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Pattern of Glaucomatous Neuroretinal Rim Loss
Pattern of Glaucomatous N euroretinal Rim Loss ]ost B. Jonas, MD, 1 Martin C. Fernandez, MD, 1 ]O"rg Sturmer, MIY Background: In advancing glaucomatous optic nerve damage, the area of the neuroretinal rim progressively diminishes, and its form continuously changes. This crosssectional study was undertaken to establish a set pattern behind glaucomatous rim loss. Methods: The authors evaluated morphometrically stereo color optic disc photographs of 801 glaucomatous eyes and 496 visually normal eyes. Resuns: Compared with the visually normal eyes, glaucomatous neuroretinal rim loss occurred in all sectors of the optic disc with regional preferences depending on the stage of the disease. In the eyes with modest glaucomatous damage, rim loss was usually most pronounced in the inferotemporal disc region. In the eyes with moderately progressed glaucomatous changes, rim was decreased most markedly in the superotemporal sector, then in the temporal horizontal area, the nasal inferior region, and finally in the superior nasal sector. In very advanced glaucoma, rim remnants usually were present only in the nasal disc region. At that stage, they were significantly larger in the superior nasal region than in the nasal inferior area. Conclusion: Other than occurring in a diffuse way, glaucomatous neuroretinal rim loss took place in a sequence of sectors. Generally, it began in the inferotemporal disc region and then progressed to the superotemporal, the temporal horizontal, the inferior nasal, and finally the superior nasal sectors. This correlates with the progression of visual field defects and the morphology of the lamina cribrosa. This finding may be important for "early" glaucoma diagnosis. Ophthalmology 1993;100:63-68
When leaving the eye, the retinal nerve fibers form the neuroretinal rim in the optic nerve head. In visually normal eyes, the rim shows a characteristic shape: it is widest in the inferior disc region, followed by the superior and the nasal regions. It is most narrow in the temporal disc sector (Fig 1). 1 This regional distribution of rim width is correlated with ( 1) the visibility of the retinal nerve fiber bundles that usually are better detected in the inferotemporal fundus region than in the superotemporal region2; Originally received: May II, 1992. Revision accepted: August 21, 1992. 1 Department of Ophthalmology and Eye Hospital, University ErlangenNiimberg, Germany. 2 University Hospital, Ophthalmology Department, Zurich, Switzerland. Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting, Sarasota, May 1992. Supported by funds from Deutsche Forschungsgemeinschaft (Klinische Forschergruppe "Glaukome," DFG Na 55/6-1/Jo). Reprint requests to Jost B. Jonas, MD, University Eye Hospital, Schwabachanlage 6, D-8520 Erlangen, Germany.
(2) the diameter of the retinal vessels being larger in the inferotemporal arcade than in the superotemporal arcade 3; (3) the location of the foveola approximately 0.5 mm inferior to a line passing through the optic disc cente~; and (4) the morphology of the inner surface of the lamina cribrosa with the largest pores and the highest summed pore area in the inferior and superior regions and the smallest pores and lowest summed pore area in the nasal and temporal areas. 4 •5 In glaucomatous optic nerve fiber loss, this characteristic rim shape is continuously changing with the progressively decreasing rim area. The current cross-sectional study was performed to examine the pattern of glaucomatous neuroretinal rim loss.
Materials and Methods The study included the optic disc photographs of 801 glaucomatous eyes and 496 visually normal eyes (Table 1). These were the eyes of visually normal subjects and glaucoma patients who were evaluated as part of an on-
63
Top left, Figure 1. Photograph of an abnormally large but otherwise normal disc with normal shape of the neuroretinal rim; the rim is widest in the inferior disc region, followed by the superior, the nasal, and finally the temporal disc regions. Optic disc area: 3.67 mm2 ; rim area: 1.54 mm2 • Center left, Figure 2A. Optic disc photograph with moderate glaucomatous damage. Notice that the neuroretinal rim is almost even all around. A localized retinal nerve fiber defect is detectable at the 12-o'clock position (white arrowheads). Optic disc area: 2.84 mm2; rim area: 1.49 mm2• Bottom left, Figure 2B. Retinal nerve fiber layer photograph of the eye shown in Figure 2A. Localized retinal nerve fiber layer defects at the 12o'clock and 2-o'clock positions (white arrowheads). Top right, Figure 3. Optic disc photograph with medium advanced glaucomatous optic nerve damage. Neuroretinal rim notching is seen in the inferotemporal disc region. Optic disc area: 2.45 mm2; rim area: 1.02 mm2 • Center right, Figure 4. Optic disc photograph with markedly advanced glaucomatous optic nerve damage. Notice that the neuroretinal rim is widest in the superior nasal disc region and smallest in the inferotemporal disc area. This is in spatial correlation with the parapapillary atrophy and optic disc hemorrhage. Optic disc area: 2.48 mm2; rim area: 0.72 mm2 • Bottom right, Figure 5. Optic disc photograph with very advanced glaucomatous optic nerve damage. Neuroretinal rim is absent in the temporal horizontal disc region; rim in the superior nasal disc region is larger than in the inferior nasal disc area; rim at the 12-o'clock position is wider than at the 6-o'clock position. Parapapillary atrophy is spatially correlated with rim loss. Optic disc area: 2.56 mm2; rim area: 0.59 mm2 •
64
Jonas et al · Glaucomatous Neuroretinal Rim Loss Table 1. Composition of the Glaucoma and Control Groups Glaucoma Group Eyes . Right/left eyes Individuals Men/women Age (yrs) Mean± SD Minimum to maximum Refractive error Mean± SD Minimum to maximum SD
=
standard deviation; D
=
Control Group
801 411/390 448 232/216
496 237/259 290 138/152
64.3 ± 13.6 9 to 94
4 to 82
-0.62 ± 2.35 D -7.25 D to +7.0 D
0.07 ± 0.191 D -7.9 D to +6.5 D
46.8 ± 17.7
diopters.
