Insulin eye drops to lower IOP and regenerate retinal ganglion cells
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16 months ago
bcdefg1 • 130
@bcdefg1

Has anyone used insulin to lower their eye pressure and to reverse vision loss per these articles?

https://coolblindtech.com/breakthrough-study-shows-insulin-eye-drops-could-restore-sight-of-glaucoma-patients/

and

Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury | Brain | Oxford Academic (oup.com) If so, could you please let us know how you did it and the results you got?

This article explains how to dilute insulin for eye drops with just water:

[https://patents.justia.com/patent/20110294730\]

iop:intraocular-pressure slt:selective-laser-trabeculoplasty insulin • 3.2k views
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Hello. This is very interesting topic. I read the link you provided, however didn't understand how to prepare this drops. Could you please share you experience with that

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I contacted a compounding pharmacy about making insulin eyes drops. They make AST drops. They are researching it but Their response to me was that drops could not be frozen and mailed so they would have a 3 day expiration date.

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I saw the human trial in Canada suspended (Pending regulatory authority clearance) . I also heard that some people have been trying the insulin eye drop but don't know whether it is effective. Can anyone share the experience? Or any side effect?

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This topic sounds very promising and hope someone has access to whatever is needed to make it work ASAP. I just posted what I had found but have not tried it. Sorry.

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2.7 years ago
JJ • 160
@jj

I am not a doctor or an expert, so this is my personal opinion from what I found online.

You need to know some chemistry to do it yourself. It would be safer and probably more effective if you could get a compounding pharmacy prepare it for you. Any doctor can write you a prescription if he believes it might help you.

Apparently insulin eye drops can be prepared by diluting plain, fast insulin with water in a 1 to 10 proportion, plus standard buffer substances so that the drops have the same pH and tonicity as the eyes. Then, an absorption agent or penetration enhancer such as polyoxyethylene-20-oleyl ether (0.5%, Brij93, Sigma-Aldrich) is added. They say that the absorption agent drives the insulin to the back of the eye where it feeds the optic nerve and makes it grow back again. This is the formulation they used in the study that restored part of the vision to the lab animals. This is a patent application filed in 2010 by a doctor who apparently used insulin eye drops to treat his glaucoma patients

https://patents.justia.com/patent/20110294730

It is a very long reading but for what I understand he apparently just diluted plain insulin with water in the proportion of 1 to 10. He says it is well absorbed through the conjunctiva:

“Our preliminary studies have shown that the conjunctiva, unlike normal skin may not act as a barrier for entry of insulin due to the paucity of the presence of reduced glutathione. It is likely that the conjunctiva hardly contains any insulin blocking agent. The insulin deposited in the conjunctival sac is rapidly absorbed and reaches the trabecular meshwork and the ciliary body without being inactivated to exert its therapeutic effect.”

He says he added penetration enhancers to make them more effective and also to reach all the way into deeper eye tissues such as the retina so that the insulin can help restore retinal function:

“transconjunctival penetration of insulin and therapeutic, pharmaceutical, biochemical and biological agents or compounds can be facilitated by enhancers that can be used to further expedite the entry of these agents into the anterior chamber, trabecular meshwork, ciliary body, choroid and retina. With these enhancers, macromolecules up to 10 kDa are able to pass through the conjunctival sac layers of the eyes reaching the site of glaucoma where the blood vessels and retina are undergoing pathological changes.”

This, he adds “can increase the cell population; … and alleviate glaucoma related to this pathophysiology of trabecular meshwork cell loss and restores retinal function.” And “may prevent the progression of this disease by improving the retinal physiology to normalcy due to insulin trophic effects.”

He explains: “Preparation of Insulin Drops Take 100 units of rapid or intermediate acting insulin (or IGF-1) and dilute in 10 ml of sterile saline or distilled water or other carriers and facilitators as described above. The pH can be adjusted to prevent the sting when dropped to the conjunctival sac. Nanograms or micrograms of local anesthetics may be added to prevent stinging. In this preparation each ml contains 10 units of insulin…each drop contains 0.5 units of insulin.

