There are almost no cases of 100% RGC axon loss in glaucoma, although some other ischemic optic neuropathies can result in total axon loss. The axons travel from the RGC soma to the brain, and traverse the lamina cribrosa along their path. Hence, if there are axons at the rim, there are axons in the lamina by definition. Generally axon loss is focal in glaucoma, and so there will be local areas of loss, which are usually associated with focal notching or rim thinning of the nerve fiber layer as it enters the ONH. Within the lamina, the corresponding areas that are devoid of axons quickly fill with glial scar, so while there may not be any viable RGC axons in a particular region, the lamina is not 'empty'.

Dear Dr. Downs, Thank you for your reply. I know you are among the top researchers in glaucoma. Histology of the normal disc reveals that it is densely packed with nerve fibers and there is hardly any empty space. I fail to understand why it is mentioned that the nerve fibers are present in the rim area only whereas the central cupped area is devoid of nerve fibers. Unfortunately, I have been unable to find even a single histology having this doughnut shaped arrangement.in any normal or diseased disc.

Even if I reluctantly believe that nerve fibers are located only in the rim then many puzzling questions arise: if someone born with 0.7 cup, would he/she be more or less prone to glaucoma. Since the central 70 % cupped area is devoid of neuronal tissue then all the force of raised IOP would be exerted and dissipated on the non-neuronal tissue therefore smaller outer rim having nerve fibers would escape injury or since all the nerve fibers are present in the outer 30 % of the disc therefore this individual would become much sooner because of smaller neural rim compared with someone born with 0.2 cup.

Secondly, if the nerve fibers are absent in the cupped area then why the nature needed the holes in the central part of LC? We are saying on one hand that physiological cups are enlarging concentrically and we we are also saying the LC is bowing posteriorly- two contradictory statements. I fail to understand what structure of the disc is indeed cupping if cupping is indeed taking place.

It is hard to convince myself that cupping is indeed taking place unless there is a histology available to support cupping phenomenon. In my opinion the term cupping was mistakenly given 150 years ago, which had put us on wrong path.

Thank you for the feedback.

It appears that there are many questions embedded in your one question. It asks; why do we have "cups" in the first place. Then it goes further to ask why different sized cups. Then an additional question arises, what do cups contain (what are they filled with)? And yes one more question that appears to me is; what is the cytological/histological relationship between empty cup (or the rim) and correspodning areas in the perforated sheet (we call Lamina Cribrosa).

1. Why do we have cups? The question has to be answered by a physiologist and/or veterinarian because physiology would give us the idea about the significance of a cup in terms of the structure and veterinary sciences would give us a comparative approach as to its function.

2. Why different sized cups? This is a good question. Since there is a wide range of RGC content in the ganglion cell layer (it ranges from .5 to 1.7 million), it become somewhat obvious that when these thread entangle in an orderly fashion to form a rim, the rim thickness would be comparable to directly proportional to the number of fibers (you may call them axons). Hence different sizes of cups.

3. What do cups contain? OCT images of cups reveal that perhaps a cup is the pupil of the retina. Pupil is not an organic structure and yet means a lot to ophthalmology. In the same way, a cup may be inevitable trade-off for the nerve fiber bundle assembly. but this is just a thought.

4. What is the cytological/histological relationship between empty cup (or the rim) and corresponding areas in the Lamina Cribrosa? There can be any relationship. The answer may range from anywhere to anywhere unless supported by some histological evidence. The interesting point that I thin is extremely relevant here is that Mice do not have a lamina cribrosa. This is a funny fact to me (an a difficult one to swallow) because lamina cribrosa seems to be inevitable given the structure and assembly of the mammalian visual system. So may be the rim/cup and the lamina cribrosa are not direct physiological cousins. They may just be aquintances.

I don't know if it makes sense, but this is what appears to me when I think of the optic nerve head.

Thank you

Why do we have cups? When we examine the optic disc with an ophthalmoscope we see a yellowish central area surrounded by reddish area - so called neuroretinal rim. In fact this yellowish central area is remnant of the Bergmeister’s papilla – a tuft of hyaloid vessels - which supplies nutrition to the lens in the fetal life. The physiological cups of different sizes are nothing more than varying degree of atrophy of the Bergmeister’s papilla.

This remnant tissue is identified as connective tissue meniscus of Kuhnt in the normal histology of optic disc. Some discs don’t have this remnant tissue and others have varying degree of this remnant, some have as large as covering the 90% of the disc surface or called 0.9 physiological cup.There is no hole or cup. Underneath the meniscus the NFs are present all the way to the center of the disc.

Then, what are the pathological cups? I am afraid we have created them to confirm to the cupping paradigm. This is the way paradigms work. We have ourselves made doughnut shaped configuration of ONH and so called neuroretinal rim and central empty cup. In fact, the neuroretinal rim is area of NFs uncovered by the remnant tissue. In the optic discs which don’t have this remnant tissue the NFS can be seen all the way to the center.

I do agree when 360 degrees of the NFs enter the optic disc a small central dimple or cup is produced but this is not what we define as cupping.

Pathological cupping is defined when the LC starts bowing posteriorly for which we have no histological evidence. OCT has been unable to define the posterior margin of the LC. We have made up posterior bowing of LC to theorize the distortion of laminar beams and thus pinching of the axons and death of the RGCs. We have made conundrum of glaucoma, ourselves, by following 160 years old wrong paradigm of cupping. I request the researchers to either confirm the cupping paradigm by histological means or discard it once for all. It is time for a paradigm change.

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Do you then think that cup (which seems to be a potential space filled with some substance of insignificance) is a physiological vestige being an inevitable remnant of developmental ophthalmology?

Does my question make any sense in the first place?

The remnant or vestigial tissue which forms the base of the physiological cup is lying superficially on the surface of the NFs layer: analogous to a leaf lying on the surface of a pond of water. There are NFs underneath the vestigial tissue as water is underneath the leaf. Physiological cup ( I think wrongly called) is a small depression like a design in the middle of a tea saucer, and not tea cup itself. There is no potential empty space underneath the remnant tissue. This is what histology reveals (Wolff).