What is chandler’s syndrome?

The uncertainty associated with rare diseases

Naturally, little is understood about many rare diseases, which can leave patients suffering with such conditions in a position of uncertainty. Imagine waking up to realise your vision has gone hazy and you are experiencing pain, but only in one eye.¹ For some, this is the first sign of Chandler’s syndrome (CS). With CS being a rare disease, there has been ambiguity regarding the condition, with an accurate diagnosis often taking over six years to be achieved.² There are ways to improve this. A disease cannot be diagnosed or treated properly if you don’t know how it works inside your body. To tackle this problem, research was conducted, which meant that the focus could be shifted to developing these methods and reducing uncertainty in patients.

The role of the cornea

CS is a condition affecting the cornea. This is a thin covering, protects the front of your eyes from external factors such as germs, but also plays a key role in functioning eyesight.³ Fluid is needed inside your cornea, but a mechanism is needed to ensure it can pass both in and out. This mechanism is operated by a built-in drainage system called an endothelium. In CS, the drainage mechanism fails, resulting in a buildup of liquid in the cornea, causing swelling, in a condition called corneal oedema.¹ This swelling can cause the characteristic blurred vision, but also the migration of abnormal cells. If the abnormal cells can migrate to the coloured part of the eye (iris), it can cause a condition known as corectopia, where the pupil will be misplaced. If migration reaches the drainage canal of the eye, called the trabecular meshwork, the endothelial cells can prevent the flow of liquid, eventually leading to a secondary glaucoma, which is a permanent loss of vision.⁴

The importance of understanding the condition long-term

The evolution of a disease over a period of time without the influence of medical intervention is called its natural history. The natural history of common diseases is generally well understood, allowing patients to prepare and have their questions answered. For rare conditions like CS, this is not always the case. To solve this, longitudinal studies have been performed. Researchers now have a basis for learning about how a disease works in a body over time, with some studies even lasting over ten years. Focus will be directed at a particular group that has the condition. Researchers will not only be taking notes on how the disease progresses, but also on the effectiveness of their treatments. For CS, these studies have meant that researchers know more about the natural history of CS. With the success of longitudinal studies, researchers have valuable information that will allow them to potentially treat the condition altogether and remove ambiguity for patients.

The natural history of chandler’s syndrome

Early stages

Before properly settling in, CS can be difficult to diagnose. This is because symptoms may be very subtle and so dismissed when in early stages. A patient may experience blurred vision in one of their eyes, with some reporting the presence of halos around bright lights.⁵ When you wake up in the morning, you may find this is when you experience your symptoms. Your vision may be blurry, but as you get up, it will vanish. Lots of people would simply dismiss this as them being tired when they wake up, meaning CS often goes undiagnosed for years. This highlights the necessity for better public knowledge in recognising symptoms.

Progression to noticeable symptoms

CS symptoms intensify over time to become noticeable. The function of the pump mechanism for draining fluid depletes, resulting in the permanent swelling of a patient’s cornea. Where the blurred vision was predominantly noticed in the mornings, it is now a permanent feature. A patient’s iris may appear distorted, having also shifted in position.¹ Noticeable without equipment, the endothelial cells within the cornea will develop a ‘hammered silver’ appearance, as well as develop the ability to migrate.⁵

The advanced stages

When you have CS and it progresses past the advanced stages, your symptoms will worsen. This can be due to not receiving treatment, which means your cornea remains swollen for a long period of time. If this happens, you may experience a condition called bullous keratopathy. Blister-like formations will appear, and when they burst, cause intense pain.⁶ If you ignore the pain and leave the blisters untreated, they will naturally heal on their own. While blisters will be healed and pain relieved, your eyesight could experience lasting damage.

Advanced-stage CS can also lead to secondary glaucoma.⁵ The abnormal endothelial cells can multiply and subsequently migrate to the drainage canal or to the iris.⁷ The migration causes a buildup in pressure in the iris, and when this becomes too great, holes can start to appear. An early diagnosis is important to prevent lasting effects.

A longitudinal study into chandler’s syndrome

To devise methods of diagnosis and to create treatment plans for CS, you will need to understand how it progresses. To do so, longitudinal studies were performed.

What did the studies show?

The cause of CS

Researchers have gained insight into the likely cause of CS. Results have pointed to CS being caused by genetic mutations.² These mutations can occur in a variety of ways, although the swelling is thought to be a result of infection with Herpes Simplex Virus and, in particular, its DNA.¹ Patients should be safe from passing on the condition during childbirth. This is because the mutation arises as a result of infection, rather than being born with it.

Who is affected?

CS has been seen to disproportionately affect the female population over the male population, although the exact reasoning for this remains unclear.¹ The condition usually onset during young adulthood to middle-aged years, although there have been reported cases of CS in a child and a teenager.

Diagnosis

Now that researchers have a better understanding of the natural history of CS, an earlier diagnosis is possible. One such method is confocal microscopy. This will allow for the endothelial cells within the cornea to be visualised, where they will be observed for abnormalities in their shape, size and quantity. When in the latter stages of CS and testing for glaucoma, techniques that measure eye pressure, the thickness of the cornea and the drainage angle of the canal are measured.

Treatment

Now that researchers know how CS progresses within a patient, they have been able to focus on treatment methods. Currently, they have developed a way of managing symptoms; however, there is no method of preventing the initial development of CS.

• Soft contact lenses - Control the swelling¹
• Eye drops - Control the swelling
• Beta-blockers - Decrease the production of liquid in the eye
• Tube shunt surgery - Allows drainage of liquid from the eye and prevents abnormal endothelial cells from migrating⁷
• Corneal transplant - Performed if vision is impaired if eye pressure can be controlled

What does this mean for patients and the future?

Studies into the cause and progression of CS have provided benefits to patients, healthcare professionals and have laid the groundwork for and highlighted future developments in the diagnosis and treatment of the disease.

Patients with CS

People with rare diseases often don’t know why they are taking medication, but are not getting better. This can be because the lack of knowledge regarding the condition means an accurate diagnosis has not been achieved. The longitudinal studies which were conducted have meant researchers know more about the progression of CS, and they can now answer more of the patients’ questions. The advancements in knowledge also mean they can reduce diagnostic time frames, which can improve treatment plans.

Healthcare professionals

Rare diseases are often misdiagnosed due to the similarity of symptoms with more common diseases, masking their own. The study helps healthcare professionals to distinguish between CS and other more common diseases that may mask the symptoms to improve the accuracy of diagnosis. The studies have also meant they can better inform their patients of the situation to prevent confusion or panic.

What is next?

The CS research journey does not stop here. The current studies have laid the groundwork for future research into improved diagnosis and treatment. Currently, diagnosis is performed from observing visible symptoms, and treatment aims to relieve patients of pain and discomfort rather than preventing them from occurring in the first place. With the knowledge that the disease is acquired through genetic mutations caused by Herpes, research can be focused on identifying these mutations. This can allow those suffering from Herpes to be screened for diagnosis of CS to occur before any symptoms are onset.

Summary

Chandler’s syndrome is a rare disease with recent longitudinal studies, meaning its natural progression and cause are better understood. It causes swelling in your cornea and will eventually lead to a loss of sight if left untreated. This knowledge has led to improved diagnostic methods being produced, meaning diagnostic wait times are reduced, and the production of treatment methods to manage symptoms can prevent lasting damage. We now know CS is caused by genetic mutations as a result of Herpes, and so further research should be directed towards solving the specific mutations to allow an even earlier diagnosis and for treatment to prevent a patient from ever experiencing symptoms.