142 replies to this topic

[floret]

Thank you, will do! I'll order up the stuff this week and get started. Will post updates on here for everyone to see how it goes.

 

How is your treatment going, by the way? Is there continued improvement?

Edited by floret, 02 November 2020 - 05:47 PM.

[hamishm00]

Yes, definitely a little progress each day, reading very small print at 22cm now.

[SearchingForAnswers]

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.

 

I experienced the exact same thing. It's absolutely sharper on NSI-189, and seemed more stable.

[hotbit]

I have a racemic mixture of ALA, i.e. R+S. Dissolved one capsule 650mg in 100ml of cheap eye wash liquid. Tested eyesight at home, found to be around ~20/50 and ~20/40.

Edited by hotbit, 08 November 2020 - 07:43 AM.

[hamishm00]

That's quite a low concentration I think, you might want to double the concentration to get it above 1% especially since we're not sure if the S-ALA does anything to disulphide bonds - does anyone have any thoughts on this?

What's in the eye wash liquid that would act as an ALA solvent?

[lrdmelchett]

Curious. I've been watching this thread very intently.

The studies on the LACE showed that ALA alone had poor performance in permeating the cornea.

I guess no one on this thread has had any luck or volunteered to look in to getting a batch of LACE synthesized?

I really do think if we started putting threads on the group buy sections we could drum up enough interest to put a volume order in and cut costs.

I contacted one synth company a few months ago. They quoted me $4500 for a few grams. Can't remember exactly how many grams.

[lrdmelchett]

I'd even volunteer to organize. I have no rep here, but been a member for a few years.

Although, care would need to be taken to prepare a proper, sterile solution with an appropriate preservative. I think benzonium alko....can't remember the name is a common one, but it has a very bad reputation for damage to the cornea. We could need some expert advice for the solution and delivery method.

I hate presbyopia - I'm pretty motivated to make this happen.

[hotbit]

What's in the eye wash liquid that would act as an ALA solvent?

 

Indeed, solubility in water is only 240mg ALA / 1000mL water.

[hamishm00]

Curious. I've been watching this thread very intently.

The studies on the LACE showed that ALA alone had poor performance in permeating the cornea.

I guess no one on this thread has had any luck or volunteered to look in to getting a batch of LACE synthesized?

I really do think if we started putting threads on the group buy sections we could drum up enough interest to put a volume order in and cut costs.

I contacted one synth company a few months ago. They quoted me $4500 for a few grams. Can't remember exactly how many grams.

 

Where are the studies that show ALA is poor at permeating the cornea?

What about this ALA study which shows decent absorption in the aqueous of human eyes:

 

https://www.research..._administration

 

Since ALA can't be patented, isn't it in the interest of pharma companies to attack its efficacy.

Indeed, solubility in water is only 240mg ALA / 1000mL water.

 

Hence we need solvents like PEG400.

[hamishm00]

Near field vision focus point hit close to 20cm today.

[hotbit]

Near field vision focus point hit close to 20cm today.

 

What test do you use to check focus point?

[lrdmelchett]

Re: ala cornea penetration

I first found the data in the LACE patent application. Then I wanted to verify that, but it just pointed back to a study funded by the original developers of LACE.

The data could be dubious - not sure

[hamishm00]

What test do you use to check focus point?

 

Using a tape measure with the beginning of the measure held to the eye and the end of the measure with an object with small black writing on a white background. I am careful to use the same lighting conditions to measure. It's clearly improved by over 10cms since I started with the ALA drops, and now I am below 20cms. As of today, I am completely convinced of the success of the experiment.

[floret]

I just got back from a trip, couldn't log on there since i don't know my password by heart.

 

My eye drops only just arrived today. Will be giving things a go starting tonight.

[floret]

4 days in and no noticeable improvements yet.

[hamishm00]

Be patient, I believe this is a 5 week experiment before you can determine the success of the experiment. I am at 19cms now, which means slow and steady improvement that is only just noticeable only on a week by week basis.

 

What is in your preparation? 100mg Na-Ra-ALA into LEF Brite eyes?

Edited by hamishm00, 15 November 2020 - 06:51 AM.

[floret]

Brite Eyes wasn't available, but I got this other NAC drop called Eficel NAC Drops.