The concentration of the insulin content can be increased to 0.75, 1.00, 1.5, or 2.00 units of insulin per drop by increasing the insulin content in the dilutant preparation. It can be also decreased by reducing the insulin units used for the preparation of the ophthalmic drops. The eye drop preparation should be isotonic with blood. As will be the ophthalmic compositions intended for direct application to the eye will be formulated so as to have a pH and tonicity which are compatible with the eye. This will normally require a buffer to maintain the pH of the composition at or near physiologic pH (i.e., 7.4) and may require a tonicity agent to bring the osmolality of the composition to a level at or near 210-320 millimoles per kilogram (mOsm/kg).”

He says that insulin eye drops can be used along with any other glaucoma eye drops and that doing it allows to reduce their dosage. The treatment seems to be very safe and to produce no side effects in the animals. I understand that it can be legally prescribed by any doctor and prepared by any compounding pharmacy that prepares custom-made eye drops because the only ingredient that needs government approval is the insulin, which has been approved by the FDA many years ago. Let us know if you try and what results you see.

Best luck!

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Hello JJ ! Thank you for detailed reply. I personally digging this topic for the last few month and find it very promising. Did you tried insulin drops? If yes, what's your result?

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2.4 years ago
JJ • 160
@jj

I have not tried it but would love to. It appears to be safe. However, I need to know what type of insulin and absorption enhancer they used. If anyone here knows it, please let us all know.

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Based on the patent it is insulin with distilled water 1:10. Need to have pure insulin and adjust PH before using. Absorption enhancer is optional by my understanding. The difficult part is to get pure insulin as well as to adjust PH. If PH is not right it will harm the cornea.

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Insulin might turn out to be the simplest and most efficient way to beat glaucoma, Alzheimer’s disease (AD) and other neuro-degenerative diseases, when delivered in an efficient manner.

From what I understand, the nerve cells and other tissue cells become insulin resistant in these diseases. This commonality with diabetes leads people with diabetes to have twice the risk of having glaucoma compared to people without diabetes. There seems to be also a connection between diabetes and AD.

This is why some researchers say that diabetic complications within the eye is the manifestation of type IV diabetes of the eye and Alzheimer's disease is a manifestation of type III diabetes of the CNS.

In plain Diabetes Type II, the patient’s body cells are resistant to insulin. This means that they do not take in glucose from the blood at normal blood insulin levels. As a result, the cells become weak and ill and glucose levels rise in the blood. When the patient adds extra insulin his body cells take the glucose in and work more normally.

The trabecular mesh (TM) and the retinal ganglion cells seem to be insulin resistant in certain types of glaucoma. As a result, they often cannot use glucose efficiently or resist the stress of even mildly elevated intraocular pressure. Then they get weaker over time, don’t perform well and eventually die, destroying the vision in that part of the eye.

Insulin eye drops seem to offer two important potential benefits for glaucoma patients while causing no serious side effects when properly formulated.

The first benefit is that insulin spreads around the inner front part of the eye (anterior chamber) where it reaches the TM. Insulin energizes the TM cells that are still alive, whether healthy or diseased, and leads them to improve their performance. This allows more aqueous to leave the eye thus lowering the IOP. This effect alone would be an important benefit to us because it could allow us to reduce or eliminate the current eye drops which often cause serious side effects.

The second potential benefit of insulin in the glaucomatous eye is even more exciting. If the insulin eyedrops are accompanied by an appropriate absorption agent, then they also travel all the way to the back of the eye (posterior chamber) where they resuscitate dying and diseased retinal ganglion cells (RGC) the same way they do the TM cells. When this is done on a regular basis, the nerve cells associated to these RGC get rejuvenated and start growing back the components they had lost when previous RGC had died. New dendrites and synapses are formed and the eyes gets reconnected to the brain as they were before the glaucoma damage occurred.

These two effects were confirmed on lab animals in the Canadian study. Let us hope the researchers demonstrate that the same benefits happen in humans in the Stanford study that is about to start.

