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Archopht 82 2_008
1. The Cup/Disc Ratio
The Findings of Tonometry and
Tonography in the Normal Eye
Mansour F. Armaly, MD, and
Roger E. Sayegh, MD, Iowa City
ied directly and significantly as that of their
parents; similar relationship was seen
among siblings. There was no significant
age effect on this ratio. Gross inspection of
the data failed to show significant relation¬
ship between appianation pressure ( )
level and the magnitude of this ratio.
In another report2 it was suggested that
enlargement of the optic cup may be the
In eyes with normal fields, the cup/disc (C/D) first ocular evidence of the damaging effect
ratio was found to be significantly related to ap- of increased ocular pressure. The question
planation pressure PA level, ratio of pressure read- arose as to whether in the normal eye varia¬
ing at the beginning of the tonogram and the tion in the cup/disc (C/D) ratio is related
tonographic estimate of aqueous outflow activity to variation in ocular pressure level. This
(Po/C), and C-value. The frequency of C/D > 0.3
increased significantly with the PA level and with is especially interesting since each of the
the magnitude of the Po/C ratio. It increased also two parameters was shown to be genetically
as the C-value became smaller. This relationship determined and to be in all likelihood con¬
was independent of age or family history of trolled by multifactorial inheritance. Of
glaucoma. equal interest is the possible relationship
between the C/D ratio and the tonographic
estimate of aqueous outflow activity (C)
1 HE RATIO between the diameter of the and the pressure reading at the beginning of
optic cup and that of the optic disc in the the tonogram (P0)/C in the normal eye.
normal eye of first degree relatives demon¬ An appropriate sample was studied to
strated relationships indicative of its genetic evaluate the above questions. Its results un¬
determination.1 The ratio in offspring var- covered a statistically significant relation¬
Submitted for publication April 6, 1969. ship between the C/D ratio on the one hand
From the Department of Ophthalmology, University and ocular pressure, C-value, and P0/C
Hospitals, Iowa City. ratio on the other. In normal eyes the fre¬
Reprint requests to the Department of Ophthalmol-
ogy, University Hospitals, Iowa City 52240 (Dr. quency of C/D ratio > 0.3 varied signifi¬
Armaly). cantly with variation in the above mea-
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2. Fig 1.—Effect of PA reading on distribution of C/D Fig 2.—Effect of age on C/D ratio, with two age
ratio, with two groups of readings: PA < 20 mm Hg group readings: < 40 years (light striation) and > 39
(light stippling) and PA == 20 mm Hg (dark stippling). years (dark striation).
sures. It increased markedly as the
increased, as the P„/C ratio became greater, Fig 3.—Effect of PA on C/D in younger age groups,
and as the C-value became smaller. with two groups of PA readings: < 20 mm Hg
(light stippling) and PA < 20 mm Hg (dark stippling).
The Sample
The sample was limited to 1,444 subjects
in whom ophthalmoscopic examination of
the C/D ratio was performed by a single
examiner (R.S.). They fulfilled the follow¬
ing requirements:
1. Absence of ocular complaint and of
history or evidence of past ocular dis¬
ease, injury, or surgery.
2. Visual acuity of 20/25 or better in
each eye.
3. Distance refraction not exceeding 3
diopters of myopia or 1.5 D of astigma¬
tism.
4. Normal visual field examination of
each eye using the Goldmann perim¬ was performed without dilating the pupil,
eter with the I-2-e. except on rare occasions when it was felt
5. Reliable and satisfactory performance that estimation of the ratio could not be
on Goldmann perimetry, applanation reliably made in the undilated pupil.
This ratio was recorded separately for
tonometry, and tonography. each eye.
Procedure 4. Applanation tonometry and tonography
were then performed by an independent
The sequence of testing was as follows: research technician who was completely
1. Determination of best corrected visual unaware of the estimated C/D ratio.
acuity for distance using Snellen-type In all cases the C/D ratio was recorded prior
chart. to and without any knowledge of the result of
2. Goldmann perimetry using the I-2-e stim¬ tonometry and tonography. All tests were com¬
ulus. pleted on the same day.
