Cataracts and AMD

Hunting around for a good topic and AMD and cataracts popped up in the search. Daddy had both and I would suspect some of you have both, too. Is there a relationship between AMD and cataracts? If so, what is it?

Turns out those are excellent questions. The experts are falling on different sides of the fence as to whether or not there may be a relationship between them.

Back in the earlier years of this century (2002) the good folks in Wisconsin, the Beaver Dam Eye Study people, again looked at their subjects after ten years had passed. Statistically, there was an indication that cataracts alone are associated with early AMD. There was also a statistical correlation between cataract surgery and late AMD.

Once again, we are looking at correlation. Correlation does not assume causality. Want a giggle over crazy correlations? Go to the website Spurious Correlations for some fun graphs. You will quickly see how just because things correlate they may not cause one another.

Anyway, like I said, they are still casting around to try to get some definitive answers on this question. The Chesapeake Watermen Study found a correlation between having cataracts and AMD but the Framingham Eye Study and some early Blue Mountain work did not.

But what about a correlation between cataract surgery and late AMD? Beaver Dam found cataract surgery before baseline (initially study measures) was associated with increased risk of late AMD. In fact, eyes that had cataract surgery were four times as likely to develop geographic atrophy and three times as likely to develop wet AMD! Holy freakin’ moley! How do you like that for being between a rock and a hard place?

Of course, like, I said, there is no certainty in any of this yet. In AREDS Report 25, Chew et al reported no correlation between cataract surgery and ARM. Hard to know who to believe.

So, what to do? No one is saying to go blind with cataract now rather than wait and go blind with AMD later. Do what you have to do to see.

FYI Blue Mountain, fortunately or unfortunately, flipped over to the significant correlation camp in reviewing results of a 2006 study. While that may not be great news for those with cataracts, Blue Mountain also shared yet another point they agree on with Beaver Dam. They discovered nonphakic eyes had a three times greater risk of developing late stage AMD as opposed to phakic eyes.

I know. I know. Don’t get your panties in a bunch.  Here is the explanation: in phakic cataract surgery, there is a small incision made in the front of the eye and the artificial lens is implanted. The natural lens is not removed. In nonphakic cataract surgery, the lens is removed.

Talk to your doctor, but as it stands now, given the choice, take the phakic procedure. Might decrease your chances of advanced AMD.

Written August 7th, 2017

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The Proper Magic Potion

Hi, home from physical therapy. My physical therapist and I looked all through the offerings of a world-famous corporation – gee, what could that be? – and picked out a new cart for me. See how this one works.

I came home from Penn State with my rotator cuff tendinitis flaring again. I had hauled my rolling crate around with some of the travel being uphill. Apparently not a plan. Not only do we become pack mules for all of the vision related stuff we get to haul around, we also get to have pack mule injuries!

How do other people handle the problems of – well, freight? Does anyone walk to the grocery? How do you haul everything? Any great ideas on carts?

I looked online for ergonomic carts and dollies and what they are showing is similar to what I just ordered. I will let you know if the new one is any better than the several I have purchased over the last year and a half.

FYI if you know someone who is mechanical and want to make some money, ask him (or her!) to design a rolling crate that can take punishment and not fall apart in three months! Not only would I buy one but I know several teachers and therapists who would also buy one.

That is the practical part of this page. Now for the not so practical but sort of cool part. Anybody ever read H.G. Wells The Island of Dr. Moreau? In that late 1800s science fiction novel Dr. Moreau creates human-animal hybrids using vivisection. Nasty business.

Today scientists are much more efficient than what Wells imagined. Today if scientists want a fish-mouse hybrid, they do it at a genetic level.

Madness, you say! (Cue demonic, mad-scientist laughter). Whoever would want them to produce a fish-mouse hybrid? Well, maybe you would.

Zebrafish are cool. They can regenerate parts. Put zebrafish genes in mice and they can regrow parts, too.

The parts the scientists are growing in mice are glial cells. The scientists have prompted the glial cells to become functional interneurons in mouse retinas.

Interneurons are connecting cells between other nerve cells. Remember I told you they are able to grow photoreceptors in eyes but cannot get them to connect? Interneurons are connectors. They receive and process signals from the rods and cones. With the proper magic potion for the job, scientists got adult mice to grow interneurons in damaged eyes. And the best part of all? They conducted signals!

This research was just published in July, 2017. It’s very early days and they have to work out many bugs, check for safety, etc. but it is the first step. Maybe some day they will inject photoreceptors into your eyes, inject zebrafish genes and magic potion, all over your lunch hour. By the end of the week you will have grown those new photoreceptors AND hooked them up to your optic nerve. Wow. Science fiction becomes science fact.

If you want to read the short version of the research findings, I found them in the ScienceDaily post. The date was July 26, 2017.

written August 1st, 2017

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Snips & Snails & Puppy Dog Tails

Snips and snails and puppy dog tails are supposed to be what little boys are made of. However, now it appears we girls are made of snips also!

