macular degeneration, macular, diagnosis anti-VEGF – My Macular Degeneration Journey/Journal

Tag: anti-VEGF

I have dry AMD. Will It Turn to Wet? What is wet AMD?

QUESTION: I have dry AMD. Will it turn to wet?

ANSWER:

Not everyone with AMD progresses to wet AMD. There is another FAQ with details about the risk of vision loss from AMD. Briefly, if you have early or intermediate dry AMD, your risk of progressing to wet is 10-14 or 15 %. That means that 85-90% of all people with AMD have the dry kind, so that’s the majority. Wet AMD is in the minority and rare, but if left untreated it can quickly cause central vision loss.

Parts of the Retina

The parts of a healthy retina.
Click on image to see it larger.

Let’s review the parts of the retina that are involved in AMD. From top to bottom there are the Photoreceptors (rods & cones) that convert light to sight, RPEs that take care of the Photoreceptors, Bruch’s Membrane, and the blood supply in the Choroid.

How and Why The Process Starts

VEGF (Vascular Endothelial Growth Factor) is a protein produced from cells that causes new blood vessels to develop when needed, such as after an injury or lack of oxygen. In most places in the body, that’s a good thing. But not when it happens in the retina.

Photoreceptors, RPEs and Angiogenesis

All AMD starts as dry even if it’s not diagnosed until it’s wet. As the disease progresses, drusen (we call it ‘eye poop’) builds up and can weaken Bruch’s Membrane. This causes inflammation which signals the release of VEGF. This process is called angiogenesis (‘angio’ refers to blood, ‘genesis’ refers to development of something).

These unwanted blood vessels grow through the weakened Bruch’s Membrane into the area of Photoreceptors and the RPEs.

Wet AMD and CNV

This process is called wet AMD and CNV (Choroidal Neo-vascularization refers to the Choroid, ‘neo’ refers to new, and vascularization refers to blood vessels).

Wet AMD is Exudative Macular Degeneration

Those new blood vessels are fragile and can leak fluid, can rupture and leak blood, or both. That’s where the ‘wet’ descriptor came from. These fluids are ‘edudates’ which is why sometimes you’ll see wet AMD referred to as Exudative AMD and dry as Nonexudative AMD.  CNV can occur in any form of macular degeneration.

Symptoms from Wet AMD/CNV

For normal vision, the macula needs to be flat. The blood or fluid collects in something similar to a blister which distorts vision and causes a person to see wavy lines and have other distortions. Have you ever had a drop of water fall on a piece of paper with writing? It distorts what is under it, right?

Make sure if you have any changes in your vision that you contact your eye doctor as soon as possible. Research has shown that the sooner treatment is started, the better the prognosis.

Inflammation

This buildup of fluid or blood causes inflammation (edema) and can form scar tissue which cannot be removed. It can also cause damage to the RPEs, so they’re not able to keep the Photoreceptors working well. It can also kill the RPEs. If the RPE dies, the Photoreceptor dies, and central vision loss occurs. That’s why it is so important to get treatment as soon as possible!

The Injections

The medications that are injected into the eye are called anti-VEGF because they block the further release of VEGF. They are also called angiogenesis medications. That stops new blood vessels from growing. You might think of a VEGF protein as a lock. The anti-VEGF medication puts the key in the VEGF lock to stop it.

Current Anti-VEGF Medications

The current anti-VEGF medications are Lucentis, Eylea, Avastin, and Beovu. For some people, the disease is slowed down by repeated treatments. For some, vision improves. Everyone is different.

‘Dried Up’ is not Dry AMD

The blood and/or fluid is then reabsorbed by the body. That’s why you’ll hear the retinal specialist say that the eye is ‘dried up.’ That’s not the same as dry AMD. Wet AMD cannot go backwards, but sometimes it goes into something similar to remission and can remain stable. You always have to be diligent to check your vision and report any changes.

The anti-VEGF medications wear off quickly, so repeated injections are necessary.

New and Better Treatments on the Horizon

There is a lot of research related to wet AMD/CNV. New treatments will extend the time between them and replace injections with eye drops and oral medications. It’s the drops and pills that many people are looking forward to! You can find out more in the article ‘Have Wet AMD and Hoping for Something Other Than Injections?’

Even better, with gene therapy, a ‘one-and-done’ treatment may stop the disease entirely. There’s more about this in ‘Gene Therapy Research for AMD.’

Great Resource

One of the best sources of information about AMD is from the Angiogenesis Foundation’s site ‘Science of AMD.’  There you can find text explanations with audio available, colorful illustrations, videos, and brochures.  They are a not-for-profit site, so they don’t sell anything. That’s a good indication that their information is not biased.

