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Topical Treatment for Presbyopia

eye health presbyopia eyesight

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#1 Daniel Cooper

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Posted 09 February 2017 - 02:35 AM


If you're presbyoptic or headed that way (and we all are) you may find this interesting.

 

Topical EV06 Improve Near Vision In Patients With Presbyopia

http://www.healio.co...with-presbyopia

 

Now, I'd tend to be pretty skeptical of that claim, but apparently Novartis has purchased the rights to EV06 from Texas based Encore Vision

 

Norvartis to buy topical presbyopia treatment

https://www.aao.org/headline/novartis-to-buy-topical-presbyopia-treatment

 

The involvement of Novartis tends to lend some credibility.

 

The claimed method of action is that EV06 breaks disulfide bonds in lens fiber cells to increase elasticity.

 

Quote from the article -

 

 

In a phase 1/2 masked, placebo-controlled, proof-of-concept study, 50 patients treated daily with 1 drop of EV06 showed improved distance corrected near vision at all time points measured, beginning as early as day 8. At the end of the 90-day study, almost twice the number of EV06 patients achieved 20/40 vision or 0.30 LogMAR compared to placebo (82% vs. 48%). EV06 was well tolerated.

 

And what is this miracle elixir you ask?  It is a lipoic acid choline ester.  Why, I think I might even cook that up at home given access to the patent.

 

Very interesting for presbyoptics.  Let's hope the FDA doesn't drag there feet too much on this (who am I kidding, of course they'll drag their feet.  It's the FDA.)

 

 


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#2 Logic

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Posted 09 February 2017 - 09:45 AM

Interesting stuff Daniel especially as substances like this can also be considered leads to Advanced Glycation Endproduct Breakers.
 

The Patent:
https://www.google.c...5134510A1?cl=en

 

"...the term "EV06," "LACE" or "lipoic acid choline ester" is understood to have the following chemical structure..."

Sadly the picture of the molecule does not show in my browser?

But it would seem EV06=LACE=lipoic acid choline ester to search for the molicule.

 

This came up in my quick search:
Dioptin™ Eye Drop to Treat Presbyopia: corneal penetration and ocular pharmacokinetics

http://iovs.arvojour...ticleid=2269217

 

Lets see if we can find the info on this molecule and perhaps get some made.

 

Also possibly of interest:
The new drug is based on a naturally-occurring steroid called lanosterol. The idea to test the efficiency of lanosterol on cataracts pertained to the researchers when they became aware of 2 children in China who had acquired a genetic form of cataract, which had actually never ever impacted their moms and dads. The scientists found that these siblings shared an anomaly that stopped the production of lanosterol, which their parents did not have.

So if the moms and dads were producing lanosterol and didn't get cataracts, however their children weren't producing lanosterol and did get cataracts, the scientists proposed that the steroid may stop the malfunctioning crystallin proteins from clumping together and forming cataracts in the non-congenital type of the illness.

They tested their lanosterol-based eye drops in 3 types of experiments. They dealt with human lens in the laboratory and saw a reduction in cataract size. They then tested the effects on rabbits, and according to Hanae Armitage at Science Mag, after six days, all however 2 of their 13 test subjects had actually gone from having serious cataracts to mild cataracts or no cataracts at all. Finally, they tested the eye drops on pets with naturally occurring cataracts. Similar to the human lens in the laboratory and the bunnies, the pet dogs reacted favorably to the drug, with severe cataracts diminishing away to nothing, or nearly nothing.

http://www.deprogram...-drop-that.html

There is also another eye drop discussed on the forum, based on carnosine:

https://cse.google.c...drops carnosine

 

 

 



#3 zorba990

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Posted 09 February 2017 - 03:16 PM

Interesting, wonder how much lanosterol is needed....it makes acetyl carnosine seem cheap
https://www.scbt.com...osterol-79-63-0

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#4 aconita

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Posted 09 February 2017 - 11:05 PM

Synthesis of the Iodide Salt of LACE
Lipoic acid is relatively insoluble in aqueous solution. Even in
freshly prepared solutions of sodium lipoate, LA precipitates
out fairly quickly. To improve on the solubility and lipophilicity
for delivery of sufficient LA to the aqueous humor to effect lens
elasticity changes, an esterase labile ester of LA with cationic
surfactant properties was designed and synthesized in a two-
step process as described as Example 3.36 of Patent number
US 8,410,162 B2.
In the first step, an ester bond was formed between N,N-
dimethylethanolamine and R-LA using dicyclohexylcarbodii-
mide as the catalyst. The reaction is carried out in dichloro-
methane containing dimethylpyridine.
The second step is the alkylation of the nitrogen using

methyliodide

 

https://www.research...net/publication

/303593049_Protein_Disulfide_Levels_and_Lens_Elasticity_Modulation_Applications_for_Presbyopia

 

At the link images of the chemical structures and passages are available.

