Diagnosis and pathogenesis of glaucomatous optic neuropathy: morphological aspects11
Introduction
The optic nerve is composed of axons of the retinal ganglion cells, the cell bodies of which are located in the superficial retinal layers. Any damage to the optic nerve, therefore, leads to changes in the ganglion cell layer and nerve fibre layer of the retina, the intrapapillary region of the optic nerve head, and the optic nerve head itself. In contrast to other optic neuropathies, glaucomatous optic nerve damage is additionally associated with atrophic alterations in the deep retinal layers, including the retinal pigment epithelium in the parapapillary region of the optic nerve head. The reason for this difference between the non-glaucomatous type of optic nerve damage and the glaucomatous type of optic nerve damage has so far remained unclear. Some studies have suggested that certain glaucoma eyes may exhibit changes in the deep retinal layers outside of the parapapillary region of the optic disc. The purpose of this review is to describe the morphologic changes occurring in eyes with glaucomatous optic neuropathy and to show up pathogenetic hints which may be deducted from the morphology of glaucomatous changes in the eye.
For evaluating the morphology of the optic nerve head, one uses descriptive, quantitative and qualitative variables. These are the size and shape of the optic disc; size, shape and pallor of the neuroretinal rim; size of the optic cup in relation to the area of the disc; configuration and depth of the optic cup; cup-to-disc diameter ratio and cup-to-disc area ratio; position of the exit of the central retinal vessel trunk on the lamina cribrosa surface; presence and location of splinter-shaped haemorrhages; occurrence, size, configuration and location of parapapillary chorioretinal atrophy; diffuse and/or focal decrease of the diameter of the retinal arterioles; and visibility of the retinal nerve fibre layer. Due to a biologic overlap of almost all quantitative variables between normal subjects and glaucoma patients, qualitative variables such as occurrence of disc haemorrhages and presence of localized retinal nerve fibre layer defects compared to quantitative variables have a higher specificity in separating glaucoma eyes from normal eyes.
Section snippets
Optic disc size
The importance of the size of the optic disc for diagnosis and pathogenesis of glaucomatous optic neuropathy is based on the finding that the optic disc area is not constant among individuals but that it shows an interindividual variability of about 0.80 mm2 to almost 6.00 mm2, or about 1:7 in a normal Caucasian population (Bengtsson, 1976; Betz et al., 1981; Britton et al., 1987; Franceschetti and Bock, 1950; Jonas et al., 1988c; Ramrattan et al., 1997; Tomita et al., 1989; Varma et al., 1994).
Optic disc shape
The importance of the shape of the optic disc for glaucoma diagnosis is again based on the interindividual variability. The optic disc has a slightly vertical oval form with the vertical diameter being about 7 to 10% larger than the horizontal one (Jonas et al., 1988c). The maximal disc diameter is nearly identical with the vertical diameter and the horizontal diameter is almost equal to the minimal diameter. The ratio between minimal-to-maximal disc diameter ranged in previous investigations
Neuroretinal rim size
The neuroretinal rim is the intrapapillary equivalent of the retinal nerve fibres and optic nerve fibres. It is, therefore, one of the main targets in the morphologic glaucoma diagnosis (Drance and Balazsi, 1984; Airaksinen and Drance, 1985; Betz et al., 1981, Betz et al., 1982; Britton et al., 1987). The neuroretinal rim size is correlated with the optic disc area: the larger the disc, the larger the rim (Betz et al., 1982; Britton et al., 1987; Caprioli and Miller, 1987; Jonas et al., 1988c;
Neuroretinal rim shape
