All of us Vs Keratoconus


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Post Info TOPIC: Some thoughts


Executive

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Date: Fri Oct 6 5:09 PM, 2006
Some thoughts
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Hi,


a little chat with a friend from the french forum set in motion some thoughts that now seem to be well glued up. He mentioned the inflamatory theory of the KC. One element of this theory being that inflamatory molecules trigger specific enzymes synthesis in keratocytes and those enzymes destroy some of the extracellular matrix (ECM), some collagen and, probably what we call crosslinks. I took this element - the ability of keratocytes to feel something and to respond to this something in a specific biochemical way through the synthesis of the enzymes. Now, I had a bit different perspective in my mind, namely the structural weekness and softness of KC corneas as well as some well documented experimental finding of mutual drift or coagulation of collagen - as being given by Nature. Having these two elements in mind, namely that a) KC corneas are by nature structurally week, soft and b)that there is this drift or coagulation phenomenon, we can imagine the following picture. Any mechanical perturbation (say, a rub of the cornea,a wink) is detected by keratocytes. This is so for they "feel" in this way any mechanical or chemical perturbation on the epithelium. This is a scientific fact. So, this signal is much stronger in KC cornea than in a normal one because KC cornea is softer. What do they, keratocytes "feel"? They "feel" that their surrounding, namely the extracellular matrix, compriced of collagen fibres, proteoglican coating and crrosslinks, pushes them or even sqweezes. So being biological units, they wiil try to neutralise the aggressive agent, in their view - the extracellular matrix. The only means they have to do this, is the enzymes that accelerate destruction of extracellular matrix (keratocytes synthesize and destroy proteins that participate in ECM and as such regulate the turnover of collagen=destruction of the old and synthesis of the new which is in balance in normal cornea). So they synthesize more enzymes to destroy the elements that they "think" are dangerous for them. It may well be the crosslinks...So keratocytes destroy crosslinks through the synthesis of specific enzymes upon any mechanical perturbation of the week KC cornea. They do it faster than they synthesise the new one for there is no signal to synthesize the new one. Henceforth, cornea becomes even more week for it becomes devoid of some structural elements that are not newly synthesised for k_cytes do not "feel" they need it. So the destruction becomes more rapid than synthesis. Which further amplifies the mechanical sqweeze of the keratocytes that further feel they are in danger and synthesize more enzymes that destroy more crosslinks...So this is an example of what is called a positive feed-back circle or link. Now why C3R is effective? Because it reinforces the cornea a) more crosslinks b) it becomes more rigid and thus less sensitive to mechanical perturbations. And thus the keratocytes do not feel these perturbations as before and hence do not synthesize the enzymes that destroy the ECM. In this way the parazite positive feed-back link is broken and we may feel safer....In fact, it just came to my mind that the fact that C3R leads to absence of KC progression rejects the inflamation hypothesis of the KC: as mechanicaly the cornea is stable post C3R, if there was inflamation agent that perturbs the k_cytes, the enzymes would continue to destroy what C3R established and there would be no stabiity. But since there is stability, it means that there is no inflamatary agent... What do you think guys about all this stuff?


-- Edited by Yarsky at 18:47, 2006-10-06

-- Edited by Yarsky at 18:50, 2006-10-06

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yarsky


Executive

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Date: Sat Oct 7 4:10 PM, 2006
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In the same shot, having all that in mind, I think that KC - without the family form - is a random event in a ruther precise sens. That it is random - there is nothig neither surprising, nor extraordinary in that. But there is more light in that dark realm of randomness. Let's take the elasticity of our corneas as measured by recent instrument, the Ocular Respons Analizer. The result of the ORA measurment is a number around 11. In KC corneas it is less, abour 8. I think in there is of course a sort of maximum - after which the biological tissue is fragiile, and correspondingly a minimum - after which it is amorphe. So, imagine a utopian experiment that all of human population of the Earth is measured their corneal hysteresis with the ORA. So we would have about 6 milliards ORA readings, or 6 milliards numbers in the range, say 5 -15. The result of this experiment may be summed in the probability distribution of the ORA readings. I make a bet that it will be bell-shaped resmbling the gausian or the normal distribution centered on about 10. In the left wing of this distribution there will be us, the KCers. And why? Just because randomness is the very profound and ubitious feature of the Nature. By pure hazard our corneas are less elastic more soft than normal ones. This means that our keratocytes are less protected and being very "simple" biological units, they have a very simple goal - self-protection. And they start to generate more enzymes to destroy the "enemy", the ECM that sqweezes them. Which, by the way, means that there is no any biochemical mechanism in us, humans, that would reinforce organically such tissues as corneas. Can we in principal develop such a mechanism? Can we learn our keratocytes to respond differently on mechanical perturbations? Instead of generating enzymes to destroy the ECM, generate substances that would create more cross-links? I doubt it...Anyway, as I said, I think it is a pure hazard that some corneas are structurally weak. For it is very Natural to have deviations from the norm, it is the way the Nature works. Our deviation is that our corneas are weak in a certain sens. And there is no natural way to strengthen them.

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yarsky


Phase Two

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Date: Sat Oct 7 10:36 PM, 2006
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Sorry I did not respond to this sooner...


