Box 11-2  Sources of error of mfVEP

Electrode position

Poor electrode contact with scalp

Refractive error

Poor fixation

Eccentric fixation

Media opacity

Miosis

Mydriasis

else is required of the patient so that reliable fields may be obtained on the elderly, those who don’t understand how to perform threshold perimetry, and children.The test does take about 20 or so minutes per eye so it takes as much time as a full-threshold SAP and is not practical as a screening instrument. Children as young as 5 years of age can give reliable, repeatable results, although caution must be exercised in interpreting abnormalities as there is an age-related

maturation.182 Significant media opacities may cause false positive defects to appear on the mfVEP.183 Small pupils may reduce the amplitude of the signal whereas dilated pupils may improve latency and mask a borderline abnormal finding.184

Despite the fact that an FDA-approved, relatively user-friendly device is commercially available, the mfVEP is technology in development. It is currently clinically useful as a functional test in some patients who are unable to perform accurate threshold perimetry; these include the very elderly or infirm, children, those unable to concentrate, developmentally disabled, and some others­ .The mfVEP may detect functional changes before SAP.The mfVEP may also be useful in the assessment of suspected malingering.185 How it performs compared to SWAP and FDT remains to be determined. Its ability to track and monitor changes over time still awaits longitudinal studies. Future improvements in stimulus algorithms, analytical algorithms, and computer processing should bring improvements in sensitivity and specificity.176 When that happens, an objective test like this stands a good chance of replacing SAP; until then the mfVEP is a useful adjunct.

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In the past decades, two significant changes have impacted how we contextualize the pathogenic mechanisms of primary open-angle glaucoma.The first change is clinically relevant: the elimination of intraocular pressure (IOP) from the essential definition of the dis- ease.1–3 In other words, glaucomatous optic neuropathy is thought of as an optic nerve disorder in which IOP is one important causative, dose-related risk factor among several others.

The other important shift has been in the conceptual framework for pathogenesis. At one time, theories of glaucomatous pathophysiology were rhetorically confined to a coarse dichotomy, considered from either a ‘mechanical’ or a ‘vasogenic’ basis. Contemporary research has elucidated many intriguing and complementary details both from biomechanical3b and from vasogenic perspectives. And in addition, multiple insights into pathophysiology at the immunologic, cellular, and biochemical levels have begun to elucidate a variety of cascades, which together or separately may manifest in final pathways detectable to us as the clinical features of glaucomatous optic neuropathy.

All glaucomatous atrophy shares the following features4: (1) progressive death of retinal ganglion cells, manifesting as (2) characteristic histopathologic alteration of the optic nerve – known as excavation – which is functionally apparent as (3) sequential visual field deterioration in characteristic patterns. Detailed understanding of the microanatomy of the optic nerve is intimately entwined with the current concepts of glaucomatous pathophysiology.

Anatomy of the optic nerve head

The optic nerve head (ONH) can be divided into four anatomic parts: the surface layer and the prelaminar, laminar, and retrolaminar portions. Each portion of the ONH is made up of axons (nerve fibers) grouped into bundles, blood vessels, and supporting glial tissue.

The superficial nerve fiber layer (SNFL) of the ONH has its most anterior limit at the point where the nerve contacts the vitreous. For histopathologic and clinical purposes, the peripheral edge of the nerve is defined by the anterior limits of the scleral ring. The posterior limit of the SNFL is recognized histologically as the point at which the axon bundles have completed their 90° turn from the plane of the retina and have reached the level of the choroid. The prelaminar portion of the ONH is the indistinct segment of the axons surrounded by the outer retina, choriocapillaris, and choroid; structurally the astroglial component here is considerably increased compared with the SNFL. The laminar portion of the nerve is contained within the lamina cribrosa; here the glial-wrapped axon bundles are confined in the relatively rigid pores of the specialized laminar scleral plates. Posterior to this is the retrolaminar portion of

the optic nerve, where its thickness is doubled by the presence of myelinating oligodendrocytes.These and other eponymic details are illustrated in Figure 12-1.

In the human eye the distribution of the nerve fibers from the peripheral retina toward the optic nerve is such that axons from peripheral ganglion cells are progressively overlayered by axons derived from cell bodies closer to the optic nerve (Fig. 12–2).5 These peripheral fibers remain peripheral as they enter the disc; central fibers enter centrally, adjacent to the physiologic cup. This topographic arrangement correlates with the clinical progression of the glaucomatous visual field: paracentral scotomas appear early in the disease as the cup enlarges, and the peripheral field remains until the peripheral axons in the nerve are affected.6

The arterial blood supply to the ONH varies among individuals,7– 11 but there is general agreement about its fundamental components (Fig. 12-3).12 The central retinal artery (CRA) and the short posterior ciliary arteries (SPCAs) all contribute directly or indirectly to a capillary plexus that supplies the ONH.The venous drainage of the ONH is almost entirely through branches of the central retinal vein, although important choroidal collaterals exist; these collaterals may appear as retinociliary shunts in instances of disturbed retinal circulation.

The branches of the CRA supply the SNFL.This is the network responsible for the flame- (splinter-) disc hemorrhages seen clinically, and it is also the vascular bed that appears in fluorescein angiograms of the ONH. The prelaminar ONH is supplied by branches of the SPCAs, which enter the disc substance through the adjacent sclera

and posterior to the choroidal bed (see Figs 12-1 and 12-3). With one prolific exception,7–10,13,14 most investigators maintain that ves-

sels derived from the peripapillary choroid make only a minor contribution to the blood supply of the anterior ONH.11,12,15–21

The laminar portion is vascularized primarily by centripetal SPCAs, although an axial longitudinal anastomotic capillary bed has been described.11 The ability of that network to provide collateral circulatory support in the event of an arteriolar blockage, however, appears to be limited. The anterior portion of the retrolaminar nerve, however, enjoys both centripetal vascular supply from the pia-meninges and a significant axial vasculature from branches of the CRA.

Mechanisms of glaucomatous optic neuropathy

A particularly cogent framework for integrating the vast amount of experimental and clinical observations of the various factors contributing to glaucomatous optic neuropathy has been elaborated by Quigley.4 His approach poses three queries: (1) What is the primary