 

I am afraid this isn't so easily feasible at homemade level...but if somebody with adequate knowledge knows how to please share.

 

Granular soy lecithin and alpha lipoic acid in a blender with a bit of sterile water? :)

 


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#5 aconita

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Posted 09 February 2017 - 11:16 PM

Preliminary studies in dogs and rabbits have shown that lanosterol can prevent and even reverse cataract formation.[2][3] However, an attempt to replicate these results in age-related cataractous human lens nuclei removed during manual small incision cataract surgery by immersing them in lanosterol solution and incubating them for 6 days according to the method of Zhao et al.,[2] failed to reverse nuclear opacity.[4]

 

https://en.wikipedia...wiki/Lanosterol

 

Which might not mean much since I am not a great believer of in vitro testing...but in vivo on animals neither, for that matter.


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#6 Logic

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Posted 12 February 2017 - 02:24 PM

 

Synthesis of the Iodide Salt of LACE
Lipoic acid is relatively insoluble in aqueous solution. Even in
freshly prepared solutions of sodium lipoate, LA precipitates
out fairly quickly. To improve on the solubility and lipophilicity
for delivery of sufficient LA to the aqueous humor to effect lens
elasticity changes, an esterase labile ester of LA with cationic
surfactant properties was designed and synthesized in a two-
step process as described as Example 3.36 of Patent number
US 8,410,162 B2.
In the first step, an ester bond was formed between N,N-
dimethylethanolamine and R-LA using dicyclohexylcarbodii-
mide as the catalyst. The reaction is carried out in dichloro-
methane containing dimethylpyridine.
The second step is the alkylation of the nitrogen using

methyliodide

 

https://www.research...net/publication

/303593049_Protein_Disulfide_Levels_and_Lens_Elasticity_Modulation_Applications_for_Presbyopia

 

At the link images of the chemical structures and passages are available.

 

I am afraid this isn't so easily feasible at homemade level...but if somebody with adequate knowledge knows how to please share.

 

Granular soy lecithin and alpha lipoic acid in a blender with a bit of sterile water? :)

 

 

Your link didnt work for me, but a quick Google of brought up the paper:

https://www.research..._for_Presbyopia

Thx Aconita, that should be enough info to see if I can find someone to make this!


Edited by Logic, 12 February 2017 - 02:38 PM.


#7 Logic

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Posted 12 February 2017 - 02:36 PM

 

Preliminary studies in dogs and rabbits have shown that lanosterol can prevent and even reverse cataract formation.[2][3] However, an attempt to replicate these results in age-related cataractous human lens nuclei removed during manual small incision cataract surgery by immersing them in lanosterol solution and incubating them for 6 days according to the method of Zhao et al.,[2] failed to reverse nuclear opacity.[4]

 

https://en.wikipedia...wiki/Lanosterol

 

Which might not mean much since I am not a great believer of in vitro testing...but in vivo on animals neither, for that matter.

 

 

From 4:

Effect of lanosterol on human cataract nucleus

...It is also possible that proteins other than lanosterol play a role in senile human lenses, given that the earlier study was done in a family with congenital cataract. The differences in the molecular pathways of congenital and senile cataracts have been elucidated by Hejtmancik et al.[5],[6] Multiple authors have shown that congenital cataracts are usually secondary to accumulation of altered protein residues due to missense mutations and ferritin levels in specific cases. They have also indicted age-related imbalance of chaperones and accumulation of degraded and denatured normal proteins in senile cataract.[7] Further, basic science research will provide us more distinction between the two pathologies.

It also remains to be seen if immersion of intact lenses with the capsule or altering lanosterol concentration or the solute may result in positive outcomes.

