Can MDG and/or ocular surface inflammation lead to aqueous deficiency?

[Milo007]

Yep, on amazon for 300 bucks. Bought a tachometer also to make sure it’s spinning correctly.

That's pretty geeky and cool!

Great information!

By the way you bought a centrifuge?

Yep, on amazon for 300 bucks. Bought a tachometer also to make sure it’s spinning correctly.

[Milo007]

Sodium citrate is sometimes used in the prp drops to prevent coagulation. Otherwise, you cannot freeze them or shake them. I have never used PRP before. I’m curious if I would have an issue with the sodium citrate.

If serum drops are working for you fine I doubt if there's a need to try PRP drops anyway!

[Milo007]

The molecule I believe you’re speaking about is TGF-B1. It’s found at 5x higher concentration in blood serum than in tears and it’s an inhibitory growth factor. Too large a quantity, could prevent epitheliazation.

So here’s what I’ve discovered. The original study used a low centrufugation speed 500-800rpm for 30 minutes. This resulted is high levels of TGF-B1 so it was diluted to 20% concentration with saline to counter that issue. however, this can be avoided by using a sharp centrifugation 3300-4000rpm for 15-10 mins respectively. When samples were assayed for TGF-B1, it was found that no dilution was required at those speeds.

In addition, a minimum 120 minute clot time and dilution (if preferred) with a balanced salt solution as opposed to saline, supported better cell migration and cell differentiation.

https://www.ncbi.nlm.nih.gov/m/pubmed/15756576/

UIC spins my serum at 4000rpm for 11 mins. I spin mine at home at 3300 for 16 mins. I do not dilute my serum.

Great information!

By the way you bought a centrifuge?

Well I read that article again and there's not much to worry if you don't have systemic inflammation of any kind. When you have systemic inflammatory conditions such as sjogren's syndrome or lupus or rheumatoid arthritis your blood serum contains elevated levels of pro inflammatory cytokines, chemokines, T-cells and other inflammatory mediators. Administering serum drops to the ocular surface in such cases would mean subjecting the ocular surface to more and more inflammatory mediators via serum drop instillations. Hence the use of serum eye drops is contradictory ONLY for patients with systemic inflammatory diseases.

PRP and autologous serum drops are basically the same thing and the only difference is that the latter is mixed with a sterile saline solution to match the osmolality of the ocular surface. PRP on the other hand is just the platelet rich plasma obtained when RBCs are isolated from whole blood via centrifugal action. PRP is one of the raw ingredients of autologous serum drops.

Sodium citrate is sometimes used in the prp drops to prevent coagulation. Otherwise, you cannot freeze them or shake them. I have never used PRP before. I’m curious if I would have an issue with the sodium citrate.

Very rightly said. I agree with your point on the reaction to artificial tears. Indeed I have noticed reaction to the ointment bases when I was on antibiotic ointments for two months. Same is the issue with artificial tear substitutes. I think in this area moisture chamber glasses and/or googles can make a huge difference since for MGD patients it significantly reduces the frequency of instillation of artificial tear drops making the patient less likely to develop an allergy. But for patients with aqueous deficiency I think the frequency of instillations would still be considerably more even while using MCG relative to MGD patients and that's where we need the most close substitute to natural tears to avoid allergy.

But even then I am more hopeful of a lacrimal gland regeneration (that has been achieved successfully recently and is under further trial) and transplant that would be the absolute best choice one can opt for.

Regarding salivary gland transplantation it is quite an efficient procedure and I have read that they use radio surgery to transplant the salivary glands. The results are very promising and patients almost get off artificial tears completely after the surgery. In India in the L. V. Prasad Eye Institute there have been quite a few salivary gland transplantations with great success. But there's one catch - since they are responsive to visual and olfactory stimulus your eyes would water like your tongue would do when you are served a delicious platter of food!

Not bad for a gain right?

Regarding use of blood serum eye drops have you considered the fact that blood serum contains pro inflammatory molecules that can actually cause or exacerbate inflammation?

The molecule I believe you’re speaking about is TGF-B1. It’s found at 5x higher concentration in blood serum than in tears and it’s an inhibitory growth factor. Too large a quantity, could prevent epitheliazation.

So here’s what I’ve discovered. The original study used a low centrufugation speed 500-800rpm for 30 minutes. This resulted is high levels of TGF-B1 so it was diluted to 20% concentration with saline to counter that issue. however, this can be avoided by using a sharp centrifugation 3300-4000rpm for 15-10 mins respectively. When samples were assayed for TGF-B1, it was found that no dilution was required at those speeds.

In addition, a minimum 120 minute clot time and dilution (if preferred) with a balanced salt solution as opposed to saline, supported better cell migration and cell differentiation.

https://www.ncbi.nlm.nih.gov/m/pubmed/15756576/

UIC spins my serum at 4000rpm for 11 mins. I spin mine at home at 3300 for 16 mins. I do not dilute my serum.

