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Topical Treatment for Presbyopia

eye health presbyopia eyesight

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#121 thomasanderson2

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Posted 18 January 2021 - 05:05 AM

So I finally mixed up my alpha lipoic acid eye drops this evening. Here's what I did::

I initially assembled all materials with the glass pipettes (per instructions posted earlier by Hamishm00.

DzzkzBc.jpg

 

But after reading instructions carefully, I decided I would just use two containers - 1. a mixing container (square clear glass spice jar) and 2. a final dispensing container (thoroughly-cleaned and distiled-water rinsed melatonin dropper)

7JRGPMy.jpg

 

 

 
To open one of the 5ml Brite Eyes containers, you need to remove the collar, then screw down to pop a hole
FRzRmgJ.jpg
 
Then, I poured the entire contents into the glass spice jar
(no photo)
 
Next, I measured out 100 mg of the stabilized NA-R-ALA
4KOOn6J.jpg
 
CiRcVCB.jpg?1
 
 
Added to the glass spice jar
5WXxjqt.jpg
 
Then mixed to dissovle. It dissolved almost immediately. And no residue at all.
z6j3ejQ.jpg
 
Finally I topped of off the spice jar with another 4ml or so of distilled water - and then transferred from glass spice jar to the final dispensing container.
(no photo)
 
My final product in the dispensing container:
JocDU7S.jpg
 

Edited by thomasanderson2, 18 January 2021 - 05:22 AM.

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#122 hamishm00

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Posted 18 January 2021 - 05:41 AM

Very thorough and exactly the way I would have done it. You have over a 1% solution there it seems.

 

BTW - those pipettes are HUGE, I am glad you decided not to use those. The ones I have are very small, and perfect for eyedropping (they also have an angled end). 

 

Good luck with progress. I had great success with the formula you have made (although I didn't use pure powder like you have). Your views on "stinging" would be appreciated.



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#123 hotbit

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Posted 20 February 2021 - 10:23 PM

Your views on "stinging" would be appreciated.

 

I do also have the same Na-R-ALA powder, but I'm using eye drops 1 week on and 2-3 weeks off. Sadly, still no breakthrough in eyesight improvements. 
 

to your question, it does sting, but slightly. However, apparently eyes get more sensitive in due time, and it stings more after a few days of continuous usage. At least this is my experience.



#124 hotbit

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Posted 12 June 2021 - 11:04 PM

I wonder, no updates,

 

1) Did everybody got perfect eyesight and now wants  monetize or keep it secret?

 

or

 

2) Did everybody got much worse and can't respond here any more?


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#125 zorba990

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Posted 13 June 2021 - 04:48 PM

I just started this again as I didn't give it long enough. I'm using a 4oz spray bottle with 1/4 tsp salt, 1/4tsp R-ala powder as shown above, and 1/4 tsp n-acetyl Carnosine.
It all dissolves to clear solution with minimal eye discomfort on use (Bright eyes burned like lava, so that's a no go on that for me).
I didn't use the salt last time which was probably a mistake as I think saline is better for this purpose and also acts to keep the mixture.
For me it's easier to spray a few times into the eye (Gently!) than to use eye drops. Similar to being hit with an ocean wave lol.

I'll try it a few times a day and see if close vision is improved.
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#126 hamishm00

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Posted 27 June 2021 - 03:06 PM

I stopped the drops for over six weeks, it seems that the improvements have mostly stayed, although slipping slightly week by week. 

 

Will start this regimen up again now.


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#127 katzenjammer

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Posted 27 June 2021 - 03:32 PM

I stopped the drops for over six weeks, it seems that the improvements have mostly stayed, although slipping slightly week by week. 

 

Will start this regimen up again now.

 

Okay, I'm going to try this.  

 

I'll use:

  • Brite Eyes + Doctor's Best Stabilized R-Lipoic Acid with BioEnhanced Na-RALA.  

I have perfect droppers for this.  

 

The only thing is, I tossed my scale last year in a fit of getting rid of things.  

 

Can I estimate?  Say,  1/4 teaspon, ? 

 

EDIT:  actually, what am I saying:  100mg would be one capsule.  Easy.  

 

I'll try for a few months and post up my results. 


Edited by katzenjammer, 27 June 2021 - 03:49 PM.

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#128 StephCThomp

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Posted 06 July 2021 - 11:09 PM

Good luck!  I was absolutely unable to do it with this formula and find it hard to comprehend how anyone can.  The sting was i-n-s-a-n-e, eyes tearing and washing it out straight away.  So stressful even once a day and I looked terrible - puffy eyes every day.  Not viable.

