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Wednesday, August 25, 2010

Vacation Photos

by Mark Dunning

I need a vacation.

Somewhere on Cape Cod
We spent last week on Cape Cod. We stay at the same rickety little cabin with the rock hard beds and the 1970 d├ęcor. It’s just a half a mile walk from the town beach. It’s a nice beach. It’s not really well maintained and more rocky than sandy, but it’s walking distance and because it’s not a premier location it’s never crowded. There are dunes there, like most of the Cape, and a broad salt marsh with a long boardwalk that crosses the winding channels that drain down with the tide. The kids love the channels because the water is shallow and warm and full of sea critters. We caught hundreds of hermit crabs and chased minnows while the terns plopped into the water around us like stones.

I like to walk down around the sandy point. It’s a good distance from the parking lot so it’s usually pretty deserted. Out there I don’t check e-mails. I don’t listen to voicemails. I don’t see the lawn that needs to be mowed or the office with the stacks of papers or the piles of toys that need to be put away. I leave most of my daily stresses behind.

Sandy Neck Beach
But I never escape Usher syndrome. Not even on vacation. I think this is true of every family that deals with Usher. It’s always there, grinding away, sneaking in to every thing you do everywhere you go. And it’s exhausting.

We walk down to the beach and my daughter keeps bumping into me. She has Usher syndrome and she has poor balance. She can’t really walk a straight line. So we keep drifting toward the center of the road until I’m staring at the grill of an oncoming UPS truck. Or I keep pushing her back in line, step after step, harder and harder, until we are jokingly jostling each other or, if we’re not in the best of moods, shoving each other in to shrubs and parked cars.

Sunset over the salt marsh
Or we have a fire on the beach. We walk down to the beach loaded with firewood and chairs and blankets and marshmallows and chocolate bars and juice boxes. It’s still light when we set up and slowly the sun burns down as the firewood dwindles. When the last of the logs is thrown on it’s dark and the moon has tossed a fistful of stars in its wake. Bella can see well enough by the light of the flames, but when we douse them it becomes a logistical disaster. Bella is a pack mule. She carries most of the chairs down to the beach. But in the dark she can’t see well enough, even by the light of the flashlight, to carry the weight and negotiate the soft sand and loose stones. So we load up my seventy year old mother-in-law with everything. No, I’m kidding. She leads Bella and the rest of us turn in to Sherpas. Of course Bella needs all the flashlights so I stumble through the dunes bristling with furniture and sticky with s’more residue.

Or we walk through the shallows in waist deep water, trailing a bucket, and dipping for snails and crabs and minnows and other sea critters. Our eyes are focused on the sand. All the action is at our feet. Bella doesn’t wear her cochlear implant because she occasionally has to dip her head in the water. She drifts beyond arm’s length and watches the rocks and sand. So when a flounder settles in the sand or a blue crab skitters past, I can’t yell to get her attention. I can’t splash her to get her to turn and see me sign because it spooks whatever would be of interest. My son Jack hears me call so he sees what I see. But Bella misses a lot, sometimes gets frustrated, and I feel guilty.

The photographer's little brother
Bella brings her camera on vacation. She likes to take pictures which is good, because none of the rest of us do. It’s nice to finally have some vacation photos with which to bore our friends. Better still, she’s becoming a good photographer. Her little brother says her pictures look like National Geographic. She has a great eye. In fact, all these photos are hers. But I find it hard to celebrate her growing skill. I’m wary of encouraging her to pursue it. I’m worried she’ll lose it in time.

Stoopid Usher syndrome.

I go for a walk around the point to try to forget about my vacation. It’s night and the moon is bright. The beach is silver and the tide is coming in. I pass one fisherman, but otherwise I’m alone. On the tips of the lapping waves, I notice fluorescent dots. They wind and loop along the sand as the sea inhales and exhales. It’s phosphorescent plankton and it blinks bright green on the sand and fades before the next wave arrives to replace the glowing dots. It looks like the stars are washing ashore. The kids would love it. But it’s dark on the beach and Bella would have a hard time walking. For all the effort it would take to get her down there, she might not even be able to see them. I might be rousting her to remind her of all she misses. So I walk back home, give them each a kiss, and keep the wonders I’ve seen to myself.

