What is Keratoendotheliitis Fugax Hereditaria?
Keratoendotheliitis fugax hereditaria is a rare genetic condition causing inflammation in the eye. People with this condition experience repeated episodes where one eye becomes intensely red, swollen, and cloudy, leading to blurred vision and sensitivity to light, lasting 2 to 5 days. The eye may also water excessively, feel painful or gritty, and cause the perception of colored rings around lights and double vision. This condition is inherited from parent to child through genes.
These symptoms usually start at one side of the eye before spreading across the whole eye. During an episode, the pain or discomfort is often so severe it can disturb a person’s sleep.
Although the redness and cloudiness in the eyes usually fully disappear within 2 to 4 days, a localized cloudy patch in the eye might remain for weeks to months after the episode. Earlier studies suggested that no matter how long the eye remains cloudy, or how many episodes a person has, the cloudiness always completely goes away, and vision returns to normal. But, more recent cases have shown people who have permanent cloudiness in the eye after many episodes. These cloudy patches, which can be seen during an eye examination, may or may not affect vision between episodes.
This eye condition was first identified in 1964 during a study of Finnish individuals. However, some later research suggests that there could be small differences in findings, indicating that the patients involved in the original study may have a similar overall condition, but with slightly different specific features.
The frequency of these painful episodes varies with age. Young patients between 15 to 20 years old are most affected, with episodes occurring 1 to 8 times a year. The number of attacks and their severity decrease with age, although patients may continue to experience moderate-to-severe episodes into their forties. By their mid-fifties, patients seem to experience less severe symptoms and fewer episodes.
What Causes Keratoendotheliitis Fugax Hereditaria?
Keratoendotheliitis Fugax Hereditaria, a rare eye condition, is believed to be a result of a genetic mutation in a specific gene called ‘NLRP3’. A ‘missense mutation’, which involves one DNA element being changed for another, causes the mutation. As a result of this change, a partially positive component, the ‘histidine’, replaces a negatively charged one, called ‘aspartic acid’. This alters the normal codes at a particular position within our DNA.
Like many mutations, this probably changes the way the proteins in our cells fold and function, leading to possible irregular activation or mishandling of these proteins. It is likely to present a problem because NLRP3 protein, for which the gene codes, plays a decisive role in forming units called ‘inflammasomes’. These units are intricate, and significantly involved in inflammation, or swelling, of body tissues.
In a study, all 30 cases that were assessed for the gene mutation were found to carry one copy of the mutated gene, which suggests that having two copies of this gene may not be feasible for survival. This could also mean that such cases are extremely rare and haven’t been observed or reported yet. Furthermore, the severity and frequency of attacks have been known to change from generation to generation. These changes indicate that other genetic factors might also be in play that are yet to be identified in this disease.
There are no known risk factors that trigger bursts of this disease, and changes in seasons reportedly have no effect on its occurrence. However, on a personal note, some patients have related mild viral illnesses, colder temperatures, or a significant reduction in physical or mental stress to repeat symptomatic attacks.
Moreover, many individuals in one family affected by this condition were also suffering from various conditions linked to ‘collagen’, a protein that provides structure to various body parts. Since collagen and the cells that the cornea (the clear front surface of the eye) comes from share the same developmental origin, called ‘mesoderm’, there might be a deep-rooted association between these conditions.
Risk Factors and Frequency for Keratoendotheliitis Fugax Hereditaria
The condition known as keratoendotheliitis fugax hereditaria hasn’t been widely studied, so we don’t know exactly how many people are affected by it. However, the gene mutation linked to this condition is believed to be found in approximately 0.02% of Finnish individuals and 0.01% of non-Finnish Europeans. While the case reports available all feature Finnish families, it’s possible that individuals from other backgrounds may also carry this gene mutation.
Signs and Symptoms of Keratoendotheliitis Fugax Hereditaria
Endotheliitis fugax hereditaria is a condition that often causes severe eye pain and redness, a decrease in vision, as well as a sensation that something is trapped in the eye or a stiff neck. In about half of the cases, it might also cause an overproduction of tears and a build-up of discharge in the nostril on the same side as the affected eye. Even though it typically affects one eye at a time, it’s not uncommon for both eyes to be affected either simultaneously or one after the other. Once the initial pain and redness reduce, patients usually complain about blurred vision due to the buildup of fluid and scarring in the cornea.
The condition typically shows up around the age of 10 or 11, but cases have been known to occur as early as 3 years and as late as 28 years. Of particular note for younger kids with a family history of the disease, is that these symptoms might indicate an initial outbreak of endotheliitis fugax hereditaria. Adults might experience similar episodes between one and six times a year. Given that this disease tends to run in families, understanding a patient’s family history is crucial for a correct diagnosis. Most commonly, the disease is inherited in an autosomal dominant pattern, but there can be spontaneous mutations that result in the disease.
An examination of the eye in the acute phase of the disease will typically show redness in the white part of the eye and fluid build-up in the cornea. There might also be opacity in the central layer of the cornea and on the cornea’s back surface. Other notable features include a “beaten silver” look of the endothelium (the thin layer that lines the interior surface of blood vessels) and swelling in the endothelial cells. Thickness of the cornea could increase by 5% to 14%, but some patients have presented with thinner areas in the center of the cornea. Between attacks, the cornea usually appears normal except for the presence of scarring and opacification.
If the patient comes around 2 to 4 days after the onset of symptoms, the only visible remnant of the disease is likely to be the stromal opacification or the accumulation of small lumps on the cornea’s back surface. This opacity might be a permanent feature and could potentially affect vision outside of acute incidents. Other findings include occasional erosions in the cornea. Some patients also show prominent iris atrophy. Between attacks, images of the patient’s eye will typically appear normal except for patients with stromal scarring and opacification.