 

I tried a different eye drop and that was 70% better, but still some ugly puffing.  I couldn't tolerate looking unwell for weeks/months.  

 

I need a purer, more elegant formulation that's genuinely eye-friendly.  Don't know what that is yet.  


Edited by StephCThomp, 06 July 2021 - 11:10 PM.


#129 katzenjammer

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Posted 08 July 2021 - 12:03 AM

Good luck!  I was absolutely unable to do it with this formula and find it hard to comprehend how anyone can.  The sting was i-n-s-a-n-e, eyes tearing and washing it out straight away.  So stressful even once a day and I looked terrible - puffy eyes every day.  Not viable.

 

I tried a different eye drop and that was 70% better, but still some ugly puffing.  I couldn't tolerate looking unwell for weeks/months.  

 

I need a purer, more elegant formulation that's genuinely eye-friendly.  Don't know what that is yet.  

 

Just tried it - yeah it's quite stingy, but not overwhelming, but just on the edge of being so.  Maybe you're using too much ?  I don't think much is needed.  

 

I'll continue and see how it is.  

 

The fellow who had success, did he have issues with stinging/puffiness?   


Edited by katzenjammer, 08 July 2021 - 01:01 AM.


#130 katzenjammer

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Posted 08 July 2021 - 12:09 AM

Btw, can anyone summarize the mechanism of ALA wrt the eye?  Does it increase lens flexibility/permability?  



#131 Advocatus Diaboli

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Posted 08 July 2021 - 01:01 AM

Re: post #130

This article is about Dioptin eyedrops. 

 

"The eye drop is a lipoic acid-based, topically instilled prodrug that penetrates the cornea. Enzymes metabolized by the crystalline lens help reduce disulfide bonds between proteins and restore elasticity. According to Dr. Richdale, increasing lens protein disulfide content may cause presbyopia through a loss of lens elasticity."



#132 katzenjammer

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Posted 08 July 2021 - 09:49 AM

Re: post #130

This article is about Dioptin eyedrops. 

 

"The eye drop is a lipoic acid-based, topically instilled prodrug that penetrates the cornea. Enzymes metabolized by the crystalline lens help reduce disulfide bonds between proteins and restore elasticity. According to Dr. Richdale, increasing lens protein disulfide content may cause presbyopia through a loss of lens elasticity."

 

 

Thanks, UNR844 is R-Lipoic AND Choline - how are we including choline in the solution?  

 

Also, further down in that article:  

 

Subjects were randomized 1:1 to receive 1.5% Dioptin (n=40) or placebo drops (n=38) in each eye, twice a day for three months. There was no significant difference in mean change in DCNVA between Dioptin and placebo, (difference of 1.6 letters), so the primary objective was not met. 

 


Edited by katzenjammer, 08 July 2021 - 10:24 AM.

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#133 Advocatus Diaboli

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Posted 08 July 2021 - 08:23 PM

Re: post 132

 

Some relevant posts for solutions are 49, 60, 98, 99, 108, 109, and 126.  None of those posts mention Choline, as you suggest in post #132.

 

The purpose of my link in post # 131 was to respond to post #130, i.e. to present a possible mechanism of action for ALA. The proposed mechanism was: "...help reduce disulfide bonds between proteins and restore elasticity." as per the link. The scope of my answer wasn't intended to address possible reasons for the introduction of Choline along with ALA or its enantiomers.

 

Following your second quote in post #132:

 

"Subjects were randomized 1:1 to receive 1.5% Dioptin (n=40) or placebo drops (n=38) in each eye, twice a day for three months. There was no significant difference in mean change in DCNVA between Dioptin and placebo, (difference of 1.6 letters), so the primary objective was not met." 

 

is  the following:

 

"Due to high variability in DCNVA measures in both groups, but to a greater extent in the placebo arm, the researchers performed a post-hoc non-parametric analysis.

 
The median difference between Dioptin and placebo was four letters closer to the Phase I/II study results, and further clinical development is planned in a Phase IIb dose-finding study. Still, the study noted that future studies should also include mitigation strategies to minimize DCNVA variability. Research is still ongoing to better understand efficacy. Nevertheless, Dr. Richdale states that there is an unmet need for pharmacological treatments in presbyopia."
 
 
The "post-hoc non-parametric analysis" showed a change from a 1.6-letters-result to a 4-letters-closer-to-Phase I/II result. The fact that, at the time, there was a planned Phase IIb study might imply that although a difference 1.6 letters between Dioptin and placebo was not significant for the initial findings, the fact that, on post-hoc analysis, there was a 4-letters-closer-to-Phase I/II finding would seem to indicate that the results were good enough for the researchers to go forward with a Phase IIb study as indicated.

