Assistive Technology

Below is a link to assistive technology for those with low vision. You may be able to have the costs of purchasing some of this equipment defrayed by yoru local state rehabilitation agency.

http://www.mdsupport.org/resources/techproducts.html

Lutein Supplementation and RP

Below are the results of a study on Lutein supplementation and RP. This is not news, the late Grace Halloran advocated this twenty years ago. However, this is the first time a formal study has been completed. Grace advised me to do this almost ten years ago. I feel, if I had been disciplined and stayed the course, my vision would be much better.
http://www.ncbi.nlm.nih.gov/pubmed/16759390?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://ghr.nlm.nih.gov/condition=neuropathyataxiaandretinitispigmentosa

Lipid Disorders and RP

There is a connection between the amino acid taurine and the abosrption of fat soluable vitamins, like Vitamin A. I remember reading somewhere, years ago, that RP is associated with lipid disorders. I also know of a naturopath who does blood work on a wide variety of people who have a variety of eye conditions. He has stated that, without fail, there are blood sugar abnormalities.

With regards to lipid processing, This makes sense. Faulty uptake of the amino acid taurine would lead to the malabsorption of Vitamin A, This leads to a breakdown of the chemistry needed in order to maintain retinal function which leads to cell death of the photoreceptors....Explains why Berson found that mega supplementation with Vitamin A has some impact on maintaining visual function some of the time. However, mega supplementation does not get the job done nor does it addres the underlying metabolic deficit which makes it necessary.

Taurine and Retinal Disease- Patent

http://www.wipo.int/pctdb/en/wo.jsp?IA=US1998026106&DISPLAY=DESC

http://www.biomedexperts.com/Profile.bme/1110527/AM_Petrosian

Petrosian's theory on the relationship between taurine and fat-soluable vitamins essential for vision:

http://www.ncbi.nlm.nih.gov/pubmed/11128549?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Would have been nice if they had not tested tuarine along with both Vitamin E and Dilitiazem, but interesting all the same:

http://cat.inist.fr/?aModele=afficheN&cpsidt=13940577

Phytochemicals

http://www.phytochemicals.info/

Two books on my wish list:

http://www.amazon.com/Nutrigenetics-Nutrigenomics-Review-Nutrition-Dietetics/dp/3805577826/ref=sr_11_1?ie=UTF8&qid=1220925547&sr=11-1

http://www.amazon.com/Phytochemicals-Nutrient-Gene-Interactions-Mark-Meskin/dp/0849341809/ref=sid_dp_dp

http://www.ncbi.nlm.nih.gov/pubmed/17045449

Dr. Amy Yasko claims to already work with nutrient-gene interactions in her practice. Hmm.....She could be ahead of her time or making false claims. Either way the premise is interesting.

Beauty and the Blind

A touching article about a woman who, after losing her sight, still is profoundly struck by beauty.

http://nfb.org/legacy/bm/bm03/bm0306/bm030611.htm

I ran across this article while researching something unrelated. It spoke deeply to me. Recently, I had a dream in which I was asking God about human suffering and pain. One of humanity's ongoing existential struggles, no doubt. Being human, I was asking God about my particular struggle, which, in the scope of human suffering, is truly nothing. But, I digress.

In this dream, God shows me a caterpillar inching its' way up a green stalk. He says, "That is you," I looked at the caterpillar make its' way, painfully slowly, up the green plant's stalk. He asked me, "What happens if the caterpillar turns around?" I answered that, I guess, it would just return to the grass. He agreed and then asked me to watch the caterpillar once more. So, I did. It reached the end of the stalk and made a cacoon. After being in total darkness, it emerges as a fragile, stained glass, backlit, ethereal looking butterfly. It was the most fragile and finely crafted glass I have ever seen, yet the creature was animate, flitting about in the night sky. Its' delicate perfection was apparent not only in its fragility but the incredibly intense colors: greens, violets, vibrant shades of orange contrasted by the coolest of electric blues.

Later in the week, my daughter went to her favorite art studio with her babysitter. She came home and gave me her creation. She said, "Look Mama! A mariposa for you!" She created a gorgeous, colorful butterfly whose vivid oranges, violets and blues are simply glorious! Did she overhear me mention the dream to my husband? Doubtful, but I suppose it is possible. Does it matter? Not at all...

I find a little bit of HOPE to be similar to putting a small amount of food coloring in a glass of water. It does not take much to color the water to an intense hue. Hope is the same way. It does not take a lot to transform an existence in to a beautiful, vibrant life regardless if one can perceive the colors or not.