The neuroretinal rim exhibits a characteristic configuration in normal eyes (Fig. 1). It is based on the vertically oval shape of the optic disc and the horizontally oval shape of the optic cup. The neuroretinal rim is usually broadest in the nferior disc region, followed by the uperior disc region, the asal disc area, and finally the emporal disc region ( rule, as termed by Elliot Werner/Philadelphia) (Jonas et al., 1988c). The characteristic shape of the rim is of utmost importance
Neuroretinal rim pallor
Increasing pallor of the optic disc and especially of the neuroretinal rim is a typical sign of optic nerve damage (Hayreh, 1972a; Hitchings, 1978; Miller and Caprioli, 1988; Nagin and Schwartz, 1985; Robert et al., 1982; Schwartz, 1973; Tuulonen et al., 1987). The increase in pallor of the neuroretinal rim may be more marked in eyes with non-glaucomatous optic neuropathy than in eyes with glaucoma. In other words, if the neuroretinal rim looks rather pale, the probability for a
Optic cup size in relation to the optic disc size
Parallel to the optic disc and the neuroretinal rim, the optic cup also shows a high interindividual variability (Bengtsson, 1976). In normal eyes the areas of the optic disc and optic cup are correlated with each other: the larger the optic disc, the larger the optic cup (Bengtsson, 1976). In the morphologic diagnosis of glaucoma this feature has to be taken into account. Early or moderately advanced glaucomatous optic nerve damage may erroneously be overlooked in small optic discs with
Configuration and depth of the optic cup
In normal eyes, the shape of the optic cup is horizontally oval, with the horizontal diameter being about 8% longer than the vertical diameter (Jonas et al., 1988c). The combination of the horizontally oval shape of the optic cup and the vertically oval shape of the optic disc explains the configuration of the normal neuroretinal rim which has its broadest parts in the inferior and superior disc regions and its smallest parts in the temporal and nasal region of the optic disc.
In addition to its
Cup/disc ratios
Due to the vertically oval optic disc and the horizontally oval optic cup, the cup/disc ratios in normal eyes are significantly larger horizontally than vertically (Jonas et al., 1988c). In less than 7% of normal eyes the horizontal cup/disc ratio is smaller than the vertical one. It indicates that the quotient of the horizontal-to-vertical cup/disc ratios is usually higher than 1.0. This is important for the diagnosis of glaucoma where, in the early to medium advanced stages, the vertical
Position of the exit of the central retinal vessel trunk on the lamina cribrosa surface
As already pointed out, the local susceptibility for glaucomatous neuroretinal rim loss partially depends on the distance to the exit of the central retinal vessel trunk on the lamina cribrosa surface (Fig. 2) (Jonas and Fernández, 1994). The longer the distance to the central retinal vessel trunk exit, the more marked can be the glaucomatous loss of neuroretinal rim and the loss of visual field in the corresponding visual field quadrant (Wu et al., 1995). The location of the central retinal
Optic disc haemorrhages
Splinter-shaped or flame-shaped haemorrhages at the border of the optic disc are a hallmark of glaucomatous optic nerve atrophy (Drance and Begg, 1970; Drance et al., 1977). Rarely or very rarely found in normal eyes (Healey et al., 1998; Jonas and Xu, 1994; Katz and Hoyt, 1995; Klein et al., 1992), disc haemorrhages are detected in about 4 to 7% of eyes with glaucoma (Airaksinen et al., 1981a; Drance, 1989; Kitazawa et al., 1986). Their frequency increases from an early stage of glaucoma to a
Parapapillary chorioretinal atrophy
Ophthalmoscopically, the parapapillary chorioretinal atrophy can be divided into a central beta zone and a peripheral alpha zone (Fig. 3) (Jonas et al., 1989b). The peripheral zone (alpha zone) is characterized by an irregular hypopigmentation and hyperpigmentation and intimated thinning of the chorioretinal tissue layer. On its outer side it is adjacent to the retina, and on its inner side it is in touch with a zone characterized by visible sclera and visible large choroidal vessels (beta
Diameter of retinal arterioles