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#134 kyle75

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Posted 08 September 2021 - 07:43 AM

I'm with you guys. I started the experience about one month ago, but haven't been very steady at it, because I forgot to take the eyedrop with me on vacation and then came back and forgot all about it for another ten days. So you could say I started about 15 days ago. Also I used to eyeball the shortest distance I could still focus on but didn't measure it, so I'm not quite sure how much it improved. But I think it did improve. 

 

For the eyedrop, I ordered pure ALA capsules off amazon (I will tell you the brand if you are interested) but the capsules were explicitly sold as having no fillers. I spilled a 600 mg caps into pure DMSO. I added tiny amounts of DSMO until the 600 mg of ALA were fully dissolved. Then I added enough distilled water to have a DMSO solution of just under 28%. Why 28%? Because I read that pure DMSO was irritating at 100% and 50% in the rabbit eye, but not at 28% where it showed anti-inflammatory properties on the contrary. I spilled that in a 5 ml eyedrop container, and have been using that solution ever since. 

 

It sure stings the eyes like a bitch for a few seconds and the game is to limit lacrimation as much as possible so as to not wash it off the eye the moment in comes in contact. I think I'm pretty good at it but who knows really. 

 

In terms of improvement, as I said, hard to tell because at first I didn't measure, but now I do. I do it by measuring the closest distance I can see the pixels on my monitor (always the same one) and am happy to report that I can get as close as 28 cm. Also I'm short-sighted and I think my short-sightedness improved substantially (I actually can drive without glasses now which was not possible at first). 

 

I will duly report further progress. 


Edited by kyle75, 08 September 2021 - 07:48 AM.


#135 kyle75

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Posted 08 September 2021 - 09:32 AM

It looks like DMSO is a mild oxidant in certain circumstances, one of them being the co-occurrence of an acid (such as ALA). This is not good. I need to investigate this. PEG seems to be a much better solvent, especially when you consider it is already widely used in eye drops. 


Edited by kyle75, 08 September 2021 - 09:33 AM.


#136 kyle75

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Posted 08 September 2021 - 10:13 AM

I wonder if this compound can be bought: if it's a potent anti-melanogenic you can bet it's a strong reducing agent and would help reduce those disulfide bonds. 



#137 ta5

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Posted 05 March 2022 - 05:11 PM

This is a new treatment, not a cure. The effect is only temporary. I'm more interested in UNR844.
 
 
NORTH CHICAGO, Ill., Dec. 9, 2021 /PRNewswire/ -- Allergan, an AbbVie (NYSE: ABBV) company, today announced that VUITY™ (pilocarpine HCl ophthalmic solution) 1.25%, the first and only eye drop approved by the U.S. Food and Drug Administration (FDA) to treat presbyopia, is now available by prescription in pharmacies nationwide. ...

 

Wikipedia:

"It works by causing the pupils to constrict, increasing depth of field, similar to the effect of pinhole glasses. Marketed as Vuity, the effect lasts for 7 to 10 hours."

 

Eur J Ophthalmol. 2021 Jul;31(4):2107-2115. 

Liyang Tong  1 , Dongmei Cui  1 , Junwen Zeng  1
Purpose: This study aimed to investigate whether topical pilocarpine affects ocular growth and refractive development as well as the underlying biochemical processes in early eye development in rabbits.
Methods: Twenty three-week-old New Zealand white rabbits were treated with 0.5% pilocarpine in the right eye for 6 weeks. The left eyes served as contralateral controls. The effects of pilocarpine on refractive error, corneal curvature and ocular biometrics were assessed using streak retinoscopy, keratometry, and A-scan ultrasonography, respectively. Eyeballs were enucleated for histological analysis. The ciliary body and sclera were homogenized to determine the mRNA and protein expression levels of five subtypes of muscarinic receptors.
Results: Compared to control eyes, pilocarpine-treated eyes exhibited approximately -1.63 ± 0.54 D myopia accompanied by a 0.11 ± 0.04 mm increase in axial length (AL) (p < 0.001, respectively). The anterior chamber depth (ACD) was reduced, whereas the lens thickness (LT) and vitreous chamber depth (VCD) increased (p < 0.001, respectively). Corneal curvature decreased over time but was not significantly different between treated and control eyes. The mRNA and protein expression levels of five subtypes of muscarinic receptors were upregulated in the ciliary body and downregulated in the sclera.
Conclusions: Based on these results, pilocarpine can induce myopic shift, increase LT, elongate VCD and AL, and reduce muscarinic receptor expression in the sclera early in development. These changes raise the possibility that pilocarpine may promote axial elongation in ocular development and facilitate the emmetropization of hyperopic eyes.
Keywords: Pilocarpine; accommodation; ciliary body; hyperopia; muscarinic receptor; sclera.
PMID: 32524847

 

JAMA Ophthalmol. 2022 Mar 3.