Swimming Blind

http://www.cbn.com/spirituallife/devotions/aspin_swimmingblind.aspx

Apocynin

http://www.answers.com/topic/apocynin-1

Apocynin is isolated from both the kurroa and Canadian hemp roots:

http://riverssourcebotanicals.com/index.php

http://www.tattvasherbs.com/liversupport.htm?gclid=CNrUguiYk5UCFQmdnAodZDAFgw

http://www.vitacost.com/Healthnotes/Herb/Picrorhiza.aspx

http://www.vedaliving.com/store/product_info.php?products_id=103

NO Synthase and RP

A possible adjunct to antioxidant therapy in RP which targets the underlying cause of excessive oxidative stress in the retina..

http://groups.google.com/group/sci.med/browse_thread/thread/d8c985e6ae69eed9

Antioxidants in Combination Fight RP

http://www.ncbi.nlm.nih.gov/pubmed/17293057?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Copper Toxicity and RP

I found the articles below interesting in light of the Vitamin A data from the early 1990s. Zinc is required to metabolize Vitamin A. If copper levels are high, zinc is low, which would explain the need for excess Vitamin A. Supplementing with Vitamin A has been advised for years. However, there are limitations because of its potential toxicity. So, if there were an issue with the metabolism of trace minerals which impact Vitamin A utilization, then there would be some interesting possible therapeutic potential.

Copper Toxicity and RP:

http://www.ijo.in/article.asp?issn=0301-4738;year=1979;volume=27;issue=4;spage=170;epage=173;aulast=Gahlot

Study of American patients showing no abnormality of copper metabolism:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1043173

Relationship between zinc and copper:

http://www.drkaslow.com/html/zinc-copper_imbalances.html

http://lpi.oregonstate.edu/infocenter/minerals/zinc/

Vitamin A and zinc, metabolic relationship:

http://64.233.179.104/scholar?hl=en&lr=&q=cache:2GP9vDa9av4J:www.idpas.org/pdf/2917_Zinc_vitaminA_interaction.pdf+author:%22Christian%22+intitle:%22Interactions+between+zinc+and+vitamin+A:+an+update%22+

Chinese abstract on zinc and RP:

http://www.ncbi.nlm.nih.gov/pubmed/2289582

Taurine is interesting in that, cats deprived of taurine will develop a condition similar to RP over time. In Australia, they accidentally received dog food in bags marked as cat food. Apparently the dog food did not have taurine in it and the cats require taurine for normal vision. They developed a disease similar in nature to what we call RP.

So, some researchers tested the blood levels of RP patients for taurine levels. The levels were normal, but apparently the uptake is not. So something in the pathway involving the metabolism of this amino acid is not functioning. In the post entitled "Successful Reversal of RP", taurine was used.

Also, in developing countries, people will go blind simply because they do not have adequate Vitamin A intake. It is interesting that, to date, the only research that has resulted in a therapy that helps some people, some of the time, is based on large doses of Vitamin A. That seems to be a cue to a metabolic issue (s) at least for some people with the diverse group of genetic mutations that contribute to a full blown case of RP.

Taurine Uptake and RP:

http://www.ncbi.nlm.nih.gov/pubmed/85058

http://www.fasebj.org/cgi/content/full/16/2/231

http://bjo.bmj.com/cgi/content/abstract/66/12/771

Vitamin A and the chemistry of vision:

http://www.elmhurst.edu/~chm/vchembook/532vitaminA.html

Anatomy of the Eye

http://www.mdsupport.org/anatomy.html

My Acetazolamide Case Study

I decided to do my own replication of the University College London acetazolamide case study (for more information, see my 2/15 post). This is not something to be entered in to on a whim. Acetazolamide is a hard core drug and I had to get blood work done regularly to monitor potassium levels and red blood cell count among other things. It has some very scary possible side effects including bone marrow stopping the production of red blood cells. It is a diuretic and it is important to monitor kidney function. So, one must commit to regular blood work. As an aside, I wish someone would attach a statistical measure to possible side effects. Then, it would be easier to make educated decisions. For example, if there is some extreme side effect, it would be helpful to know if 5% or 46% people in the clinical trial experienced it. Okay, I am off that soap box for now.

I started my dosing at 250 mg. on April 15th. I slowly ramped up to 500 mg. Then, I went to 1000 mg. for one month. I noticed colors looked brighter. I also had an improvement in my fields. I doubted if anything; other than increased color vision, was happening until I got off the drug. Then I realized that, indeed, it had helped. One would expect it to help the clarity of vision if I had any residual CME.

But, I also noticed an increase in my ability to find things. Do not get me wrong, I was still quite impaired. But, I did not run in to things in my own home. My shins had no bruises and I could wear skirts without looking like I was married to an abusive little person. I did not collide with door jambs. I could find most anything I needed independently. Still, I doubted my improvement. Now, that I am off the medication and have regressed, I notice that it was helpful in ways one would not expect if it simply resolved CME.

So, why did I discontinue using the drug? Well, I felt like absolute…..crud. At first, the 1000 mg dosing was fine. Besides having pins and needles in my extremities, being a little more tired than usual and everything tasting like metal, life was good. Then I started to become very fatigued. Getting out of bed in the morning became an act of will. If I did not have responsibilities, I probably would have spent the day in sweat pants (always my data point for a major case of the blahs). I also started having, shall we use a nice medical euphemism and say “gastrointestinal distress" on an all too regular basis.

So, better vision is not so useful when you feel awful. But, it does make me relatively optimistic about the potential of the Brimonidine Tartrate implant being developed by Allergan. For more information see the post from 4/20.

