No, thinning of NFL just means the axons of optic nerve are damaged, glaucoma is one of them to induce thinning of NFL

RNFL defect has its' unique pattern in glaucoma, RNFL defect can happen in optic nerve injury and lesions of visual pathway anterior of lateral geniculate body

I am very grateful for your reply as I am very confused about the subject of thinning of the RNFL in glaucoma. As I understand you have mentioned that thinning of RNFL can also happen in non-glaucomatous conditions but thinning of RNFL in glaucoma has unique pattern. It is very interesting know that there are different patterns of thinning of RNFL taking place. Can you kindly explain what kind of thinning of RNFL is occurring in glaucoma and what unique pattern or feature it has? Regards

A definite no, look at NFL-thinning after a small local arterial closure. The same wedge shaped RNFL defect as seen at any glaucoma patient. You will not able to differentiate between a glaucoma defect and any other RNFL defect due to a perfusion damage.

In case of glaucoma with nasal step visual field defect, the focal thinning of RNFL at temporal upper or temporal lower areas can suggest an unique pattern of glaucoma. In cases with diffue thinning of RNFL or half (upper or lower), the differential characteristic can be glaucoma or non-glaucomatous optic neuropathy

The RNFL thinning in glaucoma is initially seen in the arcuate areas as wedge defects which progress to form arcuate defects.The location and the progression of these areas of thinning which correspond to the characteristic field defects is unique to glaucoma.In other causes of RNFL thinning no such characteristic pattern is seen.As mentioned earlier damage to retinal nerve fibres at any location from retina to lateral geniculate body would lead to RNFL thinning.

i saw some patients with long standing anemia who has thinning in the RNFL

Dear Dr. Tsai, Thank you for your reply. Why should I worry about looking for thinning of RNFL in cases in which glaucomatous field defects have already occurred. At this stage the morphological changes in the glaucomatous disc are enough to tell us that nerve fibers are being damaged and also record its progression.

Why should we need a microscope when we can see the same thing in its entirety with our naked eyes much better way. I thought the role of Imaging devices was to pick up thinning of RNFL in the pre-perimetric glaucoma in which enough of the nerve fibers have not yet damaged to produce the field defects. If early thinning of RNFL neither can pick up a pre-perimetric glaucoma nor it can differentiate between glaucoma and non -glaucoma cases then why are we giving imaging devices so much importance? We want to find a tool to tell us definitely about glaucoma before and not after the occurrence of field defects.

Yes, you are right, sometimes the peripapillary NFL thickness measurement is not consistent with VF measurement. However, it is objective and very useful to detect changes in the follow-up of patients with glaucoma. As for the pre-perimetric glaucoma, several reports demonstrated that posterior pole analysis or macular retinal ganglion complex measurement may be better than peripapillary NFL measurements to detect pre-perimetric glaucoma. However, the problem is when you see NFL defect or abnormal in posterior pole analysis but normal VF in a patient with glaucoma-suspect, which one will be your judgement? Is the NFL measurement too sensitive or other artifacts? We still have to use both VF examinations and NFL measurements to make a diagnosis of glaucoma. So the real answer for your question is no.

one of the most important problems is that we never know what was the base line of the individual that we are assessing. Certainly we have statistical data concerning the normal range but where was our patient at the beginning. Consider the following the standard deviation of perimetry is +_2dB that means significant change is almost +_4dB.

A patient with a mean sensitivity of 2dB over the the age adjusted expected sensitivity and losses 4dB due to glaucoma will be still in the normal limits for his age. But a loss of 3db is already a loss of 60-80% of the ganglion cells (see Quigly). That the crux we do not know were we started.

The same patient at the same time may have RNFL that is at the lower range of the normal RNFL thickness at the beginning and due to glaucoma it will drop to abnormal.

It looks for us at that moment as a discrepancy even though it is not because we have no idea how much the patient lost only where he is at that moment- within normal range or not.

