Not long ago in ophthalmology's history, elevated intraocular pressure (IOP) and glaucoma were synonymous: any elevation of IOP was considered glaucoma, and conversely, glaucoma was considered to be caused exclusively by pressure-related damage to the optic nerve head in eyes with elevated IOP.

In the 1996 edition of the American Academy of Ophthalmology's preferred practice pattern for primary open-angle glaucoma (POAG),<sup>1American Academy of Ophthalmology  Primary open-angle glaucoma, Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology (1996). 

Cliquez ici pour aller à la section Références</sup> elevation of IOP is neither a component of the definition of POAG nor a clinical characteristic of it. IOP has been reclassified as a risk factor for the clinical process rather than a clinical feature of POAG.<sup>1American Academy of Ophthalmology  Primary open-angle glaucoma, Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology (1996). 

Cliquez ici pour aller à la section Références</sup>

This shift in importance regarding IOP came about for several reasons. First is the ongoing realization that all glaucomas are not alike and that different forms of glaucoma follow different natural histories. Second is the advancement of both subjective and objective structural and functional tests of the optic nerve that allow better understanding of the natural histories of the various glaucomas. Third is the emerging realization that despite better than ever medicines and surgical techniques that lower IOP consistently to single-digit levels, some eyes continue to experience progressive optic nerve damage and visual field loss.

The reality is that all glaucoma is not POAG. Nor do all cases of glaucoma behave like POAG. We all agree that there are differences in both clinical appearance and natural history between POAG and, for instance, acute angle-closure glaucoma. But so too is there a difference in the natural history between normal-pressure glaucoma and ocular hypertension, and in the case of that pair, outcome might appear inversely proportional to IOP. Current classifications of the glaucomas have allowed us to recognize that IOP alone does not account for the progressive nature of the disease.

Advances in both visual function assessment and structural optic nerve evaluation have afforded peace of mind to many who treat patients with ocular hypertension. It is widely accepted that there seems to be great redundancy of function within fibers of the optic nerve. Work by Quigley and colleagues<sup>8Quigley H.A., Addicks E.M., Green W.R. Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy Arch Ophthalmol 1982 ;  100 : 135

Cliquez ici pour aller à la section Références</sup> asserts that up to half of all axons in the optic nerve can be lost before the first measurable visual field defect appears using achromatic automated perimetry. When faced with the patient whose IOP is in the mid-20s. whose optic nerves exhibit generous but symmetric 0.7 cups with healthy-appearing neuroretinal rims, and whose white-on-white visual fields are full, we ask ourselves, “Is this early glaucomatous optic neuropathy (GON) that should be treated or simply ocular hypertension that can be observed?” Fortunately our glaucoma diagnostic arsenal contains other functional tests such as short-wavelength automated perimetry (SWAP, blue-on-yellow field testing), which selectively assesses magnocellular processing as well as motion automated perimetry, that preferentially tests parvocellular function. These may detect glaucomatous visual field defects years before they appear by traditional, achromatic, white-on-white testing. There are also devices designed to provide objective structural assessment of the optic nerve and nerve fiber layer, such as scanning laser topography and scanning laser polarimetry, which allow statistical comparison of global and focal nerve fiber layer and optic nerve structural parameters between individuals and an age- and race-matched normative data base. These tests, when normal, may help reassure that the patient as just described does not seem to have early nerve damage, is tolerating IOPs in the mid-20s, and probably does not need to be treated with IOP-lowering agents.

Perhaps most surprising, and most discomforting for those who treat glaucoma, has been the growing awareness that the relatively simple historical concept of glaucoma as a disease of elevated IOP is untenable. There seems to be a non–pressure-dependent aspect to GON. Lowering IOP to 15, to 12, even to 8 or below does not always halt the progression of the disease. Despite potent pharmacologic agents such as the prostaglandin analogues and the new alpha-agonists and despite antimetabolite-augmented filtration procedures resulting in near-hypotonous IOPs, progression occasionally still occurs. A damaged optic nerve may be more susceptible to additional damage at lower IOPs. Perhaps cupping begets cupping.

These observations provide the basis for the new definition of glaucoma that is not IOP dependent. Patient management, however, is still largely directed at lowering IOP to decrease the risk of further progression of pressure-related disease. This article provides a rationale for the management of IOP in the glaucomatous eye. What is the relationship between IOP and glaucoma? What is the nature of the pressure-dependent component of glaucoma? The answers to these questions have a tremendous impact on the treatment of patients.

For the purpose of the following discussion, elevated IOP will refer to eyes with statistically elevated pressure. GON is the optic nerve damage caused by glaucoma. Ocular hypertension is the condition of elevated IOP without GON, whereas normal tension glaucoma is GON in an eye without elevated IOP.