What is Iridocorneal Dysgenesis?
Iridocorneal dysgenesis (ICD) is a term that refers to a range of disorders that stem from the abnormal development of the front part of the eye, known as the anterior segment. Specifically, it affects parts of the eye that originate from a group of cells called the neural crest. These parts include the corneal stroma (a layer of the cornea, the clear front surface of the eye), the endothelium (the innermost part of the cornea), the iris stroma (the colored part of the eye), and the trabecular meshwork (a part of the eye involved in draining fluid).
If these neural crest cells don’t move or form correctly during the eye’s development, this can lead to the creation of an anterior segment that’s not normal, a condition known as anterior segment dysgenesis (ASD), and it can eventually lead to glaucoma, an eye condition that damages the optic nerve. Depending on what triggered these developmental problems, the condition can be classified as either coming from the neural crest (ASD-nc) or not originating from the neural crest (ASD non-nc).
What Causes Iridocorneal Dysgenesis?
Neural crest cells play a crucial role in the development of certain parts of our eyes. These cells start to move from a part of the developing brain called the neural tube on the 24th day of embryo development. In the eyes, they form different parts including corneal keratocytes, endothelium, trabecular meshwork, and iris stroma.
These cells move in three separate groups:
- The first group forms the trabecular meshwork and the corneal endothelium,
- The second group forms keratocytes, and
- The third group forms the iris stroma.
By the seventh month of pregnancy, parts of the eye have formed, the iris has moved backward, revealing the trabecular meshwork, and the flow of eye fluid, the aqueous, starts. If neural crest cells move abnormally or change differently than they should during the development of these eye parts, it results in a condition called anterior segment dysgenesis.
This condition can obstruct the flow of eye fluid and increase eye pressure. It can lead to various eye conditions in babies, including primary congenital glaucoma, iris hypoplasia, congenital hereditary endothelial dystrophy, and others. Apart from environmental and random factors, genetics also play a role in anterior segment dysgenesis.
Problems with the development of neural crest cells can lead to abnormalities of the iris and posterior cornea. If the first group of cells doesn’t develop correctly, it can result in conditions like Peters anomaly, sclerocornea, and congenital hereditary endothelial dystrophy. If the third group of cells develop wrongly, it can result in conditions like Axenfeld and Rieger’s anomaly.
The abnormality also results in a condition called sclerocornea, which is observed by the 7th week of pregnancy. Chromosome testing of affected family members, however, does not reveal any abnormal chromosomes.
Risk Factors and Frequency for Iridocorneal Dysgenesis
Primary congenital glaucoma is a condition that affects infants, and its frequency varies between different ethnic groups. Depending on the group, it could affect anywhere from 1 in 10,000 to 1 in 2,500 newborns. In a study of the Chinese population, nearly half of all childhood glaucoma cases were found to be congenital.
Another condition, known as Axenfeld-Rieger anomaly, occurs in approximately 1 in 200,000 births. Half of the people with this condition will develop glaucoma later in childhood or early adulthood. Congenital corneal opacity, or cloudiness of the cornea at birth, occurs in 2.2 out of every 100,000 people in the US. The Peters anomaly, which is a subtype of congenital corneal opacity, accounts for 1.5 out of every 100,000 people. Interestingly, this anomaly is the reason for 65% of corneal transplants in infants in the US.
An additional condition, known as aniridia, or a lack of the iris in the eye, occurs in about 1.8 out of 100,000 births. This genetic disease is usually inherited and can result in the development of certain types of tumors. The prevalence of CHED, or congenital hereditary endothelial dystrophy, is not known currently. Lastly, about half of the cases of sclerocornea, or a clouding that occurs over the cornea, involve either dominant or recessive genetic patterns, and the remaining cases aren’t related to genetics. More severe cases of sclerocornea are usually linked to recessive genetics.