I’d participate in the trial if I could qualify. Dr. Di Polo said in her Oct. 28, 2021 webinar that the trial was going to start very soon at Stanford under the supervision of Dr. Jeff Goldberg (1-650-723-6995) I guess that people interested in enrolling could ask there when and how to apply.

I imagine the eyedrops need to be isotonic and isomolar with the tears. I presume that a standard Hank solution would do it. People familiar with lab work know how to make it with simple, inexpensive ingredients, and so do compounding pharmacists. The problem that compounders have is that they are limited by law to making only what you can use in just a few days unless they add a preservative...I'd not use them with BAK.

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https://clinicaltrials.gov/ct2/show/NCT05206877

The clinical trial under Stanford will start soon. They will recruit volunteers.

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Thanks JJ. Some friends plan to buy insulin and make it themselves. Is there any way to get pure insulin in US? These friends plan to hire a pharmacist to do the work. Once the process is clear,they can make it themselves. Without BAK one may have to make the insulin eye drop every day.

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Hi Sherry, are your friends still planning to do it?

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2.4 years ago
joannemarion • 30
@joannemarion

I just wanted to let everyone know that I am being considered for the clinical trial of the insulin drops at Stanford. It seems that they will do an initial evaluation and then 5 days of drops in the most affected eye and then a follow up. It's starting at the beginning of next month and they need 32 participants. If anyone is in the bay area and interested they can call Esther at 650-487-5883 or 805-757-4984 I will keep you posted! Joanne

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I am happy to report that this trial is open again and is accepting new patients. It is being conducted in Stanford.

Topical Insulin for Glaucoma - Full Text View - ClinicalTrials.gov

This is not official but I have heard from a reliable source that there is still room for a few more people to enroll in the Stanford clinical trial of insulin eye drops for glaucoma. This trial is testing the most promising glaucoma treatment I have ever read about. In lab animals with glaucoma-like vision loss, insulin regenerated their lost optic nerve cells and the animals recovered their vision. This is the first time ever this has been achieved. If the Stanford trial succeeds and leads to a widely available treatment, it could help most of us and millions of people all over the world.

The sooner they enroll all the study participants they need and complete the trial, the sooner we will know if this treatment works on humans also and the sooner it can be made available to all patients who need it.

I believe that if you contact the trial organizers between now and the middle of February, you have a good chance of getting in. It is easy to qualify. If you have glaucoma and don’t have diabetes, you are probably going to be admitted. They cannot enroll people who suffer from diabetes because the drug is insulin and can conflict with the type of insulin they may be using. Pre-diabetics seem to be OK.

You don’t need a doctor referral to enter this trial. All you need to do is write to the trial coordinator and ask for instructions. The contact email on the clinicaltrials.gov web site is outdated and messages sent there don’t go anywhere. The actual email address for the trial coordinator is mcsalud@stanford.edu

This trial requires going to Stanford for about 4 hours on the first day and 2 hours on the second day, then returning one day for another 4 hours 4 weeks later, and then another day for 4 hours 8 weeks later. For this reason they prefer people who live close to the San Francisco Bay Area, or who can easily travel there 3 times within 2 months and will keep their appointments.

This is the third part of phase 1 testing for safety. There is no control group, so everybody gets insulin in their eye drops. I would not be concerned about safety. The trial uses commercially available insulin for sale in any pharmacy. Insulin has been used by people for 100 years. Every day countless people use doses much larger than the drop they use in this trial. I understand that the glaucoma patients that have already gone through this trial did not have side effects. Also, our FitEyes member Richard Yoshioka posted on Mar 6, 2022 that he had been using plain insulin in his eyes for 2 years and has not noticed any problems.

When the safety trials are completed, they will go to the phase where they will add an absorption enhancer. This helps the insulin go to the retina, where it is expected to enhance the beneficial effects of the insulin on vision. I believe that if you participate in this safety phase and follow their instructions that they would give you priority to enroll in the following phase. I’m optimistic that this treatment can be made available to the public soon because it is not a new drug that will need to be tested for years first.

I believe that the trial won’t charge participants anything for the treatment, and that most insurance will cover the labs and tests they might order. You might want to ask your doctor and your insurance company about enrolling in this trial. Good luck!

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