Overview

Chandler's syndrome is a rare eye condition that falls within a larger category of eye disease known as Iridocorneal Endothelial (ICE) syndrome^.1 This syndrome is characterised by abnormal growth of endothelial cells that form the cornea, the clear ‘film’ structure covering the front of the eye. This results in a distortion of the iris and a build up of pressure in the eye, which may cause nerve damage - Glaucoma. Chandler’s syndrome differs from other ICE syndromes in that iris distortion is negligible during early disease pathogenesis., This results in a more complicated diagnosis compared to other ICE syndromes such as Progressive Iris Atrophy and Cogan-Reese syndrome. Hallmarks of Chandler’s may include subtle changes in iris structure or a ‘shift’ in the location of the pupil.

Identifying these features early is crucial, as interventions like surgery or monitoring eye pressure may reduce the risk of vision loss or eye pain. This article further explores the initial signs of Chandler’s syndrome, alongside an explanation of the diagnostic tools used by doctors.

Hallmarks of chandler’s syndrome

Identifying Chandler’s syndrome in its early stages is difficult as the majority of changes occur in the cornea, which is clear. A doctor may identify the subtle changes in the iris in an examination, distinguishing the syndrome from other ICE syndromes or eye diseases with similar symptoms².

Subtle changes in iris structure

One of the first signs you can see is a mild iris stromal atrophy. Here, a layer of tissue in the iris called the stroma becomes slightly thin or weak, visible with a slit-lamp examination (discussed later). It differs from a progressive iris atrophy, where tissue loss is significant and ‘holes’ may appear. The changes in iris structure found in Chandler’s are thought to come from the overgrowth of corneal endothelial cells in contact the iris, applying pressure and stress.

A slight shift in pupil position

Another early sign is corectopia, a slight shift of the pupil from its center. In Chandler’s syndrome, corneal opacities are usually less noticeable compared to those in other ICE syndromes.² Correctopias are the result of a contraction of the corneal endothelial cells, which applies a pulling force on the iris and moves the pupil off-center. Slit-lamp examinations can spot early corneal opacities.

Small changes at the outer edge of the iris

Some patients experience a minimal ectropion uveae, where the contraction of the cornea pulls cells from the back layer of the iris through to the front, resulting in a visible distortion at the outer edge of the iris. This is easily missed in a regular check-up, but is a distinct sign of Chandler’s that could lead to a diagnosis.²

Techniques - diagnosis

Slit-lamp biomicroscopy

This slit-lamp test is the first-line method to examine the front of the eye. It provides a magnified view of the cornea, iris, and pupils to identify early signs of Chandler's.

Diagnostic clues for Chandler’s observed in slit-lamp tests:

• Cornea: Subtle swelling or a “blur”, usually more visible in the morning
• Iris: Wear and thinning is visible, but indistinct
• Pupils: A subtle shift can be identified with careful comparison to a healthy eye
• Ectropion uveae: A slight outward bend on the edge of the iris may be detected

Specular microscopy

Specular microscopy provides a detailed view of corneal endothelial cells and is considered one of the most sensitive techniques for early Chandler’s diagnoses. 

Diagnostic clues for Chandler’s observed in specular microscopy:

• Reflection patterns of the abnormal corneal endothelial cells produce a hallmark “hammered silver” or “beaten bronze” appearance
• Enlarged endothelial cells that vary in shape
• Loss of the typical hexagonal patterns produced by corneal endothelial cells

The importance of diagnostic clues 

Differentiating chandler’s syndrome from other causes of glaucoma

Certain diagnostic clues can help doctors distinguish Chandler’s syndrome from other conditions that result in Glaucoma: 

• Primary angle-closure glaucoma (PACG): An angle closure describes a blockage of the drainage pathway for fluid on the surface of the eye. In Chandler's, the angle closure is due to the abnormal endothelial cell growth, distinct from the mechanisms found in PACG¹
• Pseudoexfoliation syndrome (PXF): Observations from Slit-Lamp Biomicroscopy show a fiber-like deposit on the lens and iris in PXF patients with more uniform pigment loss, not like the thinning of the iris (atrophy) observed in Chandler’s²
• Uveal tumors: Tumors in the iris and ciliary body (located behind the iris) maylook like Chandler’s as they also distort the shape of the iris or cause secondary glaucoma. However, Slit-Lamp Biomicroscopy can distinguish them by the observation of a localised mass in the uvea

Differentiating Chandler’s and conditions with similar features is key, as the treatments may be completely different. 

Guiding prompt and targeted management

Identifying Chandler’s allows doctors to intervene with the necessary treatments;

• Medication: Using saline solution and eye pressure-lowering medication can slow disease progression and manage early eye swelling⁵
• Surgical planning: In advanced cases of Chandler’s, surgical procedures like trabeculectomy or tube shunts may be required
• Regular monitoring: Identifying Chandler’s early allows close monitoring of eye pressure and overall eye health, reducing the risk of vision loss

Preventing misdiagnosis and potentially harmful interventions

Patients with Chandler’s syndrome are sometimes misdiagnosed with primary angle-closure glaucoma and undergo laser peripheral iridotomy (LPI) or iridoplasty, which are ineffective due to the differing causes of angle closure. Additionally, complications of these treatments may worsen disease progression or general eye health. 

Summary

It is extremely important that doctors understand the hallmark signs of the early stages of Chandler’s as: 

• They can distinguish Chandler’s from other probable diseases that share glaucoma, like primary angle-closure glaucoma, pseudoexfoliation, or uveal tumors
• Rapid treatment can be implemented, including medication to reduce eye pressure and corneal swelling, or surgery in advanced cases
• The frequency of misdiagnosis can be reduced, preventing intervention with unsuitable treatments that provide unnecessary risks