I don’t know if any of this is right or wrong or just is. The trip was a lot of fun and the kids, particularly Bella, look forward to it every year. I do too. Family vacations are rarely relaxing. There’s always bickering and ‘tell him to stop touching me’ and uncomfortable beds and odd schedules. But in the past, they were also an escape. They were a new set of simpler problems instead of the raw, rubbing, every day problems. That’s not the case with Usher syndrome. It’s always there, like beach sand in your hair.

A self portrait of the photographer in a typically serious mood.

Tuesday, August 10, 2010

Examining the Science Behind Dietary Supplements for Retinitis Pigmentosa

by Jennifer Phillips, Ph.D.

We’ve filled a lot of blog space over the past year discussing ongoing and eminently promising research efforts to find a cure for Usher syndrome. This is a target-rich topic, as you may have observed, with hundreds of researchers all over the globe working toward future treatments. This wealth of potential stands in stark contrast to the paucity of treatments available today, particularly with respect to the progressive loss of visual function inherent to Usher syndrome. Currently, the only recommendations in the neighborhood of being therapeutic with respect to preserving the vision of USH patients are the dietary supplements.

Mark has previously discussed the particular compounds on this list a bit, emphasizing them as components of a healthy diet, as opposed to prescribed as supplementation. As some vision care specialists do recommend bona fide supplementation for their Usher patients, though, I thought it would be a worthwhile endeavor to examine the evidence for this particular recommendation. Before I begin, though, I must vehemently nod toward that long, tedious ‘Terms and Conditions’ disclaimer found on the lower right margin of this page. As it clearly states, this site does not provide medical advice. In general, it’s a terrible idea to take medical advice from anyone on the internet, regardless of his or her credentials. So, even though I’ll spend the rest of this post talking about clinical studies and the basis for their application to real patients, I am merely a scientist with an opinion, which should not be construed as medical advice.

The data:

Over the last 20 years or so, several studies have been conducted examining the effects of various dietary supplements on patients with progressive Retinitis Pigmentosa (RP) from a variety of causes. As a minor but important side note, these studies excluded patients with clinically diagnosed Usher type I, but did include some patients with diagnoses of Usher type 2.

It is generally agreed upon that the studies were soundly designed and executed. That is, the questions that these studies were addressing were clear, specific, and answerable by the data obtained; the proper experimental controls were used, and the methods of collecting data were acceptable. The first study, published in 1993, investigated the effects of high doses of vitamin A on preserving visual function in patients with RP from various diseases. The authors reported that patients who consumed these large doses of vitamin A over a 4 to 6 year period had a slowed rate of vision loss compared to control groups, and concluded with a recommendation for vitamin A supplements at this dose for typical RP patients. There was also some indication from this study that consuming larger doses of vitamin E led to an accelerated loss of vision.

The second study, published in 2004, examined the rates of vision loss over the course of several years in RP patients treated with the same high dose of vitamin A combined with DHA, compared with patients receiving the high dose of vitamin A alone. The researchers reported no differences between the ‘A + DHA’ group and the ‘A only’ group. However, when they examined a subgroup of patients who hadn’t taken vitamin A supplements before the study began, they observed that DHA in combination with A seemed to have a protective effect on vision loss in the first two years of the regimen.

The third study, which came out earlier this year, examined the effects of lutein in combination with Vitamin A supplementation on vision loss, compared to a control group taking Vitamin A alone. Again, the primary result was that there was no difference between the ‘A + lutein’ and the ‘A only’ groups, but again, a secondary examination of a subset of the data showed that for selected, specific measures of vision loss, the ‘A + lutein’ group scored better. Based on this secondary outcome, the authors made further recommendations for dietary supplementation with lutein added to high-dose vitamin A for RP patients.

