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Optic disc changes in ocular hypertension
SURVEY
OF OPHTHALMOLOGY
Optic
VOLUME 25
l
NUMBER 3
Disc Changes
l
NOVEMBER-DECEMBER
1980
in Ocular
Hypertension
BERNARD SCHWARTZ, M.D., Ph.D.
Department of Ophthalmology, New England Medical Center Hospital and Tufts University School of Medicine, Boston, Massachusetts Measurements were made of the percent areas of optic disc cupping and pallor in ocular hypertensive eyes and normal eyes. The ocular hypertensive eyes showed significant increases in pallor but not in cupping compared to normal eyes.
Abstract.
There was also a significant positive correlation of cupping with age in normal eyes but not in ocular hypertensive eyes. Fluorescein angiography of the optic disc showed an increase in the number and area of filling defects in ocular hypertensive compared to normal eyes. There were significant positive correlations in ocular hypertensives between percent area of filling defects with both age and systolic blood pressure which were not present with normal eyes. The optic disc changes which occur in ocular hypertensive eyes are primarily characterized by an increase in pallor and an increase in both the number and area of fluorescein filling defects. (Surv Ophthalmol 25148-154,
1980)
Key words. age l
optic disc
l
blood pressure . cupping ocular hypertension pallor l
l
fluorescein angiography
l
0
association of optic disc changes characteristic of glaucoma in ocular hypertensives. 16.23,24 The disagreement regarding the inclusion of glaucomatous disc changes1s*2ain the de% nition of ocular hypertension has been due, at least in part, to the lack of methods to quantitatively measure disc changes. Now, new methods for the quantitative evaluation of the disc are being developed - notably photogrammetry and microdensitometry. These, as well as a semiquantitative method developed by us, are providing data on optic disc changes in ocular hypertension. The purpose of this paper is to describe these changes and
ur present concept of the process of primary open angle glaucoma is that an increase in ocular pressure leads to changes in the optic disc with the consequent loss of visual field (Fig. 1). It is now recognized that many patients may have increased ocular pressure for many years without experiencing a loss of visual Iield.1~5~9J2J4J6 Such patients have been termed ocular hypertensives.12 The definition of ocular hypertension in the literature has generally included patients with increased ocular pressure usually greater than or equal to 21 mm Hg but without characteristic glaucomatous field loss. However, various authors differ on the 148
OPTIC
DISC CHANGES
IN OCULAR
149
HYPERTENSION
the methods of evaluating them.
Cupping and Pallor of the Optic Disc in Ocular Hypertension Cupping
Pallor
Fluorescein Defects
We have previously defined the qualitative changes which occur in the optic disc with glaucoma as increases in cupping and pallor.” Cupping is defined as the contour of the optic disc or any depression of its surface below the retinal surface, while pallor is defined as the area of maximum color contrast or lack of blood vessels. Furthermore, we have indicated that the distinction between these two signs of the optic disc is important, since both cupping and pallor increase in glaucoma - cupping usually to a greater extent than pallor. Pallor is associated with the degree of visual field loss in glaucoma.9J* The relationship between cupping and pallor can be used to distinguish the glaucomatous disc from the optic disc which shows changes due to neurological disease.*O Furthermore, methods have been devised which can measure cupping by photogrammetry separately from pallor as measured by microdensitometry.18 Pending the further development and refinement of such accurate methods as photogrammetry and microdensitometry for measuring optic disc cupping and pallor, we have been using a semiquantitative approach.18 The method consists of viewing color stereophotographs of the optic disc with a handheld stereo viewer. The margins of the cup are noted, and the photographs are then placed on a viewing light-box. A series of circles of various sizes, with areas within each circle representing various percentages of the total circle, has been drawn on transparent sheets (Fig. 2). The sheets are then placed
over the color photographs of the optic disc. By superimposition, the area of cupping or pallor is then matched with the appropriate circle under magnification. Cupping and pallor are then expressed as a percent area of the optic disc area. Using this method, we measured the optic discs of a series of 135 normal and ocular hypertensive patients. For each patient the eye having the largest percent area of optic disc cupping or pallor was characterized as the worse eye. For the measurement of percent area of cupping or pallor of both eyes, the sum of the worse eye plus the fellow eye was used. Nonparametric statistics were used to analyze the data, including the Spearman rank test for correlations, the Mann-Whitney U test for determining differences in frequency distributions, and the Chi-Square (x2) for determining independence of sampling.29 A level of p < .05 was used for determining significance. A population of 66 normal patients defined as those with ocular pressures consistently under 21 mm Hg and with normal visual fields as measured with the Goldmann perimeter both by kinetic and static means were compared with a series of 69 ocular hypertensives as previously defined. The age, sex and racial characteristics of these groups
I
55::
:
10’0
j
44;
;
9%
;
lbqb
;
FIG. 1. Model for glaucomatous indicating changes in optic disc.
