macular degeneration, macular, diagnosis Genetic Testing – My Macular Degeneration Journey/Journal

Category: Genetic Testing

Our Cub Reporter: Notes from an Awareness Program – Page 4

Continued from page 3.

Personalized Medicine for AMD – Genetic Testing & AMD

Greg Hines is the CEO of ArcticDx, the company that is leading the way in genetic testing for macular degeneration.  He lives in Canada and his mother and sister both have suffered from Wet AMD.  They have bad genes for oxygen metabolism and they both smoked.

99.9% of each of us is identical and the medical industry relies on that sameness.  60% of AMD risk is genetic and 40% is lifestyle.

The Macula Risk Test is prognostic (gives information about the future) & pharmacogenetic (gives information about eye vitamins).  The Macula Risk test is 90% accurate at predicting which 15-20% of people with drusen will progress to advanced AMD.  Vita Risk is the test for zinc risk in eye vitamins.

OCT & fluoroscopic angiograms can sometimes see early wet AMD before vision loss, but this is difficult.

The AREDS research started in the early 90s with results published in 2001 and was sponsored by the National Eye Institute (NIH).  Risk of progression from moderate dry AMD to either wet AMD or geographic atrophy (GA) was reduced by 17% with antioxidants alone, 21% with zinc oxide alone, and 25% with antioxidants & inc.  Bausch & Lomb & NEI (National Eye Institute) make $270,000,000 per year from 3,000,000 patients and other competitors create a $500,000,000 annual market for these vitamins.

Greg asked the question:  Is the 25% risk reduction for everyone with AMD?

A series of studies have been completed over the past 10 years that seem to show that some AMD patients are hurt rather than helped when zinc is part of the eye vitamin.  The NEI said that the differences “weren’t significant”.

A 2016 study by Seddon et al from Tufts & Harvard found that 2/3 of the AMD patients saw risk reduction from 35 – 85%, but that 1/3 of the AMD patients – with certain genes – saw an increase of over 150% in the progression to advanced wet AMD.  This group had the same C1A0 & C2A0 genes.

All the accepted early research combined progression to dry advanced AMD (GA) with advanced Wet AMD.  If you only look at those who progress to wet AMD, the statistics show clearly that zinc is dangerous for these gene types.  Only three studies have focused on wet AMD.

Medicare was ready to approve reimbursement for the Vita Risk test until AAO (American Academy of Ophthalmology) and NIH got them to rescind the approval.

AREDS2 and lab tests are not regulated by the FDA, but the FDA can make manufacturers put warnings on labels.  The FDA has been requested to put such a warning on AREDS2 and its clones that contain zinc.  After this request was submitted on 5/8/18, meetings were held with the FDA, and they have agreed that there is an “indication of harm” for 13% of patients.

Harvard University put out a Press Release from its Dept. of Ophthalmology which “Confirmed that 15% of patients are harmed by a 300% increased loss of vision”

“DO NO HARM” is still the Doctor’s oath.

Macularisk.com has a list of eye vitamins without zinc.

Greg was our most impassioned speaker and got the most applause from the entire conference.

He is our Facebook group’s own Rock Star as is another person at ArcticDx Gerry Belgraver – along with Sue and Linda!!

Lin/Linda here: Thanks for your kind words, Joann, and for your GREAT reporting!  For more information about the AREDS studies and about zinc, click here for Eye Vitamins: Part 6 – What’s all the talk about zinc? Introduction.

Intermediate AMD in one eye/advanced (wet or geographic atrophy) in the other eye

Intermediate AMD in one eye/advanced (wet or geographic atrophy) in the other eye

Studied in AREDS & AREDS2: showed reduction of risk of developing advanced AMD over 5 years.

