PXE Vision: By and For PXEers
by Pat Manson
The Top 10 PXE Myths
Updated July 2015
While PXE was described in medical literature as early as 1896, relatively little was known about it until the second half of the last century. In fact, our knowledge of PXE—its causes, its effects, possible treatments, etc.—has grown dramatically over the last decade or so. What we now understand about PXE is in many respects quite different from, at times even contradictory to, what was earlier believed. This has resulted in a number of beliefs that were once considered fact but which we now know to be incorrect. Some of these earlier notions have proven difficult to dispel and have taken on mythic proportions. Following the format of Dave Letterman´s popular Top Ten lists, here are the Top Ten Myths relating to PXE in ascending order as well as a layperson´s refutation of each myth. For each myth, there are also links and references to provide additional information.
10. PXE procedures and related care are always covered by insurance
Unfortunately, this is a bit of an exaggeration. Nevertheless, health insurance coverage for PXEers is moderately good, better than for many multi-system or multi-symptom disorders. Most of the manifestations of PXE that might require treatment fall into 3 categories: eyes, skin and cardiovascular problems. What will be covered for each PXEer will vary according to the terms of his insurance policy as well as his insurer´s claims philosophy.
Generally, most eye testing is covered by insurance. The issue then is getting reimbursed for PXE eye treatments, usually the anti-VEGF drugs Lucentis® and Avastin®. These injectable drugs are administered to PXEers “off label,” meaning that their usage for PXE isn´t approved by the U.S. Food and Drug Administration (FDA) even though most practitioners regard the shots to be safe and effective for that application. Still, the majority of PXEers in the U. S. are getting their shots covered as a result of either generous coverage by their insurers or careful insurance filing by their doctors.
Insurance coverage for skin issues is a different story. Some insurers take the position that any treatment of lax skin, creases or lesions, whatever the cause, is voluntary and cosmetic—and therefore not covered. Again, the way the treating physician codes the insurance claim may tip the scales in a PXEer´s favor. Accordingly, most PXEers in the U. S. report that their skin treatments are being covered although it may take perseverance in the appeals process.
That leaves cardiovascular problems like intermittent claudication, breakdowns in the vascular network within the gastrointestinal (GI) tract, hypertension, etc. Typically, this type of condition is readily reimbursed by health insurers, irrespective of the underlying cause.
PXE International regularly assists PXEers who have been denied insurance coverage. This support can include, among other things, providing appeal letters to insurers. These have proven to be helpful to many PXEers.
9. I have [Fill in the blank: fibromyalgia, chronic fatigue, neuralgia, arthritis, joint pain…]. This must be related to my PXE.
It's tempting to blame PXE for many of the problems we face as we age. After all, we now know that the mineralization (the deposition—or depositing—of minerals) that occurs in PXE is found throughout the body. However, these deposits are not generally at clinically significant levels except for the few areas that give rise to the manifestations of PXE that are well known: the eyes, skin and cardiovascular system. The epidemiological study conducted by PXE International between 1997 and 2001 showed no greater incidence of fibromyalgia, chronic fatigue, neuralgia, arthritis or joint pain than in the general population.
General FAQ - What Are the General Symptoms of PXE?
8. Because my eyes are fragile, I shouldn't do anything physical.
PXEers' eyes are indeed fragile, but not that fragile. Virtually all PXEers have angioid streaks, which are cracks in the Bruch´s membrane of the retina. In many PXEers, these cracks can lead later in life to choroidal neovascularization (CNV), which in turn can cause vision loss. The issue with physical activity is the stress that such activity may put on the Bruch´s membrane and any CNV already occurring.
In view of the above, physicians strongly recommend that PXEers avoid 2 things: 1. trauma to the eye, and 2. the Valsalva maneuver. The first is obvious: hitting, bumping or any other pressure to the eye could cause a streak to tear or a CNV process to bleed. Sports or other activities that pose that risk should be avoided, or at least the risk of injury should be minimized by wearing goggles or a helmet.
The Valsalva maneuver is the temporary condition a person experiences while straining extra hard: holding the breath, grunting, red face. This can occur with the lifting of a heavy weight, a particularly tough move in yoga or even, rarely, a difficult bowel movement. The Valsalva maneuver causes an increase in blood pressure within the eyeball, which can cause damage similar to that caused by trauma. Solution: try to avoid these activities. If you can´t, don´t hold your breath and keep your breathing steady and slow.
Subject to these 2 restrictions and common sense limitations resulting from his vision loss, a PXEer's ability to engage in physical ability should be the same as a non-PXEer.