Signs and Symptoms of Iridocorneal Dysgenesis
Primary Congenital Glaucoma is a condition that usually shows up within the first six months of a baby’s life and causes increased pressure inside the eye. Symptoms include enlarging of the corneal diameter, thinning of the area around the cornea known as the sclera, and formation of certain stretch marks (Haab striae). The main indicators of this condition are excessive tear production, sensitivity to light, and eye-spasm.
Upon examination, it’s found that the colored part of the eye (iris) may be inserted closer to the drainage area (trabecular meshwork) than normal. This condition typically doesn’t come with other systemic issues, but similar tendencies can be observed in conditions like Rubenstein Tayabi syndrome, oculocerebrorenal syndrome, and Pierre-Robin syndrome.
Iris Hypoplasia is a condition where the iris appears gray or brown. This is due to the underneath layer of the iris showing through the iris stroma layer, which is underdeveloped. When diagnosing with the gonioscopy, the angle appears normal.
Axenfeld-Rieger anomaly (AXRA) is a condition where an individual’s eye shows visible signs of abnormalities including an apparent prominent line at the back of the eyes (Schwalbe’s line), extensive iris processes, and changes in iris structures. It’s important to note that this comes in a spectrum of abnormalities like Axenfeld-Rieger syndrome that includes facial and dental anomalies, hypertelorism, hypoplasia of the maxilla, microdontia, and more.
Peters Anomaly is a disorder that causes deficient central endothelium and posterior stroma characterized by opacity. It can be classified into Type I and II, depending on whether it’s the iris or the lens forming a cataract as a result of the disorder. The classification further goes into the extent and location of corneal opacification.
Aniridia is a condition characterized by the partial or complete absence of the iris. It is usually associated with sensitivity to light and poor vision due to underdeveloped portions of the eye. Anirida can also lead to other complications like nystagmus, cataracts, and corneal opacity, which affect the transparency of the cornea. 50 to 85 percent of people with Aniridia also develop cataracts.
CHED is a condition that causes bilateral corneal opacity and deteriorates visual function from early childhood. Symptoms include corneal clouding and nystagmus. During diagnosis, there’s usually a bluish-gray and coarse appearance of the cornea.
In Sclerocornea, the cornea develops into a non-progressive scleralization from peripheral corneal scleralization to diffuse corneal involvement. Usually, this disorder comes with cornea plana, and it affects the usual demarcation between the cornea and sclera.
Congenital Iris Ectropion is a condition marked by a deviation in the structure of the iris epithelium. Other indications of this condition include a smooth and cryptless iris surface, a malformed drainage angle, a high iris insertion, and drooping of the eyelid (ptosis) on the same side.
Testing for Iridocorneal Dysgenesis
Primary Congenital Glaucoma
In children suspected of having this eye condition, doctors may need to perform an examination under anesthesia. This is because the tests they need to do could be uncomfortable or scary for a child who is awake. During this examination, the doctor will measure the size of the cornea (the clear outer layer at the front of the eye), the pressure inside the eye, the thickness of the cornea, and the length of the eyeball. The doctor will also look inside the eye using a special tool. They’ll look for signs of progressive nearsightedness, which can be a clue that the disease is getting worse.
Axenfeld-Rieger Anomaly (AXRA)
If your doctor suspects this condition, they will do a very thorough examination of the front part of your eye. They will look for certain characteristics, like a pronounced ring in the front part of your eye and specific features of the iris (the colored part of your eye). As this condition sometimes comes with other body symptoms, they’ll examine the rest of your body as well.
Peters Anomaly
In cases of Peters anomaly, certain imaging tools are used to take a detailed look at your eye, which helps in deciding the best treatment approach. If you have a severe form of this condition, the doctor will also examine the back part of your eye using sound waves.
Aniridia
In the case of aniridia, where the iris is either partially or entirely missing, your doctor will need to do a detailed examination to identify why your vision is decreased. This could be due to several factors, including certain specific eye conditions. Cataract surgery can be complicated in these patients due to other factors like rapid eye movement, specific types of cataract, and poor eye surface condition. Glaucoma, a group of eye conditions that damage the optic nerve, is common in people with aniridia, which is why a detailed evaluation for glaucoma is necessary.