The controversy

As you may have surmised from our previous vitamin discussions here, the findings described above are not universally accepted by the medical community. In particular contention are the recommendations regarding vitamin A: since the first publication of these findings, a clash of opinions has ensued, with a flurry of letters to the journal in which this and all subsequent studies were published. Researchers and clinicians questioned the strength and interpretation of the data and in particular reacted unfavorably to the unambiguous recommendation by the authors that RP patients should commence high dose vitamin A therapy—a recommendation that was widely reported in the media and which many felt was premature considering the strength of the study upon which it was based. The controversy fumed on for months, deepening when members of the Data and Safety Monitoring Committee—those charged with oversight of ethics and procedures of trials involving human subjects—wrote in contending that the raw numbers of the study did not support the conclusions. Both DSM committee members praised the study for the quality of its methodology, but expressed specific concerns about how the numbers were crunched after all the data were collected, concluding (with my bold emphasis):

“This excellent study provides useful information for future investigators, but it fails to scientifically establish a significant beneficial effect for vitamin A in the treatment of RP"


"This study was meticulously designed and extraordinarily well performed…however, I would argue that its message should be one of caution more than enthusiasm. Patients should be informed that vitamin A may be only marginally beneficial if it helps at all, and this fact must be weighed against a somewhat uncertain risk of liver or other toxic side effects…”

Although the outcry was greatest with respect to the original 1993 report on vitamin A supplementation, minor controversy has continued to dog these studies, particularly with respect to the question of how much the conclusions of these studies, which relied heavily on spotting differences between groups that were only revealed when the statistical analysis was conducted in a certain way, should inform the standard of care for RP patients.

The outcome

To the best of my understanding, this issue is nowhere close to being resolved. The authors of these three studies have stood by their original recommendations, as evidenced by the subsequent studies focusing on the effects of extra dietary supplements in addition to the baseline high dose of vitamin A. Meanwhile, clinicians appear split on whether or not to recommend these supplements to their RP patients.

Based solely on the evidence in these publications, my opinion is that there is insufficient data to recommend supplementation. I know that some other scientists and physicians have reached the same conclusion, but still others, viewing the very same body of evidence, have determined that supplementation is the way to go and have incorporated it into their limited arsenal of therapies for retinitis pigmentosa. The only way through this apparent impasse will be through additional research to provide more evidence for—or against—these clinical recommendations. In the absence of new data, however, I can only proceed from my interpretation of the existing evidence as I consider the implications of these recommendations:

As Mark has previously written, we should all try to include more DHA and lutein in our dietary intake. Even knocking down a few extra carrots and other vitamin A rich foods is a good thing, as Martha Stewart would say. As a part of a healthy diet they appear to have no side effects (beyond the yucky faces pulled by unwilling recipients of mackerel, kale et al., on their dinner plates), so making an extra effort to consume them for overall health would seem not to have a downside. Daily doses of supplements, on the other hand, can be expensive and difficult to comply with. An additional concern stems from the fact that, unlike pharmaceuticals, dietary supplements are not regulated by the Food and Drug Administration, which opens the way for disturbing variations in ingredient content and quality. As such, informed consent for this type of treatment should include a discussion of the cost to benefit ratio, based on the available data. Moreover, unlike supplementation with benign compounds like DHA or lutein, high-dose vitamin A supplementation does carry with it some non-trivial health concerns, including liver problems and developmental defects. Thus, the ‘cost’ element of the cost to benefit ratio of vitamin A supplementation must include some risk factors that should be clearly spelled out when such treatments are being discussed.

For the clinicians who recommend this therapy for their eligible Usher and other RP patients, it’s not clear to what extent this advice is based on a more favorable interpretation of the study data discussed herein, or a more general embrace of something, anything, to suggest to patients in the way of treatment. To me this latter view is an issue of medical ethics and informed consent: If the physician prescribing long-term vitamin supplementation to his or her patient is doing so based on a belief that it will help, or a desire to offer something more than a sympathetic pat on the shoulder as they watch a young person’s vision deteriorate, then he or she has left the realm of science-based medicine, and may be even edging into the gray area between hope and false hope.

The pursuit of scientific ‘truth’ is always a work in progress: What we think we know today could be dramatically altered by what we learn tomorrow. Today, I know further dietary supplement studies are ongoing. Some of them are specifically looking at Usher patients, and even particular clinical subtypes of Usher. Good, targeted information about the potential benefits of supplementation for Usher patients will be forthcoming, and there is hope—real hope—that convincingly evidence-based recommendations can be made based on the findings.

Archives of Ophthalmology vol. 111, pp 751-772; 1456-1461
Archives of Ophthalmology vol. 122, pp 1297-1314
Archives of Ophthalmology vol. 128, pp 403-411; 493-495