There is an excellent infographic explaining the angiogenesis of AMD.

GO BACK TO FREQUENTLY ASKED QUESTIONS

 

I’m Bored – Again!

Hi, there! Again, I have not been given an assignment but I AM writing for a very good reason: I am bored! Nothing I should do is appealing. So I am going to write about…whatever. Send me an assignment if you don’t want this to continue happening. [Lin/Linda: yes, PLEASE give her something to do. She’s not happy if she’s bored, and “if she’s not happy, …” Do you know the rest of this phrase? ::grin::]

First of all, I understand we have had a large number of new Facebook group members. Although I am not one of your number, welcome! I think you will find we are a “country” without strict borders. Nearly all are welcome.

We do keep a dedication to the scientific method of inquiry. That means we like to have information that has been researched and proven to have, if not a definite answer to our communal problem, at least a flicker they are on the right road. In other words, if your great aunt heard that burning pocket lint in the microwave and huffing the smoke is a cure, we don’t want to hear about it. If that same process is being written up in a scientific journal, let us know!

We are also – as of this instant – nonprofit. Very nonprofit. If we are not making money on this project, NOBODY is making money. Therefore we do not take advertising, either straightforward or covert. People who have blatantly tried to sell things on these pages have been asked to leave.

If we can get you a hot discount on something we have used ourselves, we will do so. Occasionally you will see a page about a particular brand of merchandise. It s because one of us has been able to get a good deal.

That is pretty much it. Beyond basic civility, two rules: research-based and no advertising. Simple.

From what I understand – remember I am telling you my version of the “rules”, and I am not even ON FB! The girl can have attitude! – Lin has asked some people to watch the professional and lay media and report back. Want a job? I suspect she could use volunteers. [Absolutely LOVE volunteers!]

Leaving me something like 165-160 – words to share some info. I try to keep these pages to about 500 words. I cannot say for you, but my reading speed is significantly slower than it was. I don’t do well with dense prose. I assume you have the same problem.

News? Healio is reporting there may be a new anti-VEGF “kid” in town. Klondike Sciences recently finished a phase 1 trial on a compound called KSI-301. I am thinking the 301 means the 301st attempt. Maybe? In that case they are nothing if not persistent!

Be that as it may, the results were promising enough to do what will probably be a phase 2a study. That is another safety and tolerability study with more subjects. It is still early in the game for KSI-301 but it might prove to be of value.

Running out on my word count, so allow me to again say welcome! If you have a topic you would like researched, please let us know. As you can see, I get in trouble when I have nothing to do! [She does!]

Please ask! As a value we also have member empowerment. You remember Scholastic Rock? We learn because “Knowledge is Power!” Let us empower one another.

Bye!

Written January 4th, 2019

Next: THE TIME TO PREPARE IS NOW

Happy New Year 2019!

2019. Ready or not, it is here.

Not to make anyone feel old, but 2019 will be the 50th anniversary of Woodstock. (And October, 2020, Janis Joplin will have been dead 50 years. I still hear her on the radio almost weekly). 2019 is also the 50th anniversary of the first moon landing. How many of you could have predicted those things at the start of 1969?

Prognostication is a tricky business. Just ask meteorologists. (Which brings up another subject: does anyone else find 60 degree weather at Christmas to be scary? Lin/Linda: not if you live where it’s usually 60 degrees or higher at Christmas! ::grin::) However, with help – a lot of help! – from BrightFocus Foundation website (October, 2018), I will try to predict what we with Age-Related Macular Degeneration might have to look forward to in this new year.

Looking at the wet side of things first, now that they have proven treatments for neovascular, Age-Related Macular Degeneration, it is time to expand, refine and improve. New angiogenesis inhibitors – in other words, drugs that will retard the growth of extra blood vessels – are either on the market or will be coming soon. Some of the ones already on the market are Eyelea, Lucentis, Macugen, and Avastin.

In development are new, longer lasting anti-VEGF compounds. These things include Abicipar and Brolucizumab. Several of the ones currently on the market are also coming out in longer lasting formulas.

And let us not forget the new delivery systems in development. We reported on several different medication reservoirs that will allow patients to go two or three months without having to go in for a fill-up. Down the road, combination therapies, such as filling reservoirs with long acting medications, may allow people to go for shots every six to eight months if not longer.