/’
34%
j
44%
I
44%
process
I
41%
FG 2. Template used to estimate percentage area of optic disc cupping and pallor: d = diameter of inner dark circle, equivalent to area of cupping or pallor; D = area of outer circle, equivalent to area of optic disc; S = percentage of outer circle occupied by inner circle, equivalent to percentage area of optic disc evidencing cupping or pallor. (Reprinted from Schwartz BIBwith permission of Masson Publishers.)
150
Surv Ophthalmol
25 (3) November-December
1980
TABLE 1 Breakdown of Normals and Ocular Hypertensives by Age, Sex and Race
All Ages Ocular HypertenNormals sives
Ages 2 40 Ocular HypertenNormals sives
Males Females
28 38
31 32
:;
28 31
Whites Blacks Orientals
62 3
59 4
1
0
54 1 1
55 4 0
AGE ? 40 YEARS 0 Normols ~56 a Oculor Hypertensives n=59
uLzL_ l-1920-29 30-39 40-49 SO-69 60-69 70-79 60-69 90-99
Worse Eye, Percent Area of Pallor FIG. 3. Frequeticy distribution of percent area of pallor of optic disc in normals and ocular hypertensives.
SCHWARTZ
are shown in Table 1. The total population was subdivided into two groups: (1) all ages; and (2) ages 40 years or over. There was no significant difference in the age, sex and race distribution of the two groups. The measurements for percent areas of cupping and pallor for the two groups are shown in Table 2. The frequency distributions are shown in Figs. 3 and 4. As shown in Fig. 3, the frequency distribution of pallor in the ocular hypertensive group was skewed to the right. There was no significant difference in the frequency distribution of cupping for either the worse eye or the sum of both eyes. However, there were significant differences for pallor (All ages 7 = 63: worse eye, Mann-Whitney U = 2675, p < .005; sum of eyes, MannWhitney U = 2641, p < .Ol. Age 2 40, n = 59: worse eye, Mann-Whitney U = 2010, p < .05). Correlations were determined between age and percent areas of cupping and pallor. For all ages (worse eye, n = 65, r, = + 0.4471, p < .OOl; sum of eyes, n = 65, rs = + 0.3828, p < .002) as well as those ages greater than or to 40, (worse eye, 7 = 56, equal rs = + 0.3212, p < .016), the normals showed a significant positive correlation between percent area of cupping and age (Fig. 5). However, neither the normals nor the ocular hypertensives showed a significant increase in area of pallor with age. loo r
P .8=I 0
40 AGE 240 YEARS
30 6
1
5 Fk w lk E 8 $ a
Normols,
90
i
p = ,001
80
% 70c3 2 60u
Ocular Hypertensives n=59
E 8 k a
20-
P
.
.
“.
. -. . . . .s . “am_ *I* +*.I
.
.
5040-
.
.
.
.
.
. .
. . . .
. . . .
.
IO-
50-69 70-79 SO-69 90-99
Worse Eye, Percent FIG. 4. Frequency
Area of Cupping
distribution of percent area of cupping of optic disc in normals and ocular hypertensives.
0
l
.
. . .
aa- JOG g 20-
IO-
011 ages
n 565 rs = .4471
IO
20
30
40
50
60
70
80
I 90
Age (years) FIG. 5. Correlation of percent area of cupping of worse eye with age for normals.
OPTIC DISC CHANGES
151
IN OCULAR HYPERTENSION
TABLE 2 Median (50th) and 30th and 70th Percentiles for Age and Optic Disc Characteristics of Normals and Ocular Hypertensives
Ages 2 40
All Ages Ocular Normals Hypertensives Percentile 50th (30th, 70th) 50th (30th, 70th)
Age
Ocular Hypertensives
Normals
50th (30th, 70th) 50th (30th, 70th)
66
(62,70 )
64
(53370 )
68
(64,71 )
65
(55,70 )
52
(46,58 )
51
(45361 1
53
(48,59 )
50
(44,59 )
8
( 5,13 )
13
( 9,21 )
9
(5,13)
11
( 8,20 )
100
(85, 111)
93
(78, 117)
102
(92, 114)
90
(77, 113)
15
( 9,24 )
22
(14,35 )
16
(lo,25
20
(13734 )
Worse Eye
Percent Area of Cupping Percent Area of Pallor Sum of Eyes Percent Area of Cupping Percent Area of Pallor
Fluorescein Filling Defects of the Optic Disc in Ocular Hypertension We have previously demonstrated that fluorescein angiography of the optic disc can provide useful information about ocular hypertensive and glaucomatous eyes.*l Two types of fluorescein angiographic filling defects or areas of hypofluorescence occur. In an absolute defect, there is a lack of fluorescein filling throughout the entire fluorescein cycle of the angiogram. In a relative defect, some fluorescein filling occurs, but the defect area is of less intensity than the surrounding areas or it fills later in time. We have shown that ocular hypertensive eyes are characterized by optic discs showing a greater number of absolute and relative fluorescein defects than normal eyes, either in absolute numbers or calculated as defects per optic disc (Table 3). In addition, we have measured the area of
)
hypofluorescence or Blling defects comparing a matched group of normal and ocular hypertensive eyes of patients in relation to age, sex, race, blood pressure, and incidence of cardiovascular and cerebrovascular disease.‘* There was a significant difference in the frequency distribution of areas of hypofluorescence, with the ocular hypertensives having optic discs with larger areas of hypofluorescence than the normals (Fig. 6). There were also significant correlations between area of hypofluorescence and both age and systolic blood pressure in the ocular hypertensive eyes, but not in the normal eyes (Figs. 7 and 8).