going prospective study of the biomorphometry of the optic nerve. Eyes with a myopic refractive error exceeding -8 diopters were excluded because of different optic disc morphology. 6 Criteria for the diagnosis of glaucoma, all of which had to be fulfilled, were ( 1) intraocular pressure greater than 21 mmHg; (2) glaucomatous changes of the optic nerve head such as unusual small neuroretinal rim area in relation to the optic disc size, cup-to-disc ratios that were higher vertically than horizontally, or splintershaped optic disc hemorrhages; (3) reduced visibility of the retinal nerve fiber bundles, including localized defects; and (4) glaucomatous visual field defects. The latter comprised nasal steps of at least 10°, paracentral isolated or confluent scotomata and visual field indices elevated above the normal range in the computerized perimetric tests. The visually normal group included subjects who came to the eye clinic or hospital for an ocular examination, prescription for glasses, or diseases of the contralateral eye that was not included in the study. These diseases (e.g., perforating corneal injuries) did not primarily affect the optic nerve. The differences in age and refractive error between the visually normal and glaucomatous eyes were significant. Although size and form of optic disc and neuroretinal rim have been reported to be independent of age, 1•7 a control group matched for age and refractive error with the glaucoma group was formed. This control group consisted of 273 eyes of 179 subjects with a mean age of 65.1 ± 6.5 years and a mean refractive error of -0.40 ± 1.80 diopters (-7.0 to 7.50 diopters). For all eyes, 15° color stereo optic disc photographs were taken using a telecentric fundus camera equipped with an Allen stereo separator. The disc transparencies were projected on a scale of 1 to 15. The outlines of the optic disc and optic cup were plotted on paper and analyzed morphometrically. We measured area and horizontal, vertical, minimal, and maximal diameters of the disc and cup, and width of the neuroretinal rim determined every 30°. To obtain values in absolute size units (millimeter or square millimeter) the ocular and photographic magni-
fication was corrected according to Littmann's method, noting the ametropia and the anterior corneal curvature. 8 The photographs were evaluated in a masked fashion without knowledge of the clinical diagnosis and the visual field data. The optic cup was stereoscopically defined on the basis of contour and not of pallor. The border of the optic disc was identical with the inner side of the peripapillary scleral ring. The latter was a thin white band encircling the optic disc. If no cupping was present, as was the case in many small optic discs, 1•7•9 •10 the neuroretinal rim was identical with the disc area. This method has been described in detail previously. 11 For interindividual comparison, only one randomly selected eye per patient and subject was taken for statistical analysis. To examine the significance of differences, Wilcoxon and Mann-Whitney tests were applied.
Results Neuroretinal Rim Shape in Visually Normal Eyes In the visually normal eyes, the neuroretinal rim was significantly (P < 0.001, Wilcoxon-test) wider in the inferior disc region than in the superior disc area, where it was significantly (P < 0.001) wider than in the nasal region. It was smallest in the temporal disc area (P < 0.001) (Table 2). Depending on the neuroretinal rim form, with the rim being smaller at the horizontal disc poles than in the vertical disc regions, the horizontal cup-to-disc ratios were significantly (P < 0.001; Wilcoxon-test) higher than the vertical ratios. The morphometric rim data did not differ significantly between the two control groups unmatched or matched with the glaucoma group.
Neuroretinal Rim Shape in Glaucomatous Eyes To examine the pattern of glaucomatous neuroretinal rim loss, the glaucoma group was divided into five subgroups with respect to increasing glaucomatous optic nerve dam-
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Ophthalmology
Volume 100, Number 1, January 1993
Table 2. Width (mm) of the Neuroretinal Rim (Mean and Standard Deviation) in Normal and Glaucomatous Eyes*
Number 1 o'clock 2 o'clock 3 o'clock 4 o'clock 5 o'clock 6 o'clock 7 o'clock 8 o'clock 9 o'clock 10 o'clock 11 o'clock 12 o'clock
Normals Unmatched
Normals Matched
290 0.45 ± 0.14 0.38 ± 0.15 0.34 ± 0.16 0.39 ± 0.19 0.47 ± 0.15 0.52 ± 0.13 0.50 ± 0.13 0.47 ± 0.13 0.46 ± 0.13 0.48 ± 0.14 0.50 ± 0.14 0.49 ± 0.14
179 0.46 ± 0.16 0.39 ± 0.16 0.35 ± 0.17 0.39 ± 0.16 0.47 ± 0.16 0.52 ± 0.15 0.50 ± 0.15 0.46 ± 0.15 0.46 ± 0.15 0.48 ± 0.15 0.50 ± 0.16 0.50 ± 0.16
Glaucoma Rim Area > 1.6 mm2
± 0.14 9% ± 0.14 8% ± 0.14 3% ± 0.13 5% ± 0.13 11% ± 0.14 15% ± 0.13 10% ± 0.12 0% ± 0.13 4% ± 0.14 4% ± 0.15 8% ± 0.15 12%
0.30 0.27 0.24 0.27 0.29 0.32 0.32 0.32 0.33 0.35 0.34 0.33
Glaucoma 0.8 mm2 ?: rim >0.4mm2
Glaucoma 0.40 mm2 ?: rim >0mm2
89
88 0.02 ± 0.08 96% 0.01 ± 0.07 97% 0.01 ± 0.07 97% 0.01 ± 0.08 96% 0.02 ± 0.08 94% 0.03 ± 0.08 94% 0.05 ± 0.08 90% O.D7 ± 0.09 85% 0.08 ± 0.09 83% 0.08 ± 0.09 83% 0.08 ± 0.08 84% 0.06 ± 0.08 88%
118
92
61 0.42 0.36 0.34 0.37 0.42 0.44 0.45 0.47 0.44 0.46 0.46 0.44
Glaucoma 1.2mm2 ?:rim >0.8mm2
Glaucoma 1.6 mm2 ?: rim > 1.2 mm2
± 0.09 35% ± 0.16 31% ± 0.09 31% ± 0.16 31% ± 0.09 38% ± 0.10 38% ± 0.08 36% ± O.D7 30% ± O.D7 28% ± 0.07 27% ± 0.09 32% ± 0.10 34%
0.19 0.16 0.15 0.15 0.18 0.21 0.24 0.25 0.25 0.26 O.H 0.21
± 0.08 59% ± 0.08 59% ± 0.08 57% ± 0.08 62% ± 0.09 62% ± 0.08 60% ± 0.06 52% ± 0.06 46% ± O.D7 46% ± 0.07 46% ± 0.07 52% ± 0.08 58%
0.10 0.07 0.06 0.06 0.08 0.12 0.17 0.17 0.18 0.21 0.19 0.13
± 0.16 78% ± 0.12 82% ± 0.07 83% ± 0.14 85% ± 0.16 83% ± 0.20 77% ± 0.21 66% ± 0.07 63% ± 0.06 61% ± 0.18 56% ± 0.23 62% ± 0.07 74%
*Rim width counted in a clockwise manner in left eyes and in a counter clockwise manner in right eyes (1 o'clock =superior temporal; 5 o'clock = inferior temporal). Percentage figures indicate loss in rim width as compared with the normal group matched with the glaucoma group.
