Kayser-Fleischer ring (K-F ring), also referred to as Fleischer-Kayser ring or Fleischer-Strumpell ring is the most common ophthalmologic manifestation of Wilson disease.
KR ring is seen as a golden-brown or green-yellow, bronze or reddish-brown ring in the periphery of the cornea. It occurs due to deposition of copper granules in the cornea.
The excess circulating copper is deposited in Descemet’s membrane of cornea, beginning at Schwalbe’s line and extending less than 5 mm onto the cornea.
KF ring appears commonly as a golden brown ring in the periphery of cornea. It may also appear as greenish yellow, ruby red, bright green, or ultramarine blue. It is almost always bilateral and appears superiorly between 10-2 o’ clock first, then inferiorly, and then later becomes circumferential.
KF ring occurs at the level of Descemet’s membrane of cornea, beginning at Schwalbe’s line and extending less than 5 mm onto the cornea.
It is seen in slit lamp biomicroscopy of the eye using cobalt filter. In the earlier stages of disease, gonioscopy is often needed to detect this subtle finding, but in advanced disease and light colored iris, it can be seen with the naked eye.
scheimpflug imaging detecting and quantifying a Kayser–Fleischer ring, that appears as a bright subendothelial peripheral band has also been described to examine KR ring. Recently, anterior segment-optical coherence tomography (AS-OCT) has proved effective to identify a Kayser–Fleischer ring as an intense hyperreflective band at the level of Descemet’s membrane in the peripheral cornea, even with minimal copper deposit.
The gold standard for detecting and assessing Kayser–Fleischer rings remains the slit-lamp exam. However, its identification may be challenging—mainly for the inexperienced ophthalmologist—in brown-eyed persons or in an early disease phase, and gonioscopy is recommended in these cases.
The Kayser–Fleischer ring consists of corneal granular pigments that were initially attributed to the deposition of copper at the level of the Descemet’s membrane. Copper infiltrates from the aqueous humor through the endothelial cells into Descemet’s membrane, because of the affinity of copper for basement membranes .
Mechanism in Wilson Disease
Excess circulating copper is the principal cause of Kayser-Fleischer ring.
In Wilson’s disease, copper is unable to be excreted into bile, leading to its toxic accumulation in the liver and eventual cellular death of hepatocytes. Copper leaks into the systemic circulation and accumulates in other tissues like the eye, brain (basal ganglia) and kidneys among others leading to morphological changes, functional derangements and clinical manifestations:
- K-F ring in the cornea,
- sunflower cataract in the lens,
- tremors and rigidity due to accumulation in the central nervous system,
- and renal tubular defects due to accumulation in the kidneys.
Copper chelates/granules are deposited in the inner portion of Descemet’s membrane in the cornea, leading to the appearance of KF ring. Copper is deposited into Descemet’s membrane via the limbic circulation and/or the aqueous humour.
Mechanism in Primary Biliary Cirrhosis(PBC)
Similarly, in primary biliary cirrhosis there is reduced biliary tree outflow that causes cholestasis. Copper that would normally be excreted into bile therefore accumulates in the liver, causing hepatotoxicity and leaking into the systemic circulation. As with Wilson’s disease, copper is then able to be deposited in other tissues such as cornea.
The Kayser–Fleischer ring does not interfere with visual function.Furthermore, the density of the Kayser–Fleischer ring has shown to correlate with clinical symptoms duration.
Sign Value and Prevalence
The presence of Kayser-Fleischer rings in combination with low serum ceruloplasmin is considered diagnostic of Wilson’s disease based on Sternlieb’s criteria.
Kayser–Fleischer rings are present in 99% of patients with concomitant neurological/psychiatric features of Wilson’s disease, but in only 30–50% of patients without these features. Therefore, in the absence of neurological/psychiatric features, other differential diagnoses should be considered. Kayser-Fleischer rings may be absent in up to 50% of patients with Wilsonian liver disease.
It is seen simultaneously in both eyes , occurs bilaterally when associated with systemic disorders. However, it has also been reported unilaterally in a patient with WD as a case report.
Causes and Differential Diagnosis
A Kayser–Fleischer ring is not fully specific for WD and, in rare cases, Kayser–Fleischer-like rings may be seen in other conditions such as chronic cholestasis with normal serum copper and ceruloplasmin concentrations, including children with neonatal cholestasis or autoimmune hepatitis. Other diseases have been reported to cause serum copper elevation in combination with serum proteins such as gamma-globulins in CLL.
Also, corneal iron deposition in basal epithelial cells in the Fleischer’s ring of keratoconus may mimic copper deposition. It is seen as a complete or incomplete brown-green ring in the peripheral corneal and is characterized by its increase with the age .
After the initiation of treatment, the Kayser-Fleischer ring disappears in 85-90% of cases in 2-3 years.
Wilson’s disease is treated with agents that chelate copper and hence the K-F ring could fade or disappear following successful treatment.
While the ring appears superiorly, followed by inferiorly and circumferentially, it tends to disappear in the reverse order of its formation.
Patients with end-stage liver disease related to WD who undergo liver transplant also demonstrate a partial decrease in or complete disappearance of the K-F ring.
However, it should be noted that the disappearance or reduction is independent of the stage of the disease and also the effectiveness of copper chelation.
There is no correlation between disappearance of KF ring and clinical improvement in patients.
KR fing may reappear with non-compliance, and occasionally even with successful maintenance therapy.
A hammered-metal appearance may remain in the Descemet’s membrane after Kayser–Fleischer ring disappearance
Clinical Importance of K-F Ring
Identification of the K-F ring in any patient with unexplained central nervous system disease, poorly categorized psychiatric disorder, abnormal liver function tests, chronic active hepatitis, cirrhosis of liver, rickets, renal tubular acidosis, unexplained Coomb’s negative hemolytic anaemia, especially with family history of WD or any of the conditions mentioned above should prompt the physician to undertake diagnostic workup for WD.
At times, the K-F ring could be the first detectable manifestation of WD and in such rare instances, ophthalmologists play a critical role in the early recognition of WD.
Larger K-F ring size may correlate with the severity of the disease, but not necessarily with the magnitude of urinary copper excretion.
It is one of the clinical parameters used in monitoring patients on therapy although its reduction is not necessarily a good predictor of clinical improvement. Its reappearance while on therapy may indicate non-compliance.
Kayser-Fleischer ring detection is one of the screening tests for first-degree relatives of a WD patients. Early detection and treatment of WD may prevent the associated morbidity and mortality of the disease.
Take Home Points
- Hallmark of Wilson’s disease
- Copper deposition in Descemet’s membrane
- Appears as golden brown ring in corneal periphery
- Begins superiorly, followed by inferiorly and laterally
- Not visually significant, does not cause visual impairment
- Disappears with treatment in majority of cases