Discussion Although there have been a number of studies attempting to measure cupping and pallor of the optic disc in glaucomatous patients, especially in relation to field loss,
TABLE 3 Number of Fluorescein Filling Defects Normal No. No. No. No. No.
of optic discs of absolute defects of absolute defects/disc of relative defects of relative defects/disc
Ocular Hypertension 46 37
29 18 .62 27 .93
.80 47 1.02
Glaucoma 39 62 1.59 8 .21
152
18
Surv Ophthalmol
NORMAL
1
25 (3) November-December
CONTROLS
-
6
i
i
1980
6
Ii
lb
AREA
OF
FILLING
DISC
lib i DEFECT61
2i
2r
30
33
sb
i3
.~
AREA
FIG. 6. Frequency distributions of percent areas of fluorescein filling defects of normal and ocular hypertensive eyes. [Reprinted from Loebl M, Schwartz Bls with permission of the authors and American Medical Association.]
there have been few measurements of the optic disc in ocular hypertension.**“*’ A number of qualitative observations have indicated significant changes in the optic disc in patients with ocular hypertension, especially on followup, prior to the development of visual field 10~s.‘~ Our results show that ocular hypertensive discs differ significantly from normal optic discs in the amount of pallor. We have previously shown that they also differ significantly from glaucomatous discs both in the amount of cupping and in the amount of pallor.20 The significant difference in pallor but not in cupping in this study is of great interest, This finding may be because the series of ocular hypertensives was not large enough to demonstrate any significant increase in cupping. Also, it may be related to other factors such as age. Our data indicate a significant positive correlation between percent area of cupping and age. In the older age groups
SCHWARTZ
the amount of change in cupping with age may be so large that it is difficult to distinguish these changes from the degree of cupping that occurs with increased ocular pressure in ocular hypertensives. However, it is also possible that a significant increase in pallor occurs before cupping in the glaucomatous process. These alternatives will have to be further explored with a larger series of patients and more refined measurements. Recently Johnson et al.* measured photogrammetrically the optic cup orifice area in 40 normal eyes and 106 ocular hypertensive eyes. They found a considerable overlap between the two groups with the ocular hypertensive eyes showing more cups with larger orifice areas. However, the ages of the patients were not stated and there was no indication that the normal and ocular hypertensive patients were matched for age. Our data are cross-sectional data obtained by measuring areas of cupping and pallor at one time in a series of normal and ocular hypertensive eyes. More significant observations would be those obtained on longitudinal followup by measuring each individual patient in relation to time. Such data, especially those obtained by the more sensitive and reproducible techniques of photogrammetry and microdensitometry may provide more accurate indications of the relationship between cupping and pallor in the ocular hypertensive eye compared to the normal eye or the glaucomatous eye. Our fluorescein angiographic studies definitely show what appears to be vascular impairment in the ocular hypertensive eye, especially associated with age and systolic blood pressure. Our interpretation is that the fluorescein defects represent areas of decreased vascular supply, especially at the microcirculatory level. Since the two groups of normal and ocular hypertensives differed only in respect to ocular pressure, and furthermore, since there was no significant difference in the incidence of various other systemic diseases, it appears that increasing age and systolic blood pressure have a more deleterious effect on the ocular hypertensive disc than on the normal one. The occurrence of increased areas of hypofluorescence in ocular hypertensive optic discs can be useful in the clinical management of such patients. Presently, we are using this concept to determine which ocular hypertensives may require therapy irrespective of their
153
OPTIC DISC CHANGES IN OCULAR HYPERTENSION
327 _
OCULAR
r, * to.4903
2c
p < ,009
z
2’ ia;; -
NORMAL
.
HYPERTENSION
p
24.
1
20.
HZ >* 2;
16_ ,2-
.
.
‘.
.
. .
. *
6”
. .
(:
0
g
.
*
IO
. ..
20
I
so
40
30
G-
s
-
4-
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GO
.
.
20
30
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.
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40 50 AGE (VEARSI
AGE IYEARSI
*
. . .
.. lo
.
. .
*.
0
*.
To
GO
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i
..
:
60
I
70
GO
FIG. 7. Correlation of age with percent area of fluorescein filling defects for normals and ocular hypertensives. (Reprinted from Loebl M, Schwartz B” with permission of the authors and American Medical Association.) 35-
OCULAR
HYPERTENSION rs : +0.5850
a4
2
201
.
NORMAL
r,=NS
. .
25-
k l
. .
l .
q’. 100
110
120
lx)
SYSTOLIC
.