Notes
  • Stages: In order to simplify the results of these studies, we have ‘stretched’ the stage assignments from how they were actually done in the studies.  For example, in AREDS, they looked at the lead/most advanced eye & assigned the participant that stage.  So someone with one eye at the intermediate stage & the other with no AMD, early AMD or intermediate AMD would be assigned the intermediate stage.  AREDS2 used a slightly different method.
  • Source of supplements: There are many ‘eye vitamins’ sold as AREDS or AREDS2 but they do not all have the exact ingredients that were a result of the extensive AREDS & AREDS2 research (see References section below for full study articles).
  • Importance of reading the labels: The ingredients & dosages from AREDS were antioxidants 400 IUs of Vitamin E, 500 mg of Vitamin C and 15 mg beta carotene.  Beta carotene was found to be linked to lung cancer in smokers so for that and other reasons, AREDS2 removed the beta carotene & used 10 mg Lutein and 2 mg Zeaxanthin.  The formulations from both studies included zinc (because of zinc, copper was also included), 80 mg in AREDS and both 80 mg and 25 mg zinc in AREDS2.   It was these exact ingredients that produced positive results (“showed reduction of risk  of developing advanced AMD”) so read the labels of any products carefully to make sure they match the study formulation as closely as possible.  There are 2 webpages in References below that compare selected products.
  • Warning about zinc: Several years ago, warnings were issued about the high dose of zinc in the study formulations (80mg). Those warnings were confirmed by 2018 research that found that 15% of patients with a specific combination of genetic risk variants nearly tripled their risk of developing wet AMD when treated with the AREDS formulation with 80mg zinc instead of a placebo.  For more information about genetic testing, see References below.
References

Early AMD in one eye/intermediate or advanced (wet or geographic atrophy) in the other eye

Early AMD in one eye/intermediate or advanced (wet or geographic atrophy) in the other eye

AREDS: showed reduction of risk of developing advanced AMD over 5 years.

Notes
  • Stages: In order to simplify the results of these studies, we have ‘stretched’ the stage assignments from how they were actually done in the studies.  For example, in AREDS, they looked at the lead/most advanced eye & assigned the participant that stage.  So someone with one eye at the intermediate stage & the other with no AMD, early AMD or intermediate AMD would be assigned the intermediate stage.  AREDS2 used a slightly different method.
  • Source of supplements: There are many ‘eye vitamins’ sold as AREDS or AREDS2 but they do not all have the exact ingredients that were a result of the extensive AREDS & AREDS2 research (see References section below for full study articles).
  • Importance of reading the labels: The ingredients & dosages from AREDS were antioxidants 400 IUs of Vitamin E, 500 mg of Vitamin C and 15 mg beta carotene.  Beta carotene was found to be linked to lung cancer in smokers so for that and other reasons, AREDS2 removed the beta carotene & used 10 mg Lutein and 2 mg Zeaxanthin.  The formulations from both studies included zinc (because of zinc, copper was also included), 80 mg in AREDS and both 80 mg and 25 mg zinc in AREDS2.   It was these exact ingredients that produced positive results (“showed reduction of risk  of developing advanced AMD”) so read the labels of any products carefully to make sure they match the study formulation as closely as possible.  There are 2 webpages in References below that compare selected products.
  • Warning about zinc: Several years ago, warnings were issued about the high dose of zinc in the study formulations (80mg). Those warnings were confirmed by 2018 research that found that 15% of patients with a specific combination of genetic risk variants nearly tripled their risk of developing wet AMD when treated with the AREDS formulation with 80mg zinc instead of a placebo.  For more information about genetic testing, see References below.

 

References

News Briefs

Dreary Saturday. It is cold and rainy. The chill gets into my very core. I would rather have a foot of snow than this stuff but then no one ever asks me. Also, a lot of people really don’t appreciate my preference for snow! Obviously not skiers.

All afternoon I have been curled up on the couch with my iPad. Decadent. Really don’t like to do this but I wanted to finish a BARD book I had started and I was working on level 1005 on Panda Pop. Make that STILL working on level 1005. Not going so well.

Anyway, I do need to mend my wanton ways…later.

My email is full of news briefs from eye sites. ? There is a ton of information out there. One article healio.com sent me was Specific gene variants play role in response to Anti-VEGF treatment. Once more it appears our genes are our destiny, at least for now.

We all know medicine is headed towards ‘personalization’. There is evidence for a vitamin supplement/genotype interaction and now it appears there may be an interaction between your ‘eye shots’ and your genotype. A study in Spain grouped together good responders and poor responders to ranibizumab (Lucentis). Then they did genetic testing on the two groups. Guess what. Genetically these two groups were significantly different. The genes that responded well were thought to be CFB, VEGFA and VEGFR1. Poor respondents had certain variants of SERPINF1 and CFH.