Diffuse narrowing of the retinal vessels has been described for glaucomatous and non-glaucomatous optic neuropathies (Frisén and Claesson, 1984; Jonas et al., 1989c, Jonas et al., 1991b, Jonas et al., 1993). In glaucoma, the vessel diameter reduces with decreasing area of the neuroretinal rim, diminishing visibility of the retinal nerve fibre layer, and increasing visual field defects (Jonas and Naumann, 1989). Since the reduction of the vessel calibre is also found in eyes with
Evaluation of the retinal nerve fibre layer
The retinal nerve fibre layer (RNFL) contains the retinal ganglion cell axons covered by astrocytes and bundled by processes of Müller cells. It can be assessed ophthalmoscopically (Vogt, 1913), on wide-angle red-free photographs (Airaksinen and Nieminen, 1985), by photogrammetric measurements of the retinal nerve fibre layer thickness (Schwartz and Takamoto, 1991), or by using other sophisticated techniques such as confocal scanner laser tomography (Kruse et al., 1989; Burk et al., 1993) or
Early or “preperimetric” diagnosis of glaucomatous optic nerve damage
In recent studies (Drance and Balazsi, 1984; Jonas and Königsreuther, 1994), ocular hypertensive patients with normal achromatic visual fields and normal control subjects differed significantly in the shape of the neuroretinal rim. Compared to normal eyes, the ocular hypertensive eyes had lost neuroretinal rim predominantly in the temporal inferior and temporal superior disc sectors. This resulted in a neuroretinal rim the width of which was more or less even in all disc sectors. This contrasts
Differentiation glaucomatous versus non-glaucomatous optic neuropathy
Glaucomatous and non-glaucomatous optic neuropathy have in common a decreased diameter of the retinal arterioles, including the occurrence of focal arteriole narrowing, and a reduced visibility of the retinal nerve fibre layer (Jonas et al., 1999b). Localized retinal nerve fibre layer defects can be found in glaucoma and in many types of non-glaucomatous optic nerve damage such as in optic disc drusen and long-standing papilledema (Jonas and Dichtl, 1996). In glaucomatous optic neuropathy
Differentiation of the various types of chronic open-angle glaucomas
The open-angle glaucomas are a heterogeneous group of diseases which vary in the level of intraocular pressure, age of the patients, prevalence of arterial hypotension, refractive error, and atrophic appearance of the posterior fundus. These forms of open-angle glaucomas also differ in the appearance of the optic nerve head (Nicolela and Drance, 1996; Nicolela et al., 1996; Spaeth, 1992, Spaeth, 1994; Spaeth et al., 1976, Spaeth et al., 1995; Geijssen and Greve, 1987; Caprioli, 1993).
Optic disc size
Pathogenetically, the interindividual variability of the optic disc area was reason to raise the question whether the disc size is correlated with the glaucoma susceptibility. There are several reasons in favour of a relationship between large disc size and increased glaucoma susceptibility. The larger optic disc size (Chi et al., 1989; Tsai et al., 1995, Varma et al., 1994) in combination with reportedly higher glaucoma susceptibility (Martin et al., 1985) in the Afro-American population group
Future directions
With further improvement of available instruments to quantify ocular blood flow, especially in the lamina cribrosa itself, and with the development of new, non-invasive techniques to measure cerebrospinal fluid pressure, future studies may be able to give more insight into the pathogenesis of optic nerve fibre loss in the various types of the chronic open-angle glaucomas.
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2020, Progress in Retinal and Eye ResearchCitation Excerpt :In the NRR, tissue loss corresponds to the cross-sectional area decrease due to the longitudinal course of the axon bundles. This is what we see as an increased “cup-to-disc” ratio in glaucoma, or the transverse NRR width decrease (Fig. 4) (Hayreh, 1972; Jonas and Budde, 2000; Jonas et al., 1999; Trobe et al., 1980a). The status of the glioarchitecture has not been structurally correlated with NRR thinning.
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1Supported by Deutsche Forschungsgemeinschaft (SFB 539)