Vision - Restrictions to Activities
7. I cannot live a normal life with PXE.
This dire prediction is overly pessimistic. First, many PXEers never suffer any vision loss and their other manifestations (skin, intermittent claudication and other cardiovascular issues) are minimal. Therefore, the lives of these PXEers are almost unchanged. For the remaining PXEers, the degree to which PXE alters their lives will naturally depend on the magnitude of the manifestations of the disease. And that can vary greatly. Nevertheless, many PXEers have made full lives for themselves despite vision loss and other physical problems caused by PXE.
6. My pregnancy will be different because I have PXE.
There's no reason to think that this will be the case. There have been numerous studies on PXE's effects on women and pregnancy, and the findings are quite positive. First, fertility in women with PXE is normal. Moreover, the majority of pregnancies in women with PXE progress normally. The risk to the mother and to the fetus from PXE is low, probably no greater than in the general population. Finally, pregnancy has not been found to materially affect the mother's PXE.
5. PXE and macular degeneration are different names for the same disorder.
Not really, but this mistake is understandable. The issue here is the frequent confusion over the names of different disorders of the macula, the center of the retina responsible for detailed vision and focusing. There is no disease simply named “macular degeneration.” There are, however, a number of disorders that cause degeneration of the macula including, among others, PXE and age-related macular degeneration (AMD). While these two diseases affect the macula differently and have different causes, they are enough alike to have some of the same treatments.
PXE is a multi-system disorder that may affect the eyes to the point of vision loss. Virtually all PXEers have angioid streaks—cracks actually—in the Bruch´s membrane at the back of the retina. These usually (but not always) cause no vision problems by themselves, but in some PXEers they can lead to choroidal neo-vascularization (CNV). If left untreated, CNV will result in damage to the all-important retinal pigment epithelium (RPE) and photoreceptors in the macula, thus causing central vision loss.
AMD, on the other hand, is limited to the eyes. It is caused by perforations in and weakened areas of the Bruch´s membrane in individuals at least 60 years old, and usually much older than that. Like PXE, AMD can cause loss of central vision. Unlike PXE, AMD is associated with and may be caused by the presence of excess amounts of drusen, yellow deposits, in the Bruch´s membrane. If no CNV develops in these areas, it´s called “dry” AMD. If it does, it´s called “wet” AMD. Dry AMD can be more problematic than the mere presence of angioid streaks in PXEers because with dry AMD, the perforations alone can cause greater vision loss. And there´s little treatment currently available for dry AMD. If there is CNV, however, the treatment for it has for years been the same as for CNV in PXEers: impede the growth of new blood vessels, currently with anti-VEGF injections that appear to be very effective. In years gone by, PXEers were treated like those with AMD, with photodynamic therapy (PDT) or hot laser.
PXEers have benefitted greatly from the similarities between AMD and PXE. AMD is much more common than PXE, and with the aging of the “baby boomers,” the number of AMD cases will likely grow even more. Consequently, the development of the treatments above was funded by companies seeking to treat AMD, not PXE. That trend will likely continue for the most part in the future.
PXE and AMD: different diseases, different causes, similar symptoms and the same treatment options for the eye.
4. Researchers are getting close to a cure for PXE.
PXE may never be “cured” in the simplest, take-a-pill-and-you´re-well sense, but PXE researchers have made remarkable progress in a few short years in understanding the disease and are optimistic that they will be able to develop a treatment in the future that will address PXE at its core. Pending that breakthrough, innovative new treatments have been developed for the symptoms of PXE.
Much has been accomplished within the last 15 years or so—much of it with PXE International in the lead. It all started with the discovery that PXE is not, as previously believed, a connective tissue disorder, but rather a genetic disease that affects connective and other tissues. The gene associated with PXE—ABCC6—was then identified and since Sharon and Pat Terry materially participated in its invention, Sharon was named on the patent issued for the gene. (For simplicity, they chose to have just one of them named.) Sharon assigned her patent rights to PXE International, enabling it to have a greater voice in the direction of the various studies on PXE. Within the last few years, researchers determined that PXE is a metabolic disease primarily affecting (but causing no problem to) the liver. What that means exactly is still being investigated, for researchers are seeking to understand how PXE operates within the body. Recent studies, for example, have been looking into the varying effects of different vitamins and minerals such as magnesium, vitamin K and calcium on the progress of mineralization in mice with PXE. A two-year clinical trial of magnesium supplements as a treatment for PXE, sponsored by Dr. Mark Lebwohl and the Mt. Sinai School of Medicine, began January 2013 with 44 participants.
The goal of all these efforts to drill deeper and deeper into PXE, specifically into what triggers its manifestations in the body, is to try to identify a method to “turn off” PXE or to interrupt the progress of its manifestations. Researchers at the highest scientific levels are working in numerous studies on this puzzle, and progress is indeed being made. But there won´t be a “cure” soon.