 

So sadly this looks like its probably a dead end?  :(



#8 aconita

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Posted 12 February 2017 - 03:01 PM

Your link didnt work for me, but a quick Google of brought up the paper:

https://www.research..._for_Presbyopia

 

Thanks for pointing that out!

 

I don't have any idea why the link doesn't work...but yours does and it leads exactly where mine was supposed to.

 

Yes, the paper is actually very detailed and should enable someone with adequate knowledge to make it.

 

Keep us informed about it, of course!

 

 

So sadly this looks like its probably a dead end?  :(

 

It certainly needs more research done, unfortunately seldom things are as good as they look...but seldom doesn't mean never. :)



#9 niner

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Posted 12 February 2017 - 09:19 PM

 

Preliminary studies in dogs and rabbits have shown that lanosterol can prevent and even reverse cataract formation.[2][3] However, an attempt to replicate these results in age-related cataractous human lens nuclei removed during manual small incision cataract surgery by immersing them in lanosterol solution and incubating them for 6 days according to the method of Zhao et al.,[2] failed to reverse nuclear opacity.[4]

 

Which might not mean much since I am not a great believer of in vitro testing...but in vivo on animals neither, for that matter.

 

This is a pretty bad sign for lanosterol in human cataracts.  Usually, in vitro tests work better than in vivo tests, because there is no xenobiotic metabolism removing the drug in vitro, nor are there any problems with absorption.  The "bioavailability" in a test tube is always 100%.  Thus it's typical for a drug to work in vitro, but fail in a human, not the other way around.  If there were some sort of necessary chemical modification of the drug that occurred in vivo but wasn't accounted for in vitro, that might cause the reverse of the usual case.  It also may be the case that cataracts in relatively short-lived animals are fundamentally different than cataracts in long-lived humans.


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#10 aconita

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Posted 13 February 2017 - 10:24 AM

Usually in vitro tests work much better and actually very often it is the only way they do work at all, the same goes for in vivo with animals.

 

Apart from the sometimes very reasonable technical explanations about why and the often obscure reasons why about which nobody really knows, there is another factor, maybe totally irrelevant but more likely just ignored for practical reasons: the way research is structured.

 

When theory becomes practice in vitro tests are performed, if positive or promising results are achieved the next step is in vivo starting with very short lived organisms like worms or fruit flies and, if again positive results are observed, gradually progressing to longer living ones as mice, rats, dogs, etc... ending up with clinical trials on humans if all the previous steps have been successful.

 

Research comes to an end when one of those steps reveals a failure but anyway once at the clinical trial stage most researches do fail in a way or another because humans are different from petri dishes and fruit flies...and from mice and dogs too, for that matter.

 

The doubt that thousands of compounds which have been researched didn't make to clinical trials because failed with fruit flies while would have been absolutely wonderfully beneficial to humans is an hard one to live with.

 

I am not suggesting to experiment directly on humans anything that comes to mind just to see what happens, of course, but the undeniable fact that usually in vitro and in vivo on animals tests do perform better than on humans may be at least partially due to the simple fact that if they were not performing well nobody would have tested on humans in the first place.

 

I am pretty sure there is something absolutely great for us that will kill on the spot a damn fruit fly....

 

lanosterol being an hormone maybe doesn't directly effects cataracts but triggers something else to do the job, maybe it needs an in vivo environment to do so appropriately, we do know such behaviors are quite common with hormones, that's why I wouldn't be so quick to dismiss its usefulness.

 

Would it be really so dangerous to try lanosterol eye drops on humans?

 

Maybe the eye drops route isn't even the more appropriate or effective.... 


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#11 Vernard Sloggett

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Posted 25 April 2017 - 12:28 AM

i found a lab that would make lipoic acid choline ester, minimum quantity 1 gram, price 7k dollars. 

 

anyone want to start a fund? 

 

one note:

on the novartis purchace of encore; anyone think they just bought it to shut it down? have noticed lots of articles about inlays and surgeries as treatments. These companies and doctors may be making so much money on expensive treatments for pressbyopia they may not want to discover an eye drop alternative. 