140 BLOOD
l
p c.005
ae30
15D PRESSURE
: t6D
170
180
190
H)o
110 SYSTOLIC
hWlG)
.
.
l
. . 8
.
l
. .
.: 120 BLOOO
130
140
PRESSURE
150
160
(mmHG )
FIG. 8. Correlation of systolic blood pressure with percent area of fluorescein filling defects for normals and ocular hypertensives. (Reproduced from Loebl M, Schwartz Bla with permission of the authors and American Medical Association.)
ocular pressure level. For example, patients who show increased ocular pressure and are classified as ocular hypertensives without significant fluorescein angiographic defects in their optic discs may be observed rather than treated, while those who do have significant fluorescein angiographic defects irrespective of their pressure levels will be initiated on a trial of therapy. Acknowledgments
Peter Gilbert assisted with the statistical analyses. Beverly Smith provided editorial assistance.
References 1. Armaly MF: Ocular pressure and visual fields: A ten-year follow-up study. Arch Ophthalmol
81:25-40, 1969 2. Armaly MF: The optic disc in open angle glaucoma. International Glaucoma Symposium Albi. Marseille, France, Diffusion Generale de
Libraire,
1975, pp 155-171 relationship between cupping of the optic disc and visual field loss in chronic simple glaucoma. Br J Ophthalmol
3. Gloster J: Quantitative
62:665-669, 1978 Goldmann H: An analysis of some concepts concerning chronic simple glaucoma. Am J Ophthalmol 80:409-413, 1975 5. Graham PA: The definition of pre-glaucoma.
4.
A prospective study. Trans Ophthalmol Sot UK g&153-165, 1968 6. Hart WM, Yablonski M, Kass MA, Becker B: Quantitative visual field and optic disc correlates early in glaucoma. Arch Ophthalmol 96:2209-2211, 1978
IS4
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17. 18.
SurvOphthalmol
25 (3) November-December
SCHWARTZ
1980
Hart WM, Yablonski M, Kass MA, Becker B: Multivariate analysis of the risk of glaucomatous visual field loss. Arch Ophthalmol 97:1455-1458, 1979 Johnson CA, Keltner JL, Krohn MA, Portney GL: Photogrammetry of the optic disc in glaucoma and ocular hypertension with simultaneous stereophotography. Invest Ophthalmol Vis Sci 18:1252-1263, 1979 Kitazawa Y, Horie T, Aoki S, et al: Untreated ocular hypertension. Arch Ophthalmol 95: 1180-1184, 1977 Kolker A: Optic nerve damage and visual field loss. Genesis of Glaucoma, Wesseley Symposium, Munich. Dot Ophthalmol 16: 297-298, 1978 LinnCr E: OcuIar hypertension. I. The clinical course during ten years without therapy. Aqueous humor dynamics. Acta Ophthalmol (Kbh) 54:707-720, 1976 Linn6r E, StrGmberg U: Ocular hypertension. A five-year study of the total population in a Swedish town, SkGvde, in Leydhecker W (ed): Glaucoma Tiitzing Symposium. New York, S Karger, 1967, pp 187-214 Loebl M, Schwartz B: Fluorescein angiographic defects of the optic disc in ocular hypertension. Arch Ophthalmol 95:1980-1984, 1977 N$rskov K: Glaucoma screening. II. A fiveyear follow-up carried through in relation to glaucoma screening among members of the Volunteer Donor Corps of the Island of Falster (Denmark). Acta Ophthalmologica 48:418-433, 1970 Perkins ES: Recent advances on the treatment of glaucoma. Trans Ophthalmol Sot UK 86:199-210, 1966 Perkins ES: The Bedford Glaucoma Survey. I. Longterm followup of borderline cases. Br J Ophthalmol 57:179-185, 1973 Schwartz B: Cupping and pallor of the optic disc. Arch Ophthalmol 89:272-277, 1973 Schwartz B: Correlation of optic disc changes
19.
20.
21.
22.
23.
24.
25.
with asymmetrical visual field loss in glaucoma. XXIIe Concilium Ophtalmologicum, Paris, 1974, Acta, Vol 2. Paris, Masson Publishers, 1976, pp 632-638 Schwartz B: New techniques for the examination of the optic disc and their clinical application. Trans Am Acad Ophthalmol Otolaryngol 81: OP 227-237, 1976 Schwartz B: Differences between cupping and pallor of the optic disc in glaucomatous and neurological optic nerve disease, in Shimizu K, Oosterhuis JA (eds): International Congress Series No. 450, XXIII Concilium Ophthalmologicum, Kyoto, 1978. Amsterdam-Oxford, Excerpta Medica, 1979, pp 1108-1111 Schwartz B: Rieser JC, Fishbein SL: Fluorescein angiographic defects of the optic disc in glaucoma. Arch Ophthalmol 95:1961-1974, 1977 Schwartz B, Talusan A: Spontaneous trends of ocular pressure in untreated ocular hypertension. Arch Ophthalmol 98:105-l 11, 1980 Siegel S: Non-Parametric Statistics for the Behavioral Sciences. New York, McGraw-Hill Book Company, 1956 Spaeth GL: Ocular hypertension: Reason for abandonment of the term. Int Ophthalmol Clin 19:37-49, 1979 Strijmberg U: Ocular hypertension. Acta Ophthalmol (Suppl) 69:1-75, 1962
Supported in part by Grant No. EY 00024 from the National Eye Institute of the National Institutes of Health, Bethesda, Maryland. Reprint requests should be addressed to Bernard Schwartz, M.D., Ph.D., Department of Ophthalmology, Tufts-New England Medical Center, 171 Harrison Avenue, Boston, Massachusetts 02 111.
