What is Iris Ectropion Syndrome?
Iris ectropion syndrome, also called ectropion iridis or ectropion uveae, is a condition where the coloured part of your eye (iris) turns outward or the pigmented cells of the iris can be seen on the front surface of the iris. This can be present from birth (congenital) or develop over time (acquired).
The congenital form of this condition was first reported by Dr. Colsman in 1869, although what he described was actually iris flocculi. Iris flocculi are harmless cyst-like structures that develop from the pigmented cells at the edge of the pupil. Drs. Boleslaw Wicherkiewicz and Spiro are widely acknowledged for reporting iris ectropion syndrome for the first time in the 1890s. Usually, congenital iris ectropion affects only one eye and doesn’t progress, but there have been cases where it affects both eyes. In some cases, it may be associated with a specific type of glaucoma, a condition that causes damage to your eyes’ optic nerve and gets worse over time.
At birth, the back pigmented layer of the iris is observed on the front layer. The surface of the iris is very smooth, without any irregularities. Other characteristics include the iris being attached to the front of the eye and faulty development of the eye’s drainage angle. The muscle controlling the size of the pupil and the supporting framework of the eye are typically not affected. Often, it goes hand in hand with developmental glaucoma. Other associated features may include a minor drooping of the eyelid, neurofibromatosis, Prader-Willi syndrome, overgrowth of one side of the face, prominent nerves in the front part of the eye, asthma, late-forming dental problems, and an eye disorder called Rieger anomaly.
Acquired iris ectropion can develop due to various conditions and is more common than the congenital type. In this case, a membrane develops on the front of the iris creating a pulling force that brings the back pigmented layer of the iris outward. This can be linked to the overgrowth of new blood vessels in the iris. Conditions leading to the development of this membrane include diabetic eye disease (proliferative diabetic retinopathy), blockage of the veins in the retina (venous occlusions), and conditions causing problems with blood supply, inflammation, and abnormal growth of cells. Unlike the congenital form, acquired ectropion continues to worsen unless the underlying causes are addressed.
What Causes Iris Ectropion Syndrome?
Iris ectropion syndrome is a condition that can be present from birth (congenital) or it can develop later (acquired). Simply put, it means that the pigment from the back of your iris (coloured part of your eye) moves to the front. However, it is important to note that the iris and the uvea (the middle layer of the eye) are two separate things, even though in a clinical context the term “ectropion uveae” is commonly used to describe this condition. It has not been linked to any genes except in a few cases. There have been reports, for example, of babies developing these symptoms at birth due to specific mutations in the CYP1B1 gene, which lead to severe bilateral congenital glaucoma.
Congenital iris ectropion, or congenital ectropion uveae, is where the pigment of the iris, which usually sits at the back, side of the pupil, and forms a border around it, actually starts to move to the front of the iris. Usually, the pigmentation does not reach the very edge of the iris. The cause of this could be irregular development of certain cells, called neural crest cells, and could be part of a series of related conditions known as neurocristopathy.
Neural crest cells are important for developing various eye structures like the cornea’s inner layer (endothelium), the drainage structure of your eyes (trabecular meshwork), and the iris. If these cells don’t develop, move and change correctly, it can result in what are known as anterior segment dysgenesis syndromes, which include conditions like Axenfeld Rieger syndrome and Peters anomaly.
The pigmentation of the iris usually starts at the pupil and moves outwards towards the edge of the iris. This pigmentation normally doesn’t reach the front of the iris, which stays non-colored. The muscles that dilate (open wide) and constrict (narrow down) your pupil develop from the front layer of the iris. If something goes wrong with this process, it could lead to the development of iris ectropion.
There are several conditions, including congenital glaucoma and posterior embryotoxon, that have been attributed to irregular migration of neural crest cells. In addition, conditions like Chandler syndrome and Essential iris atrophy are associated with abnormal growth of these cells, and abnormalities in the cell transformation may result in certain corneal dystrophies.
Acquired iris ectropion can develop due to conditions like neovascular glaucoma, which is associated with the formation of new blood vessels. This is commonly seen in conditions like retinal venous occlusion, a condition where blood flow within the retina is blocked. This can lead to the formation of new blood vessels, causing neovascular glaucoma, or a more severe form of glaucoma that typically occurs 90 days after the blockage is first experienced. Other causes include proliferative diabetic retinopathy, a condition where diabetes causes the retina to be damaged over time, and central retinal artery occlusion, a blockage of the main artery that supplies blood to the retina. These conditions can also cause neovascularisation, or the formation of new blood vessels, which can result in acquired ectropion uveae. Further causes include Coats disease, where the blood vessels of the retina aren’t properly developed, or even disorders like sickle cell disease and various other inflammatory conditions. In very rare cases, iris melanoma, or cancer, can cause the formation of blood vessels in the iris, leading to ectropion uveae.