 

 


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#12 zorba990

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Posted 25 April 2017 - 05:56 AM

Maybe this guy would be willing to help, since he has formulated other eye drops (glutathione) for his cataract patients.

https://www.secondop...ular-damage.htm

#13 SearchingForAnswers

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Posted 01 May 2017 - 09:40 PM

I want these drops...


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#14 SearchingForAnswers

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Posted 17 May 2017 - 01:51 PM

i found a lab that would make lipoic acid choline ester, minimum quantity 1 gram, price 7k dollars. 

 

anyone want to start a fund? 

 

one note:

on the novartis purchace of encore; anyone think they just bought it to shut it down? have noticed lots of articles about inlays and surgeries as treatments. These companies and doctors may be making so much money on expensive treatments for pressbyopia they may not want to discover an eye drop alternative. 

 

They are showing it here, however no price as of yet:

 

http://medkoo.com/products/12288



#15 Vernard Sloggett

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Posted 17 May 2017 - 06:35 PM

yeah they are the ones that sent me that quote



#16 Puppalupacus

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Posted 21 June 2017 - 10:30 PM

Any recent news from those that know?  As an aside, anyone have any supplement or stack recommendations with which they've had luck?  I swear my presbyopia fluctuates throughout every day.  So annoying.


Edited by Call of the Void, 21 June 2017 - 10:30 PM.


#17 Oakman

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Posted 21 June 2017 - 11:22 PM

Any recent news from those that know?  As an aside, anyone have any supplement or stack recommendations with which they've had luck?  I swear my presbyopia fluctuates throughout every day.  So annoying.

 

Ha! Finally someone else! My prescription in each eye varies as well, not too sure about over the course of one day, but I suppose it changes gradually, until it's noticeable. I confound the optometrists, they end up writing different prescriptions for each eye for contacts as I test different different visits. I buy -5.5 -6 contacts for one eye -6 -6.5 for the other. Which ones 'work' any particular day - trial and error. I go with the flow, so not really annoying.

 

stack: ALC drops off and on; Bilbery; Carotenall; extra Lutein, eye wash AM. Acuity is 20:20 corrected, so not sure what a 'better' would be....except less dryness, fewer spots, etc.



#18 Puppalupacus

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Posted 22 June 2017 - 12:02 AM

I swear my vision was sharper and more stable on NSI-189, and the presbyopia didn't vary so much.  It was still annoying, but it was at least stable.  Now after having been off a few months, my vision and presbyopia seem worse than they were originally.  Thanks for the stack recommendation.  I'm going to give them a shot, but I do hope these EV06 drops somehow make their way to market.



#19 Puppalupacus

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Posted 28 June 2017 - 11:52 PM

Off-topic, but I am back on the NSI-189 and have noticed my vision is much more consistent and sharper again.  This is a repeating benefit.  I'm at a loss as to the "why" it actually helps in this manner.  It wasn't intended or ever even expected.



#20 irony

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Posted 30 September 2017 - 09:23 PM

Off-topic, but I am back on the NSI-189 and have noticed my vision is much more consistent and sharper again.  This is a repeating benefit.  I'm at a loss as to the "why" it actually helps in this manner.  It wasn't intended or ever even expected.

 

one possible explanation is nsi-189 is causing your pupils to contract, which would increase your depth of field.  (pinhole camera effect)


Allergan appears to be working on something similar to this novarits/encore compound.

 

I take it nobody has found an affordable source of LACE?


Edited by irony, 30 September 2017 - 09:23 PM.


#21 Logic

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Posted 02 October 2017 - 06:01 PM

Off-topic, but I am back on the NSI-189 and have noticed my vision is much more consistent and sharper again.  This is a repeating benefit.  I'm at a loss as to the "why" it actually helps in this manner.  It wasn't intended or ever even expected.

 

An interesting observation Puppalupacus.
I haven't been 'in the game' for about half a year, but last I heard; no-one knew how NSI-189 worked.
ie:  it's just possible it gets rid some or other unwanted glycation mid/end product or something that builds up.

Anyone else notice any vision effect from NSI-189?
it certainly helps the head!



#22 Oakman

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Posted 18 December 2017 - 11:38 PM

...

lanosterol being an hormone maybe doesn't directly effects cataracts but triggers something else to do the job, maybe it needs an in vivo environment to do so appropriately, we do know such behaviors are quite common with hormones, that's why I wouldn't be so quick to dismiss its usefulness.