CHED
In CHED, a condition where the cornea becomes cloudy at birth or shortly after, a particular imaging hardware is used to measure the thickness of your cornea. Your doctor will also do an exam under anesthesia to measure the pressure inside the eye and see if there is a possibility of glaucoma. CHED is sometimes associated with hearing loss, so regular hearing tests should be done for these patients.
Sclerocornea
Similar imaging tools as used in Peters anomaly and CHED are also used for examining sclerocornea, a condition wherein the cornea blends with the white of the eye. There is a high risk of glaucoma with sclerocornea, so regular check-ups are necessary.
Congenital Iris Ectropion
In congenital iris ectropion, where the iris is turned outward and visible on the eye’s surface, evaluation for glaucoma needs to be conducted because this condition is often associated with glaucoma.
Treatment Options for Iridocorneal Dysgenesis
Primary congenital glaucoma, a severe eye condition commonly observed in infants, is mostly managed through surgical treatments rather than drugs or other non-invasive treatments. The purpose of these surgeries is to counteract irreversible damage to the optic nerve. Among such surgical procedures, goniotomy and trabeculotomy are often implemented as primary tactics. In certain stubborn cases, alternate surgical techniques such as trabeculectomy and the use of glaucoma drainage devices are sometimes employed. In general, surgical intervention is undertaken as early as possible to prevent permanent harm to the optic nerve.
Various forms of glaucoma result from different abnormalities. For instance, if the patient suffers from Iris Hypoplasia, which is a genetic disorder that affects the development of the eye, they require therapy. In the course of a condition known as Axenfeld-Rieger anomaly, patients run the risk of developing glaucoma in the long run. To manage this condition, surgery plays a critical role to regulate the pressure within the eyes. Another condition, the Peters anomaly, calls for diverse treatments depending on the intensity or kind of disease. Mild cases may necessitate simple observation while severe types may demand transplantation of the cornea. In addition, if the disorder is combined with other syndromes, further systemic treatments may be needed.
Aniridia, a condition that leads to the absence of an iris in the eye, may often result in dry eye due to the malfunction of meibomian glands that are responsible for oil production in the eye. In such cases, eye drops can help regulate dry eye. Deterioration of the cornea’s surface can be maintained via the use of anti-inflammatory agents. Vision restoration, if needed, can be accomplished through corneal transplantation.
For those suffering from glaucoma affiliated with Aniridia, surgery is usually necessary. There is a range of surgical procedures available such as goniotomy, trabeculotomy, and trabeculectomy. One often needs to make specific adjustments during cataract surgeries to avoid further damage to the eye. Other treatment options, such as corneal tranplantation or therapies to modify the cornea, are available for conditions like Sclerocornea or Congenital Iris Ectropion.
What else can Iridocorneal Dysgenesis be?
There are situations in medicine where different conditions can show similar symptoms, which can be confusing. For instance, Primary congenital glaucoma and CHED often show up with a ground glass cornea, which makes it difficult to differentiate between them. However, some distinctions are, for example, a larger corneal diameter and Haab’s striae are usually found in congenital glaucoma. When observed, it’s critical to note the difference between birth trauma and Haab’s striae. The breaks in the Descemet membrane due to birth trauma generally stand vertically, while the true Haab striae either lay horizontally or curve.
AXRA, which affects both eyes, needs to be separated from the ICE syndrome that usually only affects one eye.
- Sclerocornea and Peter’s anomaly should be seen as different from other reasons that can cause congenital corneal opacities. Usually, Sclerocornea affects both eyes and often comes with cornea plana. Conversely, Peter’s anomaly can affect one or both eyes.
- Congenital aniridia needs to be differentiated from aniridia that occurs due to an injury.