age (Table 2). The glaucomatous eyes were compared with the control eyes that were matched by age and refractive error with the glaucoma group. In the glaucoma subgroup with modest loss of visual field and neuroretinal rim (mean visual field defect: 3.3 ± 4.2 decibels [dB]; neuroretinal rim area > 1.60 mm 2), the decrease in rim width was most marked at the inferior disc pole (loss in rim width: 15% ). It was second most pronounced at the superior disc area (loss in rim width: 12%). In the temporal disc area (loss in rim width: 3%) and nasal disc region (loss in rim width: 4% ), the decrease in rim width was least marked (Table 2). In the glaucoma subgroup following next in severity of glaucomatous damage (mean visual field defect: 4.4 ± 4. 7 dB; 1.60 mm 2 ~ rim area > 1.20 mm 2), a similar pattern of rim loss was more clearly detectable. Rim loss was relatively largest at the inferior disc region (loss in rim width: 38% ), followed by the superior disc region (loss in rim width: 34%) and the temporal horizontal disc area (loss in rim width: 31% ). It was least pronounced in the nasal disc region (loss in rim width: 28%) (Table 2). In the third glaucoma subgroup with medium advanced optic nerve damage (mean visual field defect: 7.3 ± 5.0 dB; 1.20 mm2 ~ rim area > 0.80 mm2 ), the diminution in rim width was about equal at the inferior disc region (loss in rim width: 60% ), the temporal disc area (loss in rim width: 57%), and the superior region (loss in rim width: 58%). Again, it was least pronounced in the nasal area (loss in rim width: 46% ). In the glaucoma subgroup with advanced optic nerve atrophy (mean visual field defect: 13.4 ± 6.3 dB; 0.80 mm 2 ~ rim area > 0.40 mm 2), the most marked rim loss occurred in the temporal horizontal disc sector (loss in rim width: 83% ). Again, it was least marked in the nasal region (loss in rim width: 56%).
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In the subgroup with severe glaucomatous damage (mean visual field defect: 18.1 ± 7.1 dB; 0.40 mm 2 ~ rim area > 0.00 mm 2), the rim remnants were significantly largest at the nasal upper disc region (loss in rim width: 83%), followed by the nasal lower disc region (loss in rim width: 85% ), the superior disc pole (loss in rim width: 88% ), the inferior disc pole (loss in rim width: 94% ), and the temporal horizontal disc region (loss in rim width: 97%) (Table 2). At all stages of the disease, rim loss was present in all sectors (Table 2). The location of the most pronounced rim loss changed depending on the severity of the glaucomatous damage. If the visually normal and glaucomatous eyes were divided into three subgroups with respect to the optic disc size, this pattern of glaucomatous neuroretinal rim loss did not differ between the subgroups. Neuroretinal rim notches occurred significantly more often (P < 0.001) in the inferotemporal disc sector than in the superotemporal sector.
Discussion Compared with normal globes, glaucomatous neuroretinal rim loss occurred in all sectors of the optic disc with regional preferences depending on the stage of the disease (Figs 1-5) (Table 2). In eyes with modest glaucomatous damage, rim loss was found predominantly at the inferotemporal disc region followed by the superotemporal disc area. In eyes with moderately advanced glaucomatous atrophy, the temporal horizontal disc region was the location with relatively the most marked rim loss. In very advanced glaucoma, the rim remnants were located mainly in the nasal disc sector, with a larger rim portion in the upper nasal region than in the lower nasal region.
Jonas et al · Glaucomatous Neuroretinal Rim Loss This pattern of glaucomatous neuroretinal rim loss (inferotemporal - superotemporal - temporal horizontal nasal inferior - nasal superior) was independent of the optic disc size. The results confirm a recent investigation by Tuulonen and Airaksinen. 12 These authors evaluated stereo disc photographs of23 ocular hypertensive eyes that eventually developed visual field defects in a 10-year follow-up period. Ten eyes showed focal notching of the neuroretinal rim, four times in the inferotemporal sector, four times in the superotemporal sector, and twice in both sectors. On disc photographs taken during a follow-up examination, the focal notching changed to a diffuse vertical enlargement of the cup in eight eyes and to a broader local notch in two eyes. In another set often eyes, a diffuse cup enlargement was observed. Five of these eyes later changed to a diffuse cup enlargement, mainly in the vertical direction. In three eyes, no alteration of the rim configuration was detected. In the follow-up study by Tuulonen and Airaksinen, and in our cross-sectional investigation, the first disc changes were observed mainly at the inferotemporal and superotemporal disc regions, resulting in a vertical cup enlargement. The current study confirms other reports on a vertical elongation of the optic cup in medium advanced glaucoma.13-20 It is in agreement with investigations of"early" glaucomatous changes of the optic disc. In a longitudinal study, Pederson and Anderson 21 examined 259 eyes of ocular hypertensive subjects. In 29 eyes, there was an enlargement of the optic cup after a maximum follow-up period of 15 years. In 23 eyes, the cup extension was described as general extension in the vertical and horizontal direction, 5 eyes showed an enlargement mainly in the vertical direction, and in 1 eye the cup was enlarged mainly in the horizontal direction. The general extension of the optic cup in these eyes with beginning glaucomatous optic nerve damage can be interpreted as a neuroretinal rim loss predominantly in the inferior and superior disc regions. This would convert the normal rim configuration with the widest parts in the inferior and superior disc areas into a rim being even in width at all points. It would change the shape of the optic cup from a horizontally oval form to a circular form. The pattern of glaucomatous neuroretinal rim loss (inferotemporal and superotemporal - temporal horizontal - inferonasal - superonasal) agrees with visual field studies. The perimetric defects to be found in early glaucoma were described as occurring mostly in the upper nasal visual field quadrant2 2 or the superior and inferior Bjerrum areas. 23-25 The remaining visual field islands in eyes with very advanced glaucomatous optic nerve damage were usually present in the inferotemporal part of the visual field. The finding that the glaucomatous rim loss occurred in a diffuse and localized manner may be important for the discussion on the localized versus diffuse visual field loss.26,27 Extrapolating the data of this study to subjects with ocular hypertension, it may indicate that subjects with ocular hypertension, especially in the inferotemporal optic