These are the things which I seem to have noticed so far from keeping "my ear to the ground"


The "Artemis" detects one in ten people tested with it to have kc (be it before it becomes a dectable "cone") also this is done in a laser center... so people are not as random as with testing the general public.


One in ten laser treatments fail due to a "weak" cornea (as they don't have the Artemis eye testing equipment).


About one in ten have a family member with kc (? or is a weak cornea common in lesser degree's in the general population!)


I think mechanical trauma to a eye which is "weak" can have an effect of "pinging" the cone to come out.


We know that left and right corneas are structurally distinct, and so why people usually has a "good" and "bad" Keratoconus eye.


From this study


http://www.iovs.org/cgi/content/abstract/47/3/901


We have heard of contact lens use before someone was diagnosed with kc (mechanical truma on a random weak cornea), also of things like itching and so eye rubbing deemed as not being a good thing to do in KC. Laser is another mechnical trauma, high eye pressure? may cause the cone to bulge out if you have a weak cornea (I should have write does, as doctors have said it does) 


So i don't think KC is not as "fendish" as people think. A weak cornea is common, a trigger causing the corneal structure to "fall like a pack of cards" ...and from that, as the cornea gets more from being flat... its suffers from lack of nourishment which it get's from under the cornea and from tears (because the surface of the eye is not regular)...


Dry eye (which a lot of kcers have) may mean that the "bad chemicals by-products" from the cornea do not get washed away and so weaking the cornea.


The thought that because a lot of down syndrom people have kc and so it must be a genetic disorder is flawed ... big time!!


I have heard of people with ME (a muscle waisting disoder) and other disorders which makes people with such conditions have "POOR EYE TO HAND CO-ORDINATION"... so when they rub their eye's ...they cause more trauma when they rub their eye then someone with good hand to eye co-ordination... and as we have said, that a weak cornea is common... so with this bad eye to hand co-ordination with this commoness of weak corneas... then you get different degrees of KC... and only the advanced cases going on to be classed as KC at hospital.


Alleries may trigger what you was saying Yarsky... in a self distruction sort of a way... when the enemy the pollen or another distubance is combated far too much by the bodies own defence ... we see that in so many disorders...


There are many... with flat kc... until the trigger/s happens... this may be why its proving very hard to pin point the gene/s in KC... as a weak cornea is common...  



-- Edited by QuintriX at 01:09, 2006-10-09

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Date: Mon Oct 9 7:50 AM, 2006
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Hi Yarsky,


Your thoughts are very interesting and I had to think them over and over again for a long time. Hence, I reply so slowly.


Your thoughts somehow explain why keratoconus occurs exactly everywhere around the world in 1/1000 cases (no matter race, ethnicity etc.). Surely, a bacteria, virus or genetic error does not really explain this statistical phenomenon because then we would see some kind of epidemic in some countries or an increase of keratoconus in some "closed" societies because of "genetic exchange"! As far as I know, none of this is true?


I can somehow accept the idea of "randomness", but still a very important question remains unanswered: Why does the progression of keratoconus suddenly stop if we almost have a so-called runaway progression?


Best regards, Jan



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Phase Two

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Date: Mon Oct 9 4:50 PM, 2006
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Jan that's true... as well as the question why do KC start ?...the question, why does KC stop ...need's to be looked in to as well...


For some people KC stops with the cornea spliting when "hydrops" occurs... for others Kc stops when mild...


Here is a study which shows KC is more common than people think... as its the advance stages which stats of the one in two thousand are made of.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15257000


Here is a topic, in which an island community, kc is found more... may be there is a genetic link or an enviromental one or even both together... I think there is two forces at play at least...


http://www.activeboard.com/forum.spark?forumID=48159&p=3&topicID=2345496



-- Edited by QuintriX at 16:55, 2006-10-09

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Executive

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Date: Mon Oct 9 4:54 PM, 2006
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Hi guys, very good question!


But what is the true statistics of the KC that has stopped naturally for sure and for ever?  70 out 100? 



-- Edited by Yarsky at 16:55, 2006-10-09

-- Edited by Yarsky at 16:57, 2006-10-09

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yarsky


Phase Two

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Date: Mon Oct 9 5:00 PM, 2006
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The other thing is that someone may have advanced Kc in both eyes... but can see good (from at least one eye) only because the advanced cone is not that much in the field of view... so people may think they got mild kc but its advanced... I think there has not been no record keeping done by Dr's who are quick to prescribe contact lenses with out giving us the facts or collecting data...


-- Edited by QuintriX at 21:32, 2006-10-09

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Date: Mon Oct 9 9:30 PM, 2006
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Dear friends,

In all, I can have read, there are two main hypothesises to explain why KC slow down with age and finally stops (over 50, it is rare to notice an evolution).
1) C3R effect. Cross-linking is a natural phenomenom with age. It is what is responsbile for the aging of the skin. So, with time, your eye is more and more cross-linked and KC slow down. This theory can be supported by two facts : the efficiency of C3R and that fact, cross-linking of the eye is also a consequence of diabetes and it is very rare to see someone who has got both diseases.
2) The other theory isKerotocytes aging. When keratocytes are aging, their receptors become less and less good and so our keratocytes are less sensible to environment agents.

Personally, I think the first one is very interesting.

Best regards and sse you soon.


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