Moving to the dry side of the street, things are starting to move on several fronts. My personal favorite is regenerative medicine, aka stem cell replacement/regrowth. We have spoken of the groundbreaking work being done with “the patch”. While I found nothing published about this since the spring, I cannot believe the research is not going on fast and furious. There are also studies being done in retinal pigment epithelial replacement by other companies. A search for Age-Related Macular Degeneration + stem cells yielded 34 hits on clinicaltrials.gov. Many of these are phase 1 studies. At least a few of them should progress to the next level.

Since there is a fair amount of evidence AMD has a lot to do with the function of the immune system, there are continuing efforts to intervene in the complement cascade. While lampalizumab fell short in phase 3 trials, APL-2 is entering phase 3 trials and looks promising. This medication is reported to intervene higher in the cascade process and is hoped to effect a wider range of patients.

And I haven’t even touched upon gene therapy or statin treatments or some of the most recent research in mitochondrial metabolism and AMD! All of these lines of study are showing some progress and may lead to finding a treatment and possibly even a cure.

Which study will break to the front of the pack? I have no clue. But one thing I do know is there will be progress made.

So back to Neil Armstrong from the Sea of Tranquility, 1969 “It is a great honor and privilege for us to be here representing not only the United States but men of peace of all nations, and with interest and the curiosity and with the vision for the future…”

May we, of all nations, patients and researchers alike, with interest, curiosity, and vision, continue to support one another in our quest for a cure for our shared nemesis, vision loss.

Happy 2019!

Written December 28th, 2018

Next: A MINOR EPIPHANY

In the Pipeline for Wet AMD

Help! Stop me before I write again! Lin is going to shoot me. I have housework to do and a psychological evaluation report to write and what I feel like doing is pretty much exactly nuthin’, muffin. Too hot. [Lin/Linda: I don’t think that would stop the speeding train that is YOU! ::grin::]

20 minutes later
Ooopsie. Back from running after the Maggie Monster. She got out and decided to go play with the big dog down the way. That is BIG dog. Do you know what three days of a heat wave does to asphalt and bare feet???? Ouch!

But enough of the autobiographical details. I found an article entitled Wet AMD in 2018: Drugs in Development. I really swear the researchers love you guys better because they do all sorts of wonderful things for you. ?

For example, an anti-VEGF called Brolucizumab is in phase 3 clinicals. This drug is exciting because it can be dosed in larger amounts resulting in extended times between treatments.

OPT- 302 is a compound that will block the activities of the proteins VEGF-C and VEGF-D. Remember VEGF stands for Vascular Epithelial Growth Factor. The VEGFs cause the growth of substandard veins. Blocking these in wet AMD is a good thing.

According to this article, ranibizumab blocks VEGF- A. Not too sure how many letters there actually are, but combining OPT-302 with ranibizumab will take care of more of the alphabet.

OPT- 302 is in phase 1/2 clinicals. It will take a while.

Ok. Get out your water wings ladies and gents because it is getting a little deep?.

Platelet growth factor binds to a tyrosine kinase receptor. The receptor is essential for the survival, recruitment, and maturation of pericytes.

No, not parasites. It just sounds almost the same. According to Wikipedia, pericytes are associated with allowing cells to differentiate, multiply and form vascular branches among other things. The bottom line is: disable the platelet growth factor and you can stop or significantly slow the growth of new blood vessels. One more way to get to the goal. Not anti-VEGF. This one is anti-PDGF. Auntie Pidge? [No, I have no clue where she comes up with some of this!! ::grin::]

Names to look for: pegpleranib and rinucumab. So far pegpleranib has done little to nothing in clinical trials but they are combining it with anti-VEGFs to see if there will be a combined effect. Rinucumab did not do much either. Same with DE-120 (Santen). However, you never know. The concept appears sound and they will probably keep working on them.

They continue to look at tyrosine kinase inhibitors in other studies. Vorolanib is in this category. The APEX study is in phase 2. Maybe one day you can have Auntie Pidge to thank for saving your vision!

The article goes on and talks about drugs that attack angiopoietin 2. This is a blood vessel growth factor. They are also targeting substances that require a lot more knowledge of biochemistry than I ever wanted to have or thought I would need to understand what they do. Suffice it to say they are all compounds that have a role in making those nasty, extra blood vessels grow.

So that is what is in the pipeline for you wet folks. Seems like a lot. Are you SURE they don’t love you better?

[Just so that we don’t forget, there is research going on for dry AMD as well.  Here’s Summary of Research and Development — 2018 by Dan Roberts with research in both dry and wet AMD.]

Written July 3rd, 2018

Next: It Might Be That Pony

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Why Drop Out?

I wanted to start this page by saying I am enjoying the halcyon days of summer but then realized I do not know what ‘halcyon’ means!