It is the same if you evaluate a visual field according to the raw mean sensitivity values without adjusting to age and sex and using mean deficiency. It has no relevance

Dr. Wagner, I agree with your points. In visual field evaluation and in NFL measurements, individual and focal point evaluation are valuable than the mean normal range equipped by their database, very important points

;The retina is neural tissue and processes impacting neural tissue; if involved in vision ---can have retrograde damage to the retina. So if the damage is in a neural structure and the structure is represented axonally in the optic nerve, there can be thinning/drop out of functional cells in retina and thus retinal thinning. An example of this (although still poorly understood) is retinal thinning that occurs in Alzheimer's disease and Parkinson's disease. A very early histo study on this was published by Banks. Since then there are numerous studies using OCT. There are damages in the brain that are reflected in retrograde loss in the retina. Parkinson's doses have direct retinal neuroprocessing deficits so that is a variable that is confounding the findings. However, if one looks at the work of Gupta and Yucel where they have demonstrated how very early in glaucoma pathology there are findings of damage in brain structures.

AD and PD are simply the reverse.

However, the point that not knowing baseline is critical.

There are findings that in normal, non pathology that lower volume of brain tissue is related to thinner RNFL.

Surely, we would be noticing some thinning of the nerve fibers layer (NFL) on imaging devices in the non-glaucomatous optic atrophies as well since there would be diminution and collapse of the nerve fibers in such atrophies. However, the extent and the amount of thinning of the NFL is different as is the histology between the glaucomatous disc and non-glaucomatous optic atrophies such as due to multiple sclerosis. .

Histology of the end-stage glaucoma disc (ESGD) reveals a large excavated area (empty space or crater), totally devoid of nerve fibers whereas the histology of optic atrophy due to MS reveals LC full of nerve fibers though shrunken and disorganized.

Where did the all the nerve fibers disappear from ESGD?

I hypothesize that thinning of the NFL in glaucoma is due to severance and thus total disappearance of the nerve fibers, whereas the thinning of the NFL in non-glaucomatous optic atrophies is due to actual atrophy of the nerve fibers as evidenced by their collapse, shrinkage and disorganization but not their total disappearance.

What I have read in literature is that the thinning of NFL in the non-glaucoma atrophies is mild and coincides with the active phase of the disease in non-glaucoma cases. Once all the nerve fibers have atrophied and collapsed then the further thinning of NFL would be minimal if any.

Then what kind of thinning of NFL differentiates glaucomatous from non -glaucoma cases?

I believe the continuous or progressive thinning of the NFL appears to be the unique feature of glaucoma. The continuous thinning of the NFL can be easily observed looking directly at the glaucomatous disc. As the NFL starts thinning the scleral rim of the scleral opening would become more transparent and visible. As the thinning progresses, the scleral rim becomes more and more visible due to severance of the nerve fibers. In the ESGD once all the nerve fibers are severed and gone the entire scleral opening becomes visible in contrast to no such visibility of the scleral rim in non- glaucomatous optic atrophies because in these cases the thinning is mild and non-progressive. I find this simple test very valuable in determining the thinning of NFL.

Why is the thinning of the NFL continuous?

I hypothesize that LC is anchored in the scleral opening (in addition to the border tissue) by 360 degree of nerve fibers as roots anchor the tree. As the nerve fibers are being severed and depleted the anchorage to the LC is reduced resulting in further sinking of the disc thus bringing in next in line fibers closer to the scleral rim to be stretched and severed. The process of sinking LC and severing of nerve fibers would become self-propagated until the central most fibers is severed. In the ESGD the entire scleral opening is visible since there are no more nerve fibers present to obscure the rim of the opening. If the thinning of NFL was not occurring continuously in glaucoma, then in my opinion, the role of imaging devices would be meaningless in glaucoma, in my opinion at least.

I hypothesize that continuous thinning of the NFL is unique feature of glaucoma in contrast to non-glaucoma atrophies where thinning is mild and non-continuous.