Risk Factors and Frequency for Iris Ectropion Syndrome
Acquired ectropion uveae, a condition of the eye, is more common than the inherited type, known as congenital ectropion uveae (CEU). Not many cases of CEU have been reported in history. For instance, until 1914, there were only twenty-four known patients. Further research from 1984 indicated the existence of thirty patients in total. In this research, the majority of the cases, 7 out of 8, developed a condition called glaucoma. A different study reported nine patients who had one-sided CEU with glaucoma and other conditions.
- Later on, there have been individual reports of one-sided or two-sided CEU.
- In 2022, a study found 13 newborn babies with two-sided ectropion uveae and serious glaucoma.
The number of people getting acquired ectropion uveae can change based on what’s causing it. In a study that looked at 317 patients with iris melanoma, a type of eye cancer, over 40 years, twenty-four of them were found to have ectropion uveae. This condition also appears quite often in patients with neovascular glaucoma and absolute glaucoma.
Signs and Symptoms of Iris Ectropion Syndrome
Congenital iris ectropion is a condition that can appear at any stage from childhood to adolescence, and it is usually not passed down genetically. More often than not, it impacts one eye. Some patients with this condition may have normal vision, while others might experience diminished visual acuity, headaches, red eyes, and increased tearing. This condition usually does not present with common signs of congenital glaucoma such as light sensitivity, excess tear production, and involuntary eye closure.
Upon examination using a slit-lamp microscope, the doctor may find uneven coloration on the front of the iris. The colour gradient does not extend to the angle of the eyes. The rest of the iris may appear transparent and flat without any radial lines or circular grooves. The iris’ muscular connective tissue may show varying degrees of underdevelopment. The round shape of the pupil might get distorted in cases where a portion of the iris is affected by ectropion. The pupil may also be large or situated off-center.
The pupil might not always respond normally to light. Other findings may include a clear cornea, a slight droop in the eyelid on the affected side, slight bulging of the eye, and the presence of pronounced corneal nerves. This condition might also be associated with syndromes such as neurofibromatosis type 1 and Prader Willi syndrome. Increased ocular pressure (IOP) leading to glaucoma may develop at any stage from infancy to adulthood.
An examination of the drainage angle within your eye may show an anterior iris insertion, prominent iris processes, a prominent Schwalbe line, coloration at the angle, and an underdeveloped trabecular meshwork – the tissue that drains fluid from the eye. Additionally, upon examining the optic nerves, varying stages of damage due to glaucoma can be detected.
In cases where this condition is acquired later in life, there may be new, fine blood vessels on the iris and within the angle of the anterior of the eye. This condition may lead to increased IOP due to neovascular glaucoma. The doctor may also find other associated issues such as inflammation and possible nerve damage. Other causes of these new blood vessels could be vein occlusions, proliferative diabetic retinopathy, persistent retinal detachment, and arterial occlusions. Severe eye inflammation could also lead to the formation of new blood vessels.
Testing for Iris Ectropion Syndrome
In cases of iris ectropion syndrome, whether it’s something you’re born with (congenital) or something that develops over time (acquired), a basic eye examination is usually enough for a doctor to make a diagnosis. If the condition appears in a newborn and affects both eyes, genetic testing may be carried out.
Several standard procedures are performed as part of this examination. These include a slit-lamp examination, which is a close up look at your eyes under a special focused light; a gonioscopy, which helps the doctor look at the drainage angle of your eye; and a fundus evaluation, which involves examining the back of your eye. The doctor may also measure your eye pressure. A photo of the front part of your eye, called an anterior segment photo, may also be taken to record the state of the disease.
In some cases, additional tests might be needed. These could include an ultrasound of your eye, an optical coherence tomography (OCT) which uses light to create detailed images of your eye, or a fundus fluorescein angiography – a procedure that involves injecting a special dye into your bloodstream and taking photographs as the dye passes through the blood vessels in the back of your eye.
In some instances, an ultrawide field fundus fluorescein angiography might be necessary. This can help doctors identify problems in the far edges of the retina, even in cases where the pupil is small or there are issues with the clarity of the eye.
If you also have glaucoma, a group of eye conditions that can cause vision loss, further tests would be required. Your doctor may need to measure the thickness of your cornea (the clear front surface of your eye), examine your optic disc (which is where the optic nerve connects to your eye) and the layer of nerve fibers in your retina via an OCT, take a picture of the back of your eye, and carry out a Humphrey visual field test to assess your side (peripheral) vision and central vision.
Treatment Options for Iris Ectropion Syndrome
In the case of NO-CEU, a type of eye condition, early surgical interventions are needed. These procedures, such as trabeculotomy and trabeculectomy, help in managing the condition. However, another technique called goniotomy might not work well. If you have NO-CEU, you would need frequent check-ups as glaucoma, an eye condition that can cause vision loss, can develop at any age.
Certain treatments might not be successful for everyone, and you may need to undergo multiple procedures. For older patients, procedures that include inserting a small device (shunt or valve) may be necessary to control eye pressure. On average, NO-CEU tends to have a more challenging prognosis than primary congenital glaucoma, another type of eye disorder.