Among the non-genetic markers? Smoking and high blood pressure were both associated with poor outcomes.

In coming years it should be interesting to see what is going to happen between genetic testing and privacy rights. Also with genetic testing and attempts to withhold services. Will you have to pay more for insurance if you have ‘bad’ genes? Thinking I may be glad if I miss THAT aspect of our brave new world.

Healio.com also reported the Argus II was recently implanted in the eye of a man with retinitis pigmentosa in Singapore. Remember RP people are generally ‘big B’ blind. This thing is not for us who have comparatively good vision.

And for our friends with RP here in the States, Medicare will now pay for the Argus II in 28 states, two territories and DC. Recognition of such innovations as ‘medically necessary’ is paving the way for other innovations that will be coming. Read, accepting the Argus II for RP patients will ‘soften up’ policy makers so they are more likely to pay for things we as AMD patients will be able to use. I find that a lovely thought. (So I am manipulative, conniving and self-centered. Wanna make something of it?)

Pretty much it for now. I have not done much today and I am feeling like a bit of a waste of space. Need to accomplish something. Maybe just one more shot at that level in Panda Pop? ?

Written February 24th, 2018 Continue reading “News Briefs”

Studying the Study

Lin found the paper discussing results from the phase 2 study of lampalizumab. It is a little dense but I will try to pre-digest it a bit for you. [Lin/Linda: we’ve been calling it ‘lamp stuff’.]

The study design itself was somewhat basic. There were two independent variables and two controls or shams. Independent variables are the things the researchers are manipulating. In this case it was two dosage schedules. Shots of the drug were given every month and every other month.

Controls, or sham treatment groups, were given shots on the same schedules. However, their shots did not contain lampalizumab. They just thought they did.

Overall, when the every month dosage of lampalizumab people were compared to the every month fake treatment people (sham condition), their rate of degeneration was slowed by a fifth. That is where the 20% number comes from.

However, when the researchers looked at their raw scores, they made a discovery. Some of the subjects absolutely rocked it! They were showing decreases of 44% in rate of deterioration. Others did not differ at all from the controls. Their eyes just continued to get worse at the usual rate. What the hey?

Thinking the difference might be genetic, the researchers thought about which genes to consider. They ended up with the complement factor I at-risk allele as a possible suspect.

An allele is half a gene pair. Genes come in pairs; remember? One from Mom and one from Dad. Alleles can be matched or mismatched. Terms are homozygotes and heterozygotes, but that’s not important in this case. It wasn’t important to the researchers either. They decided to look at people with one and two ‘bad’ alleles of complement factor I.

When they put everyone with good CFI alleles in one pile and everyone with at least one bad one in another pile, they made another discovery. It was the people with the bad CFI alleles who had responded to the lampalizumab. There appeared to be something about that gene that interacted with the lampalizumab in a way that slowed things down.

Looking back at their numbers, the researchers decided all of the ‘work’ done in the initial, whole group was done by the bad CFI allele people. There was an overall difference of 20%; right? But remember we are talking arithmetic averages here. If half of your group ‘improves’ by 40% but the rest of the group improves by 0% when you add them together and divide by 2, you get 20%. 20% is sort of misleading. No research subject showed a 20% rate decrease. They were either at somewhere around 44% or somewhere around 0%.

There are some things that need to be further studied. The number of subjects was not large and they need to replicate things with lots more people, for example. However, for right now the takeaway message for us is this: as suspected, AMD is looking like not one disease but a family of diseases. It is created by several different genetic flaws. The lampalizumab phase 2 study results suggest this drug will only be good for the AMD ‘family member’ that is caused by complement factor I at-risk allele. Those of us – like me – who do not have bad CFI alleles will have to wait for another breakthrough.

Those of you with CFI at-risk allele can rejoice! It looks as if they have found the first real TREATMENT and it is for you! Congratulations! We are all happy for you and want to follow you very soon.