Hold on…OK, synonyms are “calm, peaceful and tranquil”. We’re good…except for Etta jumping on my head in the pool. I am thinking I won’t actually be able to swim when they are in the pool area. Etta swamped me!

Oh, well. If that is the worst that happens today, I am ahead of the game.

Moving right along. Halcyon days of summer, etc, etc. I have been outside walking and hanging out at the pool with the puppygirls most of the afternoon. Blessedly sunny today but I am reasonably sure I have gotten burnt.

Remember to wear your shades. Yes, your eyes can actually get sunburnt. More importantly, UV rays contribute to oxidative stress and that leads to all sorts of things ending in more vision loss.

Since I have some days with nothing to do, I have gotten a load to the animal rescue yard sale and bagged up all the recyclables to transport to the recycling center. Among other things, of course. I have high hopes of using this time wisely to do a lot around the house.

Please note I am sitting by the pool and writing this page. Sigh. The best-laid plans of mice and men. Did I mention I really dislike anything to do with housekeeping?

Found an interesting website. It’s news-medical.net. A while back Lin did a page on eye drops for wet AMD. News-Mediçal reported PanOptica announced at the end of May they had dosed their first patient in a 1 / 2 clinical trial with PAN 90806. PAN 90806 is a once-daily eye drop containing a very small molecule anti-VEGF. PanOptic is hoping to avoid the cornea problems that occurred in earlier trials.

They also, of course, are looking to reduce the “injection burden.” The article says they hope a reduced burden will lead to folks staying in treatment longer.

Whoa there! Discontinue rate for anti-VEGF shots? Let’s look.

A 2017 journal article by Polat, Inan, Ozcan, et al (and yes, this was Turkey) reported a dropout rate of nearly 18% and a non-compliance rate of nearly 40%! Oh, good grief!

Not sure what the dropout rates are for the US, UK or EU. The only article I found based in the US was with the very old. Does anyone know what it is for us under 90?

The article from Turkey talked about the “usual suspects” as being related to compliance rates. You know: age, education, distance to the hospital, finances, etc.

Any way you look at it, it is scary. I never gave a thought to treatment compliance. If I had, I would have assumed dropout rates were low. Maybe not.

Any thoughts on this? What makes you folks getting shots want to quit? What do you think could be done to help people stay in treatment? Let’s start a discussion.

Written June 9th, 2018

Next: Forewarned is Forearmed

HOme

From the Inbox

Monday morning and I am waiting for the van to go to work. Thus endeth another weekend.

Next week at this time I will be just about starting a five day long seminar. My life just keeps pulling me along….by the hair…as I scream.

No, not really. It is all by choice. I could always say “no!” But I don’t.

Taking a minute to look at my old email, I found a really old Medscape post from 2015.  And no, I am not THAT far behind. It was an article referenced by another article. Anyway, the article was about how Pegpleranib is being used as a pretreatment for wet AMD. They are experimenting with this stuff in patients who are treatment resistant. The hope is that Pegpleranib will increase the effectiveness of anti-VEGF medications.

Although it was a preliminary study the results suggested pretreating with Pegpleranib will not only lead to better visual acuity but it will also increase the duration of effectiveness of the anti-VEGF medication and, in addition, prevent fibrosis. Hold on…fibrosis? Be back soon with some info on THAT little wrinkle.

I’m back. After a day that finally saw 70 degrees Fahrenheit and a hip hop class, all is right in my little world. Keep me warm and let me dance. It appears I am pitifully easy to please!

Onward…I am looking in EyeWiki and found an interesting bit of info – not related to fibrosis, but interesting. EyeWiki quotes the cost of neovascular AMD as being $5.396 billion annually and the cost of dry AMD as being $24.395 annually. That is loss of GDP, gross domestic product. I TOLD you this stuff is breaking the bank. Now do you believe me? ?

OK. EyeWiki says there are fibrous disciform scars formed when there are bleeds. Regular Wikipedia says fibrosis is related to the process of scarring. The process apparently starts when the macrophages – remember the big eaters? – that are sent to clean up the mess from the bleed start secreting a chemical that will trigger the fibrosis. It all keeps coming back to the complement immune system. It appears the Pegpleranib dampens down the chemical signal the macrophages send out and reduces the fibrosis.

The Wikipedia piece goes into a whole lot of explanation about the chemical process that I about half understood. Feel free to look at it if you are interested in that sort of stuff.  Social scientist here; remember?