3. Ophthalmoscopy to rule out gross abnor¬
mality to the posterior pole and to esti¬ Results
mate the ratio of the horizontal diameter
of the optic cup to that of the optic disc The distribution of the C/D ratio in the
and record it to the nearest tenth. This normal eye was shown to differ significantly
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3. Fig 5.—Effect of P, on C/D ratio, with percentage
frequency of C/D = 0.00-0.3, inclusive, in light stip¬
pling and that of C/D > 0.3 in dark stippling.
Fig 4.—Effect of PA on C/D in older age group, with
two groups of PA readings: PA < 20 mm Hg (light
stippling) and PA > 20 mm Hg (dark stippling).
Fig 6.—Effect of C-value on C/D ratio, with per¬ Fig 7.—Effect of P„/C on C/D ratio, with percentage
centage frequency of C/D = 0.00-0.3 in light stippling frequency of C/D = 0.00-0.03 in light stippling and
and that of C/D > 0.3 in dark stippling. that of C/D > 0.3 in dark stippling.
from the gaussian statistical distribution.1 C/D values occurred more frequently in
The same was true for the distributions of eyes with > 19 than in those with
PA, C, and ,,/C.3"5 Therefore, in the analy¬ PA < 20. An appropriate boundary for this
ses that follow, the chi-square test will be used trend seems to be at C/D ratio of 0.3. To
to evaluate the statistical significance of a evaluate this trend statistically, C/D ratios
difference in frequency of certain observa¬ were divided into two subgroups: One in¬
tions. cluded C/D values of 0 to 0.3 inclusive, and
Applanation Pressure and C/D Ratio.— the other included C/D values > 0.3. The
The sample was divided into two groups percentage of eyes falling into each sub¬
depending upon the PA readings: the first group of C/D values was calculated in each
included eyes with a PA < 20 mm Hg and PA group. In eyes with lower PA readings
consisted of 2,467 eyes, and the second in¬ (PA < 20 mm Hg) 15.5% had a C/D ratio
cluded those with > 19 mm Hg and > 0.3; whereas in eyes with higher PA read¬
consisted of 421 eyes. The frequency distri¬ ings (PA > 20 mm Hg) 23.3% had a C/D
bution of the C/D ratio in each group ap¬ ratio > 0.3. This increase in frequency is
pears in Fig 1. The frequency was expressed statistically highly significant at the 1%
in percentage instead of absolute number to level of confidence using the chi-square test.
permit visual comparison of the two groups. In the group with high PA readings, one
It is obvious that small C/D values oc¬ expects to find older individuals to predomi¬
curred less frequently in eyes with PA > 19 nate because of the increase in PA with age
than in those with PA < 20; similarly large in the normal eye.3 One might argue that if
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4. age alone had a similar association with Table 1.—Percentage Frequency of CID > 0.3 ¡
Different PA, C, and P0/C Values
large C/D ratios then the results of the
preceding analysis may reflect that effect Total Frequency of C/D >
rather than an effect of PA level. In a No. 0.3 in %
preceding study no age effect could be un¬ Pa in mm Hg
covered on the C/D ratio. The distribution <16 1,432 12.8
16-19 1,036 19.4
of C/D ratios in children did not differ 20-23 307 23.3
from that of their adult parents. However, >24 115 35.7
because of the significance of this uncertain¬ C-value in µ /mm Hg/min
194 11.8
>0.30
ty it became important to rule out such 0.25-0.34 868 12.3
association between age and C/D ratio in 0.15-0.24 1,136 16.9
<0.15 686 23.2
this present sample. The sample was di¬
vided into two age groups: One included P0/C Ratio
0-99 2,216 14.5
those whose age was < 40 years and the 100-150 474 20.0
>150 194 32.1
other included those whose age was > 39
years. The first consisted of 690 eyes and the
second included 2,198. The median age for Table 2.—Percentage Frequency of Limit Values of
the first was 31 years and for the second it Pa, C, and Z,. in Different C/D Ratios
was 59 years. The percentage frequency dis¬ Percentage Frequency
tribution of C/D ratio in each age group ap¬ C/D Total .-'-.