- The condition most similar to congenital iris ectropion is the Axenfeld-Rieger anomaly and the iridocorneal endothelial syndrome (also known as the ICE syndrome). However, congenital iris ectropion usually does not come with iris holes.
Being aware of these differences will make diagnoses more accurate.
What to expect with Iridocorneal Dysgenesis
Primary Congenital Glaucoma
In simple terms, primary congenital glaucoma is a condition that can affect the eye health of a newborn. The effect of this condition and how it impacts the patient’s life depends on how old the child is when the disease starts to show signs, and how severe the disease is at that time. It is known that if this condition is diagnosed and treated early, there’s a positive chance of successful recovery.
Axenfeld-Rieger Anomaly
Next is Axenfeld-Rieger anomaly, a rare genetic disorder that affects the eyes. To manage this condition, it’s important to have frequent medical check-ups. The future health condition, or prognosis, of a patient with this anomaly depends on their age at which symptoms appear and how severe the disease is at that time. If a person with Axenfeld-Rieger anomaly also has heart problems or other systematic anomalies, the prognosis might be more challenging.
Aniridia
Aniridia is a disease that can cause partial or total absence of the iris, the colored part of the eye. Standard glaucoma surgeries usually are not efficient for patients with this condition. Still, they’ve found that glaucoma drainage devices, devices that help control eye pressure, seem to produce more effective results.
CHED
CHED, also known as Congenital Hereditary Endothelial Dystrophy, is a condition that makes the corneas, the outer layer of your eyes, become cloudy. However, it’s known that certain types of transplant surgeries on the cornea can help patients have a positive outcome. The risk of the new cornea getting rejected post-surgery is 1% for DMEK, 12% for DSAEK, and 18% for PK.
Sclerocornea
Sclerocornea is a rare eye disorder where the cornea gets covered by a white, opaque layer. However, certain types of procedures can help patients overcome this condition.
Congenital Ectropion
Lastly, congenital ectropion is when the lower eyelid turns outwards at birth. If accompanied by glaucoma, the outlook may not be good and early surgery is often recommended.
Possible Complications When Diagnosed with Iridocorneal Dysgenesis
In primary congenital glaucoma, complications like Haab’s striae that lead to significant corneal opacity can develop. This condition can cause significant astigmatism and blindness if not controlled well. The axial length may progressively increase leading to nearsightedness and lazy eye.
In AXR anomaly cases, approximately 50% of patients develop glaucoma.
In cases of Peters anomaly, if left untreated, it may result in severe lazy eye. Post-surgery, patients may face complications related to cornea transplant.
For Aniridia patients, complications may include total corneal opacity, continuous epithelial defect (a type of cornea injury), and lens dislocation due to total limbal stem cell failure.
For CHED cases, blurry vision and graft-related complications are common risks.
In case of Sclerocornea, complications can include glaucoma, cornea degradation, cataract, small eyes, nystagmus, internal squint combined with hypermetropia and astigmatism, and weak or lazy eye.
In the Congenital Ectropion Syndrome, patients may face complications such as congenital glaucoma, early onset glaucoma, lazy eye, and a severe eye condition known as phthisis.
Main complications:
- Haab’s striae leading to significant corneal opacity
- Absolute corneal opacity
- Continuous epithelial defect
- Lens dislocation
- Glaucoma
- Cornea degradation
- Cataract
- Small eyes
- Internal squint
- Hypermetropia and astigmatism
- Lazy eye
- Severe eye condition known as phthisis
- Complications related to cornea transplant
- Blurry vision
- Graft-related complications
Preventing Iridocorneal Dysgenesis
It’s very important to talk about the progression of the disease with patients and/or their families. This helps the patient understand what to expect in the future and promotes the necessity of timely check-ups. The risk of developing glaucoma, a condition that damages the eye’s optic nerve, within the range of the disease being discussed should also be explained. If appropriate, family members may also need to be checked.