 

I had to dilute the whole solution by about 30% with more water just because it stung pretty bad. :P So i'm probably going to either take much longer to see results or not at all. If nothing happens within another week or two I'll just suck it up and redo the formula at full strength.

[hamishm00]

I highly doubt that you won't be getting ALA absorption, so keep going - perhaps increase frequency to 4 x per day in the beginning. I suspect we will reach a point where improvements stop and there will be a "maintenance dose", which could be also be a lower concentration of the ALA, meaning less discomfort (less "sting").

[floret]

This morning I can't focus even as well as i did a couple days ago. My near vision is worse. It is worse by almost two inches.

 

I'll up the daily drop solution and just ride out the pain. This gets sorted out one way or another.

Edited by floret, 17 November 2020 - 02:01 PM.

[Daniel Cooper]

I highly doubt that you won't be getting ALA absorption, so keep going - perhaps increase frequency to 4 x per day in the beginning. I suspect we will reach a point where improvements stop and there will be a "maintenance dose", which could be also be a lower concentration of the ALA, meaning less discomfort (less "sting").

 

For what it's worth when I had an interest in this I found a study that showed very decent absorption of ALA through the capsular bag.

 

Don't assume that EnVision was being completely honest when they said they went after LACE because ALA didn't absorb well. It's at least equally likely that they pursued LACE because it was a patentable compound, as opposed to ALA.

 

I apologize for not being able to post the study I found on ALA absorption in the eye, but I purged that folder after I got cataract surgery.

[floret]

So go figure  - I was just at the Chinese restaurant when I realised I was reading the menu and then my phone closer than I normally do. Could be that my eyes just needed time to warm up this morning? Hard to say, but this made me think that maybe I am improving...I will continue to go day by day and see. At the very least I was able to actually -focus-. You see, I am also quite myopic. So for the past year or so, I have never been able to fully focus my eyes at all. Today I just barely could.

[hotbit]

I'm using my simple solution for slightly over a week now, but don't have any measurable effects yet. However, subjectively, I felt my eyesight was more relaxed last days when looking at far objects like trees or clouds. But it seems there might be other problems than presbyopia. I have booked an appointment with an optometrist, but they moved my visit to next week. My near point might be over one meter now... not sure. I'm going to continue with what I have started to simply test it a bit longer.

I've read parts of the original article: https://iovs.arvojou...ticleid=2526363
Interestingly, they used ALA in vitro and as per Figure 4 concentrations {?} from 50µM/L to 500µM/L were effective in the experimental setup. I understand these numbers are solution concentrations, not amounts of the ALA. However:
 

 

Then, the medium was replaced with fresh medium supplemented with selected levels of LA (experimental lenses) or with fresh medium (contralateral control lenses). Lipoic acid levels ranged from 1 μM to 500 μM.

 

This would suggest amount of ALA, not a concentration, and they do not say what was the volume of the bath. I don't like it, frankly, not as tidy as I would like to see it.

But under the Figure 4 in the description they used the word "concentration":

 

 LA concentration (μM)

Anyway, I assume these are concentrations of baths. As ALA solubility in water is 127mg/L, it gives concentration of 615µM/L, even higher than what they have used for lenses in vitro. (Unless I've made some silly mistake in calculations). Still, 50µM number they give was almost as effective as 500µM.

If the above is correct, we can achieve easily these concentrations, but it's unrealistic to provide 12-h exposure in vivo.

OK, why LACE (choline ester of LA)?

 

 

Because 50.0 μM to 96.7 μM medium concentrations were needed to significantly increase the elasticity of mouse lenses in culture, four old mice were treated with 5 μL of a formulation of LA, OD. The formulation consisted of LA (0.121 M, 2.8%), tris(hydroxymethyl)aminomethane for increased LA solubility and pH adjustment, as well as 0.1% benzalkonium chloride (BAC). Benzalkonium chloride is not only a biocide, but also a cationic surfactant believed to increase corneal permeability. Forty-five minutes after topical ocular dosing, the aqueous humor LA concentration reached 17.5 ± 5.6 μM, a level well below that needed to affect elasticity. Forty-five minutes after drop application, after euthanasia, the aqueous humor was collected from the treated eye and analyzed by HPLC. 