Ratio No. Pa>19 C<0.15 Zp>2.00
pears in Fig 2. There is a suggestion that in
the older age group the frequency of large 0.0-0.2 1,822 13 9.7 4.17
0.3-0.5 952 15.1 11.2 5.25
C/D ratios may be greater. In the younger 0.6-0.8 114 29 37.7 17.69
age group, C/D > 0.3 occurred in 14.2%,
whereas in the older age group it occurred in
17.5%. Chi-square test revealed this increase groups with similar PA readings reveals no
to be significant at the 5% level, but not at significant effect of agethis ratio (P >
on
the 1% level of confidence. Nevertheless, this 0.05). We must then conclude that the
finding makes it greatly desirable to dis¬ relationship uncovered in the sample be¬
tinguish more definitely between the effect of tween PA and C/D is real and is not re¬
PA and that of age on this ratio. flecting a possible age effect; on the contra¬
In each age group, eyes were divided into ry, the possible age effect depicted in Fig 2
two categories depending upon the PA is seen to reflect the fact that higher PA is
reading. The first included those with more frequent in the older age group.
PA < 20 and the second those with PA > In an attempt to describe better the rela¬
19. The frequency of the C/D ratio in each tionship between PA and C/D ratio, the
PA group was calculated and appears in sample was divided into different
Fig 3 and 4. In the younger age group (Fig groups and the frequency of C/D ratio was
3), the frequency of C/D > 0.3 was 13.4% investigated in each. The results appear in
in eyes with PA < 20 and 25.5% in those Fig 5 and Table 1. They demonstrate clear¬
with PA > 19. The chi-square test shows the ly that the frequency of C/D > 0.3 in the
increase to be statistically highly significant normal eye increases with PA reading. The
at the 1% level of confidence. Similarly in chi-square test shows this increase to be
the older age group (Fig 4), the frequency statistically highly significant at the 1%
of C/D ratio > 0.3 was 16.5% in eyes with level of confidence.
PA < 20 mm Hg and 23.2% in those with C-value, PJC Ratio, and the C/D Ratio.—
PA > 19 mm Hg. The chi-square test In order to evaluate the relationship between
showed this increase to be highly significant C-value of tonography and the C/D ratio,
at the 1% level of confidence. Thus, in each eyes were divided into four groups depending
age group the frequency of C/D ratio > 0.3 upon the C-value. The following ranges of
is greater with higher pressure, indicating C-value were used: 0.00-0.14; 0.15-0.24; 0.25-
that the association cannot be explained by 0.34; and > 0.34. In each group the distri¬
a possible age effect. In fact, comparing the bution of the C/D ratio was investigated and
frequency of C/D > 0.3 in different age the percentage frequency of C/D ratios >
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5. 0.3 was calculated. These appear in Fig 6 they share
and C-value. This indicated that
and Table 1. It is obvious that the frequency common genetic determinants; the alíele
of C/D > 0.3 increases significantly as the pair which determines the magnitude of
C-value becomes smaller. This increase is ocular pressure response to topical dexa-
statistically highly significant at the 1% level methasone sodium phosphate was found to
of confidence using the chi-square test- be one of these common determinants, low
The relationship between P0/C and C/D response (PL), high response (PH). In the
ratio was investigated in a similar manner. case of C/D ratio, the positive correlation
Eyes were divided into three groups de¬ with PA and the negative correlation with
pending upon the P0/C ratio. The range in C-value may also imply the sharing of com¬
the different groups was 0-99, 100-150, and mon genetic determinants. It is clear from
>150. In each the frequency distribution of the results that this is not an all or none as¬
C/D ratio and the percentage frequency of sociation where large C/D values are always
C/D > 0.3 were calculated and appear in associated with high PA and low C-values.