disc sector, should be checked for glaucomatous alterations. For that purpose, one must take into account that in visually normal eyes the neuroretinal rim is not even at all locations but is widest in the inferior disc region and smallest in the temporal horizontal disc sector (Fig 1). Consequently, a neuroretinal rim shape being equal in width in the inferotemporal disc sector and the temporal horizontal disc region could indicate glaucomatous optic nerve damage. This may be important, especially for eyes with "early" glaucomatous damage. It must be emphasized that the pattern of rim loss as described in the current study is based on a general statistical analysis. For the individual patient and eye, many exceptions may be valid. They will depend on the parametersinfluencingtheregionalglaucomatousvulnerability inside the optic disc. These factors may be ( 1) the physiologic configuration of the rim being broader at the inferior and superior disc poles than at the nasal and temporal poles 1; (2) the morphology of the inner surface of the lamina cribrosa with the larger pores and the higher ratio of pore to interpore connective tissue area in the inferior and superior regions as compared to the temporal and nasal regions4•5·28 ; a high ratio of pore area to total area is considered to predispose to glaucomatous nerve fiber loss; (3) the glaucomatous bowing of the lamina cribrosa to the outside mainly in the inferior and superior disc regions as shown on scanning electron microscopic photographs of glaucomatous eyes 29; and (4) the regional distribution of thin and thick retinal nerve fibers, with thin nerve fibers coming from the foveola, passing through the temporal aspect of the optic disc, and being less susceptible to glaucoma than thick nerve fibers, which originate predominantly in the fundus periphery, lead to the inferior, superior, and nasal disc regions, 30·31 and are more sensitive to glaucoma than thin retinal ganglion cell axons. 32 The latter parameter may explain why glaucomatous rim loss occurs later in the temporal horizontal disc sector with predominantly thin nerve fibers than in the inferotemporal or superotemporal disc sectors containing thin and thick axons. It is contradictory to the fact that in far advanced glaucoma, rim remnants are usually located in the nasal disc sector. There, preferentially thick retinal ganglion cell axons leave the eye. 30
References l. Jonas JB, Gusek GC, Naumann GOH. Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. Invest Ophthalmol Vis Sci 1988;29:1151-8. 2. Jonas JB, Nguyen NX, Naumann GOH. The retinal nerve fiber layer in normal eyes. Ophthalmology 1989;96:627-32. 3. Jonas JB, Nguyen XN, Naumann GOH. Parapapillary retinal vessel diameter in normal and glaucoma eyes. I. Morphometric data. Invest Ophthalmol Vis Sci 1989;30:15991603. 4. Radius RL. Regional specificity in anatomy at the lamina cribrosa. Arch Ophthalmol 1981;99:478-80.
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Ophthalmology Volume 100, Number 1, January 1993 5. Quigley HA, Addicks EM. Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthalmol 1981 ;99: 13 743. 6. Jonas JB, Gusek GC, Naumann GOH. Optic disk morphometry in high myopia. Graefes Arch Clin Exp Ophthalmol 1988;226:587-90. 7. Britton RJ, Drance SM, Schulzer M, et al. The area of the neuroretinal rim of the optic nerve in normal eyes. Am J Ophthalmol 1987;103:497-504. 8. Littmann H. Zur Bestimmung der wahren GroBe eines Objektes auf dem Hintergrund des lebenden Auges. Klin Monatsbl Augenheilkd 1982; 180:286-9. 9. Betz Ph, Camps Fr, Collignon-Brach C, Weekers R. Photographie stereoscopique et photogrammetrie de !'excavation physiologique de la papille. J Fr Ophtalmol 1981 ;4: 193203. 10. Caprioli J Miller JM. Optic disc rim area is related to disc size in normal subjects. Arch Ophthalmol 1987;105:1683-5. 11. Airaksinen PJ, Drance SM, Douglas GR, Schulzer M. Neuroretinal rim areas and visual field indices in glaucoma. Am J Ophthalmol 1985;99:107-10. 12. Tuulonen A, Airaksinen PJ. Initial glaucomatous optic disk and retinal nerve fiber layer abnormalities and their progression. Am J Ophthalmol 1991; Ill :485-90. 13. Armaly MF. Cup/disc ratio in early open-angle glaucoma. Doc Ophthalmol 1969;26:526-33. 14. Becker B. Cup/disc ratio and topical corticosteroid testing. Am J Ophthalmol 1970;70:681-5. 15. Kirsch RE, Anderson DR. Clinical recognition of glaucomatous cupping. Am J Ophthalmol 1973;75:442-54. 16. Gloster J. Vertical ovalness of glaucomatous cupping. Br J Ophthalmol 1975;59:721-4. 17. Hart WM Jr, Yablonski M, Kass MA, Becker B. Quantitative visual field and optic disc correlates early in glaucoma. Arch Ophthalmol 1978;96:2209-11. 18. Radius RL, Maumenee AE. Optic atrophy and glaucomatous cupping. Am J Ophthalmol 1978;85:145-53. 19. Herschler J, Osher RH. Baring of the circumlinear vessel. An early sign of optic nerve damage. Arch Ophthalmol 1980;98:865-9.
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20. Betz Ph, Camps F, Collignon-Brach J, et al. Biometric study of the disc cup in open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol 1982;218:70-4. 21. Pederson JE, Anderson DR. The mode of progressive disc cupping in ocular hypertension and glaucoma. Arch Ophthalmol 1980;98:490-5. 22. Gramer E, Gerlach R, Krieglstein GK, Leydhecker W. Zur Topographie friiher glaukomatoser Gesichtsfeldausfalle bei der Computerperimetrie. Klin Monatsbl Augenheilk 1982; 180:515-23. 23. Drance SM. The early field defects in glaucoma. Invest Ophthalmol 1969;8:84-91. 24. Hart WM Jr, Becker B. The onset and evolution of glaucomatous visual field defects. Ophthalmology 1982;89:26879. 25. Caprioli J, Sears M, Miller JM. Patterns of early visual field loss in open-angle glaucoma. Am J Ophthalmol 1987;103: 512-17. 26. Glowazki A, Flammer J. Is there a difference between glaucoma patients with rather localized visual field damage and patients with more diffuse visual field damage? In: Greve EL, Heijl A, eds. Seventh Int'l Visual Field Symposium. Dordrecht: Martinus Nijhoff/Dr W. Junk, 1987;317-20 (Doc Ophthalmol Proc Ser; 49). 27. Drance SM. Diffuse visual field loss in open-angle glaucoma. Ophthalmology 1991 ;98: 1533-8. 28. Jonas JB, Mardin CY, SchlOtzer-Schrehardt U, Naumann GOH. Morphometry of the human lamina cribrosa surface. Invest Ophthalmol Vis Sci 1991;32:401-5. 29. Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol 1981 ;99: 635-49. 30. Sanchez RM, Dunkelberger GR, Quigley HA. The number and diameter distribution of axons in the monkey optic nerve. Invest Ophthalmol Vis Sci 1986;27:1342-50. 31. Jonas JB, Miiller-Bergh JA, SchlOtzer-Schrehardt UM, Naumann GOH. Histomorphometry of the human optic nerve. Invest Ophthalmol Vis Sci 1990;31:736-44. 32. Quigley HA, Sanchez RM, Dunkelberger GR, et al. Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci 1987;28:913-20.
