Respected Doctor i went through the literature and found something which might give some answer to your query, like to share with :-

According to current physiological

knowledge, the microvessels in the pre-

laminar region of the optic disc lack

classical blood–brain barrier properties

and display non-specific permeability

(Hofman et al. 2001).

Simultaneous increase of ET-1 and

MMP-9 in the surrounding tissue of

retinal vessels may lead to an impair-

ment of the blood–retinal barrier at the

border of the optic disc. A leakage in

the area of the optic disc has indeed

been demonstrated in fluorescein

angiograph.

Ref:- http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0420.2005.00590.x/pdf

Dear Dr. Farah,

Thank you for your comments. I believe LC is detaching and sinking in the scleral canal with a result that nerve fibers and its vasculature are being stretched and broken (severed) at the scleral edge (mechanical problem). Sloping /Kinking of the vessels at disc margin are indicative that LC may be sinking, not cupping in glaucoma. I hypothesize that sinking of the LC is due to atrophy of the border tissue of Elschnig resulting from chronic ischemia induced due to high IOP in HTGs whereas due to poor systemic circulatory problems in NTGs.

Do we have any evidence of severance of the nerve fibers and its vasculature?

I believe there is ample evidence provided we look at the glaucomatous disc in context of severance, not cupping and atrophy of the nerve fibers.

Severance of the vasculature is resulting in splinter hemorrhages, whitish pallor and most importantly the characteristic baldness around the glaucomatous disc resulting from severance and thus disappearance of smaller vasculature.

The leakage in the area of the optic disc, which you have mentioned can also occur if the vessels are being severed.

Wedge shaped empty spaces in the retina and notching (localized excavation) in the superior and inferior part of the disc can only be explained due to severance and early depletion (being fewer in number) of the arcuate fibers, not due to their atrophy. Orderly destruction of retinal fibers from periphery to central fibers can only be explained by sinking disc/systematic severance of nerve fibers. Most importantly, the end-stage glaucomatous disc appears to be huge crater left over after severance of nerve fibers and may not be a cupped LC as believed.

In my opinion the mystery of glaucoma hinges on whether the nerve fibers are being severed or atrophied in glaucoma. If severance is indeed taking place then it should answer all the unanswered questions in glaucoma. My colleagues are the judge.

Dear Dr.syed we can generate any number of hypotheses .however there must be good scientific evidence to support the hypothesis.Can you please provide any good published evidence in peer reviewed journals either experimental or in humans .The researchers may then be able to view your hypothesis with interest and carry out research in this field.regards

Dear Puneet,

I fully agree with you that hypothesis is just an idea unless proven scientifically. However, all the scientific discoveries have originated with a different idea despite the fact that vast majority of new ideas are thrown in trash and my idea may be one of them but I consider worth trying.

I am a general ophthalmologist, an odd fish swimming against the stream. Although my hypothesis has not only been published in peer- reviewed journals but endorsed as well. However, I believe that the best peer-review is not accomplished by one dozen or so top notch editors but by entire ophthalmologists on this globe , thanks to the internet where now even an ordinary ophthalmologist like myself can freely express his ideas, an opportunity which unluckily was not available to my predecessors.

My hypothesis is straightforward: nerve fibers along with its vasculature are being severed in glaucoma. My biggest supporting evidence lies in the glaucoma textbooks describing the histology of the end-stage glaucomatous disc (ESGD) as fully cupped optic disc.

I would request my colleagues to have a second critical look at ESGD and then decide for themselves. Is ESGD really a 100% cupped LC or a crater left over after severance and disappearance of all the structures which were once so nicely arranged in a normal disc. If after a second look my colleagues still decide that ESGD is indeed a cupped LC then I would be certainly wrong and I will salute those who gave us the term ‘cupping’ 160 years ago. Regards

Dr. Schrage, It was interesting to read your hypothesis of splinter hemorrhages resulting from bursting of the capillaries due to increased hydrostatic pressure resulting from osmosis.

There is one thing quite certain in glaucoma: One million or so nerve fibers densely packed in 1.5 mm optic disc are always being destroyed in an orderly fashion starting with the peripheral fibers and ending with the central, and never haphazardly or other way around. We can’t deny this aforementioned fact. If the nerve fibers in glaucoma would have being destroyed randomly then the role of perimetry in glaucoma would be useless. If the nerve fibers are being destroyed in an orderly and predictable fashion then we should expect the mechanism for their destruction to be an orderly one as well.

On the basis of orderly destruction of nerve fibers I can’t agree with the prevailing theories of glaucoma. Concept of cupping is absolutely wrong because if cupping was indeed occurring then the central most fibers should have been destroyed first, not the peripheral as we find in glaucomatous field defects. I can’t agree with other theories like neurodegenerative disease, apoptosis, direct role of IOP or undue sensitivity of the disc to IOP since none of them would always result in orderly destruction of nerve fibers. I can’t convince myself that aforementioned theories should never cause haphazard destruction of nerve fibers in glaucoma.

Can your theory of increased hydrostatic pressure/osmosis explain an orderly destruction of nerve fibers in glaucoma? If so, then surely your theory has merit.