OF OPHTHALMOLOGY
Optic
VOLUME 25
l
NUMBER 3
Disc Changes
l
NOVEMBER-DECEMBER
1980
in Ocular
Hypertension
BERNARD SCHWARTZ, M.D., Ph.D.
Department of Ophthalmology, New England Medical Center Hospital and Tufts University School of Medicine, Boston, Massachusetts Measurements were made of the percent areas of optic disc cupping and pallor in ocular hypertensive eyes and normal eyes. The ocular hypertensive eyes showed significant increases in pallor but not in cupping compared to normal eyes.
Abstract.
There was also a significant positive correlation of cupping with age in normal eyes but not in ocular hypertensive eyes. Fluorescein angiography of the optic disc showed an increase in the number and area of filling defects in ocular hypertensive compared to normal eyes. There were significant positive correlations in ocular hypertensives between percent area of filling defects with both age and systolic blood pressure which were not present with normal eyes. The optic disc changes which occur in ocular hypertensive eyes are primarily characterized by an increase in pallor and an increase in both the number and area of fluorescein filling defects. (Surv Ophthalmol 25148-154,
1980)
Key words. age l
optic disc
l
blood pressure . cupping ocular hypertension pallor l
l
fluorescein angiography
l
0
association of optic disc changes characteristic of glaucoma in ocular hypertensives. 16.23,24 The disagreement regarding the inclusion of glaucomatous disc changes1s*2ain the de% nition of ocular hypertension has been due, at least in part, to the lack of methods to quantitatively measure disc changes. Now, new methods for the quantitative evaluation of the disc are being developed - notably photogrammetry and microdensitometry. These, as well as a semiquantitative method developed by us, are providing data on optic disc changes in ocular hypertension. The purpose of this paper is to describe these changes and
ur present concept of the process of primary open angle glaucoma is that an increase in ocular pressure leads to changes in the optic disc with the consequent loss of visual field (Fig. 1). It is now recognized that many patients may have increased ocular pressure for many years without experiencing a loss of visual Iield.1~5~9J2J4J6 Such patients have been termed ocular hypertensives.12 The definition of ocular hypertension in the literature has generally included patients with increased ocular pressure usually greater than or equal to 21 mm Hg but without characteristic glaucomatous field loss. However, various authors differ on the 148
OPTIC
DISC CHANGES
IN OCULAR
149
HYPERTENSION
the methods of evaluating them.
Cupping and Pallor of the Optic Disc in Ocular Hypertension Cupping
Pallor
Fluorescein Defects
We have previously defined the qualitative changes which occur in the optic disc with glaucoma as increases in cupping and pallor.” Cupping is defined as the contour of the optic disc or any depression of its surface below the retinal surface, while pallor is defined as the area of maximum color contrast or lack of blood vessels. Furthermore, we have indicated that the distinction between these two signs of the optic disc is important, since both cupping and pallor increase in glaucoma - cupping usually to a greater extent than pallor. Pallor is associated with the degree of visual field loss in glaucoma.9J* The relationship between cupping and pallor can be used to distinguish the glaucomatous disc from the optic disc which shows changes due to neurological disease.*O Furthermore, methods have been devised which can measure cupping by photogrammetry separately from pallor as measured by microdensitometry.18 Pending the further development and refinement of such accurate methods as photogrammetry and microdensitometry for measuring optic disc cupping and pallor, we have been using a semiquantitative approach.18 The method consists of viewing color stereophotographs of the optic disc with a handheld stereo viewer. The margins of the cup are noted, and the photographs are then placed on a viewing light-box. A series of circles of various sizes, with areas within each circle representing various percentages of the total circle, has been drawn on transparent sheets (Fig. 2). The sheets are then placed
over the color photographs of the optic disc. By superimposition, the area of cupping or pallor is then matched with the appropriate circle under magnification. Cupping and pallor are then expressed as a percent area of the optic disc area. Using this method, we measured the optic discs of a series of 135 normal and ocular hypertensive patients. For each patient the eye having the largest percent area of optic disc cupping or pallor was characterized as the worse eye. For the measurement of percent area of cupping or pallor of both eyes, the sum of the worse eye plus the fellow eye was used. Nonparametric statistics were used to analyze the data, including the Spearman rank test for correlations, the Mann-Whitney U test for determining differences in frequency distributions, and the Chi-Square (x2) for determining independence of sampling.29 A level of p < .05 was used for determining significance. A population of 66 normal patients defined as those with ocular pressures consistently under 21 mm Hg and with normal visual fields as measured with the Goldmann perimeter both by kinetic and static means were compared with a series of 69 ocular hypertensives as previously defined. The age, sex and racial characteristics of these groups
I
55::
:
10’0
j
44;
;
9%
;
lbqb
;
FIG. 1. Model for glaucomatous indicating changes in optic disc.
