The mission of this site is to provide an information source
for patients, families, doctors and researchers interested in
Familial Exudative Vitreoretinopathy (FEVR) as well as to
provide support for patients and families through education,
outreach and the knowledge that they are not alone.
GENERAL INFORMATION ABOUT FEVR
WHAT IS FEVR
Familial Exudative Vitreo-retinopathy, written as, "FEVR," and pronounced by doctors as, "Fever," is a an eye disease affecting the retina, found at the back of the eye, the vitreous, the clear, "gelatin like," substance inside the center of the eye and the blood vessels that feed the retina. It is a genetic disease, meaning that it occurs in one or more family members. Its severity is vary unpredictable, even within the same family and even between eyes of the same person. When it occurs in a person, it usually occurs without any symptoms and causes no eye problems. Unfortunately for some, it can cause minor to serious eye problems. In the cases where FEVR is serious, it usually shows up before the age of ten. When FEVR occurs in childhood it's severity can be extremely variable causing some vision problems to almost complete blindness at birth.
PROBLEMS FEVR CAUSES
FEVR is a progressive disease, meaning that it continues to develop symptoms which can over time in some people lead to more and more serious problems but every FEVR case is different and many can slow there progression especially with medical intervention. Often when FEVR occurs in it's most aggressive form many problems can occur. The most common problem is the growth and rupture of abnormal blood vessels (vascularization) in the outer edges of the retina called the peripheral region. Blood vessel growth can occur at a rapid and continuous pace. Bleeding of these blood vessels can lead to dragging of the retina called retinal traction, and may result in scarring and/or retinal detachment due to the pulling of the retina. A common occurrence seen in FEVR retinas is blood vessel exude which shows up as milky white substance on the retina where bleeding of abnormal blood vessels occur. (see picture of exudate).
Another serious problem is the growth of thin fibrous membranes into the vitreous gel in the center of the eye. These membranes can grab the retina and cause complications such as retinal dragging, detachment and retinal tearing due to the membranes pulling on the retina.
Progression of symptoms can continue into adolescence. Much medical intervention is needed throughout this time and the closer the child is watched and treated, when necessary, the better the chances of vision being saved. Usually FEVR stops progressing around age 20 but recent evidence shows that in the more aggressive cases, defined by the development of FEVR before age 10, FEVR can start progressing again in later life after a non-symptom (asymptomatic) period so the FEVR patient needs to be seen by a retinal specialist there entire life.
Another problem a FEVR child can be born with is called a retinal fold. In these cases the retina grows abnormally before birth and falls or folds over onto itself often over the central vision causing partial blindness. If this can be caught at birth it may be possible to unfold the retina but most are not caught and the fold grows together and then it can not be treated. This can occur in one or both of the child's eyes.
Three other common problems found in FEVR patients are cataracts in the lens of the eye, the iris not dilating due to the iris sticking the lens and glaucoma. All of these problems can be treated with much success.
WHO GETS FEVR, IS IT A, "RARE" DISEASE
Scientists have shown that FEVR is found throughout the world but no scientific evidence has shown that it occurs at a higher frequency in one population over another. Scientists have shown that 85% of affected individuals can be asymptomatic, that is, showing no symptoms. Given this knowledge it is unknown whether FEVR is actually a, "Rare" disease, as it has been thought in the past. Today genetic researchers believe that it is not as rare as it has been thought, but no concrete, scientific studies have been conducted to show what percentage of the population actually has FEVR . In addition, it is known to be a complex disease with many genetic causes and is slowly being shown to be in some cases, more like a syndrome, rather than a disease since it can cause problems in other parts of the body and can occur along side other syndromes.
THE GENETICS OF FEVR
FEVR can occur in all three forms of genetic inheritance; 1. Recessive, 2. Dominant, and 3. x-linked,. As well as another mutation in the gene of another syndrome called Norrie disease. Both recessive and dominant FEVR can be caused by mutations in the same gene or mutations in different genes. More genes are found as time goes on by gene hunters around the world. The X-linked gene is known, and can be tested for. Some of the dominant and recessive FEVR's genetic defects can also be tested for. You doctor can point you to a genetic expert who can help in determining if you have a known FEVR gene mutation and if they know what it may tell you about your specific FEVR.
For the United States (USA) the below genetics links may be useful resources for more information.
A paper outlining the some genetic research by researchers from around the world can be read by going to the web link below. It describes some of the genetic work being done to understand FEVR and recently the link between the underdevelopment of the retina and the defective development of bone cells causing low and high bone density. The FEVR with low bone density is called osteoporosispseudoglioma syndrome (OPPG) and causes mild to sever bone loss depending on where the mutation on the gene is. Again most FEVR patients do not have these gene mutations so don't panic. When looking at all this scary information keep in mind that it is estimated that 60-80% of FEVR cases don't even show any problems and do not come to the attention of an eye doctor.
In FEVR's x-linked form, it occurs only in the males of the family and most of the time is a mutation of Norrie Disease. Many times this form is caused by a mutation in the Norrie gene but there may be other genes causing this form too. A test is available to test for the Norrie Disease mutation which causes most X-linked forms of the disease. In its rarest form, recessive, it can occur with no family history.
Mutations in three genes (LRP5, FZD4, and NDP) are known to cause FEVR. "The proteins encoded by these FEVR genes form part of a signaling complex that activates the Norrin-beta-catenin signaling pathway" (ref) The full names of the first three genes are below. TSPAN12 is the latest gene to be found to cause FEVR. All of these genes are thought to cause FEVR by disrupting the cell signals required for the normal development of blood vessels in the retina at the back of the eye. (ref)
FZD4: frizzled homolog 4 (Drosophila)
LRP5: Low density lipoprotein receptor-related protein 5
NDP: Norrie disease (pseudoglioma)
CAN FEVR LOOK LIKE OTHER DISEASES AND BE MISDIAGNOSED?