When leaving the eye, the retinal nerve fibers form the neuroretinal rim in the optic nerve head. In visually normal eyes, the rim shows a characteristic shape: it is widest in the inferior disc region, followed by the superior and the nasal regions. It is most narrow in the temporal disc sector (Fig 1). 1 This regional distribution of rim width is correlated with ( 1) the visibility of the retinal nerve fiber bundles that usually are better detected in the inferotemporal fundus region than in the superotemporal region2; Originally received: May II, 1992. Revision accepted: August 21, 1992. 1 Department of Ophthalmology and Eye Hospital, University ErlangenNiimberg, Germany. 2 University Hospital, Ophthalmology Department, Zurich, Switzerland. Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting, Sarasota, May 1992. Supported by funds from Deutsche Forschungsgemeinschaft (Klinische Forschergruppe "Glaukome," DFG Na 55/6-1/Jo). Reprint requests to Jost B. Jonas, MD, University Eye Hospital, Schwabachanlage 6, D-8520 Erlangen, Germany.
(2) the diameter of the retinal vessels being larger in the inferotemporal arcade than in the superotemporal arcade 3; (3) the location of the foveola approximately 0.5 mm inferior to a line passing through the optic disc cente~; and (4) the morphology of the inner surface of the lamina cribrosa with the largest pores and the highest summed pore area in the inferior and superior regions and the smallest pores and lowest summed pore area in the nasal and temporal areas. 4 •5 In glaucomatous optic nerve fiber loss, this characteristic rim shape is continuously changing with the progressively decreasing rim area. The current cross-sectional study was performed to examine the pattern of glaucomatous neuroretinal rim loss.
Materials and Methods The study included the optic disc photographs of 801 glaucomatous eyes and 496 visually normal eyes (Table 1). These were the eyes of visually normal subjects and glaucoma patients who were evaluated as part of an on-
63
Top left, Figure 1. Photograph of an abnormally large but otherwise normal disc with normal shape of the neuroretinal rim; the rim is widest in the inferior disc region, followed by the superior, the nasal, and finally the temporal disc regions. Optic disc area: 3.67 mm2 ; rim area: 1.54 mm2 • Center left, Figure 2A. Optic disc photograph with moderate glaucomatous damage. Notice that the neuroretinal rim is almost even all around. A localized retinal nerve fiber defect is detectable at the 12-o'clock position (white arrowheads). Optic disc area: 2.84 mm2; rim area: 1.49 mm2• Bottom left, Figure 2B. Retinal nerve fiber layer photograph of the eye shown in Figure 2A. Localized retinal nerve fiber layer defects at the 12o'clock and 2-o'clock positions (white arrowheads). Top right, Figure 3. Optic disc photograph with medium advanced glaucomatous optic nerve damage. Neuroretinal rim notching is seen in the inferotemporal disc region. Optic disc area: 2.45 mm2; rim area: 1.02 mm2 • Center right, Figure 4. Optic disc photograph with markedly advanced glaucomatous optic nerve damage. Notice that the neuroretinal rim is widest in the superior nasal disc region and smallest in the inferotemporal disc area. This is in spatial correlation with the parapapillary atrophy and optic disc hemorrhage. Optic disc area: 2.48 mm2; rim area: 0.72 mm2 • Bottom right, Figure 5. Optic disc photograph with very advanced glaucomatous optic nerve damage. Neuroretinal rim is absent in the temporal horizontal disc region; rim in the superior nasal disc region is larger than in the inferior nasal disc area; rim at the 12-o'clock position is wider than at the 6-o'clock position. Parapapillary atrophy is spatially correlated with rim loss. Optic disc area: 2.56 mm2; rim area: 0.59 mm2 •
64
Jonas et al · Glaucomatous Neuroretinal Rim Loss Table 1. Composition of the Glaucoma and Control Groups Glaucoma Group Eyes . Right/left eyes Individuals Men/women Age (yrs) Mean± SD Minimum to maximum Refractive error Mean± SD Minimum to maximum SD
=
standard deviation; D
=
Control Group
801 411/390 448 232/216
496 237/259 290 138/152
64.3 ± 13.6 9 to 94
4 to 82
-0.62 ± 2.35 D -7.25 D to +7.0 D
0.07 ± 0.191 D -7.9 D to +6.5 D
46.8 ± 17.7
diopters.
going prospective study of the biomorphometry of the optic nerve. Eyes with a myopic refractive error exceeding -8 diopters were excluded because of different optic disc morphology. 6 Criteria for the diagnosis of glaucoma, all of which had to be fulfilled, were ( 1) intraocular pressure greater than 21 mmHg; (2) glaucomatous changes of the optic nerve head such as unusual small neuroretinal rim area in relation to the optic disc size, cup-to-disc ratios that were higher vertically than horizontally, or splintershaped optic disc hemorrhages; (3) reduced visibility of the retinal nerve fiber bundles, including localized defects; and (4) glaucomatous visual field defects. The latter comprised nasal steps of at least 10°, paracentral isolated or confluent scotomata and visual field indices elevated above the normal range in the computerized perimetric tests. The visually normal group included subjects who came to the eye clinic or hospital for an ocular examination, prescription for glasses, or diseases of the contralateral eye that was not included in the study. These diseases (e.g., perforating corneal injuries) did not primarily affect the optic nerve. The differences in age and refractive error between the visually normal and glaucomatous eyes were significant. Although size and form of optic disc and neuroretinal rim have been reported to be independent of age, 1•7 a control group matched for age and refractive error with the glaucoma group was formed. This control group consisted of 273 eyes of 179 subjects with a mean age of 65.1 ± 6.5 years and a mean refractive error of -0.40 ± 1.80 diopters (-7.0 to 7.50 diopters). For all eyes, 15° color stereo optic disc photographs were taken using a telecentric fundus camera equipped with an Allen stereo separator. The disc transparencies were projected on a scale of 1 to 15. The outlines of the optic disc and optic cup were plotted on paper and analyzed morphometrically. We measured area and horizontal, vertical, minimal, and maximal diameters of the disc and cup, and width of the neuroretinal rim determined every 30°. To obtain values in absolute size units (millimeter or square millimeter) the ocular and photographic magni-
fication was corrected according to Littmann's method, noting the ametropia and the anterior corneal curvature. 8 The photographs were evaluated in a masked fashion without knowledge of the clinical diagnosis and the visual field data. The optic cup was stereoscopically defined on the basis of contour and not of pallor. The border of the optic disc was identical with the inner side of the peripapillary scleral ring. The latter was a thin white band encircling the optic disc. If no cupping was present, as was the case in many small optic discs, 1•7•9 •10 the neuroretinal rim was identical with the disc area. This method has been described in detail previously. 11 For interindividual comparison, only one randomly selected eye per patient and subject was taken for statistical analysis. To examine the significance of differences, Wilcoxon and Mann-Whitney tests were applied.