I think back to everything I have tried, from acupuncture to stem cell implants. Glaucoma drugs to microcurrent……there always seems to be a bit of efficacy to each. I think of microcurrent’s basis in sending an electrical current to the retina. Then, I see the implantable chip which generates electricity and stimulates the retina. Acupuncture is also an electrical process. So, there are some interesting parallels. My fields responded to acetazolamide. If it could be delivered locally, then we would have a more realistic therapeutic option. But, the devil is always in the details.

Now it is time to soldier on and be grateful for the desire to do so. An old friend called me, he is in his late thirties, a single dad and dying of a rare disease for which not ONE clinical trial has been conducted. So, we are relatively blessed compared to many. But, it is only human to lose sight of that when one is losing sight.

Muller Cells and RP

Scientists at Schepens, at Harvard, have discovered that Muller cells within our own retinas may have the capacity to turn in to various types of cells. According to this study, these cells have the possible potential of healing diseased retinas.

Why wouldn’t our bodies have the potential to heal themselves in this context? The human body is a miracle. A mundane miracle, but a miracle all the same.

http://www.schepens.harvard.edu/press_releases/march_24_2008.html

Fetal RPE Transplantation

Dr. Norman Radtke is doing RPE transplantation again. When I researched this procedure three years ago, he and his team were transplanting one sheet of fetal retinal pigment epithelial cells (RPE) in to the diseased retinas of people with RP and ARMD. He is now doing transplants with two sheets of cells, both neural and RPE cells. He has some recent case study data on his site.

If you go to the “clinical trials” section of this informative website, you will find information on the trial. He also has a section entitled “outside trials” as well as “trial bulletins”. Both are excellent resources for keeping up with the latest in retinal research, regardless of who is funding it. The “bulletins” section is one I find particularly notable.

http://www.rvrc.com/_drradtke.cfm

I did find some published work by Dr. Radtke on this procedure.

This article was published in 2004, and reflects the results when transplanting one sheet of fetal RPE cells.

http://www.ncbi.nlm.nih.gov/pubmed/15302656?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Information from 2002:

http://www.ncbi.nlm.nih.gov/pubmed/11931789?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

From 1999:

http://lib.bioinfo.pl/meid:112531

A Swedish rabbit study on "full thickness implant", which I believe may be both the RPE and neural retina layers.

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=27472&Ausgabe=226339&ProduktNr=224269

Swedish pigs:

http://www.ncbi.nlm.nih.gov/pubmed/17072635?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
An 2002 overview of retinal transplantation:

http://www.djo.harvard.edu/site.php?url=/physicians/oa/379


I keep an eye on Steve Wynn, Las Vegas casino developer and gazillionaire, since he has RP and is one of the wealthiest people on the planet. In the blogosphere, there are numerous references to a "government approved experimental eye surgery" he had done in May of 2007 at Johns Hopkins. So, I tried to find any trials at Wilmer (Johns Hopkins) that are recruiting RP patients to see if I could make an educated guess as to which procedure he had done. I did not have much success. But, I will keep searching. According to the articles in the blogosphere (always suspect), he disclosed this surgery plan to his dealers on the eve of a union vote. They still unionized, but the information was made public. If you believe what you read, anyway.

Obviously, there are numerous ethical concerns when using fetal retinal tissue from aborted babies. Someone, I believe it may have been Mark Twain, stated something along the lines of, "Ethics are the luxury of the well fed." In other words, it is easy to extol lofty ideals and virtue when in a position of relative ease. The real test comes when "the rubber hits the road" and life becomes more challenging.

My personal opinion is, until you have navigated a busy intersection with a toilet paper roll encircling each eye and a stick, then you do not get an opinion. Okay, maybe you can have one. But, do not express it. At least, not around me, unless you come bearing dark chocolate and red wine. :)

Gene Therapy and RP

This is old news at this point, but I just have not found the time to write about it. Below is the article published in the New England Journal of Medicine regarding the recent gene therapy trial for LCA, a severe, early-onset form of RP.

http://content.nejm.org/cgi/content/full/NEJMoa0802268

There have been press releases issued to major news outlets. You can see the media coverage at the FFB website:

http://www.blindness.org/

It is worth the time to read the academic article. While it is difficult for a layman to understand all of the jargon, it gives a realistic picture of the actual results achieved.

Yes, it is very exciting. But, it is the result of, at least in the study published above, one person's improvement in one aspect of vision, contrast sensitivity. Apparently there is the study above as well as another one using a different set of three adults. This is the only published peer reviewed article I have been able to locate in PubMed (thanks for the share, G.). And, as all of the scientific types are quick to remind us RPers, one person's experience does not usually mean much and we should not invest too much time in being hopeful. Unless it is gene therapy, apparently.

I suppose I must be missing something. It certainly would not be the first time. Maybe the other study, which I cannot locate, had better results.

This is the first gene therapy trial, to my knowledge, done for a condition which is not fatal. I have to admit, I am floored the FDA approved gene therapy for a non-lethal condition. The exciting thing about this trial, based on the little I know about gene therapy, is no one had "adverse events", like dying, from the viral vector used.

A vector is a virus used to carry the normal copy of the gene to the target gene. The tricky part is using a virus that is not harmful to humans. In other (non RP related) gene therapy trials in the past, people have died from immune reactions resulting from the virus. This may be worth the risk to someone dying of a fatal condition. There is also the risk of the replacement gene not just going to the target area and inserting itself in other cells, leading to cancers.