George O Waring 4th  1, Francis W Price Jr  2, David Wirta  3, Cathleen McCabe  4, et al.
Importance: AGN-190584 (Allergan, an AbbVie company) is an optimized topical formulation of pilocarpine hydrochloride, 1.25%, designed for managing presbyopia and enhanced with a proprietary vehicle.
Objective: To evaluate the efficacy and safety of pilocarpine hydrochloride, 1.25%, in individuals with presbyopia.
Design, setting, and participants: This vehicle-controlled, participant- and investigator-masked, randomized, phase 3 clinical study, GEMINI 1, enrolled individuals with presbyopia, aged 40 to 55 years, at 36 sites in the United States from December 21, 2018, to October 31, 2019. Analysis took place between February 2020 and December 2021.
Interventions: AGN-190584 or the AGN-190584 formulation vehicle was administered bilaterally, once daily for 30 days.
Main outcomes and measures: The proportion of participants with improvement of 3 or more lines in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) at hours 3 and 6 on day 30 were the primary and key secondary efficacy end points, respectively. Safety measures included adverse events.
Results: Of 323 participants who were randomized, 235 (72.8%) were female and 292 (90.4%) were White. The mean (SD) age was 49.6 (3.5) years, and the baseline mean (SD) mesopic DCNVA was 29.2 (6.3) letters. A total of 163 individuals were randomized to AGN-190584 and 160 were randomized to vehicle. GEMINI 1 met its primary and key secondary efficacy end points. On day 30, hour 3, the percentage of participants with improvement of 3 or more lines in mesopic DCNVA was 30.7% (50 of 163) in the AGN-190584 group and 8.1% (13 of 160) in the vehicle group (difference, 22.5% [95% CI, 14.3%-30.8%]; adjusted P < .001). At hour 6, those percentages were 18.4% (30 of 163) and 8.8% (14 of 160), respectively (difference, 9.7% [95% CI, 2.3%-17.0%]; adjusted P = .01). At hour 8, the between-group difference in 3 or more lines of mesopic DCNVA gains was not statistically significant, but clinically relevant prespecified outcome measures demonstrated AGN-190584 superiority to vehicle in least-squares mean (SE) mesopic DCNVA change from baseline at hour 8 (5.4 [0.51] vs 3.6 [0.52] letters; P = .009) and photopic distance-corrected intermediate visual acuity at hour 8 (3.9 [0.44] vs 2.4 [0.45] letters; P = .01) and hour 10 (3.5 [0.46] vs 1.7 [0.47] letters; P = .004). No participants with mesopic DCNVA improvement of 3 or more lines at hour 3 had losses of more than 5 letters in mesopic, high-contrast, binocular-corrected distance visual acuity. The onset of effect was at 15 minutes. AGN-190584 demonstrated an acceptable safety and tolerability profile.
Conclusions and relevance: AGN-190584 demonstrated superiority over vehicle in mesopic DCNVA on day 30, hours 3 and 6, with an acceptable safety profile. AGN-190584 is a safe and efficacious topical therapy for presbyopia through 30 days.
PMID: 35238902
 


#138 ta5

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Posted 26 October 2022 - 02:20 AM

I'm so disappointed, Novartis has dropped Dioptin aka UNR844 after it failed phase 2b trial.

 

"Interim analysis of the Ph2b dose ranging study evaluating safety and efficacy in patients aged 45-55 years with presbyopia did not meet its primary endpoint of demonstrating a statistically significant dose response at Month 3. Based on these results, Novartis has taken the decision to discontinue the Ph2b study and UNR844 program"

 

:sad:



#139 Woody42

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Posted 26 October 2022 - 02:06 PM

My presbyopia first started bothering me about 6 years ago and I only need a very weak lens

I believe it's just a +1 and some days I could get by without them but about 2 years later I needed

them all the time.  Then about 3 years ago I started taking about 10mg of Lutein and 1mg of Zeaxanthin

a day. Now I notice I seldom need my reading glasses prehaps this is helping my presbyopia or

it could be those water fast I have done.   Oh one caution about Lutein. There was one case where 

a woman who was already eating a diet very high in these compounds started suplimenting with 20 mg

of Lutein a day. After quite a while doing this some Lutein deposits were observed on the back of her 

eye but cleared up after discontinuing the supliment.  