That is about it for now. I have places to go, people to see, dogs to walk , a lesson plan to write and all sorts of housework to avoid?. I will try to check in later with more gems from my mailbox…or not. Caio!

written April 29th, 2018

Next: That Little Summer Dress

HOme

News from Research

Hey, hey, how y’all doing? I did my Zumba class and half a yoga class and then walked up to the street fair to help with the Y’s demonstration class. Had a hamburger and fresh cut fries as well as an ice cream. I did mention I have a horrible diet; right? Then I waited nearly an hour for transportation. Geez.

If I did not have to walk along a busy road, I would consider walking the three or four miles it is to get home. I probably would get home faster.

Sometimes I actually consider just staying home because of the hassles with the damnable transportation. Then common sense grabs me – or I revert to my old, ornery self – and decide they are not going to break me!

Oh, forgot to mention, I begged, finagled, whatever a ride to Mom Prom tonight. I bought a ‘new’ prom gown at Sal Val. It was $7.50. Also silver high heels. $4.00. Very thrift store chic here! [Lin/Linda: if you are just joining us, the Mom Prom is a party for females over 21.  You buy a gown at the Salvation Army (Sal Val) thrift store.  And you don’t have to be a mom.]

Okay, enough of me. Let’s actually do some eye news.

One of those Healio articles from November, 2017, indicated they are now combining therapies for diabetic macular edema. They dosed people with Lucentis and then shot them with a focal laser. While they did not find any significant difference in the number of treatment required between the dose plus laser and the treat and extend groups or even differences in the visual acuity numbers of the groups, all treatments tried were effective.

So, in essence, they have started to ‘play around’ with treatments and may just find some combo treatments that give better results than singular ones. Personally, I am on two blood pressure medications. Either of them alone did not do a thing for me but together I have good control. There may be some people who will respond beautifully to the one, two punch of an anti-VEGF and laser combo just like I respond to my two, blood pressure medications. You never know.

Also in Healio last November – I did mention I got a bit behind; yes? – they reviewed trials of another anti-VEGF treatment. You wet people sure are popular with the researchers!

This new one is called brolucizumab and it is a “single chain antibody fragment VEGF inhibitor”. They were dosing every 12 weeks and the results were comparable to those obtained with Eylea. Also, side effects were less. In short, one more option for keeping your bleeds at bay. Pretty good.

And one more thing before I go, also back in November Healio ran a follow-up on a concept they reviewed in 2016. It appears about 100 people are now running around with macular hole repairs using transplanted autologous retina tissue. Cool.

Autologous means they get the tissue from the same person they are transplanting the tissue into. The tissue to be transplanted is taken from the superior peripheral retina.

Now, will the vision be as sharp? What are they doing to ensure the transplanted retina connects with the neural network? No clue. What I do know is they have started talking about using this technique to treat macular degeneration.

All told, ophthalmological research is speeding along on a number of different trajectories. Things are happening everyday and it really is the best time in history to be going blind! Hang in there.

Written April 27th, 2018

Next: From the Inbox

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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”

Cool Things

Greeting! I decided to stay home today. Too much to do. So instead of doing housework or work work I am working on a page.? Hey, makes sense to me!

I was doing a little web browsing and came upon the site for the “American Association of Ophthalmology. Protecting Sight. Empowering Lives”. Nice motto. Established 1896. Fairly old for ‘the colonies’.

I was looking through the sight site ? and discovered the pages from the annual meeting in New Orleans. There, in living color, was my doc! Carl Regillo was program co-director for the retina section. How about that?

Ever play Six Degrees of Kevin Bacon? It is a silly game based on the theory of six degrees of separation. The theory is anyone can get to anyone else in six moves or less through associations. I used to be able to get to the president in four moves. I was friends with the father of the secretary of the state department of agriculture. He knew the federal secretary of agriculture. The federal head knew the president. The president was my fourth jump. Done in four moves!

Anyway, started to think how many moves it would take to certain people through Regillo. He cuts it down considerably! But that is not my point…

My point is: they are doing some cool things in ophthalmology!

For example? Well, do you remember I said it would not be long before they are using gene therapy with AMD? Boy, was I behind the curve! Things in that field are happening now!

The AAO stuff was in abstract form and pretty scientific. Allow me to go to the popular press and get my info? If I sit down and try to analyze the other stuff, that is all I will get done today!

BrightFocus and WebRN both ran pages on gene therapy for macular degeneration. The BrightFocus article highlighted a gene therapy called Retinostat. Retinostat is for wet AMD. It sounds as if the inserted gene programs the cells in the eye to produce anti-VEGF. Sort of like refitting a factory to produce a different product.

Retinostat is nct01678872 at clinicaltrials.gov. What is listed is a phase 1 study (safety and tolerability) and they are recruiting by invitation only.