/’
34%
j
44%
I
44%
process
I
41%
FG 2. Template used to estimate percentage area of optic disc cupping and pallor: d = diameter of inner dark circle, equivalent to area of cupping or pallor; D = area of outer circle, equivalent to area of optic disc; S = percentage of outer circle occupied by inner circle, equivalent to percentage area of optic disc evidencing cupping or pallor. (Reprinted from Schwartz BIBwith permission of Masson Publishers.)
150
Surv Ophthalmol
25 (3) November-December
1980
TABLE 1 Breakdown of Normals and Ocular Hypertensives by Age, Sex and Race
All Ages Ocular HypertenNormals sives
Ages 2 40 Ocular HypertenNormals sives
Males Females
28 38
31 32
:;
28 31
Whites Blacks Orientals
62 3
59 4
1
0
54 1 1
55 4 0
AGE ? 40 YEARS 0 Normols ~56 a Oculor Hypertensives n=59
uLzL_ l-1920-29 30-39 40-49 SO-69 60-69 70-79 60-69 90-99
Worse Eye, Percent Area of Pallor FIG. 3. Frequeticy distribution of percent area of pallor of optic disc in normals and ocular hypertensives.
SCHWARTZ
are shown in Table 1. The total population was subdivided into two groups: (1) all ages; and (2) ages 40 years or over. There was no significant difference in the age, sex and race distribution of the two groups. The measurements for percent areas of cupping and pallor for the two groups are shown in Table 2. The frequency distributions are shown in Figs. 3 and 4. As shown in Fig. 3, the frequency distribution of pallor in the ocular hypertensive group was skewed to the right. There was no significant difference in the frequency distribution of cupping for either the worse eye or the sum of both eyes. However, there were significant differences for pallor (All ages 7 = 63: worse eye, Mann-Whitney U = 2675, p < .005; sum of eyes, MannWhitney U = 2641, p < .Ol. Age 2 40, n = 59: worse eye, Mann-Whitney U = 2010, p < .05). Correlations were determined between age and percent areas of cupping and pallor. For all ages (worse eye, n = 65, r, = + 0.4471, p < .OOl; sum of eyes, n = 65, rs = + 0.3828, p < .002) as well as those ages greater than or to 40, (worse eye, 7 = 56, equal rs = + 0.3212, p < .016), the normals showed a significant positive correlation between percent area of cupping and age (Fig. 5). However, neither the normals nor the ocular hypertensives showed a significant increase in area of pallor with age. loo r
P .8=I 0
40 AGE 240 YEARS
30 6
1
5 Fk w lk E 8 $ a
Normols,
90
i
p = ,001
80
% 70c3 2 60u
Ocular Hypertensives n=59
E 8 k a
20-
P
.
.
“.
. -. . . . .s . “am_ *I* +*.I
.
.
5040-
.
.
.
.
.
. .
. . . .
. . . .
.
IO-
50-69 70-79 SO-69 90-99
Worse Eye, Percent FIG. 4. Frequency
Area of Cupping
distribution of percent area of cupping of optic disc in normals and ocular hypertensives.
0
l
.
. . .
aa- JOG g 20-
IO-
011 ages
n 565 rs = .4471
IO
20
30
40
50
60
70
80
I 90
Age (years) FIG. 5. Correlation of percent area of cupping of worse eye with age for normals.
OPTIC DISC CHANGES
151
IN OCULAR HYPERTENSION
TABLE 2 Median (50th) and 30th and 70th Percentiles for Age and Optic Disc Characteristics of Normals and Ocular Hypertensives
Ages 2 40
All Ages Ocular Normals Hypertensives Percentile 50th (30th, 70th) 50th (30th, 70th)
Age
Ocular Hypertensives
Normals
50th (30th, 70th) 50th (30th, 70th)
66
(62,70 )
64
(53370 )
68
(64,71 )
65
(55,70 )
52
(46,58 )
51
(45361 1
53
(48,59 )
50
(44,59 )
8
( 5,13 )
13
( 9,21 )
9
(5,13)
11
( 8,20 )
100
(85, 111)
93
(78, 117)
102
(92, 114)
90
(77, 113)
15
( 9,24 )
22
(14,35 )
16
(lo,25
20
(13734 )
Worse Eye
Percent Area of Cupping Percent Area of Pallor Sum of Eyes Percent Area of Cupping Percent Area of Pallor
Fluorescein Filling Defects of the Optic Disc in Ocular Hypertension We have previously demonstrated that fluorescein angiography of the optic disc can provide useful information about ocular hypertensive and glaucomatous eyes.*l Two types of fluorescein angiographic filling defects or areas of hypofluorescence occur. In an absolute defect, there is a lack of fluorescein filling throughout the entire fluorescein cycle of the angiogram. In a relative defect, some fluorescein filling occurs, but the defect area is of less intensity than the surrounding areas or it fills later in time. We have shown that ocular hypertensive eyes are characterized by optic discs showing a greater number of absolute and relative fluorescein defects than normal eyes, either in absolute numbers or calculated as defects per optic disc (Table 3). In addition, we have measured the area of
)
hypofluorescence or Blling defects comparing a matched group of normal and ocular hypertensive eyes of patients in relation to age, sex, race, blood pressure, and incidence of cardiovascular and cerebrovascular disease.‘* There was a significant difference in the frequency distribution of areas of hypofluorescence, with the ocular hypertensives having optic discs with larger areas of hypofluorescence than the normals (Fig. 6). There were also significant correlations between area of hypofluorescence and both age and systolic blood pressure in the ocular hypertensive eyes, but not in the normal eyes (Figs. 7 and 8).