However, by some miracle, these scientists actually were able to get this trial approved in this country for a disease that is not killing people. So, in the scientific community, that must make them rock stars. I am not talking some bubble gum boy band either. More like Keith Richards, able to defy the odds and astonish medical professionals time and time again.

Aging rock star jokes aside, It seems like there are multiple standards at work. Again, I am sure I am missing something. But, take our UCL acetazolamide case study. That is a case of one person having improvements in contrast vision. However, there were no press releases, no buzz or continued funding. Granted, her gains were not nearly as dramatic as the gains of the subject in this study.

But, the results obtained by one young person in the study are very encouraging to me. The increases in his ability to detect contrast are undeniable and unlikely to be explained away. The fact that the dogs who have received the same procedure, eight years ago, have maintained their gains is even more encouraging. And, this is gene therapy's first barbecue for RP in humans. This was just to test safety, and that anyone had any benefit at the most conservative dosing level is encouraging.

My personal belief is gene therapy may be able to help me one day maintain the results of a stem cell procedure. I think it holds an enormous amount of potential for young people who are newly diagnosed and identified. Hopefully the incredibly brave young people who participated in this study will have more improvement and stable general health.

The "subjects" are courageous, pioneering and inspiring. With all of the things I have tried, gene therapy would still terrify me, regardless of who was doing it. Kudos to the researchers as well. Firstly, for getting results. Secondly, for managing to get a trial with this amount of inherent risk done in this country. It has no doubt been a long, laborious road and I look forward to more good news.

Yet Another Glaucoma Drug and RP

Below is some information on yet another glaucoma drug that has some result in RP. Keep in mind the drug in this study was delivered topically. So, in actuality, it is a relatively small amount of medication that actually makes it to the target area.

If you check out http://www.clinicaltrials.gov/ and enter "retinitis pigmentosa", look for the clinical trial for the "Brimonidine Tartrate Implant". Brimonidine is a glaucoma drug. You will see the drug manufacturer, Allergan, has invested the research and development dollars to create a retinal drug delivery system in the form of an implant. The drug of choice has traditionally been used for glaucoma.This study is going to take place in Europe.

I find this of particular interest given the acetazolamide (another glaucoma drug) case study from the University of London. No one has ever accurately replicated that woman's experience in the form of a larger scale pilot study. In the one attempt, the dosing was incorrect and the study was prematurely terminated.

Now, another glaucoma drug is emerging and a company has invested major funds in an implant in order to deliver it directly to the retinas of RPers.

Interesting....

Below is a link to a pilot study done in Israel. Its results will not enthrall, but keep in mind this is eye drops, not even a systemic delivery in the form of an oral pill.

http://www.liebertonline.com/doi/abs/10.1089/jop.2007.0022

Interview with David Paterson

I found David Paterson, the first legally blind governor of New York, to have an interesting perspective. I can relate to him in living in a world that is between the sighted and non sighted worlds and how very difficult it is for people to grasp partial sightedness.