The second wet AMD gene therapy possibility mentioned in BrightFocus is AAV-sFLT. This is also supposed to block VEGF. This study is nct01024998. It is active but not recruiting. That is also phase 1. At the end of the first year, gene alterations from AAV-sFLT were still blocking the production of VEGF. Bottom line may be fewer or even no shots!

And, as for usual, wet AMD advances seem to happen first and our third potential gene therapy is also for ‘youse guys’. Specifically it is REGENXBIO’s RGX-314. The number is nct03066258. It is phase 1 – once again – safety and tolerability and absolutely no promises. They are recruiting. Santa Barbara, Baltimore, Boston, Philadelphia, Memphis and Houston.

So, yes. There is progress there in gene therapy for wet AMD, too. Gene therapy is in its infancy and some people object. It is up to you to decide for yourself if you believe manipulating the very code that makes up who we are is moral or are we playing God. Not my call. If you are alright with it, they could have it for you in a few years. Good luck!

Written January 28th, 2018

Continue reading “Cool Things”

Three Types of Wet AMD

Well, the kitchen floor is now mopped. Took a deep breath and went back into the housekeeping fray after that last page. How do people get motivated for that sort of thing every day?

With a nod to our ‘wet’ readers, I am going to tackle an article on how to image different types of neovascularization. Not sure I am going to get very far because I never even ‘knew’ there were different types of choroidal neovascularization.

First off, to the article talking about imaging retinal angiomatous proliferation. Huh? Back to EyeWiki.

Choroidal neovascularization starts in the choroid. It erodes through the RPEs and results in chorioretinal anastomosis. Anastomosis? Lovely. Anastomosis is the connection of two vessels that were not previously connected. Sort of like a shunt. Got it? Good; moving on.

Retinal angiomatous proliferation is a process that happens ‘backwards’. It starts in the retina and progresses into the subretinal areas. It eventually connects the retina and choroid by forming an anastomosis. That is a connection where there is not supposed to be one. See previous paragraph.

Retinal angiogenesis proliferation has been called type 3 neovascularization. This begs the question: what are types 1 and 2? Type 3 is rare with 10% to 20% of people with wet AMD having this type of disease. This may be a good thing because the article lists all sorts of complications that are common in type 3 but rare in the other two types.

So now I have to do a little more digging and find neovascularization types 1 and 2. Back to EyeWiki where I discovered this: In type 1 the new veins are below the RPE layer. In type 2 the neovascularization passes through the RPE layer and compromises the neurosensory retina. That means it gets far enough to directly mess with the photoreceptors. Type 1 is hidden and type 2 is classic.

As far as treatment is concerned, ResearchGate.net (7/15) suggests type 1 can be treatment resistant. My guess – please note this is a guess – would be this is because type 1 is ‘buried’ in lower regions of the eye and anti-VEGF may have a harder time getting to it. That buried nature of type 1 – and another article – makes me think what we are talking about here is the occult type. Saw that classification before. Just needed to make the connection. Dawn does occasionally breaks over Marblehead.

Anyway, anti-VEGF treatments are still first choice although I am starting to see references to photodynamic therapy (“cold laser”) and even surgery. Maybe we should look into that, too.

Type 2 is the classic type. My reading suggests ‘shots’ are the treatment of choice there.

And as far as type 3 is concerned, it appears that in spite of the complications reported, type 3 can be treated rather successfully. Anti-VEGF injections do the trick, sometimes even on the first try.

So there you are the three types of wet AMD. Learn something new everyday.

written October 24th, 2017 Continue reading “Three Types of Wet AMD”

A Dozen Years of Progress

Here I am again, trying to offer a balanced look at AMD. Rumor has it the wet folks are wondering when they will get consistent coverage of their issues. Dunno.

When are we getting someone with wet AMD to write for us? You write. We publish. Until then, I can throw a few pages together, but my problem is dry. I cannot even begin to speak to the subject as well as someone with wet could. Consider it.

Found an article from BrightFocus Foundation. Title: How Effective are Age-Related Macular Degeneration Treatment? At the risk of sounding like a broken record, I like how the author points out there were very few treatments a scant 12 years ago. As the baby boomers we continue to drive many, many things in the world. Pig through the python; yes? We are now losing our vision and unless something is done, we are going to break the bank with our care needs. People respond to numbers, large numbers.

Which brings me to, did you know there are something like 200,000 new cases of CNV (wet AMD) every year in the United States alone? That is from CATT at 2 years: the facts.