Just when I had decided I am not appropriate for lamp stuff (lampalizumab) because I do not have the complement factor I (CFI) at risk allele, Lin informed me the snips ArcticDX tested for are not the same ones as in the study! I may be saying I don’t qualify because I don’t have ‘fruit’ but Arctic tested for oranges and the researchers tested for apples. Apparently all ‘fruit’ was not created equal. My CFI test that was fine may not really have tested what should have been tested if I want to make a decision about the study. I am so confused! [Sue talks about CFI & lampalizumab in pages I Want to Be a Mutant and I Am Not a Mutant.]

So what in Hades am I talking about? See above. The part about being confused. Let us delve further into this mystery.

A snip is actually SNP (it is pronounced snip). That is a Single Nucleotide Polymorphism. SNPs are tiny, little parts of genes. They are a variation in the spelling of our genetic code. Clear as mud, right?

Let us try again. The alphabet of genetics is made up of four letters: A, C, G,and T. Each of them is a nucleotide. Vary the order of the nucleotides on an allele and you can get any one of a variety of characteristics being expressed. Life in all of its diversity is written with a four- letter alphabet.

Sometimes Nature doesn’t spell too well. Sometimes she gets sloppy and copies a C for an A or whatever. These spelling errors do not cause disease but they can affect how the cell will function. They can also predict a response to certain drugs.

Spelling errors or SNPs are very common. According to my source, the Genetics Home Reference again, any one of us can happily harbor 10 million SNPs. However, even with that number of errors, Mom Nature still earns top grades in spelling. 10 million letters in error is a drop in the bucket when you consider how many letters were written for each of us.

We have gone from chromosomes to genes to alleles to SNPs. We are getting smaller and more specific as we go. Pages to paragraphs to words to letters. The SNPs are letters in error in the book of Life. Apparently the genetic testing I had found no spelling errors at the top of a paragraph while the researchers found spelling errors at the bottom of the paragraph. These bottom of the paragraph spelling errors caused the fantastic response to lamp stuff.

Looking at the perfect spelling of words at the top of the paragraph cannot tell me if I harbor those magic mistakes at the bottom. I am back to where I was. Indecisive as to what to do once again.

written July 30, 2017 Continue reading “Snips & Snails & Puppy Dog Tails”

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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 stuf”.]

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.

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Overcoming Uncertainty

Medical treatment is a very uncertain proposition. Writing for the Journal of Graduate Medical Education Wray and Loo quoted Sir William Osler as saying “Medicine is a science of uncertainty and an art of probabilities”. The authors report that rarely is evidence of benefit totally clear-cut when a treatment has been administered. Also, it is rare for practitioners to agree totally on a treatment.

Sometimes opinions are expressed in such a robust manner by both that the patient is left in a quandary. How are we supposed to know who is correct? What are we supposed to do now?!?!

Wray and Loo suggest doctors (and others) look at the evidence. Is there evidence suggesting one treatment is superior to another? What does the research say?

Lin and I are big on research. The truth will be seen in the research. Notice I used the word will, future tense.

Work being done on AMD causes, treatments and maybe even cures is in its infancy. Like all infants, things are subject to change. The infant with blonde hair and a little button nose who you think looks just like your father may grow up to have brown hair and a ‘beak’ just like his uncle on the other side of the family! Final results subject to change without notice. Wait and see.

So many doctors don’t like to say they don’t know. Wray and Loo say it is a mark of professionalism to be able to discuss the pros and cons AND the uncertainties of a treatment, but how often does that happen? Maybe there is not enough time. Maybe they are uncomfortable being fallible. Maybe they think we can’t take it.

Wray and Loo talk about the emotional burden of uncertainty. Uncertainty is nerve-wracking. Many of us feel better believing any plausible nonsense than being told there is, as of yet, no answer.

The problem with believing strongly in something uncertain just so we HAVE an answer? When you find out your life-preserver is actually a cement block, you are too invested in it to let go!

How to handle uncertainty. I actually had to smile because when I went online what I found was totally in line with DBT.😉 If you want to go back to the DBT pages, have at it.

Travis Bradberry, a positive psychology proponent, shares 11 Ways Emotionally Intelligent People Overcome Uncertainty. Bradberry tells us our brains are hardwired to react to uncertainty with fear. He quotes a study in which people without information made increasingly erratic and irrational decisions.The diagram Bradberry showed was a brain and his caption said “uncertainty makes your brain yield control to the limbic system. You must engage your rational brain to stay on track”. Sounds three states of mind-ish to me.

Beyond that, Bradberry suggests calming your limbic system by focusing on the rational and real, being mindful of positives, taking stock of what you really know and don’t know, embracing what you cannot control (also known as accepting reality), focusing on reality, not trying to be perfect, not dwelling on problems, knowing when to listen to your gut, having a contingency plan (what I have always called plan B), not asking what if questions and – guess what! – breathing and being in the moment.