first legally blind governor in U.S. historyDavid Paterson to become new New York governorBy Reuters / March 12, 2008NEW YORK (Reuters) - New York Lieutenant Governor David Paterson was setto become the state's first black governor and the first legally blindgovernorin U.S. history, after the resignation of Gov. Eliot Spitzer Wednesday.Paterson, 53, became New York's first African-American lieutenantgovernor in November 2006. He has been legally blind since childhood,with only partialsight in his right eye.Spitzer resigned after media reports linked him to a prostitution ring.He said Paterson would take over Monday.The following are some facts about Paterson:Paterson was born in Brooklyn to Portia and Basil Paterson. His fatherwas the first non-white secretary of state of New York and the firstAfrican-Americanvice chair of the national Democratic Party.He earned his bachelor's degree in history from Columbia University,graduating in 1977, and completed his law degree at Hofstra Law Schoolin 1982.Paterson became a public servant in 1985 when he began representingHarlem in the New York State Senate, according to the New Yorkgovernor's Web site.In 2002, he became the body's minority leader, the first non-whitelegislative leader in New York state history.In 2004, he became the first legally blind person to address theDemocratic National Convention.In 2006, Paterson was elected New York's first African-Americanlieutenant governor.Paterson ran the New York City marathon in 1999.Paterson, an adjunct professor at Columbia's School for Internationaland Public Affairs, lives in Harlem with his wife, Michelle PaigePaterson, and theirtwo children.Additional information from a New York Times article FROM January, 08"As a disabled person, there's certain times that I don't want to appeartoneed that much help. When I was in college, when I was at Columbia, Ihad aprofessor - I actually Googled him, he passed away in 1986 and his namewasBasil Ruch, and he was a professor of history at Barnard College, and heshowedme a picture of Franklin Delano Roosevelt being carried into the 1932Democraticconvention. And he said that Roosevelt by 1932 was still able to walk acertaindistance, but not quickly, and he wanted to walk in, he wanted thecountry tosee him standing, and but what happened was, when he started to walk,and he gottoward the end, he was starting to be a little jittery, that a bunch ofsupporters, thinking they were helping him, grabbed him and picked himup andcarried him in. And you see in this picture - and I couldn't really seeit, buthe described it to me - he has this stern, angry look, because theymessed uphis moment. And I know what he was feeling. Because sometimes you wantto project a certainamount of strength. And you can project it if you're a woman, you canproject itif you're disabled, you can project it, but often the people who loveyou don'tsee the need for you to project it.I remember when I was in the D.A.'s office, and I conducted a hearingand it hadto do with a stalker who was bothering this woman. And I got to feelingwhen thewoman saw me holding the file up to my face and that kind of thing, andthestalker's looking at her, and she's kind of - I got that she didn'treally knowif I was able to handle this.And I went over to her and I said, "Listen, just in case we lose thishearing,don't worry, because when he goes outside, I'm going to kick his butt."I saidthat to her because I wanted her to know that I'm in charge of her case.Andthat's what I'm saying about projection."Q: Did you always think, with your disability, that you could followyour fatherinto politics, or was that something you came to over time?A: When I was 10 years old I watched Robert Kennedy speak at theDemocraticNational Convention and I wished I was him. And I think, again, therewas thatfamily connection - he was following in the footsteps of John, Hillaryfollowsin the footsteps of Bill, so I always relate to that, you know, kind offamilymember who has to deal with that shadow.When I was in college, though I had academic ability, I don't know thatI wasall that socially developed, or had a real difficult problem askingpeople forassistance, and had a lot of problems as a result of that. And I thinkas I hadmore problems, my ideas about being in politics, or following my fatherdwindled. I didn't see myself as - I think my self-esteem reallysuffered fromthat. ...Q: In terms of your vision, how much can you see?A: I am legally blind in my right eye, and totally blind in my left eye.I'mlooking at Armen [Meyer, a press aide who was in the room]. I know hehas awhite shirt on, I know he has a tie on, but from this distance I can'ttell youwhat color it is. I think it's a darker color. ...When I am in places where I am familiar, I will appear to see betterthan inplaces where I'm not. If I walked around my house, and you didn't know,you'dprobably think I have no vision problems.When I say I saw something, it's more like I sensed it. So when I saidthat wewere on a plane with the Clintons, and we're all eating pizza, I knewthat I waseating pizza and I knew they took pizza off the tray, so I assumethey're eatingit. I think people's perception of me sometimes is that I see more thanIactually do. But I play basketball, and I've done things that peoplewith my vision aren'tsupposed to do. I'm in this interesting sort of zone between the sightedand theunsighted, and have never really met anyone who I visually relate to,I've nevermet anyone who is kind of like me. ...My truest disability has been my ability to overcome my physicaldisability. Soin other words, as soon as people see that I can be independent, thenthey holdme to the standard that everyone else is. So I remember once I told theairlinesthat I had a sight problem, and they put me on this bus to go to a hotelbecausethere were no other flights out of the airport that night, and I gave upmy seatto everyone got on and they passed me, and then like this 90-year-oldwoman, whowas trying to get up the steps, and I couldn't take it anymore so Ihelped herup the steps, gave her my seat and took another seat. First stop, thebus drivertells me to get off. And I know that he's doing this now because hethinks Ihave no problem. He goes, "Go that way." And I almost fell in thewishing wellin front of this hotel. That's because he saw me able to fend formyself.And I think that's been my greatest disability, that as I've overcome myphysical disability, it just leads to other problems. So I think I havenowlearned - and I'm not doing this to be deceptive - but I don't act theway I didwhen I was 17, like I can do everything myself, because I realized theminute Ido that, no one helps me. So I learned to be a little more pragmaticabout life

RP, supplementation and MS unit

http://www.altoonamedicalsupply.com/retinits%20pigmetosa.htm

First Legally Blind Governor

Not only is David Paterson New York's first Black governor, he is NY's first legally blind governor. His blindness was caused by a childhood illness. He has some vision in one eye and no vision in the other. He went to law school AFTER being legally blind.

What is his message to me? Blindness is no excuse to not hold yourself to the highest standard of achievement. Many people, out of ignorance, will coddle us. The "tough love" mentality has to come from within. Hard? Absolutely! Worth it? Well, what is the alternative?

http://www.ny.gov/ltgov/

Rebuttal to my 2/15 Post

Facts quite often, I fear to confess, like lawyers, put me to sleep at noon. Not theories, however. Theories are invigorating and tonic. Give me an ounce of fact and I will produce you a ton of theory by tea this afternoon. That is, after all, my job. -Ray Bradbury, From the foreward to "Mars and the Mind of Man"

In my post from 2/15, I present two case studies and one larger scale study to make a theoretical case for the use of acetazolamide and RP, independent of CME. I am by no means in a position to advise anyone to take anything. I am simply presenting information I find interesting as well as connections that intrigue me.

An anonymous researcher replied to me via email. I am including his response below. It gives another perspective. He was kind enough to provide his input. If you have the time to read the full text of the University of London acetazolamide case study, you will find that the subject's visual field expanded substantially. The authors maintain this only happened after several months at a dose of 1000 mg. In the larger study the anonymous researcher comments on, the dosing was cut in half and the duration in a third, if memory serves. So, it was not really a valid replication of the case study.