I got to the CATT study because the BrightFocus article (above) referred to it. It is a 2010 study that seems to remain pertinent today. It was mentioned with ANCHOR, MARINA and HORIZON. These are all efficacy studies for your ‘shots’.

In the ANCHOR and MARINA studies Lucentis was proven to improve vision several lines on the chart. This was in the short term. The HORIZON and CATT studies were longer term and in these some gains were lost.

The VIEW trials suggested Eylea every eight weeks is superior to Lucentis every four weeks. However, more study is needed.

Avastin is a cancer drug. Injected into the body, it inhibits growth of new blood vessels in tumors. It tries to starve those, nasty things. Off-label use of Avastin for CNV has shown similar efficacy to Lucentis.

A big selling point for Avastin is cost. The article suggests it is $50 a shot. The others are thirty to forty times that much! Insurance problems? Talk to your retinologist about Avastin.

The BrightFocus article ends with good news. Did I mention I like this guy’s attitude? He reported a more recent CATT finding was 50% of patients retained 20/40 vision in the treated eye five years after the start of anti-VEGF treatments. Only 20% had 20/200 or worse! What do you think of those apples?

Again, these gains are in little more than a decade. How can you doubt more great things are coming and coming fast?

OK. How’d I do?

written July 1st, 2017

Continue reading “A Dozen Years of Progress”

Blast From the Past

And now, you have been asking for it, I present WET AMD!

Not that I have any first hand experience with the stuff nor do I wish to but I found an article on the history of treatment and thought I should share it. Feel free to chime in.

Preview of coming attractions…or a review depending upon how fast Lin gets her AMD timeline done…the first treatment for wet AMD was laser coagulation in 1979. That folks was less than 40 years ago. That would have been when some of your parents were dealing with AMD and vision loss. Before lasers? Nada. Again, this is not your parents’ AMD.

Since zapping little, tiny bleeders was not an exact science (remember, this was before Blaster Master and other now classic video games. Few people were that skilled), there were some misses. That’s when they came up with Visudyne, a drug that helped to ‘light up’ the target. A specially designed laser activated the Visudyne which selectively destroyed the bleeders. Better but still not great.

The article, Macular Degeneration Treatment from AMDF, went on to talk about 3 problems with laser treatment of CNV bleeders. First, because bleeders may have been too large or poorly delineated, only about 10 to 15% of them could be treated with lasers. Second, there was a 50% chance the leak would reoccur in two years and third, 50% of the treated patients still had subfoveal leakage. Also mentioned was the possibility of technicians with bad aims and further, inflicted damage.

Anti-VEGF is put into use in 2004. We land a Rover on Mars. Lord of the Rings is best picture and Harold Shipman is found hanged in his cell in Manchester, UK. Remember 2004? That was not that long ago! 2004 seems like yesterday, but since then, 13 short years ago, in some parts of the world, Anti-VEGF has reduced the rate of legal blindness by 50%. Wow!

Of course nothing is perfect. Vascular function in the rest of the body has been a worry for some. However, stroke data has been inconclusive. There have been cases of eye infections, increased eye pressure, retinal detachment and floaters.

Not sure where we will be going from here with wet AMD. Some of the work being done on dry AMD will head off both cases of wet and GA. Recall wet and GA are both advanced stages of the disease. New delivery systems are being developed and researchers are kicking around phrases like platelet-derived growth factors, receptor antagonists and immunomodulatory therapy whatever they are. It is a brave new world and we are getting to be part of it. [Click here for the most recent review of research for both dry and wet AMD.]

There you have it: my attempt at fair and unbiased reporting. I will try to do some more about wet AMD but, frankly, the effort may not last. We really need someone to cover this ‘beat’. Any takers? Continue reading “Blast From the Past”

Reading Modern Retina

Never thought I would be skimming back issues of Modern Retina, but here I am! Let us get back to some of the science stuff.

Amyloid beta is a major component of plague found in the brains of those with Alzheimer’s. There has been some suspicion AMD and Alzheimer’s are related at a genetic level. A recent study completed by Cheryl Guttman Krader failed to show any positive effects of injecting an antibody that targets amyloid beta into the eyes of those of us with geographic atrophy.

For the time being this means this line of inquiry will be abandoned or re-worked. Proof of concept did not occur and these researchers might go on to investigate something else.

Why are negative findings good news? One less blind alley to investigate! Since we don’t know which ideas may bear fruit, they all have to be investigated. Eventually we get to only the ones that have the most promise. Scientific method.

And another reason I think this finding is good news? It sort of suggests the Alzheimer’s and AMD connection may not be so cut and dry. Phew!