FEVR can be misdiagnosed at birth as the non-genetic eye diseases Persistent Hyperplastic Primary Vitreous (PHPV) but unlike PHPV, FEVR may continue to change the retina and other parts of the eye over time so many times it will become apparent over time whether it is PHPV or FEVR.. Many of the features of FEVR at birth also resemble Retinopathy of Prematurity (ROP). Whether you know which disease you have it is important to know that all the diseases should be followed by a retina specialist and more important you should know that the treatment of all the diseases are similar if not the same. Most retina specialists that see patients for all of these diseases treat all three forms of the disease. All the diseases also differ in there degree of how bad the disease is in each person and in each eye.
Genetic testing can sometimes help doctors determine whether a child has FEVR or not. See Paper - "Genetic testing for eye disease is providing vital information about complex retinal diseases, especially when used to confirm a clinicianís diagnosis"
FEVR is congenital (present at birth) and bilateral (affect both eyes) although not necessarily with the same intensity. FEVR may affect one eye more than the other, may affect one child more than another and in many cases may not affect sight at all or only slightly. Its outcome for each person is thus frustratingly unknown. Careful watching by a Vitreo-retinal specialist with experience with FEVR is essential for the best outcome. Many FEVR patients also are born with retina folds in one or both eyes which cause blindness in that area of the vision. In these cases the retina does not form correctly in the womb. This condition, when present at birth, can potentially be helped but only in cases where the problem is found very early. In most cases the retina fold becomes permanent and can not be unfolded. FEVR is a progressive disease which may change and worsen throughout the entire lifetime of a FEVR patient but how much and how radical and how fast it progresses can not be predicted. In cases where it progresses, FEVR progresses commonly by bleeding in the abnormal areas of the eye which usually is the outer regions. Abnormal blood vessels break and bleed into the center region of the eye which is filled with a clear gel-like substance called the vitreous. The person can often see wavy lines which is the blood floating in the vitreous. These abnormal blood vessels in FEVR also exude a milky white substance which can be seen on the retina near blood vessels. If bleeding, a common problem, occurs, laser surgery (laser photocoagulation) may be warranted other drug treatments are being tried to treat abnormal blood vessels but it is unknown whether drug treatments help FEVR. These drug treatments are similar to the same treatments used for the eye disease macular degeneration. The blood vessel growth which usually occurs in the outer edges of the retina can also occur anywhere on the retina. Fibrous membranes are also associated with FEVR and grow into the vitreous and attach to the retina and can cause traction or detachment of the retina. A surgeon can remove the membranes with a procedure called a vitrectomy. The most important thing a FEVR parent or patient can know is to find a good doctor who knows FEVR well and sees him/her whenever changes in sight occur no matter how small.
Most cases of FEVR donít show any symptoms and never become a problem but for a minority it can be a devastating disease. With diligent and at times aggressive treatment for these people, FEVR does not have to lead to blindness. Normal to impaired sight is common in at least one eye. Sometime complete blindness occurs. The closer a patient is watched and the knowledge of the doctor about FEVR and how to treat it can affect the outcome of a person. FEVR is a lifetime disease and should always be watched closely by a trained eye retinal & vitreous specialist.
WHEN TO OPERATE
Any operation has risks and thus the potential to cause other, sometimes serious problems, so care should be taken when deciding whether to perform an operation. The benefits must always outweigh the risks. If it is possible, it can be advantages to get a second and if needed third opinion. This will give you confidence that you have done all that you can do in deciding to operate. If the retina is already detached then you must act fast to save sight. It is better to get another FEVR doctor's opinions when you are not in an emergency situation.
FINAL AND IMPORTANT THOUGHTS
The FEVR patient and his or her family are encouraged to take one day at a time and if there are many operations both can benefit from some type of mental health help during their entire life. A mental health advocate can help enormously and should be incorporated into the treatment of FEVR especially if the patient is a child and it is thought that FEVR will remain active throughout their entire life. Pre and Post-Operative mental health care should be administered. FEVR does not just affect the eyes, it affects the entire person's mind and body, and should therefore be treated as such. This important fact can often be overlooked by eye specialists and the family most of the time need to seek out help themselves or bring up the subject with their doctor themselves taking a more active approach to holistic (whole body and mind) treatment. A psychiatrist, which is an M.D., (doctor), deals best with an eye doctor and has the ability to help in the hospital as well. Much trauma can occur when a whole mind and body approach is not taken. One must understand that the eye doctor has no training in mental health and thus can miss major psychological problems caused by the continued treatments of FEVR. To loose ones sight is one of the top most feared disabilities people have. How the parents and people around the legally blind person can affect how she or he see her or himself. One doctor that became a patient said, "I am wounded, not stupid so treat me with respect and equality." Many stigmata's still exist about seeking this kind of help but it may save your child's life in the end. Eye surgeons and mother's and father's can't diagnose treatable mental health issues such as post-operative depression, pre-operative anxiety or post-operative major depression from loss of sight or major surgery. You wouldn't treat your daughter or son's FEVR yourself so it isn't smart to think you can treat the emotional problems that will accompany FEVR your self. Talk to a mental health expert for that aspect of FEVR's treatment as well.
Jane A. Young
FEVR Patient for 43 years and over 30 surgeries and counting...
Feb 28, 2010
A good bulletin board where doctors answer questions is at The Public Forum. sponsored by American Association for Pediatric Ophthalmology and Strabismus (AAIPOS). I can't guarantee all the answers are correct but some helpful answers can be found. You can search the database for previously answered questions. Search for "FEVR" or "Familial Exudative Vitreoretinopathy"