Researchers do not find one case of an RPer making substantial gains in visual field of much interest. I, as a patient, do find it interesting. I also believe, when blindness is the alternative, RPers should have the option of trying experimental therapies with informed consent. RPers should not have to be in a clinical trial to have access to prescription drugs or other readily available therapies that could, possibly, help them. I do not believe we need to be babysat. RPers can understand risk/ benefit analysis and come to their own conclusions, with information on risks and management of those risks. Physicians need to be partners with patients, not gatekeepers.

For argument's sake, say I had some experimental therapies. Even with a positive change in my ERG, I am convinced I could walk in to the university near my house, get an ERG that shows normal vision from my flat line now and no one would raise an eyebrow. They would say, "Hmmm....that is unusual. She must not have had RP. It must have been something else." They would say this even if I presented in-depth information on the protocol I followed, backing it up with published research. My retinal specialist is a proactive guy, maybe he would write up a case study. When people read it they would say, "But she did so many things. How can we even attempt to make a causal connection?"

As RPers interested in actually trying to treat this thing, this is the mentality we face. Do not misunderstand, research is vitally important. But, do not count on these people to make any kind of common sense connections. Until something is effective in very large scale studies, no one cares.

Below is the research scientist's response. It was very kind of him to send this information. I appreciate his involvement and interest.

I read portions of the Friday, February 15 blog entry . In your point #2 you say, "There have been studies that have shown acetazolamide improves visual function in those who have RP but no CME." ... but the study that you cited does not say that at all. I think you have misunderstood the results. The authors, two of whom I know personally, merely reported the results that three patients showed improvement in their visual field -- an improvement that was not reproduced in the crossover study. In quantifying these visual field changes, they used the word "significant" which in conversational English almost always means "huge", but in research it means “unlikely to be explained by chance” (more on that later). But no matter how you define the term, these "significant improvements" in three patients would never cause a medical researcher to as much as raise an eyebrow or utter the sound “hmmmm” -- for a variety of reasons. Pilot studies by definition lack the statistical power of the gold standard placebo-controlled, double-blind large study, and therefore the goal of the pilot study can never be more ambitious than to suggest a interesting trend that might be worthy of further investigation (and the health risks and enormous expense of further investigation). It is a mistake of the highest order to suggest that the results of this pilot study demonstrate causation as your statement implies. Again, by definition, no one in the research community would ever interpret the results of any pilot study as causing anything. And especially since, as in this case, the numerically small positive observations were:
a) derived from subjective psychophysical rather than objective electrophysiologic measurements.
b) not reproduced in the crossover study Regarding A: An automated threshold-related 60° visual field is a brutally boring and stressful test (as I'm sure you probably know). Improvement or decline in performance after repeated trials can easily be attributed to "the learning effect" or fatigue respectively. In our glaucoma practice (where visual fields were, until recently, widely used), significance is usually reserved for changes observed in comparison to an average of three baseline measurements -- and even then, it is regarded with suspicion if the patient has false positive responses (suggesting anxiety or eagerness) and/or false negative responses (suggesting boredom, fatigue, Munchausen syndrome or malingering ). This "catch trial invalidation" can be factored out if the visual field is performed manually (Goldmann perimetry) by the same skilled perimetrist on each successive patient-visit. But these kind of visual fields are rarely done nowadays because it is slow, personnel-intensive and therefore quite expensive in terms of resources. For these reasons the visual field is seldom (or should I go out on a limb and say never) taken by itself to make patient management decisions. There are just too many opportunities to be wrong in any single interpretation. But fortunately, in glaucoma management at least, new, more sensitive and more objective technologies have emerged that will make the visual field a medical anachronism in the next few years. However, patients will still get serial visual fields as long as the test is still being paid for by the insurance companies, in spite of the fact that glaucoma docs rely upon them less and less.Regarding B:I just flipped a coin 13 times and got ThhTThhhThhhT = 8 Heads + 5 Tails. There are also two runs of three heads in a row. What should I make of this apparent bias towards heads? If I didn't tell you that I was flipping a coin, but instead I just simply showed you some results where there were 8 positive outcomes and 5 ambiguous or negative outcomes, you might be justified in thinking that "something is going on here" that is worthy of further investigation.After 13 more flips I get: TTThhhhThhhhT = a repeat of 8 positive outcomes + 5 negative or ambiguous outcomes! Even more exciting is the fact that in this series there are two runs of four heads in a row! We could be seduced into thinking that we are definitely on to something in our little "pilot study."Now I'm going to put my 13 pennies in a shot glass, shake it up and then dump it on the table. I get: 5 positive outcomes + 8 negative or ambiguous outcomes. Repeating the shot last method yields: 6 positive outcomes + 7 negative or ambiguous outcomes. If I repeat these trials enough times, regardless of the method, I will eventually, according to statistical theory, achieve the results predicted by the known mathematical probability, which is of course 0.5 -- or 6.5 Heads + 6.5 Tails. But if we do not know the probability of any event occurring, which of course is the case in every study (otherwise it would not be a study), then much larger numbers are needed to detect a "significant" event and then to announce that such an event was statistically unlikely to have occurred as a result of chance alone.So in summary, the three solitary "positive" findings would be more interesting if they were objective measurements (i.e. electrophysiologic) and if they were reproducible. With more concrete objective data, the authors might get funding and FDA approval for an even larger (but still pilot) study -- say, with 20 or 30 people. But because no reproducible, unarguably positive result was found, this paper serves as a warning to other researchers who discover it during their literature review "don't travel down this particular rabbit-hole." The NIH is never going to fund a full blown study using such weak data, and the FDA would object to a large study for similar reasons -- authorizing the "off label" use of a drug that can produce significant side effects on the basis of a one-time observation of 3 visual field improvements -- which could not be reproduced even within the same pilot study. The in-vitro studies that you cited offer a biochemical mechanism of action which no doubt fueled, and might continue to fuel, occasional research interest. But the lack of hard evidence means that medical research is a long long long long way away from suggesting any of the carbonic anhydrase inhibitors as a treatment for RP, and any physician who prescribes it to a patient who does not have a proven case of glaucoma is taking a huge medical-legal risk. The statement at the bottom of one of the papers you cited "These experiments suggest a promising approach to treatment of RP17 that might delay the onset or possibly prevent this autosomal dominant form of RP"... is pretty standard "research speak" for .... "I want my paper to be cited in more treatment-related journals." It is the, "how is this research relevant" statement that nearly every research paper optimistically and triumphantly makes in closing, and it should not be taken as if a new cure has been discovered. However, the presumed strategy of getting it cited in journals other than biochemical abstracts didn't work, as to date it has been cited only by four other papers -- all of them biochemical works, and none of those were follow-up studies pertaining to RP.You probably regard the response you're getting from U.S. doctors as somewhat gutless, uncaring and maybe even inhumane. But demonstrating a promising in-vitro mechanism is light years away from prescribing it as a therapy -- at least in the United States. A colleague sent me an e-mail suggesting that I watch 60 minutes tonight for a segment on FDA surveillance gone wrong. I got busy and missed it. Did you watch it? I'll try to find the video or transcript online later but the very existence of such a story supports the "damned if you do and damned if you don't" criticism that no doubt influences the FDA's usual abundance of caution when it comes to authorizing new treatments.