In the meantime, new treatments are being developed to treat the most common symptoms of PXE. The anti-VEGF drugs, for instance, are relatively new, only introduced in 2005. They have proven very effective at arresting, even reversing at times, vision loss caused by CNV. If the effectiveness of these drugs (and their successors—there are hundreds more in the pipeline) holds up, these drugs will positively change the outlook for future generations of PXEers.
Similarly, innovation in both cardiovascular health and cosmetic surgery and other dermatological treatments is occurring every day. Fortunately, a PXEer's manifestations in these two areas can also be caused by other disorders, so PXEers will continue to benefit from a broader range of research.
Clinical Trial of Magnesium Supplements reporting
Avastin and Lucentis are Equivalent in Treating AMD: CATT Two-year Results
Parabiotic Mouse Pairing Experiments: More Evidence that PXE Is a Metabolic Disease
Clear Evidence: PXE Is a Metabolic Disease
Research News section of the website
3. I can´t have PXE because no one else in my family has it.
All it takes to have PXE is for your mother and father to be carriers of the PXE gene and to both pass that gene on to their child. In other words, your parents don´t have to have PXE. In fact, PXEers´ parents usually don´t have PXE. But because PXE is a recessive genetic disorder, it does take 2 people who carry mutations in the ABCC6 gene to parent a PXEer. Fortunately, any one person having the gene is a rarity. So the odds of two PXE carriers finding one another are very low.
Variation on the same myth: If I have PXE, my brother/sister must also have PXE.
The inheritance pattern of a recessive disease doesn't work that way. When the parents are both carriers of the gene associated with PXE, each child born has a 25% chance of having PXE, a 50% chance of being a carrier, and a 25% chance of being neither, of being unaffected. And the process starts anew with each conception. It´s like flipping a coin. It starts over with each flip, no matter how the last flip turned out. It works the same way for each new birth. The above odds remain the same irrespective of whether the earlier-born siblings are PXEers, carriers or neither.
The PXE International website provides thorough, easy-to-understand explanatory information and materials on PXE and inheritance.
2. I will lose my vision because of my PXE.
No, you won't. This can be stated categorically: PXE does not cause blindness. While virtually all PXEers have angioid streaks, many PXEers´ eye conditions don´t progress beyond that. In other words, those PXEers never sustain any vision loss. For those whose eyes are affected, only their central vision is affected. While this can reduce fine focusing and may therefore limit reading, driving, etc., the deterioration is limited to that area. (This type of vision loss may be deemed “legal blindness” by some countries and states, depending on the degree of vision loss.) Accordingly, peripheral vision is unchanged, and many PXEers report that they are able to live normal lives subject to some adaptation. Such adaptation isn´t easy, but many PXEers have done it and done it successfully.
Variation on the same myth: If I'm diagnosed with PXE, my chances of eventually becoming legally blind are 1 in 3.
Up until a few years ago, this was the estimated breakdown of PXEers' final status, but it isn´t any longer. PXE International's epidemiological study showed that one-third of PXEers experienced no vision loss, while the other two-thirds suffered some vision loss. Of those, about half sustained sufficient loss to be regarded legally blind, and the other half lost some vision but something less than that. So it was generally true that one-third of individuals affected by PXE would have no vision loss, one-third would have some vision loss and one-third would lose enough vision to be regarded as legally blind.
All that changed with the introduction in 2005 of Lucentis and Avastin. These drugs, injected into the eye, can stop and in some cases reverse vision loss. So far, the results have been very favorable. There are other treatments in the pipeline, too, so PXEers have even more reason to be optimistic about their future.
And—drum roll—the Number 1 myth about PXE is:
1. I should restrict my calcium intake to slow down my PXE.
This is a very persistent myth, but here goes. Long ago, one very questionable study might have showed that PXE progression was slowed by severely reducing one´s intake of calcium. However, we now know that PXE signs and symptoms and their progression are unrelated to calcium ingested in food or drink. On the contrary, the mineralization of 3 elements—calcium, magnesium and phosphorus—that causes a PXEer´s symptoms is actually caused by a malfunction in the ABCC6 gene, not the ingestion of dietary calcium. Accordingly, a PXEer should follow the same dietary recommendations for all vitamins and minerals as someone without PXE and also consult with his physician.
Other Health Questions FAQ - Calcium Restriction Not Advisable
That's it, but that's plenty. If all PXEers and others within the PXE community would take the time to learn these facts about PXE (while unlearning these myths), we´d all have a better understanding of what we're dealing with and how to deal with it. You can't be an effective advocate for yourself or your loved one if you can´t talk the talk. You can start by getting these facts down.