An examination of the endothelium using a special form of photography might reveal a reduced number of endothelial cells. During an attack, the cells might appear normal, but larger, black, non-reflective areas between them (pseudoguttata) might be visible. Between attacks, there might be marked variability in cell shape and black spots may be visible in the center of cells in an otherwise normal-appearing endothelial mosaic.
Testing for Keratoendotheliitis Fugax Hereditaria
If you have certain symptoms and a known family history of a particular disease, you might not need genetic testing to confirm the diagnosis. But for those who are showing signs without clear reasons, genetic testing could provide a definite answer.
Examining the eye can be different depending on whether or not you’re currently experiencing an attack of symptoms. During an acute attack, the thickness of the cornea (the front surface of your eye) may increase, associated with something called pseudoguttata. Pseudoguttata can be detected using different microscope techniques.
Even when an attack is not happening, various scans and tests can be used to rule out other potential causes of your problems. Our eye’s internal pressure is expected to be stable, even during an acute disease event. The fluid in your eyes, known as the aqueous humour, will appear clear because the main problems are happening on the cornea. It’s also noteworthy that synechiae, another type of eye problem, aren’t likely to develop with this condition.
There’s a variety of imaging methods doctors can use to investigate. However, OCT might not be very helpful in this case, while tomography and topography results may appear normal if an acute episode isn’t happening. Since the changes to the eyes can still be clearly seen in between attacks using something called specular photography, this method might be the best way to identify patients who may have the condition when it’s not an active episode.
Treatment Options for Keratoendotheliitis Fugax Hereditaria
Keratoendotheliitis fugax hereditaria is a condition caused by genetic factors and its detailed mechanism is not fully understood. The treatment, as suggested by case reports, is mostly supportive. Topical corticosteroids, which are ointments or drops applied to the eye, are considered the best treatment although the precise frequency and dosage haven’t been established. However, it’s important to note that not all patients respond to this type of treatment.
It has also been noted that oral antihistamines, a type of medicine usually used for allergies, can help with symptoms. These medicines can cause drowsiness, so might be helpful for patients who find it difficult to sleep because of their symptoms. Another option that can help ease the pain linked with the condition is using nonsteroidal anti-inflammatory drugs (NSAIDs), which can be taken orally or applied to the eye.
No matter what treatment is chosen, it’s important to start it as soon as possible. Early treatment can help to limit symptoms. Some patients have reported that starting treatment with topical corticosteroid drops or ointments early can either stop their symptoms from getting worse or make them feel better more quickly. At this point in time, there haven’t been any reports of needing invasive or surgical management for this condition.
In terms of vision, some people find that wearing rigid contact lenses gives them better results than wearing glasses.
Since this eye condition is known to be related to inflammation caused by a NLRP3 activation, a protein associated with inflammation, various modulators that can affect this protein’s action might be beneficial. These include medicines like MCC950, beta-hydroxybutyrate, type 1 interferon, and interferon beta, resveratrol, arglabin, CB2R agonists, and MicroRNA-223. These medicines may turn out to be useful in treating or preventing acute episodes of the condition and preventing corneal scarring. Many of these medications have shown promise in limiting inflammation in other eye-related conditions. However, more research is required to better understand how these inhibitors affect corneal cells and their impact on this specific condition.
What else can Keratoendotheliitis Fugax Hereditaria be?
If someone has a known family history of the condition and typical symptoms, doctors can diagnose it without much difficulty. Yet, in cases where the condition appears unexpectedly, it’s often much more difficult to identify. This issue can come up with a condition called keratoendotheliitis fugax hereditaria. After the condition’s acute phase settles, doctors can mistake the remaining inflammation for acute anterior uveitis.
The conditions that doctors then consider when trying to make a diagnosis are mostly other inflammatory eye diseases. These can be uveitis or endotheliitis, either with or without an extra condition called pseudoguttata. These eye problems can be caused by various factors, like infections (bacterial, viral, fungal, and so on), an autoimmune response, drugs, or rare hereditary conditions.
The conditions that needs to be considered as possible diagnosis include:
- Iridocorneal endothelial syndrome,
- Anterior uveitis,
- Chandler syndrome,
- Angle-closure glaucoma,
- Relative anterior microphthalmos,
- Brown-McLean syndrome,
- Posterior polymorphous corneal dystrophy.
What to expect with Keratoendotheliitis Fugax Hereditaria
For patients dealing with keratoendotheliitis fugax hereditaria, their outlook is generally fair. While the symptoms usually lessen in both frequency and severity over time, around half of the patients may experience a permanent effect on their vision due to scarring in the cornea (stroma). This permanent cloudiness (opacifications) seems to become more severe and impactful with each recurring episode, especially in older patients.
It’s also possible that there may be individuals with milder forms of this eye disorder, or with subtle symptoms that may not be easily noticeable (subclinical symptoms). If there are such cases, the outlook for these individuals is likely to be good to excellent, and they may not even require any treatment.
Possible Complications When Diagnosed with Keratoendotheliitis Fugax Hereditaria
The main long-term problem from many acute episodes is a decrease in the sharpness of vision. Too many bouts with this condition could lead to lasting scars on the cornea, the eye’s clear surface, and a lowered quality of life.
Common Long-Term Effects:
- Decrease in vision sharpness
- Permanent scars on the cornea
- Reduced quality of life
Preventing Keratoendotheliitis Fugax Hereditaria
Since the disease is inherited and doesn’t have a specific known trigger for occasional episodes, there aren’t any known prevention measures that patients can take to reduce the number or intensity of these incidents. Patients should be aware that if they experience reduced vision, it’s important to schedule an eye doctor’s appointment. This can help detect and manage any potential issues early on.