Hope this helped some. Remember this journey is not a sprint, it is a marathon. In fact it is a marathon that we don’t even know the course. Keep an open mind and don’t latch onto anything out of fear. Eventually we will find the way.
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That Preachy Zealot

Here she is again, that preachy zealot for clean living! How are you all doing?

I was looking for new info on AMD and I found this article.

I know I harp on this topic ad nauseam but seeing this in the new releases I could not help myself. I am basically weak (and can be profoundly irritating😎).

Anyway, a recent article on nature.com presented research suggesting AMD does not like clean-living folks. People working on the Blue Mountain Eye Study evaluated a group in the late 1990s and then again 15 years later. They looked at physical activity, diet, smoking and alcohol consumption as it relates to AMD. After all was said and done, the researchers decided it would be helpful if people could be encouraged to engage in good health habits.

They quoted data that women who eat well, are physically active and don’t smoke are three times less likely to develop AMD than women who do not have a healthy lifestyle. If you add the complement factor H at risk allele into the mix, the poor souls who eat crap, don’t exercise and smoke really don’t have much of a chance of dodging the disease at all.

What I just quoted was an older study, CAREDS. It used only women. The Blue Mountain people decided to replicate it but to include both genders. They also added alcohol consumption as a variable.

Blue Mountain concluded the combined effects of the four, healthy living variables were better than only one of the habits alone. They hypothesized each of the healthy habits helps to reduce oxidative stress and therefore reduce inflammation, generally thought to be a huge factor in the development of AMD.  [Lin/Linda: Sue talks explains what oxidative stress in her page Electron Rustlers.]

In addition, good health habits can affect the density of macular pigment. Thicker macular pigment can be protective. And BTW, levels of macular pigment can be negatively affected by obesity.

Since I always like to support our friends Down Under, I am making a pitch for healthy living just like the Blue Mountain people. Avoiding bad habits and developing good ones can decrease your chances of developing AMD. It can also reduce the rate of progression of the disease.

Hard to change habits? Absolutely. I am a carbs and salt girl. Horrible for me, but that is what I crave. I have never been a fruit eater.

However, since getting my diagnosis I am drinking a cup of fruit juice every morning. Enough of a change? I doubt it but at least I feel as if I am making the effort.

How long does it take to establish a habit? Google says 66 days. If you can change one thing in your lifestyle and stick with it for 66 days, you have dealt a blow against AMD. Lifestyle changes are one way we can take some of our power back from this disease. Worth a try. Continue reading “That Preachy Zealot”

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Re-educating Our DNA

Back to the Genetic Home Reference. I have been seeing things that say gene therapy is one possible avenue of treatment for AMD and I have not been too sure what it is.

The Genetic Home Reference says gene therapy is the replacing of a mutated gene that causes disease with a ‘good’ copy of the gene. It may be used to deactivate a problematic gene or be introduced to help to fight a disease.

Because it is a new and potentially dangerous field of exploration, gene therapy is limited to diseases and conditions with no, known cures. That’s us, guys.

If you are not familiar with viruses, I offer a quick tutorial on how they work. Viruses are barebones ‘life’. There is debate as to whether or not they even meet criteria for being considered living organisms. Part of the definition of a living organism is that it can reproduce its own kind. Viruses cannot do that. Since viruses are no more than a strand of DANA wrapped in protein, a virus must ‘hijack’ a cell to make little viruses. The baby viruses eventually kill the host cell. This is why we get sick when we have a virus. Our cells have become factories/hosts for baby viruses. Sort of like the movie Alien in miniature. Yuck.

Since viruses have the ability to pierce cell membranes and mess with the cell’s ability to reproduce – effectively ordering the cell to reproduce a slew of baby viruses – it was decided they would be perfect for introducing ‘replacement parts’ into defective cell DNA.

The name for something that transfers things from one organism to another is called a vector. Therefore gene therapy uses viral vectors to get new DNA into cells. Researchers replace the basic, virus DNA with genetic material it hopes will repair the defective genes, then it ‘launches’ the viral vector to ‘attack’ and ‘hijack’ the cell.

How this relates to AMD is sort of basic. We know AMD is a genetically based condition. Change our genetics and we may eliminate the disease.

Johns Hopkins researchers have completed a phase 1 clinical trial during which they ‘infected’ retina cells with a virus carrying a gene that would cause the retina cells to produce a protein that interferes with the signals leading to the growth of new veins. The goal is to genetically alter enough cells they will produce enough of the protein to totally halt the neovascularization process and eliminate the need for shots.

Of course these studies are in very early days. One of the problems encountered was many people have developed resistance to the viruses use. They had met these enemies (the protein in the sheaths of the viruses) before and their defenses were in place. If the vectors are destroyed before they get to the targets, they cannot very well plant the new gene.

Still early days on gene therapy but it most definitely has promise. Remedial instruction to ‘re-educate’ our DNA may be on the way.

written July 16th, 2017

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