07 The Normal Optic Nerve

75

CHAPTER 7 THE NORMAL OPTIC NERVE

7.1 Introduction We studied the optic nerve head in 108 normal cases with the Heidelberg Retina Tomograph [1]. Three tomographies were taken from each eye, and only those eyes having a mean topography with an average standard deviation lower than 30 µm were included in our study. The examiner draws the contour line on the external limit of the optic disc, that is, on the internal limit of Elschnig's Ring. The computer processes the information of all the structures inside the contour line and provides the necessary parameter values to study the optic nerve head. In order to achieve this, the computer searches for the retinal surface in the angle between -4 and -10 degrees (region of the papillomacular bundle), and places a reference plane at 50 µm beneath this area. This reference plane is known as the "new standard reference plane" in software version 2.01. It is based on the finding that the papillomacular bundle is the last bundle to deteriorate throughout the evolution of glaucoma (figure 7.1). From this point on, the computer provides the parameters measured throughout the 360 degrees, which are divided into "related to the reference plane" and "not related to the reference plane", and it also provides the same parameters individually measured in octants and in quadrants. This arrangement is shown in figure 7.2. All the basic parameters measured within the 360 degrees were used in this study

Fig 7.1

Fig. 7.2

76 and the parameters "mean height of contour line" and "rim volume" were measured in each quadrant and octant. 7.2 Exclusion criteria The 154 volunteer patients were chosen at random. Their age ranged between 5 and 85 years. Patients with myopia and hypermetropia over 6.0 diopters, astigmatism over 2.0 diopters, or pathological lens opacity factor (measured with the Opacity LensMeter) were excluded. Likewise, patients with abnormal visual field, according to M.D., C.L.V. and R.F. values, analyzed with the Octopus 1-2-3, and processed with the PeriData program (version 6.2a) were also excluded, as well as those patients with IOP over 22 mmHg. Finally those patients with fixation problems and/or unstable behavior were also excluded. The final number of cases was 108. 7.3 Definition and importance of the mean standard error SEM, which stands for "Standard Error of the Mean", is used to find out how much the sample’s mean differs from the population’s mean, that is, to confirm the degree of representation the sample has on population. Mathematically, the SEM equals to the mean standard deviation divided by the square root of the number of cases analyzed. The mean value, plus and minus two times the SEM, yields an interval referred to as "Confidence Interval", in which the population’s mean or the statistical universe is found with a 95% degree of certainty. For this reason, the lower the SEM value, the smaller the interval will be, and thus, the sample representation will be higher (figure 7.3). The variation of a parameter below 30 µm, in a longitudinal study, can merely represent a normal long-term fluctuation. Therefore the lower the SEM value, the lower the normal variation will be. Consequently, the values from a given patient falling above this variation can be considered to be abnormal.

Fig. 7.3

77 If the SEM value were very high, the normal variation would be very large, which would allow inclusion of pathological or borderline values, considered to be normal, into the normal variation. 7.4 Normal parameters The HRT provides a great variety and volume of data, from which the physician must choose the main parameters which, added to the observation of the qualitative and topographical features (camel hump chart, profile sections, animation, etc.), will provide the basis for a diagnostic conclusion. In the following table, the six most important and reliable parameters for the evaluation of the optic nerve head condition are shown. The rest of the basic parameters - to be shown later - should, however, be kept in mind [2].

RIM VOLUME CUP VOLUME CUP SHAPE MEASURE CUP AREA RIM AREA MEAN RETINAL NFL THICKNESS CONTOUR LINE HEIGHT VARIATION

The values of the contour line mean height and the neuroretinal rim volume in the different quadrants and octants should also be studied, in order to rule out the onset of a localized defect, that is, the alteration of a fiber bundle, which may not cause major changes in the optic nerve, in its early stages. Finally, it is necessary to take a tomography at 20 degrees image size, and observe each of its 32 sections, in black and white, in order to see if those defects can be found; this can be correlated with the presence of localized depression of the contour line. Figure 7.4 shows the different parameters that are outlined to better understand them. The volume of the neuroretinal rim is divided in a flat neuroretinal rim (in green) and a tilted neuroretinal rim (in blue). The addition of both is equal to the volume referred to as "rim volume" (figure 7.5). It is interesting to verify that the tilted neuroretinal rim (in blue) is the first to decrease when the optic nerve head starts to deteriorate, and only then does the neuroretinal rim decrease. This concept can also be correlated with surface analysis [3]. These surfaces, due to their arrangement, cause the blue area to turn red (cup increase), later disappearing and joining the flat neuroretinal rim area (green) with the cup area (red). When the area in red (cup) locally or asymmetrically invades the area in green (flat neuroretinal rim), fiber defects are produced. As a consequence of this alteration in the retina, these will become localized defects of the visual field in the future. Figure 7.6 lists the main parameters and other secondary parameters that provide the quantitative diagnosis of the optic nerve head within 360 degrees. This analysis may fail to evidence localized defects. To each parameter there is attributed the mean, the maximum and minimum value, and the SEM to demonstrate its representation and usefulness.

78

Fig. 7.4

Fig. 7.5

Fig. 7.6 7.5 Normal profile and structure Among other data, the HRT provides us with the cross section area of the whole optic nerve head, in the anteroposterior axis direction and in sections performed every 50 µm starting at the retina (0 µm) and ending at the lamina cribrosa or at 1,550 µm of depth.

