It is widely mentioned that due to elevated IOP, the Lamina Cribrosa starts bowing posteriorly, which in turn distorts the laminar beams and starts pinching the axons and thus triggers the apoptosis of the RGCs in glaucoma?
Can the above scenario be that simplistic ? We have to answer two main questions.
1). Chronic glaucoma can be caused even by elevation of 5-10 mmHg of IOP which is very insignificant compared the fact that partial pressure of CO2 of the normal exhaled air is around 35 mmHg with which we can’t even blow out a birthday candle. We have to use forced exhalation to do the job. It is hard to comprehend: how can an elevation just 10 mmHg of IOP will cause bowing posteriorly of multilayered rigid, densely packed with NFs LC with a 10mmHg pressure which is one third of normal exhaled air? Normal exhaled air can’t even move a thin sheet of paper. Is LC really that flimsy?
Is it our assumption or we have scientific data showing an elevation of even 20 or 30 mmHg resulting in bowing posteriorly of LC?
I am curious because we don’t see acute cupping occurring in acute glaucomas where the IOP is extremely elevated.
2). Even if I believed that LC is bowing posteriorly and thus triggering apoptosis: But the most puzzling question is, then, how is the apoptosis resulting in the orderly loss of NFs in glaucoma. Apoptosis is supposed to get rid of randomly occurring diseased cells. But in glaucoma we are talking about normal RGCs dying in an orderly sequence from peripheral to central, which will be out of scope of apoptosis.
Can some proponent of apoptosis theory kindly explain the bowing of LC by elevation of IOP and also how the apoptosis is resulting in the orderly loss of NFs in Glaucoma? Many thanks
Sir, some years back I attended the SSY-QOL program conducted by Allergan. The speaker shared with us a study conducted in UK which found that visual field defects in early Glaucoma are very random and so it’s not right to look for typical visual field defects. There are also some reports where VF defects occurred initially on 10-2 tests, while 24-2 tests were normal. This shows that it’s not correct to assume a characteristic pattern of VF loss in glaucoma.
Dr Imtiaz, what do you think of OCT images showing posterior bowing of the LC ?
Dear Imtiaz and Shoeb,
In some of the images the LC may appear bowing posteriorly but it will be variation, not true bowing. Bowing of LC has been assumed to conform to the cupping paradigm under which we are working since 1850s.
Since 2010, it is well documented that LC is displacing posteriorly from the very early stages of glaucoma. Therefore, it will be inconceivable that a loosened and detached LC while migrating posteriorly could also become bowed posteriorly especially with just a rise of about 10 mmHg of IOP. I don’t think LC is so flimsy and delicate that it will move back even with a small rise of IOP, yet it wouldn't move in cases of acute glaucoma when IOP is extremely elevated.
We have assumed so many wrong things in glaucoma to justify the cupping paradigm, given mistakenly 160 years ago. Biggest wrong assumption: glaucoma is considered as an optic neuropathy, in other words the NFs are being atrophied. Analogy: Leg is atrophied, not amputated.
In glaucoma the NFs are being broken or amputated. Proof of axotomy of NFs and its vasculature lies in front of own eyes.
All we need is to look at the glaucomatous disc in context of sinking LC and severance of NFs along with its vasculature. If someone can prove that NFs are in fact being atrophied and not being severed in glaucoma, then I will accept everything associated with cupping paradigm like bowing posteriorly of LC, cup/disc ratios and salute those ophthalmologists who gave us term cupping 160 year ago. Thanks
Dear shoeb,
In response to your question about Allergan speaker stating that visual field defects are very random in early glaucoma.
I don’t know in what context the speaker was mentioning the random field loss in glaucoma. There are one million NFs which are being destroyed (severed in my opinion). In the early stages their loss may not be 100% identical since we may not know which NFs are affected first given the amount of sinking LC and other variable factors.
For example, isolated scotomas are being produced in the paracentral area. There is no definitive pattern the way isolated scotomas are located in the begining, but bottom line is that the these isolated scotomas eventually coalesce to form superior and inferior arcuate scotomas or ring scotoma.
I can’t agree that in some cases of glaucoma the field loss is random while in other cases the field loss is orderly. If visual loss is both ways then the role of perimetry in glaucoma becomes meaningless.
Visual field loss in glaucoma can’t be both ways. It will be unscientific, Field loss is either random or orderly. Let us we all settle on this basic issue.
This week the German journal "Ärztezeitung" issued an article of some researchers describing they found T-cells on the retina of early glaucoma patients. Their hypthesis is, a short increase in IOP creates a hole/breakthough in the eye blood barrier and in result the formerly immunepriviliged tissue is invaded by immune cells. These cellls start attacking + damaging the retina then.Similar they expect for the brain blood barrier.
Dear Cord Timo Abbe, I would forget about finding T- cells in the retina in glaucoma subjects. They can be found in multiple diseases and can never be diagnostic of glaucoma. My question is simple: can apoptosis or in other words suicide occur in an orderly and predictable sequence. If the RGCs were dying randomly, as would happen if apoptosis was occurring then we wouldn't be doing perimetry in glaucoma. I don't think our RGCs are so smart that they will first perceive impending glaucoma then they would start committing suicide in an orderly and predictable way. Apoptosis can never occur in glaucoma. Science is not collection of assumptions.
DARC technology has clearly shown how appptosis of retinal ganglion cells occurs. Other studies have shown that the damage occurs more in the optic nerve head around the neuroretinal rim. As I mentioned before, a researcher from UK has shown that VF loss occurs randomly and patients start losing patches of their VF, not in an orderly manner to produce typical changes. Since Perimetry is done only by Humphrey and Octopus machines, we need to see if there is bias in these instruments. Just a thought.
My hypothesis” Scleral edge, not optic disc or retina is the primary site of injury in chronic glaucoma” was published in 2006. Nutshell of my hypothesis is that LC is sinking and as a result the prelaminar NFs along with vasculature are being stretched and broken. It can be proved or rejected very easily by present technology. If severance of NFs is not occurring then my hypothesis will be wrong. Why should we waste our time?
To me, the severance of NFs explains all the unanswered questions in glaucoma. Severance of NFs along with vasculature can explain, the orderly loss of NFs from peripheral to central, excavation (wrongly called as cupping), retrograde degeneration of RGCs ( wrongly called as apoptosis), loss of neurons in LGN ( due to wallerian-anterograde degeneration), glaucomatous field defects including sharply defined arcuate field defects and ronnie’s nasal step, sloping and kinking of blood vessel, splinter hemorrhages at disc margin, characteristic whitish pallor ( due to severance of vasculature), nasal shifting of central vessels (due to severance of NFs, normal-tension glaucoma, and histology of end-stage glaucomatous disc - empty crater devoid of NFs and vasculature (wrongly called as 100% LC) and other features of glaucoma. If someone does not agree or does not want to agree, then nothing I could do about it except to leave it to future generations.
Sir, for a hypothesis to become a law, it has to pass a lot of stages. I’m sure we will have a more clearer picture of glaucoma someday. But it’s not going to happen in the near future. Overall, your hypothesis is revolutionary.
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