Results Neuroretinal Rim Shape in Visually Normal Eyes In the visually normal eyes, the neuroretinal rim was significantly (P < 0.001, Wilcoxon-test) wider in the inferior disc region than in the superior disc area, where it was significantly (P < 0.001) wider than in the nasal region. It was smallest in the temporal disc area (P < 0.001) (Table 2). Depending on the neuroretinal rim form, with the rim being smaller at the horizontal disc poles than in the vertical disc regions, the horizontal cup-to-disc ratios were significantly (P < 0.001; Wilcoxon-test) higher than the vertical ratios. The morphometric rim data did not differ significantly between the two control groups unmatched or matched with the glaucoma group.
Neuroretinal Rim Shape in Glaucomatous Eyes To examine the pattern of glaucomatous neuroretinal rim loss, the glaucoma group was divided into five subgroups with respect to increasing glaucomatous optic nerve dam-
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Ophthalmology
Volume 100, Number 1, January 1993
Table 2. Width (mm) of the Neuroretinal Rim (Mean and Standard Deviation) in Normal and Glaucomatous Eyes*
Number 1 o'clock 2 o'clock 3 o'clock 4 o'clock 5 o'clock 6 o'clock 7 o'clock 8 o'clock 9 o'clock 10 o'clock 11 o'clock 12 o'clock
Normals Unmatched
Normals Matched
290 0.45 ± 0.14 0.38 ± 0.15 0.34 ± 0.16 0.39 ± 0.19 0.47 ± 0.15 0.52 ± 0.13 0.50 ± 0.13 0.47 ± 0.13 0.46 ± 0.13 0.48 ± 0.14 0.50 ± 0.14 0.49 ± 0.14
179 0.46 ± 0.16 0.39 ± 0.16 0.35 ± 0.17 0.39 ± 0.16 0.47 ± 0.16 0.52 ± 0.15 0.50 ± 0.15 0.46 ± 0.15 0.46 ± 0.15 0.48 ± 0.15 0.50 ± 0.16 0.50 ± 0.16
Glaucoma Rim Area > 1.6 mm2
± 0.14 9% ± 0.14 8% ± 0.14 3% ± 0.13 5% ± 0.13 11% ± 0.14 15% ± 0.13 10% ± 0.12 0% ± 0.13 4% ± 0.14 4% ± 0.15 8% ± 0.15 12%
0.30 0.27 0.24 0.27 0.29 0.32 0.32 0.32 0.33 0.35 0.34 0.33
Glaucoma 0.8 mm2 ?: rim >0.4mm2
Glaucoma 0.40 mm2 ?: rim >0mm2
89
88 0.02 ± 0.08 96% 0.01 ± 0.07 97% 0.01 ± 0.07 97% 0.01 ± 0.08 96% 0.02 ± 0.08 94% 0.03 ± 0.08 94% 0.05 ± 0.08 90% O.D7 ± 0.09 85% 0.08 ± 0.09 83% 0.08 ± 0.09 83% 0.08 ± 0.08 84% 0.06 ± 0.08 88%
118
92
61 0.42 0.36 0.34 0.37 0.42 0.44 0.45 0.47 0.44 0.46 0.46 0.44
Glaucoma 1.2mm2 ?:rim >0.8mm2
Glaucoma 1.6 mm2 ?: rim > 1.2 mm2
± 0.09 35% ± 0.16 31% ± 0.09 31% ± 0.16 31% ± 0.09 38% ± 0.10 38% ± 0.08 36% ± O.D7 30% ± O.D7 28% ± 0.07 27% ± 0.09 32% ± 0.10 34%
0.19 0.16 0.15 0.15 0.18 0.21 0.24 0.25 0.25 0.26 O.H 0.21
± 0.08 59% ± 0.08 59% ± 0.08 57% ± 0.08 62% ± 0.09 62% ± 0.08 60% ± 0.06 52% ± 0.06 46% ± O.D7 46% ± 0.07 46% ± 0.07 52% ± 0.08 58%
0.10 0.07 0.06 0.06 0.08 0.12 0.17 0.17 0.18 0.21 0.19 0.13
± 0.16 78% ± 0.12 82% ± 0.07 83% ± 0.14 85% ± 0.16 83% ± 0.20 77% ± 0.21 66% ± 0.07 63% ± 0.06 61% ± 0.18 56% ± 0.23 62% ± 0.07 74%
*Rim width counted in a clockwise manner in left eyes and in a counter clockwise manner in right eyes (1 o'clock =superior temporal; 5 o'clock = inferior temporal). Percentage figures indicate loss in rim width as compared with the normal group matched with the glaucoma group.