[Milo007]

I'm aware of this being an issue for whole blood (as used with fingerprick autologous blood). Wasn't aware it was an issue for spun serum though. Do you know how PRP and autologous serum compare in this aspect?

Well I read that article again and there's not much to worry if you don't have systemic inflammation of any kind. When you have systemic inflammatory conditions such as sjogren's syndrome or lupus or rheumatoid arthritis your blood serum contains elevated levels of pro inflammatory cytokines, chemokines, T-cells and other inflammatory mediators. Administering serum drops to the ocular surface in such cases would mean subjecting the ocular surface to more and more inflammatory mediators via serum drop instillations. Hence the use of serum eye drops is contradictory ONLY for patients with systemic inflammatory diseases.

PRP and autologous serum drops are basically the same thing and the only difference is that the latter is mixed with a sterile saline solution to match the osmolality of the ocular surface. PRP on the other hand is just the platelet rich plasma obtained when RBCs are isolated from whole blood via centrifugal action. PRP is one of the raw ingredients of autologous serum drops.

[Milo007]

So after having the procedure done, I could carry some food around in my pocket and have a sniff of it when my eyes feel dry? Sounds good!

LOL......excellent thinking!

But in practice one can lightly press the the glands to make the glands secrete saliva. But this is usually not needed since salivary glands are active throughout your life!

[quattroboy]

Even the NHS mentions salivary gland transplantation as an option

https://www.nhs.uk/conditions/dry-eyes/treatment/

Not sure whether it's actually been done but I'd be up for it!!!

[Meibum Ian]

Regarding use of blood serum eye drops have you considered the fact that blood serum contains pro inflammatory molecules that can actually cause or exacerbate inflammation?

I'm aware of this being an issue for whole blood (as used with fingerprick autologous blood). Wasn't aware it was an issue for spun serum though. Do you know how PRP and autologous serum compare in this aspect?

[Meibum Ian]

Regarding salivary gland transplantation it is quite a efficient procedure and I have read that they use radio surgery to transplant the salivary glands. The results are very promising and patients almost get off artificial tears completely after the surgery. In India in the L. V. Prasad Eye Institute there have been quite a few salivary gland transplantations with great success. But there's one catch - since they are responsive to visual and olfactory stimulus your eyes would water like your tongue would do when you are served a delicious platter of food!

Not bad for a gain right?

So after having the procedure done, I could carry some food around in my pocket and have a sniff of it when my eyes feel dry? Sounds good!

[Milo007]

Well, from my understanding they can place a salivary gland where your lacrimal gland was. Not sure how good the surgery is, but I know we’re already working on replacing the aqueous portion.

now , for the tear substitute. Everything you said is true. However, all things being equal, if I need to use an artificial tear, I’d rather it be the components of my real tears rather than a polymer. Yes it will be washed away, yes it’s not continuos flow, yes it will not replace our tears. But I’m not asking for that. I just want it to be a better option to artificial tears because artificial tears now, I react to all of them. My hope with a more natural artificial tear is to avoid a chemical reaction to the product. Hence why I only use my blood serum as an eye drop.

Very rightly said. I agree with your point on the reaction to artificial tears. Indeed I have noticed reaction to the ointment bases when I was on antibiotic ointments for two months. Same is the issue with artificial tear substitutes. I think in this area moisture chamber glasses and/or googles can make a huge difference since for MGD patients it significantly reduces the frequency of instillation of artificial tear drops making the patient less likely to develop an allergy. But for patients with aqueous deficiency I think the frequency of instillations would still be considerably more even while using MCG relative to MGD patients and that's where we need the most close substitute to natural tears to avoid allergy.

But even then I am more hopeful of a lacrimal gland regeneration (that has been achieved successfully recently and is under further trial) and transplant that would be the absolute best choice one can opt for.

Regarding salivary gland transplantation it is quite an efficient procedure and I have read that they use radio surgery to transplant the salivary glands. The results are very promising and patients almost get off artificial tears completely after the surgery. In India in the L. V. Prasad Eye Institute there have been quite a few salivary gland transplantations with great success. But there's one catch - since they are responsive to visual and olfactory stimulus your eyes would water like your tongue would do when you are served a delicious platter of food!

Not bad for a gain right?

Regarding use of blood serum eye drops have you considered the fact that blood serum contains pro inflammatory molecules that can actually cause or exacerbate inflammation?

Dowork123

I am afraid even if we can synthesize a perfect substitute of our natural tears it won't be of use since the mechanical action of spreading the lipid layer over aqueous layer of the tear film needs continous and controlled delivery of lipids onto the lid margins that won't be the case with artificial instillation of tear drops even if it had ALL the components of natural tears including meibum. Such a tear drop would be drained away within minutes through the tear ducts and you would need to keep on instilling artificial tears every 10-15 minutes to be asymptomatic.

