Pathogenesis of Primary Open Angle Glaucoma: An Optic Disc Axotomy - Syed S. Hasnain MD

In this video, Dr. Hasnain explains that the direct effect of elevated IOP, in a single action, cannot account for the orderly, peripheral-to-central loss of nerve fibers in glaucoma. In fact, there is no known biological mechanism acting directly on the nerve fibers which could result in their orderly loss.

He discusses that there must be some mechanical scenario which will first separate the densely packed nerve fibers individually for their orderly one-by-one loss; even though that mechanism may have resulted from the direct biological effect of elevated IOP on some important component of the optic disc. Thus, it is proposed that glaucoma may be a two-stage disease.
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Glaucoma is the leading cause of irreversible blindness in the world. Currently, we still don't have an agreement on its pathogenesis. About one million nerve fibers originate from the retina and leave the eyeball via the lamina cribrosa (LC) and the optic nerve carrying images of, what we see, to the brain for processing.

However, there are two established facts in glaucoma. First elevated intraocular pressure (IOP) is definitively the cause of glaucoma. Second, the nerve fibers are always being destroyed in an orderly sequence - from peripheral to central. A feat which couldn't be accomplished by the direct action of elevated IOP on the NFs. This is the mystery of glaucoma.

Syed S. Hasnain MD has used a different approach in explaining glaucoma. Instead of looking for various factors causing glaucoma, his research has focused primarily on the reason for the orderly loss of nerve fibers. If any factor or theory couldn't explain or result in the orderly loss of nerve fibers, it was immediately discarded.

Keeping in mind that elevated IOP is the definitive cause and the orderly loss of nerve fibers as a salient feature, Dr. Hasnain proposes that glaucoma is a two-stage disease.

In the first stage, there is slow and chronic compression of the circulation of the border tissue of Elschnig due to elevated IOP resulting in chronic ischemia and its degeneration. The degeneration of the border tissue results in sinking of the LC. During the second stage, due to sinking of the LC, the nerve fibers are being stretched and severed at the scleral edge starting with the most peripheral nerve fibers and ending with the most central in an orderly sequence.
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“For any glaucoma theory to be valid, it must explain the reason for the orderly, peripheral-to-central, loss of nerve fibers occurring in glaucoma. Otherwise it would be of no scientific value”. - Syed S. Hasnain MD
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List of Publications:
1. Hasnain SS. Scleral Edge, not Optic Disc or Retina is the Primary Site of Injury in Chronic Glaucoma (Medical Hypothesis, 2006; 67: 1300-1325).
2. Hasnain SS et al. Pathogenesis of Arcuate Field Defects in Glaucoma. Highlights of Ophthalmology 2012 Vol 40, No. 6. Panama.
3. Hasnain SS et al. Arcuate Field Defects in Glaucoma. Ophthalmology Update Vol 11, No.1, January-March 2013. Pakistan.
4. Hasnain SS. Pathogenesis of Chronic Glaucoma: A Two-Stage Disease (EC Ophthalmology, 2019)
5. Hasnain SS. Arcuate Field Defects do not Validate the Lamina Cribrosa as the Primary Site of Injury in Chronic Glaucoma (EC Ophthalmology, 2020), Syed S. Hasnain MD
6. Hasnain SS. Rethinking the Pathogensis of Primary Open-Angle Glaucoma: An Optic Disc Axotomy (EC Ophthalmology, 2023), Syed S. Hasnain MD