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#140 korpesh

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Posted 27 October 2022 - 12:28 AM

So what does that mean with UNR844? If Novartis drops it, can another company potentially start making it, or does the knowledge and legal ability to make the drops just die for all time in some Novartis warehouse now? Weird that there seemed to be prior tests from the originating Encore company that showed it did work, and now it's just suddenly all over with.


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#141 korpesh

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Posted 03 November 2022 - 11:11 AM

So I don't know if someone can orchestrate a group buy, but the LACE substance is available through this medical lab (pricing provided). https://www.medkoo.com/products/12288 They will not sell to anyone who isn't a medical or educational "research" company (or can convince them they are), but I'd be up for contributing to the purchase, if anyone can get it from them. Looks like we'd just need to dissolve the LACE in DSMO and then add saline to basically have the eye drop.



#142 ta5

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Posted 26 October 2023 - 01:16 AM

Nagashima H, Sasaki N, Amano S, Nakamura S, Hayano M, Tsubota K.

Oral administration of resveratrol or lactic acid bacterium improves lens elasticity.

Sci Rep. 2021 Jan 26;11(1):2174.

Hayato Nagashima, Nobunari Sasaki, Sachie Amano, Shigeru Nakamura, Motoshi Hayano, Kazuo Tsubota

A decrease in the elasticity of the ocular lens during aging is associated with loss of the accommodative ability of the eye, leading to presbyopia. Although near vision impairment is a social issue affecting the length of healthy life expectancy and productivity of elderly people, an effective treatment to improve near vision has not yet become available. Here we examined the effect of Enterococcus faecium WB2000, Lactobacillus pentosus TJ515, and resveratrol on lens elasticity in rats, where the stiffness of the ocular lens increases exponentially during the aging process. A combination of WB2000 and resveratrol improved lens elasticity not only in the long term but also with just short-term treatment. In addition, TJ515 decreased stiffness in the eye lens with long-term treatment. Therefore, the oral administration of WB2000 and resveratrol or TJ515 may be a potential approach for managing the progression of near vision impairment.
PMID: 33500490

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#143 ta5

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Posted 26 October 2023 - 01:36 AM

Delanghe JR, Beeckman J, Beerens K, Himpe J, Bostan N, Speeckaert MM, Notebaert M, Huizing M, Van Aken E.

Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia.

Int J Mol Sci. 2023 Apr 16;24(8):7343.

Presbyopia is an age-related vision disorder that is a global public health problem. Up to 85% of people aged ≥40 years develop presbyopia. In 2015, 1.8 billion people globally had presbyopia. Of those with significant near vision disabilities due to uncorrected presbyopia, 94% live in developing countries. Presbyopia is undercorrected in many countries, with reading glasses available for only 6-45% of patients living in developing countries. The high prevalence of uncorrected presbyopia in these parts of the world is due to the lack of adequate diagnosis and affordable treatment. The formation of advanced glycation end products (AGEs) is a non-enzymatic process known as the Maillard reaction. The accumulation of AGEs in the lens contributes to lens aging (leading to presbyopia and cataract formation). Non-enzymatic lens protein glycation induces the gradual accumulation of AGEs in aging lenses. AGE-reducing compounds may be effective at preventing and treating AGE-related processes. Fructosyl-amino acid oxidase (FAOD) is active on both fructosyl lysine and fructosyl valine. As the crosslinks encountered in presbyopia are mainly non-disulfide bridges, and based on the positive results of deglycating enzymes in cataracts (another disease caused by glycation of lens proteins), we studied the ex vivo effects of topical FAOD treatment on the power of human lenses as a new potential non-invasive treatment for presbyopia. This study demonstrated that topical FAOD treatment resulted in an increase in lens power, which is approximately equivalent to the correction obtained by most reading glasses. The best results were obtained for the newer lenses. Simultaneously, a decrease in lens opacity was observed, which improved lens quality. We also demonstrated that topical FAOD treatment results in a breakdown of AGEs, as evidenced by gel permeation chromatography and a marked reduction in autofluorescence. This study demonstrated the therapeutic potential of topical FAOD treatment in presbyopia.

PMID: 37108506

 

Patent: WO2022189344A1 Treatment of eye diseases with fructosyl-amino acid oxidase


Edited by ta5, 26 October 2023 - 01:46 AM.

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