EC Ophthalmology

Primary open angle glaucoma (POAG), commonly known as glaucoma, is the leading cause of irreversible blindness in the world. The recognition of glaucoma as a separate entity dates back to the 1850s when ophthalmologists of the time observed the fundus of blind subjects with painless but firm eyes for the first time with the newly invented ophthalmoscope.

They observed that their optics discs were ‘cupped' in glaucoma instead of the normal flat appearance. This observation led to the belief that the optics discs had become cupped as a result of the direct force of elevated intraocular pressure (IOP). The term ‘cupping’ was not seriously questioned at the time. However, this term gained acceptance which then gave birth to a cupping paradigm - a concept that persists to this day.

Within this paradigm, cupping of the optic disc implies that the pathology starts from the central part of the disc and extends concentrically to its peripheral part in glaucoma. Logically, this would suggest that the central vision nerve fibers (NF) should be destroyed first, and the peripheral vision NFs at the end stage, in accordance with the normal arrangement of nerve fibers in the optic disc. However, in actuality, the glaucomatous visual field defects show that the exact opposite field loss is occurring: the peripheral vision is destroyed first, while the central vision remains until the end stage, in an orderly sequence.

This fundamental contradiction challenges the credibility of the long-standing cupping paradigm introduced 170 years ago.

There are two established facts in the realm of glaucoma. Firstly, that elevated IOP, even as a stand-alone factor, is an established cause of glaucoma. Secondly, there is an orderly, peripheral-to-central loss of nerve fibers. This nerve fiber loss never occurs randomly. These two facts combined present a puzzling question: How does elevated IOP acting directly on the nerve fibers result in the orderly and systematic loss of nerve fibers in glaucoma?

The direct effect of elevated IOP, in a single action, cannot account for the orderly loss of nerve fibers in glaucoma. In fact, there is no known biological mechanism acting directly on the NFs which could result in their orderly loss. Thus, there must be some mechanical scenario which will first separate the densely packed NFs individually for their orderly one-by-one loss; even though that mechanism may have resulted from the biological effect of elevated IOP on some important component of the optic disc. Therefore, it is proposed that glaucoma may be a two-stage disease.

First stage: degeneration of the border tissue of Elschnig due to chronic ischemia induced by elevated IOP. This border tissue degeneration then results in the loosening of the lamina cribrosa. This is followed by the second stage: the sinking of the lamina cribrosa, leading to the stretching and severance (or axotomy) of nerve fibers from peripheral to central, in an orderly sequence, at the scleral edge. This progressive sinking of the lamina cribrosa and severance of nerve fibers will continue until the central-most nerve fiber has moved to the scleral edge and is severed. The vasculature is also being severed along with the nerve fibers resulting in splinter hemorrhages at the disc margin.

The progressive sinking of the lamina cribrosa and the orderly, peripheral-to-central severance of nerve fibers corroborates with the observed visual field defects in glaucoma. The severance of nerve fibers can explain the orderly loss of nerve fibers in glaucoma. Glaucoma may not be an optic neuropathy, but an optic disc axotomy - a paradigm shift.

 Keywords: Pathogenesis; Primary Open-Angle Glaucoma; Optic Disc Axotomy; Intraocular Pressure (IOP); Nerve Fibers (NF)

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