There is an abundance of theories about the pathogenesis of chronic glaucoma such as direct effect of elevated IOP on the nerve fibers, neurodegeneration, apoptosis, autoimmune disorder and others. However, none of the prevalent theories has ever questioned the orderly loss of nerve fibers which is the most pathognomic feature and the reason for doing perimetry in glaucoma. In chronic glaucoma, one million or so densely packed nerve fibers are being destroyed in an orderly tandem sequence from peripheral to central, never randomly.
Although elevated IOP is the accepted and established risk factor for the development of glaucoma, elevated IOP can never result in the orderly loss of nerve fibers by its direct effect. This mystery cannot be solved in one stage. Thus, glaucoma is hypothesized as a two-stage disease.