If you really want to look at the scientific paper from the study, click here.

written July 24th, 2017

Continue reading “Studying the Study”

Piles of Articles

Long, holiday weekend. I am on the second day of four and have gotten pretty much nothing done. Oh, well. Procrastination is us.

Be that as it may, Happy Fourth of July whenever you may be!

Part of the ‘straightening up’ task for me is going through piles of articles I have found interesting and printed out. That word is actually PILES.

Just rediscovered one – Update on Genetics and Age-Related Macular Degeneration by Jerome Dunaierf – that has some good stuff in it. Did you know people with a parent with AMD have DOUBLE the risk of getting the disease? Make sure the kids get their eye exams!

Jerome talks about the complement immune system and does a nice job – much clearer and nowhere near as fanciful – in describing how the ‘friendly fire’ bit works. He shared the proteins that activate the complement system have been found around drusen. (Maybe a demented garbage men analogy would be better? Coming for the trash but hauling away the house?)

Jerome also talks about the ARMS2/HTRA genes. Enticing and mysterious those. No true clue what they do but we with AMD often have certain variants of them.

Other genes that seem to be somehow in the mix include genes that code for collagen formation, cholesterol formation and cell signaling. You might not realize it but the chemical ‘chatter’ going on in our bodies is deafening! Eavesdrop on that and we could intervene in amazing ways.

Jerome agrees with me lampalizumab will open up a HUGE market for genetic testing. (Probably the reason I kinda like Jerome). He shared it is now possible to sequence an entire human genome in a few days. The cost? About $1,000.

Wow. Have your code read and know exactly which drug is going to work on you. How far in the future before genetic sequencing becomes a requirement for getting health insurance? Ethical nightmare that.

And a little filler here: Pubmed published an abstract on a meta analysis of 10 trials about the risks and benefits of aspirin. Bottom line was this: aspirin can keep those of us with cardiovascular problems alive. Proven. Aspirin might, maybe, could have a negative effect on your AMD. The authors, Small, Garabetian, and Shava decided most of us would want to be alive. Their advice was to take your aspirin.

OK. A few more things off the pile. Time to wander off to something else. Maybe some housework. Gasp!

I am staying home from yoga today. Self diagnosis of rotator cuff tendinitis. Doctor’s appointment next week by which time I will not only have diagnosed but also treated myself!

My yogini is digging out a ‘no arms’ practice she found so I can try that tomorrow. Movement continues to be important to – and for! – me. Where there is a will, there often is a way.

That is what is happening here. Hope you are all doing well. Bye!

written July 2nd, 2017

Continue reading “Piles of Articles”

I Want to Be a Mutant

I want to be a mutant. Oh, not like the X-Men although it might be cool to be Storm. I want to be a mutant because those are the people who respond the best to lampalizumab.

A friend emailed me an Associated Press piece entitled Drug shows progress against vision-robbing disease in seniors. Although this was the first time I have heard this, according to the article, ‘lamp stuff’ doesn’t do a bit better in people with the specific gene mutation, it does a LOT better!

I had heard that lampalizumab produced a 20% regression in lesion progression. That, folks, appears to be an average.

Those with the complement factor I risk allele actually had a 44% reduction in geographic atrophy progression. Wow!

To me, this is the first BIG indication genetic testing and AMD treatment have to be closely associated. I really do NOT want to be poked in the eye with a needle every month if the treatment won’t do any good. Likewise, I will be more amenable to said needle poking if I know I have the gene and I can slow my vision loss by nearly half. Not to mention how insurance companies would respond if they knew they could save money by eliminating non-responders from the pool.

Now, you need to remember all of the hard sciences are not my forte, but it seems to me complement factor I is a molecule that helps to trigger the action of the immune system. Remember all that stuff about whether or not AMD is an autoimmune disorder? It appears complement factor I is able to slow down some aspects of immunity that are running amok and attacking the good guys as well as the bad. Once again the theory appears to be our sight is being wiped out by friendly fire.

Musing here a moment, I have a very strong immune system. Never had mumps or chickenpox. Only had one form of the measles. In the 50s and 60s when I was small, kids got those things all of the time. Once more, I was the odd one. But what if my great immunity is not the result of a strength but actually of a weakness? To wit, I have an immune system with bad brakes. That is a thought. After vanquishing all the bad germs, it turned on itself. Put that with a strong family history of RA, another autoimmune disorder and it makes you wonder. Things that make you say Hmmmm….