 

Would it be really so dangerous to try lanosterol eye drops on humans?

 

Maybe the eye drops route isn't even the more appropriate or effective.... 

 

Well, your dog can try these readily available Lanosterol drops, at least.

But of course, we can't, so we'll never know if they work in humans.



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#23 lrdmelchett

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Posted 16 June 2018 - 11:52 PM

My adventurous (stupid) friend tells me that alpha lipoic acid 5% drop in the eye burns like hell.  I have a feeling this is why the ester route that decomposes to AL acid after absorption.

 

 

Still, here's this study where it seems to read that straight AL acid was used just prior to cataract surgery as an opportunity to take 'aqueous' samples during surgery to understand absorption rates.

https://www.ncbi.nlm...pubmed/20456443

 

 

Here's a good study comparing use of LACE and ALA on old and young mice lenses.  The LACE compound was more effective at increasing ALA in the aqueous humor.

 

Still  "In most instances, the lenses of the treated eyes [in 8 month old mice] were even more elastic than the lenses of the 8-week-old mice."  

 

 

https://www.ncbi.nlm...les/PMC5995025/

 


Edited by lrdmelchett, 17 June 2018 - 12:28 AM.


#24 zorba990

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Posted 17 June 2018 - 02:52 AM

MSM eye drops?
http://determinedtosee.com/?p=860
Seems easy enought to diy but a bit at odds with the premise of some of the other drops in terms of sulfur.

#25 lrdmelchett

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Posted 17 June 2018 - 05:17 PM

Just in case people want to run with this idea.  There are some options.  One approach is ALA DMSO solution (might as well start with a N-Acetyl-Carnosine eye drop readily available and add to it).  Another is a commercially available eye drop with ALA 0.1% wt/vol.

 

This is a case of contact dermatitis resulting from use of ALA eye drop.  This gave a clue as to where to find an existing eye drop with ALA in it (Tioretin A).

 

https://pdfs.semanti...382c3fc04bd.pdf

 

 

However, 0.1% ALA is simply not enough based on the ALA vs. LACE research.  It might be possible to enhance this product by adding a bit more solvent and ALA.  I like the idea of starting with a commercial eye drop since it has buffering and preservative compounds.  One should also consider that a surfactant, e.g. Benzalkonium_chloride, (if not using DMSO) would be good to increase permeability since getting sufficient amounts of ALA to absorb is problematic.


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#26 OP2040

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Posted 17 November 2018 - 09:20 PM

Another great opportunity once again going nowhere fast.   We desperately need clinical trial reform.


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#27 korpesh

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Posted 27 November 2018 - 02:21 PM

Did anyone find a source and organize a group buy on the EV06 drops? Mid-40's and presbyopia issues are getting pretty damn annoying. If anyone knows how to get it, I'm in.



#28 Puppalupacus

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Posted 28 November 2018 - 05:15 PM

I absolutely hate progressive lenses and ended up getting two regular pairs of glasses, one for distance and the other for reading/computer.  Presbyopia is such a pain in the ass.


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#29 xEva

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Posted 29 November 2018 - 12:35 AM


I am afraid this isn't so easily feasible at homemade level...but if somebody with adequate knowledge knows how to please share.

 

Granular soy lecithin and alpha lipoic acid in a blender with a bit of sterile water? :)

 

 

 

MSM eye drops?
http://determinedtosee.com/?p=860
Seems easy enought to diy but a bit at odds with the premise of some of the other drops in terms of sulfur.

 

adding sterile water to ALA, and especially soy lecithin, will not make them sterile and we don't wanna put anything unsterile into our eyes. Same for diy MSM.

 

 

towards the bottom of the page linked below is the podcast interview with Dr. Gestwicki whose lab came up with lanosterol for cataracts. Very interesting, especially about how the fiber cells (lens proteins)  from transparent become opaque -- apparently, these proteins were meant to last a lifetime! Lots of other interesting stuff, including why it is so difficult to make eye drops with lanosterol.

 

https://www.ucsf.edu...tified-chemical



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#30 Rocket

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Posted 29 November 2018 - 01:33 AM

Deleted

Edited by Rocket, 29 November 2018 - 01:34 AM.






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