Some previous cases show that trabeculectomy—a surgical procedure to relieve intraocular pressure—with a medicine called mitomycin C led to good results, effectively controlling eye pressure and reversing the optic nerve’s damage. These positive results underline the importance of early surgical treatment for glaucoma in patients with NO-CEU.
If acquired ectropion uveae—a condition where the inner surface of the eyelid turns outwards—presents, the treatment should focus on the underlying cause. Often, this condition happens due to a lack of adequate blood flow to the eye (ischemia) and insufficient oxygen supply to the retinal capillaries. These cases can be managed with laser treatment (pan-retinal photocoagulation) and injections of anti-VEGF drugs, which help reduce abnormal blood vessel growth.
However, treating a form of glaucoma caused by new blood vessel growth (neovascular glaucoma) can be challenging. Several treatments are used, including filtration surgery, in which a small piece of tissue in the drainage angle of the eye is removed, and implanting devices that help with drainage. If the eye becomes very painful and blind due to neovascular glaucoma, options include different types of laser treatments, injections, or even eye removal in severe cases.
Some patients may develop fluid build-up in the retina (macular edema) which can be managed with anti-VEGF injections, steroids, or a surgical technique known as pars plana vitrectomy. Care should be taken when using steroids as they can increase eye pressure and worsen neovascular glaucoma.
Lastly, if the cause is blockage in the neck arteries (carotid artery occlusive disease), removing the blockage and inserting a small mesh tube (stent) into the artery can reverse symptoms related to poor blood flow to the eyes.
What else can Iris Ectropion Syndrome be?
Congenital iris ectropion is a condition that happens when a part of the eye called the neural crest doesn’t develop properly in the womb. This can often be mistaken for other conditions that show a coloring of the front surface of the iris. One such condition is Axenfeld Rieger syndrome, which can also cause iris ectropion. This syndrome can either be present at birth or develop later in life. People with this syndrome have a smooth, cryptless iris surface and can develop secondary glaucoma. However, unlike those with congenital iris ectropion syndrome, they can also have misshapen pupils and holes in the iris. It usually affects both eyes and treatments such as goniotomy often do not work well.
Another condition that can be confused with congenital iris ectropion is the iridocorneal endothelial (ICE) syndrome. However, this is typically a condition that only affects one eye and presents later in life. In this condition, the pigmented epithelium, or colored layer of cells, increases in size. The endothelial cells, which are a type of cell that lines the eyes, start to behave like epithelial cells and begin to multiply and spread. This is different from congenital iris ectropion and Axenfeld Rieger syndrome, in which these endothelial cells are originally there from birth and don’t change.
What to expect with Iris Ectropion Syndrome
Congenital ectropion, which is a birth defect where the eyelid turns outward, linked with glaucoma, a condition that damages your eye’s optic nerve, often has a bad outcome. Congenital glaucoma requires early surgical treatment that involves two procedures – trabeculotomy and trabeculectomy. These are basically surgeries that help drain fluid from the eye to decrease high eye pressure.
However, there might be times when a ‘bleb’ or a small blister-like swelling filled with fluid that is often created as part of the surgery, fails to function properly, leading to a need for repeated surgeries. NO-CEU, which is a severe form of congenital glaucoma, often leads to decreased clarity of the cornea, which is the front surface of the eye, and poorer control of intraocular pressure (IOP) which is the fluid pressure inside the eye. This is especially the case when surgery is not performed.
As for acquired ectropion uveae, which is a condition where the internal part of the iris moves towards the white of the eye, but develops sometime after birth, the prognosis greatly depends on its cause.
Possible Complications When Diagnosed with Iris Ectropion Syndrome
Congenital ectropion uveae, a rare eye condition present from birth, can lead to several complications:
- Congenital glaucoma (increased pressure in the eye from birth)
- Juvenile glaucoma (increased pressure in the eye during childhood)
- Refractive error (issues with the eye’s ability to focus light)
- Amblyopia, specifically when only one eye is involved in children (a condition often referred to as ‘lazy eye’)
- Squint (when the eyes do not look in the same direction at the same time)
- Blindness
- Phthisis (shrinkage or atrophy of the eye)
Preventing Iris Ectropion Syndrome
For cases of congenital iris ectropion, which refers to a rare condition where the iris (the colored part of the eye) is turned outward, parents must know the importance of regular doctor visits as glaucoma (an eye disease that can cause blindness) may appear at any stage of the child’s life. It’s vital to manage any vision problems such as refractive error (an issue with focusing light accurately onto the retina), squint (when the eyes look in different directions), and amblyopia (often known as ‘lazy eye’) to enhance the child’s sight and improve coordination between both eyes.
Moving over to acquired ectropion of the iris, one that develops later in life, it might occur alongside neovascular glaucoma, which is a severe type of glaucoma caused by new, abnormal blood vessels growing on the iris. Here, immediate treatment is necessary to prevent the eye from getting blind and painful. This treatment commonly involves pan-retinal photocoagulation, a type of laser treatment, and anti-vascular endothelial growth factor agents, which are drugs to stop new blood vessels from forming. To ensure the treatment’s success, it is important to note that more than one doctor visit may be required.