FURTHER more an artificial tear drop replicating the exact composition of natural tears would be hopelessly expensive to produce that won't be a feasible solution at all.

This is the reason why Dr. Korb says the incredible role of the meibomian glands can NEVER be substituted by any means let alone artifical tear drops.

For me the only hope is meibomian gland regeneration or tissue engineering to reproduce meibomian glands somehow and then transplant them. I would like to mention that a group of scientists had already reproduced a fully functional lacrimal gland using tissue engineering under laboratory conditions. Sounds fascinating?

Well, from my understanding they can place a salivary gland where your lacrimal gland was. Not sure how good the surgery is, but I know we’re already working on replacing the aqueous portion.

now , for the tear substitute. Everything you said is true. However, all things being equal, if I need to use an artificial tear, I’d rather it be the components of my real tears rather than a polymer. Yes it will be washed away, yes it’s not continuos flow, yes it will not replace our tears. But I’m not asking for that. I just want it to be a better option to artificial tears because artificial tears now, I react to all of them. My hope with a more natural artificial tear is to avoid a chemical reaction to the product. Hence why I only use my blood serum as an eye drop.

[Milo007]

You and every dry eye doc in the world wants to know how this works lol. What I’m saying is, even the professionals have very little to work with in regards to how this is happening. That’s why the doctor I see now took a bunch of tears from me to look at T cells, cytokines, chemokines, and he took another vial I totally forgot what for. But I think they’re tracking these inflammatory markers to see how the disease and the treatment effect inflammation and vice versa. There are so many inflammatory markers other than T cells, my god where do you begin. Way over my head. I just hope someone figures this out soon.

The new reports on Lacritin sound promising. My hope is we get more new drugs/drops coming out the mimic the tear film and reduce inflammation safely AND effectively. I would love prescription artificial tears that mimicked our own tears. I think someone provided a study that showed over 200 components in human tears. The Australians did the analysis I believe. Would love to see that drop come out.

Dowork123

I am afraid even if we can synthesize a perfect substitute of our natural tears it won't be of use since the mechanical action of spreading the lipid layer over aqueous layer of the tear film needs continous and controlled delivery of lipids onto the lid margins that won't be the case with artificial instillation of tear drops even if it had ALL the components of natural tears including meibum. Such a tear drop would be drained away within minutes through the tear ducts and you would need to keep on instilling artificial tears every 10-15 minutes to be asymptomatic.

FURTHER more an artificial tear drop replicating the exact composition of natural tears would be hopelessly expensive to produce that won't be a feasible solution at all.

This is the reason why Dr. Korb says the incredible role of the meibomian glands can NEVER be substituted by any means let alone artifical tear drops.

For me the only hope is meibomian gland regeneration or tissue engineering to reproduce meibomian glands somehow and then transplant them. I would like to mention that a group of scientists had already reproduced a fully functional lacrimal gland using tissue engineering under laboratory conditions. Sounds fascinating?

[Milo007]

I am curious how that works. T-cells are on the eye surface, I wonder how the lacrimal gland gets into the cycle. Assuming it is not originally inflamed from Sjogren’s.

update: this study induced desiccating stress in mice* resulting in Sjogren-like symptoms though T-cell activity. Lots of medical jargon but the example they have mentioned is people with medically induced dryness who do not get better after stopping the medication. You could expand it to MDG, same idea.




*Side note

I absolutely hate experiments on animals. Science and all is not worth it for me personally. Knowing how painful/uncomfortable DED can be, I feel so sorry for these poor creatures. Born to be ok for a few weeks and miserable until the day experimenters kill them. I get they want to control their variables, but I think it would be just as appropriate to recruit people who are already on drying meds and observe them after they quit. Harder, yes. More expensive, yes. Exponentially more ethical, absolutely yes. Plus humans and other animals do not have identical lacrimal units.

hopeful_hiker

Inflammtory mediators can reach the lacrimal gland through the same channels as as drugs like restasis or xiidra or steroids do. How do you think a drop of restasis or xiidra instilled on the ocular surface is supposed to reduce the inflammation of the lacrimal glands if they don't reach the glands?

The inflammatory markers can flow with the residual tear to the lacrimal glands causing inflammation there. Remember punctal plugs are contradictory to the use of restatis or xiidra? In the website of restasis it's mentioned that restasis didn't work on those who had punctal plugs inserted. This indicates the tear ducts might have a channel to the lacrimal glands and blocking the tear ducts prevents the delivery of restasis, xiidra or steroids to the lacrimal glands.

I agree with Dowork123 that inflammation damages all parts of the system and left untreated MGD will translate to lacrimal dysfunction or vice versa.