Discussion Although there have been a number of studies attempting to measure cupping and pallor of the optic disc in glaucomatous patients, especially in relation to field loss,
TABLE 3 Number of Fluorescein Filling Defects Normal No. No. No. No. No.
of optic discs of absolute defects of absolute defects/disc of relative defects of relative defects/disc
Ocular Hypertension 46 37
29 18 .62 27 .93
.80 47 1.02
Glaucoma 39 62 1.59 8 .21
152
18
Surv Ophthalmol
NORMAL
1
25 (3) November-December
CONTROLS
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i
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FIG. 6. Frequency distributions of percent areas of fluorescein filling defects of normal and ocular hypertensive eyes. [Reprinted from Loebl M, Schwartz Bls with permission of the authors and American Medical Association.]
there have been few measurements of the optic disc in ocular hypertension.**“*’ A number of qualitative observations have indicated significant changes in the optic disc in patients with ocular hypertension, especially on followup, prior to the development of visual field 10~s.‘~ Our results show that ocular hypertensive discs differ significantly from normal optic discs in the amount of pallor. We have previously shown that they also differ significantly from glaucomatous discs both in the amount of cupping and in the amount of pallor.20 The significant difference in pallor but not in cupping in this study is of great interest, This finding may be because the series of ocular hypertensives was not large enough to demonstrate any significant increase in cupping. Also, it may be related to other factors such as age. Our data indicate a significant positive correlation between percent area of cupping and age. In the older age groups
SCHWARTZ
the amount of change in cupping with age may be so large that it is difficult to distinguish these changes from the degree of cupping that occurs with increased ocular pressure in ocular hypertensives. However, it is also possible that a significant increase in pallor occurs before cupping in the glaucomatous process. These alternatives will have to be further explored with a larger series of patients and more refined measurements. Recently Johnson et al.* measured photogrammetrically the optic cup orifice area in 40 normal eyes and 106 ocular hypertensive eyes. They found a considerable overlap between the two groups with the ocular hypertensive eyes showing more cups with larger orifice areas. However, the ages of the patients were not stated and there was no indication that the normal and ocular hypertensive patients were matched for age. Our data are cross-sectional data obtained by measuring areas of cupping and pallor at one time in a series of normal and ocular hypertensive eyes. More significant observations would be those obtained on longitudinal followup by measuring each individual patient in relation to time. Such data, especially those obtained by the more sensitive and reproducible techniques of photogrammetry and microdensitometry may provide more accurate indications of the relationship between cupping and pallor in the ocular hypertensive eye compared to the normal eye or the glaucomatous eye. Our fluorescein angiographic studies definitely show what appears to be vascular impairment in the ocular hypertensive eye, especially associated with age and systolic blood pressure. Our interpretation is that the fluorescein defects represent areas of decreased vascular supply, especially at the microcirculatory level. Since the two groups of normal and ocular hypertensives differed only in respect to ocular pressure, and furthermore, since there was no significant difference in the incidence of various other systemic diseases, it appears that increasing age and systolic blood pressure have a more deleterious effect on the ocular hypertensive disc than on the normal one. The occurrence of increased areas of hypofluorescence in ocular hypertensive optic discs can be useful in the clinical management of such patients. Presently, we are using this concept to determine which ocular hypertensives may require therapy irrespective of their
153
OPTIC DISC CHANGES IN OCULAR HYPERTENSION
327 _
OCULAR
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FIG. 7. Correlation of age with percent area of fluorescein filling defects for normals and ocular hypertensives. (Reprinted from Loebl M, Schwartz B” with permission of the authors and American Medical Association.) 35-
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FIG. 8. Correlation of systolic blood pressure with percent area of fluorescein filling defects for normals and ocular hypertensives. (Reproduced from Loebl M, Schwartz Bla with permission of the authors and American Medical Association.)
ocular pressure level. For example, patients who show increased ocular pressure and are classified as ocular hypertensives without significant fluorescein angiographic defects in their optic discs may be observed rather than treated, while those who do have significant fluorescein angiographic defects irrespective of their pressure levels will be initiated on a trial of therapy. Acknowledgments
Peter Gilbert assisted with the statistical analyses. Beverly Smith provided editorial assistance.