Anyway, lampalizumab tightens loose brakes on immune reaction in those who have the complement factor I risk allele. It keeps the immune system from running wild and reduces the rate of damage about 44% in geographic atrophy.

I don’t believe the genetic testing we were given for trial measured the complement factor I risk allele. However, I should suspect changing the genes they highlight may not be that big a job. I also suspect making that adjustment would be a big moneymaker (This is America, after all).

So, next we should probably all find out if we are mutants. I have dibs on being Storm. Who wants to be Wolverine or Charles Xavier? [Can I be Wolverine? Love what he does with his nails!]

written June 28th, 2017

Continue reading “I Want to Be a Mutant”

Not Created Equal

We heard from a reader who has vitelliform macular dystrophy. I had never heard of it. Therefore you can image my surprise when I picked up an article I had downloaded last week and – guess what! – the article talked about vitelliform dystrophy! Sometimes the synchronicity in the Universe is scary.

Anyway, it appears the Universe has declared we are to learn about vitelliform dystrophy. Here we go!

I have discovered all macular diseases are not created equal. There are dozens of them and researchers are discovering more on a regular basis.

Vitelliform dystrophy may look like age-related macular degeneration and act like macular degeneration but it is not macular degeneration. (Don’t worry. We are not throwing you out of the group!)

Vitelliform dystrophy is a pattern dystrophy. They are so called because the damage tends to ‘draw’ things on the retina. For example, one manifestation of the disease looks like a butterfly (photo to the right is a fundus photograph of butterfly pattern).

Vitelliform 2 is called Best disease. This is not because it is the best disease to have nor is it because Dr. Best hijacked the disease and named it for himself. It is because the disease comes as a result of a mutation on the BEST1 gene. (Apparently that means we all have BEST genes and there are at least two of them. How about that.)

Best disease is a pattern dystrophy because – all together now! – it makes a PATTERN on your retina. The pattern is a sunny-side-up egg. The yolk is centered on the fovea.

One of the nice things about Best disease is you may never know you have it.  According to the Hereditary Ocular Disease site 7 to 9 percent of those with Best disease are asymptomatic. Others may experience vision loss but recover most of their function. A much smaller percentage may proceed to neovascularization and serious loss. Of course, the older we get the better chance we have of having some really serious problems. And by the way, children can have this one.

That is because, once again, it is genetic. Best disease is an autosomal dominant condition. That means it is on a body-forming chromosome – not the chromosome that has the x or the y and makes you a boy or a girl.  It is also dominant and can express itself whether or not its partner gene wants it to. You only need one of these babies to be in trouble.

Of course there are all sorts of things that may or will affect whether or not this gene does actually express. However, this is not a place to discuss epigenetics. Nor am I the one to explain THAT baby! Suffice it to say, you should warn everyone you are related to by blood that it has expressed in the family and they need to have regular eye exams.

Like AMD there is absolutely no treatment and no cure. (I get so tired of typing that). If you have Best disease and progress to CNV you may profit from shots.

And that, my dears, is that. Continue reading “Not Created Equal”

Hindsight is 20/20

Good evening! How are you all?

Lin has noticed I seem to have written soooo many pages they are overwhelming and confusing some people. She feels this is particularly true for some of the newbies who probably feel like they have walked in on the (boring and confusing) middle of a movie. [Lin/Linda: to be clear, those are Sue’s words! ::grin::]

Understood. Some of you are back in the shock and doom phrase and I am talking about getting newspapers on your phones and other trivial matters. Who wants to hear about that sort of thing while your world is unraveling?

In the interest of pointing you towards something that might actually be helpful, Lin is republishing some earlier pages for your attention and discussion. And I – always helpful – am going to add to the confusion by writing another page!?

This page will have a catchy title thanks to Lin, but right now I am going to call it “What I know now that I wish I had known a year and a half ago”.

First, you are not going everything black and dark blind.