Yet another hyperbarics case study

Yet another hyperbarics case study showing an increase in visual field. I think the patient in the German case study is going to have the best long term result because he continues to go five times per month after the initial intensive treatment phase.

http://www.ncbi.nlm.nih.gov/sites/entrez

I really would have appreciated knowing about this ten years ago. It is interesting how the minds of researchers work. Nothing is of particular interest unless it is large scale, uses the most objective testing method was conducted during a full moon and so on and so forth...Well, I added the last one, but you get my drift. .It is even more noteworthy how s-l-o-w the process is to move a treatment from the lab to clinical practice.

I feel it is up to me to fend for myself. I am blessed to be able to do so. I think patients are entitled to any information which may prove remotely promising. Particularly something like hyperbarics that is relatively low risk and currently available. People should be able to weigh the risks and proceed or not, their choice. But, if there is a treatment that has helped and is not widely available or known about because no one has bothered to fund a large scale trial....and patients are not aware it is out there....well, that is just not acceptable.

Alternative Explanation-Diamox

Below is a link to a research article from South Africa. To put it in context, I will give a little background on acetazolamide (Diamox) and RP....

1) Your RS will view this from a "majority of the evidence" perspective. This is the difference between being a doctor and a patient. S/he will tell you acetazolamide was used to treat CME associated with RP. They will tell you this is the reason why visual acuity improves in those with RP and CME who use Diamox (generic name acetazolamide).

2) There have been studies that have shown acetazolamide improves visual function in those who have RP but no CME. See the following link for more info:

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8425835&dopt=AbstractPlus

Okay, so what gives? If the standard line of thinking among the RS community is correct, and acetazolamide only works because it helps the CME (and is replaced by other drugs now) , then WHY is it helping people with RP who do not even have CME?

That means either:

a) The researchers who reported the visual measures improved in people with RP and no CME while on acetazolamide were not telling the truth OR

b) The "significant peripheral field gains" in 3 out of 13 no CME/ RP patients was due to some testing flaw not experienced by the controls OR

c) Our three out of thirteen visual field testing rock stars were all just having a bang up day OR

d) There is another factor influencing the improvement in visual field gains in the RP no CME folks.