age (Table 2). The glaucomatous eyes were compared with the control eyes that were matched by age and refractive error with the glaucoma group. In the glaucoma subgroup with modest loss of visual field and neuroretinal rim (mean visual field defect: 3.3 ± 4.2 decibels [dB]; neuroretinal rim area > 1.60 mm 2), the decrease in rim width was most marked at the inferior disc pole (loss in rim width: 15% ). It was second most pronounced at the superior disc area (loss in rim width: 12%). In the temporal disc area (loss in rim width: 3%) and nasal disc region (loss in rim width: 4% ), the decrease in rim width was least marked (Table 2). In the glaucoma subgroup following next in severity of glaucomatous damage (mean visual field defect: 4.4 ± 4. 7 dB; 1.60 mm 2 ~ rim area > 1.20 mm 2), a similar pattern of rim loss was more clearly detectable. Rim loss was relatively largest at the inferior disc region (loss in rim width: 38% ), followed by the superior disc region (loss in rim width: 34%) and the temporal horizontal disc area (loss in rim width: 31% ). It was least pronounced in the nasal disc region (loss in rim width: 28%) (Table 2). In the third glaucoma subgroup with medium advanced optic nerve damage (mean visual field defect: 7.3 ± 5.0 dB; 1.20 mm2 ~ rim area > 0.80 mm2 ), the diminution in rim width was about equal at the inferior disc region (loss in rim width: 60% ), the temporal disc area (loss in rim width: 57%), and the superior region (loss in rim width: 58%). Again, it was least pronounced in the nasal area (loss in rim width: 46% ). In the glaucoma subgroup with advanced optic nerve atrophy (mean visual field defect: 13.4 ± 6.3 dB; 0.80 mm 2 ~ rim area > 0.40 mm 2), the most marked rim loss occurred in the temporal horizontal disc sector (loss in rim width: 83% ). Again, it was least marked in the nasal region (loss in rim width: 56%).
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In the subgroup with severe glaucomatous damage (mean visual field defect: 18.1 ± 7.1 dB; 0.40 mm 2 ~ rim area > 0.00 mm 2), the rim remnants were significantly largest at the nasal upper disc region (loss in rim width: 83%), followed by the nasal lower disc region (loss in rim width: 85% ), the superior disc pole (loss in rim width: 88% ), the inferior disc pole (loss in rim width: 94% ), and the temporal horizontal disc region (loss in rim width: 97%) (Table 2). At all stages of the disease, rim loss was present in all sectors (Table 2). The location of the most pronounced rim loss changed depending on the severity of the glaucomatous damage. If the visually normal and glaucomatous eyes were divided into three subgroups with respect to the optic disc size, this pattern of glaucomatous neuroretinal rim loss did not differ between the subgroups. Neuroretinal rim notches occurred significantly more often (P < 0.001) in the inferotemporal disc sector than in the superotemporal sector.
Discussion Compared with normal globes, glaucomatous neuroretinal rim loss occurred in all sectors of the optic disc with regional preferences depending on the stage of the disease (Figs 1-5) (Table 2). In eyes with modest glaucomatous damage, rim loss was found predominantly at the inferotemporal disc region followed by the superotemporal disc area. In eyes with moderately advanced glaucomatous atrophy, the temporal horizontal disc region was the location with relatively the most marked rim loss. In very advanced glaucoma, the rim remnants were located mainly in the nasal disc sector, with a larger rim portion in the upper nasal region than in the lower nasal region.
Jonas et al · Glaucomatous Neuroretinal Rim Loss This pattern of glaucomatous neuroretinal rim loss (inferotemporal - superotemporal - temporal horizontal nasal inferior - nasal superior) was independent of the optic disc size. The results confirm a recent investigation by Tuulonen and Airaksinen. 12 These authors evaluated stereo disc photographs of23 ocular hypertensive eyes that eventually developed visual field defects in a 10-year follow-up period. Ten eyes showed focal notching of the neuroretinal rim, four times in the inferotemporal sector, four times in the superotemporal sector, and twice in both sectors. On disc photographs taken during a follow-up examination, the focal notching changed to a diffuse vertical enlargement of the cup in eight eyes and to a broader local notch in two eyes. In another set often eyes, a diffuse cup enlargement was observed. Five of these eyes later changed to a diffuse cup enlargement, mainly in the vertical direction. In three eyes, no alteration of the rim configuration was detected. In the follow-up study by Tuulonen and Airaksinen, and in our cross-sectional investigation, the first disc changes were observed mainly at the inferotemporal and superotemporal disc regions, resulting in a vertical cup enlargement. The current study confirms other reports on a vertical elongation of the optic cup in medium advanced glaucoma.13-20 It is in agreement with investigations of"early" glaucomatous changes of the optic disc. In a longitudinal study, Pederson and Anderson 21 examined 259 eyes of ocular hypertensive subjects. In 29 eyes, there was an enlargement of the optic cup after a maximum follow-up period of 15 years. In 23 eyes, the cup extension was described as general extension in the vertical and horizontal direction, 5 eyes showed an enlargement mainly in the vertical direction, and in 1 eye the cup was enlarged mainly in the horizontal direction. The general extension of the optic cup in these eyes with beginning glaucomatous optic nerve damage can be interpreted as a neuroretinal rim loss predominantly in the inferior and superior disc regions. This would convert the normal rim configuration with the widest parts in the inferior and superior disc areas into a rim being even in width at all points. It would change the shape of the optic cup from a horizontally oval form to a circular form. The pattern of glaucomatous neuroretinal rim loss (inferotemporal and superotemporal - temporal horizontal - inferonasal - superonasal) agrees with visual field studies. The perimetric defects to be found in early glaucoma were described as occurring mostly in the upper nasal visual field quadrant2 2 or the superior and inferior Bjerrum areas. 23-25 The remaining visual field islands in eyes with very advanced glaucomatous optic nerve damage were usually present in the inferotemporal part of the visual field. The finding that the glaucomatous rim loss occurred in a diffuse and localized manner may be important for the discussion on the localized versus diffuse visual field loss.26,27 Extrapolating the data of this study to subjects with ocular hypertension, it may indicate that subjects with ocular hypertension, especially in the inferotemporal optic
disc sector, should be checked for glaucomatous alterations. For that purpose, one must take into account that in visually normal eyes the neuroretinal rim is not even at all locations but is widest in the inferior disc region and smallest in the temporal horizontal disc sector (Fig 1). Consequently, a neuroretinal rim shape being equal in width in the inferotemporal disc sector and the temporal horizontal disc region could indicate glaucomatous optic nerve damage. This may be important, especially for eyes with "early" glaucomatous damage. It must be emphasized that the pattern of rim loss as described in the current study is based on a general statistical analysis. For the individual patient and eye, many exceptions may be valid. They will depend on the parametersinfluencingtheregionalglaucomatousvulnerability inside the optic disc. These factors may be ( 1) the physiologic configuration of the rim being broader at the inferior and superior disc poles than at the nasal and temporal poles 1; (2) the morphology of the inner surface of the lamina cribrosa with the larger pores and the higher ratio of pore to interpore connective tissue area in the inferior and superior regions as compared to the temporal and nasal regions4•5·28 ; a high ratio of pore area to total area is considered to predispose to glaucomatous nerve fiber loss; (3) the glaucomatous bowing of the lamina cribrosa to the outside mainly in the inferior and superior disc regions as shown on scanning electron microscopic photographs of glaucomatous eyes 29; and (4) the regional distribution of thin and thick retinal nerve fibers, with thin nerve fibers coming from the foveola, passing through the temporal aspect of the optic disc, and being less susceptible to glaucoma than thick nerve fibers, which originate predominantly in the fundus periphery, lead to the inferior, superior, and nasal disc regions, 30·31 and are more sensitive to glaucoma than thin retinal ganglion cell axons. 32 The latter parameter may explain why glaucomatous rim loss occurs later in the temporal horizontal disc sector with predominantly thin nerve fibers than in the inferotemporal or superotemporal disc sectors containing thin and thick axons. It is contradictory to the fact that in far advanced glaucoma, rim remnants are usually located in the nasal disc sector. There, preferentially thick retinal ganglion cell axons leave the eye. 30
References l. Jonas JB, Gusek GC, Naumann GOH. Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. Invest Ophthalmol Vis Sci 1988;29:1151-8. 2. Jonas JB, Nguyen NX, Naumann GOH. The retinal nerve fiber layer in normal eyes. Ophthalmology 1989;96:627-32. 3. Jonas JB, Nguyen XN, Naumann GOH. Parapapillary retinal vessel diameter in normal and glaucoma eyes. I. Morphometric data. Invest Ophthalmol Vis Sci 1989;30:15991603. 4. Radius RL. Regional specificity in anatomy at the lamina cribrosa. Arch Ophthalmol 1981;99:478-80.