Here is another failure in proof of concept. Aflibercept is called Eylea when it is used as an inhibitor of vascular endothelial growth factor (VEGF – read “one of the things that makes the extra veins grow in AMD”). Michelle Dalton tried implanting stem cells in the eyes of patients who had been getting Aflibercept. She hoped the stem cell would produce the natural vascular endothelial growth factor and make the shots unneeded.

Unfortunately, many more patients than she had hoped required rescue doses of the drug. However, she also had people who kept the stem cells alive and these imported new stem cells did produce some of the Anti-VEGF molecule. Quantities were just too far below a therapeutic dose.

While this may be a failed experiment on the face of things, it is not all bad. Knowing there was some production of the desired molecules means this procedure may be very helpful once they figure out why it worked the little bit it did. Magnifying that effect may lead to fewer injections.

Last one, David S. Boyer wrote a review on multiple strategies being investigated for treating dry AMD. While many protective strategies for our photoreceptors and RPEs have failed, one they are still looking at with interest is brimonidine, brand name Allergen. Allergen is once again an intravitreally administered drug. (That is needle in the eye. We appear to be destined to join our wet AMD friends in that fate!) Coming out of phase 1 trials, brimonidine looks good. Next for it is phase 2, proof of concept. Will it perform as hoped?

Glatiramer acetate is looking good for reducing drusen. Glatiramer is used to treat multiple sclerosis, a disease in which the immune system wears away at the covering on the nerves. The theory is that glatiramer acts as a decoy to mitigate the autoimmune reaction. This treatment is based on the idea AMD really is an autoimmune disease.

There has been some evidence glatiramer reduces drusen, but Dr. Boyer warned us drusen can become fewer on their own. Drusen regression.

And that is a topic for another page.

written June 26th, 2017

Continue reading “Reading Modern Retina”

Hodge Podge

This may end up as another chatty, hodge podge affair. There is really nothing major happening and in the world of progressive eye disease nothing major happening is a good thing!

So, actually, I guess that is my first offering here. Those of you who have recently received your diagnosis or have had a crisis and are really distressed – it is not all drama and disease focus for the rest of your life.

You adjust and other things take center stage. That is not only normal but it is a good thing.

Second offering is something I picked up last month at the support group. When I said dry AMD is the base disease, they looked at me as if I had three heads. What I meant – and what they had not gleaned. Why won’t people do their research! Or minimally ask questions? – is that even though the shots have stopped the neovascularization, the growth of new blood vessel that lead to a bleed, you still have the underlying cause of the problem. The cause is regular, old, dry AMD.

This is why, even though you think the stuff we publish on dry AMD does not relate to you, it does.

Wet AMD is one type of end stage AMD and geographic atrophy is the other. Stopping the bleeding does not eliminate the underlying disease. It just eliminates the symptom.

Which brought me to another thought. I have never seen anything that says if an eye prevented from going wet will go to geographic atrophy. Hmmmmm…..

Nuts! More to worry about. Kaszubski et al in Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review stated there are people who can have both forms at the same time. Geographic Atrophy generally happens first. (That part is bad news for me although I am under the impression that for me there is very little left to ‘save’ by building new blood vessels.)

To follow the question posed above, though, they also say there is some evidence anti-VEGF shots can increase the chances of GA development.

While that is bad news for you getting the shots it does NOT mean to stop your shots. No shot and you will bleed. Bleeds lead to scarring and certain vision loss now. GA is slow and lead to vision loss later. Given a choice, battle the bleeds and worry about the atrophy later.

End of lecture.

Other than that, in real time Memorial Day approaches and I am thinking summer. Although I know there is ‘no rushing city hall’ (to paraphrase another old chestnut), I started looking up Astellas and Robert Lanza again. Just to see what the dear boy is up to. I have been hoping to get to Philly and the clinical trials this summer. It would be perfect timing for me but I am not sure about the Astellas Institute of Regenerative Medicine (AIRM). They will need to give Wills the go ahead to start one of ‘my’ clinical trials before anything happens for me.

Astellas is gearing up for something, though. Something big. A couple of years back they bought OCATA for $379 million. Now they are on a hiring binge and are looking for a bigger location in or near Marlborough, Mass.

In the business articles I read Lanza purposely hyped the work they are doing on AMD. I am assuming that is still their big thrust. (That is even though AIRM is in a variety of areas of regenerative medicine and Lanza himself is intellectually all over the place, including developing a theory of the Universe!)

Anyway, seeing this big a build-up with lots of business chatter tells me something is going to happen. Just hope it is in the trial I have volunteered for. My eyes and I are not getting any younger! Continue reading “Hodge Podge”

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