Introduction

Chandler’s syndrome (CS) is a rare eye condition that affects the cornea (the clear outer dome at the front of your eye), iris (the coloured part of your eye), and the drainage system, found between the cornea and iris, which helps fluid leave the eye. Chandler's Syndrome is the most common form of a group of conditions called Iridocorneal Endothelial (ICE) Syndrome, accounting for half of all cases.¹

Chandler’s syndrome arises from changes to the inner layer of the cornea (endothelium), leading to symptoms such as:

• Cloudy, blurred vision
• Changes in the shape and size of the pupil
• High pressure within the eye, also known as Glaucoma

Chandler’s syndrome, which commonly affects just one eye, is more often found in people assigned female at birth (AFAB), between the ages of 20-50 years.^6,7 While the exact cause of CS is unknown, some studies have suggested that viruses, such as Herpes simplex (HSV) or Epstein-Barr virus, may be a trigger for the condition.¹

Early symptoms of CS are often subtle and can go unrecognised at routine optical examinations for long periods of time. To effectively treat patients with CS, it is important to understand the key changes that occur within the corneal endothelial layer, and how the recognition of symptoms at an early stage to pivot the outcome of CS, including the successful management of symptoms, reducing the risk of complications, and maintaining CS in an early stage of progression.¹

Overview of iridocorneal endothelial (ICE) syndrome

ICE syndrome refers to a small group of rare eye diseases that share similar features. The three main variants are:¹  

1. Chandler’s syndrome (CS) – The mildest form, which mainly affects the cornea
2. Progressive Iris Atrophy (PIA) – The most severe form, which mainly affects the iris
3. Cogan-Reese Syndrome (CRS) – mainly affects the iris by causing dark spots or nodules

Variants within the group of ICE syndrome similarly share characteristics of abnormal endothelial cells within the cornea. In turn, leading to several progressive symptoms, such as corneal swelling, changes in the iris, and sometimes high eye pressure (Glaucoma).¹

Endothelial cell abnormalities in chandler’s syndrome

The abnormal behaviour of the inner layer of the cornea (endothelial cell) is the main determinant for the progression and development of symptoms in Chandler’s syndrome. The abnormal behaviour of these cells can cause changes in the shape and size of the pupil, changes to the normal function of the eye, and can spread to other parts of the eye.^4,5

Why does chandler’s syndrome develop?

While Chandler’s Syndrome, like other forms of ICE Syndrome, does not run in families and cannot be passed down;⁶ CS is seen to be particularly prevalent within the Caucasian population, specifically within middle-aged people assigned female at birth (AFAB), between the ages of 20-50 years.^4,5

To date, the exact cause of CS remains unknown. Despite this, research can suggest a close link between patients with ICE Syndrome, including CS, and Herpes Simplex Virus. In turn, patients with ICE syndrome presented a higher percentage of presenting HSV and HSV DNA within their corneal endothelial cells [5]. In turn, it is believed that viruses can make changes to the regular programming of cells; programs which control, function, appearance, and where they are located.⁷

Symptoms of chandler’s syndrome and disease progression

While CS is difficult to diagnose due slow development of the disease. Early on, no observable symptoms are present. In turn, they are often overlooked at routine optical examinations. Despite this, as the disease progresses, patients may notice/experience symptoms such as:⁴

• Cloudy/Blurred vision – a result of swelling within the eye, caused by the gradual build-up of fluid within the cornea.
• Eye pain or pressure – also known as Glaucoma.
• Distorted or off-centre pupils, also known as Corectopia  
• Usually, only one eye is affected
• Eventual loss of vision (in advanced stages)

Diagnosis

CS is a deceptive condition, difficult to diagnose due to the slow development and late presentation of symptoms visible within routine optical appointments. Despite this, optical professionals are able to use specialised equipment to examine the eye and diagnose CS.⁸

• Specular microscopy – can look at corneal cells closely
• Anterior segment OCT or ultrasound – can see iris changes and the drainage system at the back of the eye

Upon inspection of the eye under microscopy or ultrasound, CS can be easily differentiated from other ICE variants because of the prominent changes within the cornea, such as corneal swelling, and fewer changes to the iris.⁸

It is important to monitor the progression of the disease in order to personalise an effective treatment plan to manage the symptoms of CS.

At each visit, eye specialists will:

• Check Intraocular pressure (IOP) – monitoring the risk of Glaucoma
• Examine the cornea for swelling and thickness
• Look for iris and pupil changes
• Access your vision

How often should you get a check-up?

The intervals of check-ups are dependent on the severity and how advanced the condition is, and whether Glaucoma is present or not. However, it is suggested to attend regular check-ups approximately every 3-6 months.⁹

Treatment options

At present, there is no permanent cure for Chandler’s syndrome, due to the irreversible changes to the features of endothelial cells within the cornea.⁹

Despite this, several treatment options are effective for managing symptoms and protecting vision, for example:

Managing corneal swelling4

• Saline eye drops – used to reduce swelling. This is a temporary option, requiring recurrent application. 
• Special contact lenses – ease patients' discomfort and can aid vision
• Corneal transplant surgery – usually required in advanced stages of CS

Managing high pressure within the eye

• Eye pressure-lowering drops, i.e., Beta-blockers, alleviate high pressure within the eye temporarily; however, not a long-term option
• Surgery, i.e., trabeculectomy, is often needed to keep eye pressure under control

To note, there are currently no accepted options to ‘straighten’ and restore the shape and size of the pupil. High risk is associated with surgery on the iris. 

Future research

Current research surrounding cell-based treatment therapies, which directly target abnormal corneal endothelial behaviour, provides promising new treatments for patients with CS, helping to manage and control symptoms.¹⁰

Conclusion

Chandler’s Syndrome is the most common form of ICE syndrome, caused by abnormalities in the corneal endothelial cells. Viral triggers, such as Herpes Simplex Virus (HSV), are suggested to play a key role as the cause of Chandler’s syndrome, causing significant changes within corneal endothelial cells, leading to the development of corneal swelling, pupil distortion, and glaucoma.

The slow progressive development of symptoms associated with CS, which are commonly overlooked at routine eye examinations, is one of the main problems that prevents early diagnosis of the disease. Despite this, there are many ways to check for Chandler’s syndrome; in turn, with regular monitoring, patients can be diagnosed early and obtain the correct treatment plan.. In turn, treatment options focus on managing and controlling the disease, helping patients to manage symptoms, reduce progression, and protect their vision. Furthermore, new research shows a promising new strategy to bring more effective therapies, which are cell-based, for patients with Chandler’s syndrome.