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Ophthalmology Volume 100, Number 1, January 1993 5. Quigley HA, Addicks EM. Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthalmol 1981 ;99: 13 743. 6. Jonas JB, Gusek GC, Naumann GOH. Optic disk morphometry in high myopia. Graefes Arch Clin Exp Ophthalmol 1988;226:587-90. 7. Britton RJ, Drance SM, Schulzer M, et al. The area of the neuroretinal rim of the optic nerve in normal eyes. Am J Ophthalmol 1987;103:497-504. 8. Littmann H. Zur Bestimmung der wahren GroBe eines Objektes auf dem Hintergrund des lebenden Auges. Klin Monatsbl Augenheilkd 1982; 180:286-9. 9. Betz Ph, Camps Fr, Collignon-Brach C, Weekers R. Photographie stereoscopique et photogrammetrie de !'excavation physiologique de la papille. J Fr Ophtalmol 1981 ;4: 193203. 10. Caprioli J Miller JM. Optic disc rim area is related to disc size in normal subjects. Arch Ophthalmol 1987;105:1683-5. 11. Airaksinen PJ, Drance SM, Douglas GR, Schulzer M. Neuroretinal rim areas and visual field indices in glaucoma. Am J Ophthalmol 1985;99:107-10. 12. Tuulonen A, Airaksinen PJ. Initial glaucomatous optic disk and retinal nerve fiber layer abnormalities and their progression. Am J Ophthalmol 1991; Ill :485-90. 13. Armaly MF. Cup/disc ratio in early open-angle glaucoma. Doc Ophthalmol 1969;26:526-33. 14. Becker B. Cup/disc ratio and topical corticosteroid testing. Am J Ophthalmol 1970;70:681-5. 15. Kirsch RE, Anderson DR. Clinical recognition of glaucomatous cupping. Am J Ophthalmol 1973;75:442-54. 16. Gloster J. Vertical ovalness of glaucomatous cupping. Br J Ophthalmol 1975;59:721-4. 17. Hart WM Jr, Yablonski M, Kass MA, Becker B. Quantitative visual field and optic disc correlates early in glaucoma. Arch Ophthalmol 1978;96:2209-11. 18. Radius RL, Maumenee AE. Optic atrophy and glaucomatous cupping. Am J Ophthalmol 1978;85:145-53. 19. Herschler J, Osher RH. Baring of the circumlinear vessel. An early sign of optic nerve damage. Arch Ophthalmol 1980;98:865-9.
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20. Betz Ph, Camps F, Collignon-Brach J, et al. Biometric study of the disc cup in open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol 1982;218:70-4. 21. Pederson JE, Anderson DR. The mode of progressive disc cupping in ocular hypertension and glaucoma. Arch Ophthalmol 1980;98:490-5. 22. Gramer E, Gerlach R, Krieglstein GK, Leydhecker W. Zur Topographie friiher glaukomatoser Gesichtsfeldausfalle bei der Computerperimetrie. Klin Monatsbl Augenheilk 1982; 180:515-23. 23. Drance SM. The early field defects in glaucoma. Invest Ophthalmol 1969;8:84-91. 24. Hart WM Jr, Becker B. The onset and evolution of glaucomatous visual field defects. Ophthalmology 1982;89:26879. 25. Caprioli J, Sears M, Miller JM. Patterns of early visual field loss in open-angle glaucoma. Am J Ophthalmol 1987;103: 512-17. 26. Glowazki A, Flammer J. Is there a difference between glaucoma patients with rather localized visual field damage and patients with more diffuse visual field damage? In: Greve EL, Heijl A, eds. Seventh Int'l Visual Field Symposium. Dordrecht: Martinus Nijhoff/Dr W. Junk, 1987;317-20 (Doc Ophthalmol Proc Ser; 49). 27. Drance SM. Diffuse visual field loss in open-angle glaucoma. Ophthalmology 1991 ;98: 1533-8. 28. Jonas JB, Mardin CY, SchlOtzer-Schrehardt U, Naumann GOH. Morphometry of the human lamina cribrosa surface. Invest Ophthalmol Vis Sci 1991;32:401-5. 29. Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol 1981 ;99: 635-49. 30. Sanchez RM, Dunkelberger GR, Quigley HA. The number and diameter distribution of axons in the monkey optic nerve. Invest Ophthalmol Vis Sci 1986;27:1342-50. 31. Jonas JB, Miiller-Bergh JA, SchlOtzer-Schrehardt UM, Naumann GOH. Histomorphometry of the human optic nerve. Invest Ophthalmol Vis Sci 1990;31:736-44. 32. Quigley HA, Sanchez RM, Dunkelberger GR, et al. Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci 1987;28:913-20.