Large diameter ganglion cells are more susceptible to raised IOP. Such ganglion cells are more predominant in inferotemporal area and then in superotemporal region. The axons of these ganglion cells occupy the central part of inferior and superior parts of the disc respectively. Since these are damaged in the initial stages, the axons central part of inferior and superior disc are lost leading to notch. Other optic nerve diseases do not usually cause such selective ganglion cell damage in early stages, and most of them are acute in nature with generalised damage.

Your answer about notching is very interesting, which you believe is due to loss of axons pertaining to large diameter cells or magnocellular ganglion cells. It is new to me that they are destroyed in the early stages of glaucoma being more susceptible to raised IOP. Is it your theory or there are published articles supporting this phenomenon? I would appreciate if you would kindly guide me to locate these studies

I think the nerve fibers in inferotemporal and superotemporal region of the disc belong to arcuate fibers. If you agree then it would imply that arcuate axons belong to magnocellular ganglion cell bodies and that is why they are selectively destroyed in glaucoma. In fact the peripheral vision fibers are destroyed first in the early stages of glaucoma so do you think magnocellular gangion cells are present in the peripheral retina as well?

As we know the nerve fibers in glaucoma are always being destroyed in an orderly fashion starting with peripheral fibers and ending with central. Never randomly. Your statement of more susceptibility of magnocelluler ganglion cells to IOP would raise more puzzling questions. It would imply that RGCs are being destroyed in glaucoma from the peripheral to central because of their varying degree of susceptibility to IOP. Can you please clarify as I am very confused about your reply. Many thanks

There is another, alternative explanation for this phenomenon. It may well be that simply the lamina cribrosa is weaker at these locations, and may suffer a "fracture" due to raised IOP.

see reference below.

2013 Mar;131(3):314-20. doi: 10.1001/jamaophthalmol.2013.1926.

Focal lamina cribrosa defects associated with glaucomatous rim thinning and acquired pits.You JY, Park SC, Su D, Teng CC, Liebmann JM, Ritch R.

If notching is due to fracture of the weak lamina cribrosa resulting from raised IOP then why is fracture occurring in NTG when the IOP is within the normal range?

My hypothesis that notching in the superior and inferior poles of the disc are produced due to severance and depletion of the arcuate fibers have been endorsed and confirmed by a recent article from Saudi Arabia. Link is at the end.

Nerve fibers are being severed, not atrophied in glaucoma is the nutshell of my hypothesis. Analogy: Leg is not atrophied but amputated.

I believe the ‘severance of the nerve fibers along with its vasculature’ is the missing wild card in the mystery of glaucoma, and it should answer all the unanswered questions in glaucoma.

You will find following citation on page 1947 with reference 32.

“ The vertical elongation of the optic disc observed here is thought to be due to severance and depletion of the superior and inferior arcuate fibers, which occurs in the early stages of glaucoma” P 1947 Ref: 32

“It also confirms that the severance of the nerve fibers and excavation of the disc are unique features of glaucoma." ref;32 page1947

32. Hasnain SS. Scleral edge, not optic disc or retina is the primary site of injury in chronic glaucoma. Med Hypotheses 2006;67(6) 132-1325

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792954/

focal notching is typical of normal IOP glaucoma, it has been demonstrated that there is a fracture of the lamina cribrosa at that location, and the glaumatous damage tends to be symmetrical in both eyes (i dont mean that both eyes do develop the damage simultaneously, but that the damage affects the same hemifield first in both eyes).

All theses proven facts are consistent with the hypothesis that focal glaucoma occurs because there is a predisposition of the ONH (lamina cribrosa) to suffer it, that is why only moderate increases of the IOP do induce damage (in other words, not every eye has the susceptibility to develop this kind of damage, and that "weak lamina cribrosa" is inherited, because the susceptibility to develop the focal damage in always bilateral, and quite symmetrical in terms of the first hemifield to show damage.

On the other hands, this would explain why some eyes do have a "resistant" lamina cribrosa, and can withstand elevated IOPs for a long time.

I call this ONH property as "optic nerve head vulnerability to glaucomatous damage", which has two aspects, a) which type of damage a ONH can develop (focal, myopic type, diffuse cup enlargement) and the amount of the damage in response to increase IOP.

This variety of types of glaucomatous optic nerve damage are better explained, in my mind, with ONH centered explanations than with RGC centered ones.

Miguel, Thank your for your response. It appears that you strongly believe that Lamina Cribrosa(LC) is the primary site of injury. You are among the majority who have similar views. According to Thomas Kuhn, a great philosopher of science says in his famous book “ Structure of scientific revolutions” that science works under some kind of paradigms.

At present the glaucoma research is being done under cupping disc paradigm given 150 years. Ago. Kuhn also says that the paradigms once get established (even if wrong) never die of their own death or are self corrigible. There is no such thing as self- falsification, on the contrary we would find things to fit into the wrong paradigm. Established paradigms only die when they are confronted with an alternate paradigm available to compete, where scientists can compare and contrast the old and new paradigms and decide which one is more appropriate. For example Geocentric -paradigm could not be self-falsified or self- corrigible for almost 1400 years until Coppernicus offered an alternate Sun-centered paradigm.

Now we have two paradigms in glaucoma: old cupping/atrophy of nerve fibers paradigm and new sinking disc/severing of nerve fibers paradigm. Only time would tell which paradigm is going to succeed. Nevertheless, we would have at least second look at the cupping paradigm and if cupping found to be correct then we all would be happy.

Regarding the concept of cupping occurring in glaucomatous disc: honestly, I fail to understand what structure of the disc is really cupping, physiological cups or LC. According to Wolf’s anatomy the various sized physiological cups are produced due to varying degree of atrophy of the Bergmeister’s papilla, a tuft of hyaloid vessels. Cupping is defined as an enlargement of physiological cups. It is puzzling: why should a fibrous plate enlarge concentrically in response to raised IOP?

It is also stated that nerve fibers are present in the rim area only whereas the central cupped area is devoid of nerves. Unfortunately I have been unable to find a single histology having this doughnut shaped arrangement in any normal or glaucomatous disc. It supports Kunh’s philosophy that we would speculate things to fit into a paradigm even if it is basically wrong.

Returning to subject of Lamina cribrosa. We should always keep in mind the fact that in glaucoma the peripheral fibers are always invariably destroyed first and the central at the last. How is it possible that any pathology within the LC (pore size/ focal defects/posterior bowing) can to so precise and perfect that would always result in in the destruction of peripheral fibers first and central at the end in an orderly fashion. If the answer is NO: then LC could never be the primary site of injury in Glaucoma .

Bottom line of my hypothesis: the nerve fibers along with its vasculature are being severed, not atrophied. Analogy: leg is amputated, not atrophied.

For details you may visit my facebook.

https://www.facebook.com/pages/Glaucoma-Paradigm-Shift-Project/516804278413418

Are we on Right Path in Glaucoma?

For discussion on sinking disc/ severance of n fibers and vasculature in glaucoma you will find  articles, images on glaucomaparadigmshift.com   Thanks