Overview of ICE syndrome

The eye works in a very precise and organised way, where each part has a specific job to do to help us see clearly, for example, the iris and the cornea. The iris is the coloured part of the eye that controls the amount of light that can be absorbed and enter the eye. The cornea is the clear front surface of the eye that protects the eye from dust and germs. To help the eye maintain its focus and achieve sharp, clear vision, there are cells on the inside of the cornea called endothelial cells. These cells are in control of the amount of fluid passing into the cornea to avoid excessive fluid from entering, thus keeping it from swelling and becoming cloudy.

When the endothelial cells stop working properly, the iris becomes misshapen, leading to a disruption in the eye and causing vision loss. In other cases, the cornea can become swollen, leading to blurred and cloudy vision due to the excessive fluid gathering in the eye. Iridocorneal endothelial syndrome (ICE syndrome) occurs when the balance of the eye is disordered. It involves the endothelial cells lining the back of the cornea, to start behaving abnormally. These cells begin to grow, multiply and spread into areas they don’t normally belong, such as:

• The angle of the eye, which is a structure that plays a vital role in maintaining the eye pressure
• The iris of the eye

As these abnormal cells spread, they form a thin, skin-like membrane, which can cause two major problems:

• Glaucoma which is a rise in eye pressure due to the drainage channels being blocked. This can cause damage to the optic nerve and lead to vision loss if not treated immediately¹
• Corneal decompensation, which is the swelling and clouding of the cornea due to the abnormal behaviour of the endothelial cells, hence causing blurry or reduced vision¹

If ICE syndrome is not managed accordingly, it could affect day-to-day activities such as reading, driving or working, especially if the eye becomes blurry and cloudy.

ICE syndrome is a rare and irreversible eye disorder; it normally affects only one eye. It is typically not inherited, meaning it is not something that runs in the family. It could affect both males and females. However, it is more commonly found in women between the ages of 20-50 years.²

ICE syndrome is not just a single disease; it is a group of three related eye conditions. While the original cause is the same, the subtypes look and behave differently depending on how and where the changes occur. They all come from the same root problem, the abnormal behaviour of the endothelial cells. The cells start to grow and migrate to other parts of the eye where they don’t belong. These changes will lead to the disruption of the internal balance of the eye, the structure and fluid balance. If not managed properly, this will lead to cloudy blurred vision, glaucoma and the misshape of the iris, hence leading to impairment in vision and eventually vision loss.

The three subtypes are:

• Chandler’s Syndrome
• Essential Iris Atrophy
• Cogan-Reese Syndrome

Chandler’s syndrome

Chandler’s Syndrome (CS) is the most common type of ICE syndrome; it accounts for about 50% of the ICE cases. Patients with CS are often characterised by the swelling of the cornea, while the iris usually appears normal and is less affected.⁵ The swelling of the cornea leads to blurry or foggy vision. This is due to the endothelial cells being disrupted. The endothelial cells start to interfere with the normal function of the eye. This results in the build-up of fluids in the cornea, causing swelling and hence blurred vision. Unlike the other subtypes, the iris of the eye is usually unimpaired and looks normal, although glaucoma (a rise in eye pressure) could be evident in CS; it tends to be milder and slower to progress compared to the other ICE subtypes.

Essential iris atrophy

In Essential Iris Atrophy (EIA), the iris is severely affected. The abnormal membrane formed by the overgrowth of the endothelial cells starts to pull towards the iris, causing it to shrink, shift the pupil off-centre (a condition called ectopia) or even create holes in the iris. These changes will cause severe changes in the shape and appearance of the eye, making it appear misshapen and interfering with vision, eventually leading to vision loss. This can also damage the eye drainage system, leading to the buildup of fluid inside the eye. As a result, it is more likely that patients with this type of syndrome will develop glaucoma earlier compared to other subtypes. EIA generally tends to be more violent than other forms of ICE syndrome. If not diagnosed and treated promptly, vision loss might occur faster due to the aggressive damage to the internal structure.

Cogan-reese syndrome

With Cogan-Reese syndrome (CRS), it is shown that small, dark coloured bumps are formed on the surface of the iris of the eye.⁵ The changes are normally represented by bumps appearing as subtle yellow in early stages and becoming darker, larger and more noticeable as the condition progresses.^4,5 These bumps are made of the same abnormal growth of endothelial cells, although they don’t cause the iris to change shape, those bumps on they can still interfere with the eye’s fluid management. Research has shown that patients with CRS are more likely to develop more serious and harder-to-control glaucoma than the other subtypes.³

Even though each type of ICE syndrome is unique, all the subtypes could lead to serious vision problems, either due to glaucoma or due to the cornea being swollen. They are caused by the same abnormal growth of the corneal endothelial cells. They start to multiply and spread onto parts of the eye where they shouldn’t.

Medical management

Treating ICE syndrome can be challenging. Currently, no treatment is available that targets the abnormal growth that occurs in ICE syndrome. This means that the abnormal cell growth cannot be treated; hence, the treatment is aimed at controlling the glaucoma and preserving corneal clarity to maintain vision. This usually involves eye drops to manage the eye pressure. In more advanced cases, some reports also showed that medical surgery is necessary. Without proper treatment, care and monitoring, blindness could occur in patients with ICE syndrome.

Possible causes of ICE syndrome

The exact causes of ICE syndrome are still not known. However, old research has associated some viral infections, such as Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV) and Epstein-Barr Virus (EBV) with it.⁵ However, evidence is conflicting, and some studies do not agree with this and have found no such evidence.^{6, 7} No direct cause has been confirmed yet. More research involving larger studies and more patients is needed to develop a better understanding of what leads to ICE syndrome.

Iris reconstruction could also be done surgically.  This means the iris could be fixed and rebuilt. However, it is very difficult in these cases because the iris is a very fragile tissue.⁷ It is also very challenging due to the glaucoma, hence keeping the incision as small as possible is necessary.⁷

Conclusion

In conclusion, detection and monitoring of ICE syndrome is very important to maintain quality of life and vision. This could be done by having regular check-ups with an eye specialist. Patients with ICE syndrome will notice small changes in eye vision, such as blurry vision, halos, misshapen pupils and yellowish spots on the eye. Once these symptoms are apparent, it is important to see an eye specialist. Even though the abnormal growth of the endothelial cells cannot be stopped or reversed, by diagnosing ICE syndrome and addressing these symptoms early gives a greater possibility to manage the symptoms by controlling the eye pressure and slowing down vision loss.

Figure 1