It is not good but neither is it quite that bad. You are losing central vision. Things will not be good for anywhere from about 15 to 60 degrees of arc. Since normal visual fields are 170 or so degrees of arc, you have the potential to lose about a third of your vision. Not anything to cheer about but better than 100%.

You may not be doomed to progress to end stage AMD.

About 15% of patients become ‘wet’. About 15% progress to geographic atrophy. That means you – starting out with drusen and a diagnosis of early AMD – have a 85% chance of dodging the proverbial bullet for end stage AMD. You may very well not get as bad as I am and a year and a half after my second eye went to hell, I am still functional. [Lin/Linda: a person can have both wet AMD and geographic atrophy in the same eye.  I don’t what that does to the %, if anything.]

You did not cause this.

Yes, AMD is caused but it was not caused by anything you did or did not do. The causes are in your genes. This is a heritable disease. There are dozens if not hundreds of genes that are being investigated to try to figure out how AMD is created. It appears AMD may just be the result of a genetic ‘perfect storm’ and there is no one to blame.

There may come a time you are seeing things.

I saw some odd stuff when my brain was working overtime to assign meaning to the faulty images my eyes were sending it. You are not psychotic (I hope you are not psychotic). This is Charles Bonnet Syndrome. When your brain gives up trying to assign meaning to false signals you will stop seeing weird ‘stuff’. In the meantime, enjoy the fantasy.

Point number last: There is an amazing amount of hope for treatment and eventually a cure for AMD.

Research is going on everyday. New discoveries are announced with regularity. The medical community is hot on the trail of something that will arrest the progression and may even reverse this disease. All we have to do is hold on.

OK. Those were my biggie when I first lost my second eye. What are you worried about? Please share and we can discuss it. Continue reading “Hindsight is 20/20”

Sue’s Journal Pages

WOW, there are a LOT of pages!  We want to help you access them.

June 2023 There’s an announcement that since Sue has not written any new journal pages for some time, the site has been archived until we can decide if the work necessary to make sure all information is accurate and up-to-date can be made. In the meantime, you’ll get some pages ‘not found’ or ‘private’ until that decision has been made. The emphasis for several years has been on the Facebook group.

You can choose:

  1. To START AT THE BEGINNING and follow the pages from one to another like chapters in a book
  2. To get a list of ALL pages
  3. To get a list of pages by MONTH and YEAR (not updated)
  4. To get a selection of Sue’s Best Pages and Musings
  5.  If you want to access pages by a particular CATEGORY, look to the right of this page or at the bottom and choose a category (for example, Cognitive Therapy, Research, etc)
  6. If you want to access pages by a particular KEYWORD, look to the right of this page or at the bottom and choose a keyword (for example, sunglasses, vitamins, etc)
  7. You can also enter a word or phrase to SEARCH the pages in a Google-based search
  8. Below are the MOST RECENT PAGES

Most Recent Pages

Pages for 2020
Pages for 2021

 

Sue on Assignment

Starting in September 2018, Sue’s been doing research and writing on special topics.  Do you have a topic for her? If you do, let me know at light2sight5153@gmail.com.

Current topics include research on several supplements (bilberry, resvertrol, astaxanthin, CBD Oil), independence (what it means to Sue, how to get food to come to you), AREDS2 & geography atrophy, how to conduct an experiment on yourself, non-genetic causes of MD, research on calcified eye spots, money for assistive technology, eccentric viewing, high altitudes & the eye, coping fatigue, research about mitochondria.

Sue on Assignment – Special Topics

Sue’s Musings

Too many pages to read? Here are some of Sue’s quotes with links to her pages.

Sue’s Musings: Then and Now – Part 1 Revisited in 2018

Sue’s Musings: Then and Now – Part 2 Revisited in 2018

Sue’s Musings Then and Now – Part 3 Revisited in 2018

Sue’s Musings Then and Now – Part 4 Revisited in 2018

Sue’s Best Pages

It’s hard to reduce Sue’s many pages to her best ones but these are ones that have been highly rated by our readers in several categories.

Sue’s Toolkit – What She Uses to Do What She Does

Sue’s Toolkit – 2 Years Later – Part 1

Sue’s Toolkit – 2 Years Later – Part 2

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