So since I come from the "weigh the risks and give it a whirl" versus a "preponderance of the evidence" school of thought, I decided to keep digging. The link below offers an alternative explanation for the effectiveness of acetazolamide in treating RP.

http://www.ncbi.nlm.nih.gov/pubmed/15295099?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

A possible explanation from a genetic perspective:

http://www.ncbi.nlm.nih.gov/pubmed/17652713?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

The authors of this case study also make a case for an alternative explanation and increased potential of this drug in RP:

ARTICLES AND REPORTSLong-term effect of acetazolamide in a patient with retinitis pigmentosaJC Chen, FW Fitzke and AC Bird Department of Clinical Ophthalmology, University of London, England.The authors studied the therapeutic effect of acetazolamide on a patient with autosomal dominant retinitis pigmentosa complicated by retinal edema. In addition to reduction of macular edema and some improvement of central vision, they found an unexpected progressive increase in extrafoveal retinal sensitivity with prolonged medication. It is proposed that the therapeutic effect is mediated by alteration of retinal pigment epithelial function and that disturbed polarity is restored to a more normal state. 12

So what if our "preponderance of the evidence" thinkers are wrong? What if the British case study explanation above can be further supported by the technical details in the South African article? WHAT IF THEY ARE RIGHT? And I am sitting here not at least trying a drug available on every corner within a five mile radius of my house? The acetazolamide, not the other one commonly used for glaucoma by old ladies in garden clubs. :)

I guess this drug is very difficult to take. Well, I know people with glaucoma who have been on it for decades and are happy to have vision. Everyone's body is different. There is no way to know how it will affect a person until they try it. It is not like it is an opiate.

The problem is there is no creativity in medicine because everyone gets sued. A lot. Sigh....

Japanese Hyperbarics Abstract

I have linked to quite a few hyperbaric studies. After reading through the research, I have come to my own conclusion. It seems as if hyperbarics must be continued in order to maintain the same level of visual improvements it provides. However, it does not seem to need to be at the same intensity.

The German case study seems to be the most easy to replicate. The patients in the Italian study went every day for two years. This would not be practical for most people. However, the German case study in which the patient started with an intense schedule for four months, tapering off to five treatments per month thereafter, seems more practical. He is maintaining his improvements.

So, it is my belief that in order to keep the gains one must continue HBOT to some degree. It is encouraging to know the patient in the case study is able to maintain his visual gains by going five consecutive times per month.

It is important to use a "hard chamber" with hospital grade oxygen. It is also critical to note how many atmospheres of oxygen are being used and for how long.

Mechanism of action? Hmm...Well, the simple answer would be that it saturates the blood with oxygen thus providing more nourishment to the ailing retinal cells. However, hyperbarics constricts vessels. So, either the hyperoxygenation of the blood is so beneficial that it more than compensates for the constricted vasculature OR there are additional/ other factors at play.

One of the articles I link to discusses how exposure to hyperbarics increases the number or circulating stem cells in situ. Our body has its own stem cells which cruise around and do their work. One of the articles discusses how exposure to hyperbarics increases the number of these stem cells significantly. So, this also could be a factor in its effects as well as the fact that, even ten years later if you believe the Italian study, the hyperbaric group maintained more vision than the controls.

There is also a nitric oxide component which is interesting. I know, I need a new hobby. Wine tasting is the only one on the radar and it seems like a slippery slope in to overindulgence! I mean, whomever decided that a red wine glass should be the size of a small globe?! :)

More RP Stem Cell Research- India

http://www.sciam.com/article.cfm?id=stem-cell-eye-repair

Hyperbarics Protocol

Below is some information on a relatively practical HBO therapy protocol.

http://archive.rubicon-foundation.org/1635

Interview with Attorney

The link below is an interview with an attorney who has Usher's. It helps me to read it when I am experiencing my own personal pity party.

http://query.nytimes.com/gst/fullpage.html?res=9E01E7DB153FF931A15751C0A96E958260&sec=&spon=&pagewanted=all

Another inspirational attorney...It is not an oxymoron! :)

http://www.abanet.org/disability/spotlight/jan08.shtml

Could not Resist

Okay, turn your speakers up and enjoy! Try not to get so disoriented that you vomit. :)

http://www.youtube.com/watch?v=Z4osbcmbSkc

FFB Advises Antioxidant Combination

Okay, vitamins are nothing new. But, empirical data showing that, only in combination, they slow retinal disease and an accompanying formula which is currently available? That is news. I heard the Foundation Fighting Blindness recommended the use of "New Focus" at their L.A. conference. They cite studies in England which support its use. I did some surfing and found one in PubMed from Sweden.

Many have maintained the reason supplementation has been difficult to study under the current scientific framework is because supplements generally work in a synergistic manner, not an isolated one. A "one variable at a time" scientific structure makes it hard to prove nutritional supplementation. It is good to see researchers testing them in combination as well as isolation.

I know nothing about the company below. I have no commercial interest in them. But, this is the formula recommended by the FFB. Before you roll your eyes thinking, "another airy fairy thing that is supposed to work and does not", read the data. Also note this formula was made to replicate the proportions of the elements included in the study.

http://www.goodhealthusa.com/pd_pure.cfm

Data from the Swedish study. The FFB mentioned English studies as well, if you are motivated to do more research and find them.

http://www.ncbi.nlm.nih.gov/pubmed/17293057?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Gene Therapy

Some scoop on the LCA trials. One of the commenters on the blog below had a gene therapy procedure for LCA currently in clinical trials. LCA is a genetic retinal degenerative disease. Once there is one successful gene therapy trial, then it will be extended to different types of rd disease for which there are identified genes. Verdict is still out. If you want to get a genetic test and be added to a registry, contact the Carver Lab at the University of Iowa.

http://lcablog.blogspot.com/2007/11/one-more-lca-trial-for-rpe65.html