Topical ocular treatment of four old mice with 5 μL 0.119 M (3.4%) formulation of LACE led to LA levels sufficient to effect disulfide reduction and increase elasticity. Forty-five minutes after topical ocular dosing, LA levels in the aqueous humor were 98.2 μM ± 14.8 μm. These levels were 5.6-fold higher than those when the topical ocular treatment was with the 0.121 M (2.8%) LA formulation. Furthermore, the increased levels of LA in the aqueous humor after topical ocular dosing with LACE indicate that ocular esterases hydrolyze LACE into its component parts: LA and choline.

They have determined that aqueous humor LA concentration using ALA solution (2.8%, 0.121M) was lower than the effective 50µM/L in vitro, but LACE solution (3.4%) delivered almost 100µM/L. Magnitudes higher concentration of ALA in eye drops did not deliver the theoretical therapeutic levels.

 

For in vivo experiments authors used only LACE (5%). I think it would be neat to have another "control" group of mice treated with plain ALA solution, as as we know, we cannot be 100% sure of translating conclusions from in vitro experiments to in vivo.


 

[hotbit]

Very interesting, Novartis spent $465 million on Encore Vision
https://ois.net/enco...ngel-investors/

But within 4 years they only managed to do one level 2a study and now starting to plan level 2b study to find optimal dose?
https://www.healio.c...resbyopia-drug#

 

Conclusions:

1) They have too much money.
2) They are in no hurry.

[floret]

I measured again today and it's back to being very poor. No measurable progress at all so far and going on 2 weeks now.

 

Will keep everyone posted.

[hamishm00]

Mine is holding under 20cms. It's also clear that the muscles need to be trained as well, or they need rehab, as the lens gets softer, to be able to focus properly at shorter distance. I would strongly recommend to exercises (moving objects back and forth while you are measuring the distance on your ruler/measure, and remember to blink a lot). The EV06 studies showed improvement over a period of 3 months, although I suspect you should start seeing improvement earlier than that. So I recommend the dual approach of lens softening eye drops + exercises to build the muscles back up, as they have been weakened as a result of the lens stiffening and lack of proper range of motion / use as a result.

[floret]

Thanks Hamish! Will do. Does it count that I regularly try to focus closer than I can anymore anyway? I'm always trying to because I have to be able to focus clearly to do my job. Because I also have myopia, I can't anymore. But I try anyway because now and then I can get it to focus a little better.

 

Are you continuing to see progress under 20cm or does that seem to be the limit?

[Woody42]

Floret, I noticed that you said you also have myopia.   About 6 years ago I started taking some vitamin D because it cal ofton help

with Seasonal Affective Disorser AKA The winter blues or SAD. It did help with that but the next time I went to the eye DR I needed

a weaker perscription and the next 2 or 3 times I went to the eye DR my perscription was lowered 2 or 3 more times. All in all my 

eysight changed from 20.80   to 20/30 unless I skip my vitamin D for a couple of weeks then it deteriorates some . But keep in mind

you need to have your vitamin D checked as too much can definitely be harmful.  But as a side note there is some indication  that low

vitamin D is associated with more sever cases of coved19 .

[hamishm00]

Thanks Hamish! Will do. Does it count that I regularly try to focus closer than I can anymore anyway? I'm always trying to because I have to be able to focus clearly to do my job. Because I also have myopia, I can't anymore. But I try anyway because now and then I can get it to focus a little better.

 

Are you continuing to see progress under 20cm or does that seem to be the limit?

 

At 19cms now, it's still improving slowly.

[hamishm00]

18cms now. This stuff is great.

 

We are talking a ten year age reversal in approx 2 months.

Edited by hamishm00, 29 November 2020 - 08:12 AM.

[hotbit]

I've been to optometrist last week and also printed Snellen chart (and more) for home testing. Due to dry eye and some other conditions still can't precisely find my near point, but it seems to be a disappointing 60+cm! 
I'm using ALA eye drops based on popular sodium hyaluronate eye drops, and also a bunch of supplements. After a week of daily use (once a day usually before bed) I feel there might be some small improvements, but not obvious enough to quantify. BTW - these eye drops sting for about 20s quite nasty!