance of testing for GJA8 mutations in patients with severe anterior segment abnormalities.
RAD21 Variant: Another study linked a RAD21 variant to peripheral sclerocornea, suggesting that this mutation alters chromosome structure and gene expression, contributing to the condition.
One of the main challenges in sclerocornea research is the rarity of the disease, which makes large-scale studies difficult. However, ongoing collaborative efforts and case reports are helping to expand understanding, particularly in developing new treatment strategies and documenting unique cases
References
External links
Congenital Clouding of the Cornea- eMedicine; by Noah S Scheinfeld, MD, JD, FAAD and Benjamin D Freilich, MD, FACS
{{Congenital malformations and deformations of eye
Eye diseases