References 1. Armaly MF: Ocular pressure and visual fields: A ten-year follow-up study. Arch Ophthalmol
81:25-40, 1969 2. Armaly MF: The optic disc in open angle glaucoma. International Glaucoma Symposium Albi. Marseille, France, Diffusion Generale de
Libraire,
1975, pp 155-171 relationship between cupping of the optic disc and visual field loss in chronic simple glaucoma. Br J Ophthalmol
3. Gloster J: Quantitative
62:665-669, 1978 Goldmann H: An analysis of some concepts concerning chronic simple glaucoma. Am J Ophthalmol 80:409-413, 1975 5. Graham PA: The definition of pre-glaucoma.
4.
A prospective study. Trans Ophthalmol Sot UK g&153-165, 1968 6. Hart WM, Yablonski M, Kass MA, Becker B: Quantitative visual field and optic disc correlates early in glaucoma. Arch Ophthalmol 96:2209-2211, 1978
IS4
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SurvOphthalmol
25 (3) November-December
SCHWARTZ
1980
Hart WM, Yablonski M, Kass MA, Becker B: Multivariate analysis of the risk of glaucomatous visual field loss. Arch Ophthalmol 97:1455-1458, 1979 Johnson CA, Keltner JL, Krohn MA, Portney GL: Photogrammetry of the optic disc in glaucoma and ocular hypertension with simultaneous stereophotography. Invest Ophthalmol Vis Sci 18:1252-1263, 1979 Kitazawa Y, Horie T, Aoki S, et al: Untreated ocular hypertension. Arch Ophthalmol 95: 1180-1184, 1977 Kolker A: Optic nerve damage and visual field loss. Genesis of Glaucoma, Wesseley Symposium, Munich. Dot Ophthalmol 16: 297-298, 1978 LinnCr E: OcuIar hypertension. I. The clinical course during ten years without therapy. Aqueous humor dynamics. Acta Ophthalmol (Kbh) 54:707-720, 1976 Linn6r E, StrGmberg U: Ocular hypertension. A five-year study of the total population in a Swedish town, SkGvde, in Leydhecker W (ed): Glaucoma Tiitzing Symposium. New York, S Karger, 1967, pp 187-214 Loebl M, Schwartz B: Fluorescein angiographic defects of the optic disc in ocular hypertension. Arch Ophthalmol 95:1980-1984, 1977 N$rskov K: Glaucoma screening. II. A fiveyear follow-up carried through in relation to glaucoma screening among members of the Volunteer Donor Corps of the Island of Falster (Denmark). Acta Ophthalmologica 48:418-433, 1970 Perkins ES: Recent advances on the treatment of glaucoma. Trans Ophthalmol Sot UK 86:199-210, 1966 Perkins ES: The Bedford Glaucoma Survey. I. Longterm followup of borderline cases. Br J Ophthalmol 57:179-185, 1973 Schwartz B: Cupping and pallor of the optic disc. Arch Ophthalmol 89:272-277, 1973 Schwartz B: Correlation of optic disc changes
19.
20.
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with asymmetrical visual field loss in glaucoma. XXIIe Concilium Ophtalmologicum, Paris, 1974, Acta, Vol 2. Paris, Masson Publishers, 1976, pp 632-638 Schwartz B: New techniques for the examination of the optic disc and their clinical application. Trans Am Acad Ophthalmol Otolaryngol 81: OP 227-237, 1976 Schwartz B: Differences between cupping and pallor of the optic disc in glaucomatous and neurological optic nerve disease, in Shimizu K, Oosterhuis JA (eds): International Congress Series No. 450, XXIII Concilium Ophthalmologicum, Kyoto, 1978. Amsterdam-Oxford, Excerpta Medica, 1979, pp 1108-1111 Schwartz B: Rieser JC, Fishbein SL: Fluorescein angiographic defects of the optic disc in glaucoma. Arch Ophthalmol 95:1961-1974, 1977 Schwartz B, Talusan A: Spontaneous trends of ocular pressure in untreated ocular hypertension. Arch Ophthalmol 98:105-l 11, 1980 Siegel S: Non-Parametric Statistics for the Behavioral Sciences. New York, McGraw-Hill Book Company, 1956 Spaeth GL: Ocular hypertension: Reason for abandonment of the term. Int Ophthalmol Clin 19:37-49, 1979 Strijmberg U: Ocular hypertension. Acta Ophthalmol (Suppl) 69:1-75, 1962
Supported in part by Grant No. EY 00024 from the National Eye Institute of the National Institutes of Health, Bethesda, Maryland. Reprint requests should be addressed to Bernard Schwartz, M.D., Ph.D., Department of Ophthalmology, Tufts-New England Medical Center, 171 Harrison Avenue, Boston, Massachusetts 02 111.