79

Fig. 7.7 In this study, the radius was deduced from these section surfaces in all the sections and the normal profile of the optic nerve (a cross section of the same) was built together with the values of the depths and the volumes. Then the profile was related to the structures containing it, i.e. with the lamina cribrosa, the retina, the sclera and the choroid. When evaluating the optic nerve, it is very useful to transfer the basic parameters to this graph in order to see if a similar structure or a distorted one can be found and with this information, find out if it is normal or not. If it is not normal, this graph will help find out what the evolution of its morphology was since the very start (figure 7.7). 7.6 Normal parameters by sectors As mentioned before, the parameters measured within 360 degrees may be normal, and yet there may be a localized fiber defect not expressed by these parameter values. The following example illustrates this case: If we have a pie that is cut in ten servings, and only half a serving is taken, when we measure the volume of the pie, we will notice that 5% is missing, which may be part of a normal variation. Now, if we measure the volume of each serving, we will realize that 50% of the volume of a serving is missing, which is very significant. In the same fashion, a localized fiber defect may not be noted when analyzing the parameters within 360 degrees. Dr. Reinhard Burk from Heidelberg, Germany, initially measured the height of the contour line in each quadrant and verified this situation. We measured this parameter as well as the rim volume in each sector, to decide which was the best parameter for an early diagnosis and follow-up in a longitudinal study. We found out that both parameters are reliable, but whereas the SEM value for the "mean height of the contour line" is 0.025 mm, the SEM value for the "rim volume" is 0.002 mm3. Compared to the mean values, the variability of the “rim volume” is less than that of the “mean height of the contour line” within the same population, so it is more accurate. Therefore, a small decrease may mean a pathological reduction of the fiber volume in the sector studied which is not due to a normal variation.

80

Fig. 7.8a

Fig. 7.8b

The normal values found for each sector and for each parameter can be observed in figures 7.8a and 7.8b. Figures 7.9a and 7.9b show the summation and topographical images of two 20degree tomographies. In the topographic image, the cup is not concentric and it has a notch in the inferior pole (arrow), where the most altered of the three bundles is observed. As we said before, in this zone, the red cup area invades the green flat neuroretinal rim, there is no blue area representing the tilted neuroretinal rim. The second figure shows the alteration of several fiber bundles (surrounded by arrows) very clearly. These can only be evidenced by a decrease in the neuroretinal rim volume in this sector (parameters by sectors, volume above reference) and they appear as localized depressions in the camel hump diagram. 7.7 Conclusion The most reliable and reproducible parameters for the quantitative analysis of the optic nerve are: rim volume, cup shape measure, cup volume, rim area, cup area and mean retinal nerve fiber layer thickness. It is important to understand that the beginning of an optic nerve lesion is always based on the alteration of two of these parameters: rim volume and cup volume. A lesion is considered to have begun when the rim volume decrease becomes evident simultaneously with a cup volume increase. The alteration of any of these parameters alone does not indicate that there is a lesion, but it must be followed to verify whether or not it leads to pathology. These patients with only one alterated parameter are classified as borderline. If the alterated parameter corresponds to a rim volume decrease in the superior and/or inferior temporal sectors (when the rest of the parameters are normal), we are dealing with a pseudonormal optic disc (according to R.O.W. Burk’s classification). It should be noted that the decrease of the rim volume is the most frequent phenomenon. On the other hand, the SEM value evidences that the parameters with volume units, i.e. those raised to the third power, are more representative and therefore more sensitive to changes between normality and pathology. The cup shape measure and the mean retinal nerve fiber layer thickness are also very valuable parameters. The height variation of the contour line is a very useful parameter,

81

Fig. 7.9a: Topographical image

Fig. 7.9b: Summation image

though it must be used carefully, as its modification may be due to a localized defect as well as to a decrease in the total number of fibers (diffuse defect with a flattening of the camel humps). In order to distinguish between both situations a qualitative and topographic analysis is required. Besides the quantitative data, the tomography with 20 degree image size should be examined to see if there are any peripapillary alterations or any altered fiber bundles, a study by sectors should be performed, the internal cup margins should be analyzed in relation with the cup shape measure, and a profile section of the different axes should be carried out in order to verify the disc steepness in each sector. All of this, added to satisfactory image acquisition control, image processing and drawing of the contour line by an experimented observer [4], lead to high reliability and reproducibility of results, that together with perimetry and the monitoring of intraocular pressure, both by single-spot checks and daily pressure curves are a complement to the early diagnosis of glaucoma and other optic nerve lesions.

82 Bibliography 1.

Burk ROW, Rohrschneider K, Noack H, Völcker HE, Zinser G: Analysis of three-dimensional optic disk topography by laser scanning tomography. Parameter definition and evaluation of parameter interdependence. In: Nasemann JE, Burk ROW (eds): Scanning laser ophthalmoscopy and tomography. Quitessenz, München, 1990, pp 161-176.

2.

Boeglin RJ, Caprioli J: Contemporary clinical evaluation of the optic nerve in glaucoma. In: Caprioli J, Stamper RL (eds): Opthalmology Clinicas or North America Contemporary Issues in Glaucoma 1991; Vol. 4. pp 711-731. W.B. Saunders Company, Philadelphia, 1991.

3.

Quigley HA: Changes in the appearance of the optic disc. Surv Ophthalmol 1985;30:117-126.

4.

Dannheim F, Pelka S. Sampaolesi JR: Reproducibility of optic disk measurements with the Heidelberg Retina Tomograph. In: Mills RP, Wall M (eds): Perimetry Update 1994/1995, pp 343-350.

83