Fig 7 and Table 1. Here again the frequen¬ Instead, it is a question of relative frequency
cy of C/D > 0.3 increases progressively as of limit values of these measures in groups
the P0/C ratio increases. This increase is with different C/D ratios. It is a relation¬
statistically highly significant at the 1% ship resulting from the interaction of more
level of confidence using the chi-square test. than one factor and as such offers interesting
C/D Ratio and Values of PA, C, and possibilities in terms of classifying the nor¬
Age-Corrected Standard Score for PA (Zp). mal eye, and in terms of future prediction of
—It is of interest to inquire whether the fre¬ the development of glaucomatous visual func¬
quency of limit values of PA, C, and Zpe tion loss. Now one can classify the normal
varies significantly with the C/D ratio. eye in terms of PA readings and classify
Eyes were divided into three groups de¬ further eyes with similar PA readings ac¬
pending upon the C/D ratio: 0-0.2, 0.3-0.5, cording to the C/D ratios; similarly with the
and 0.6-0.8. The percentage frequency of C-values and the P0/C ratio. There is a clin¬
PA readings > 19 mm Hg was calculated in ical impression that in eyes with normal
each group. Similarly, the percentage fre¬ visual fields the development of future glau¬
quency of C-values < 0.15 and Zp > 2.00. comatous visual field loss is related to the
The results appear in Table 2. They indi¬ presence of a certain combination of PA, C-
cate clearly that the frequency of these limits value, P0/C, and C/D ratio. This intriguing
becomes greater as the C/D ratio increases. possibility will be elucidated in long-term
The chi-square test shows the difference be¬ studies of normal eyes. Along the same line
tween the third group and either one of the of speculation the acquired enlargement of
first two to be highly significant at the 1% the optic cup at varying levels of PA may be
level of confidence. Comparing the second dependent upon the initial C/D ratio as well
group with the first, we find the increase in as upon the level and magnitude of change in
frequency of limit values not significant at PA or C-value with time. Furthermore, the
the 1% level, but significant at the 5% level. finding that the percentage frequency of
It is apparent that the increase in frequency Zp ^ 2.00 increases significantly as the C/D
in limit values is not linear in the three ratio increases indicates clearly that the
groups of C/D ratio. It is markedly greater association between C/D and PA is inde¬
in the group with C/D ratio of 0.6 to 0.8. pendent of age.
This may mean that a different type of asso¬ Finally, one cannot escape the temptation
ciation exists between these limit values and to distinguish two types of association be¬
the higher C/D ratios. tween C/D and PA: the first, in which
common genetic factors are shared in this
Comments and Discussion determination, in which case the relation¬
ship may be less dependent on time; the
In the normal eye, the C/D ratio, PA, second, in which this relationship is ac¬
and C-value have been shown to be geneti¬ quired due to the influence of PA level on
cally determined.7·8 A significant negative the blood supply of the optic disc, thus
correlation was found to exist between P. producing an acquired large C/D ratio.
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6. This latter is more likely to be dependent two samples a relationship between C/D
upon time and to change with duration of and PA that is similar to that encountered
observation. To help distinguish between in this study. This means that this relation¬
these possibilities, investigations of families ship is between C/D and PA and is not
and of individuals tested with dexametha- significantly modified by the presence or ab¬
sone sodium phosphate eye drops are in sence of family history of glaucoma.
progress in which the appearance of the cup This investigation was supported in part by research
is monitored yearly by stereophotography grant CD-00017 from the Neurological and Sensory
with fixed-image displacement,9 in the hope Disease Program, Division of Chronic Diseases, and
NB-07328 from the National Institute of Neurological
that their comparison will elucidate some of Diseases and Blindness.
these intriguing speculations.
In a preceding study,1 the distribution of Key Words.—Cup/disc ratio; optic cup; op¬
the average C/D ratio of the two eyes did tonography; tonometry.
tic disc;
not differ in a sample of first-degree rela¬
tives of patients with glaucoma and that of Generic and Trade Names of Drug
the general population. Reexamination of Dexamethasone—Decadron Phosphate, Respi-
the data in different PA groups in the man¬ haler Decadron Phosphate, Hexadrol Phos¬
ner described above revealed in each of the phate, Turbinaire Decadron Phosphate.
References
1. Armaly, M.F.: Genetic Determination of Cup/ Therapy of the Glaucomas, ed 2, St. Louis: The C.
Disc Ratio of the Optic Nerve, Arch Ophthal V. Mosby Co., Medical Publishers, 1965, p 108.
78:35-43 (July) 1967. 6. Armaly, M.F.: Age and Sex Correction of
2. Armaly, M.F.: The Correlation Between Ap- Applanation Pressure, Arch Ophthal 78:480-484 (Oct)
pearance of the Optic Cup and Visual Function, 1967.
Trans Amer Acad Ophthal Otolaryng, to be pub-
7. Armaly, M.F.: The Genetic Determination of
lished.
Ocular Pressure in the Normal Eye, Arch Ophthal
3. Armaly, M.F.: On the Distribution of Applana-
78:187-192 (Aug) 1967.
tion Pressure: I. Statistical Features and the Effect
of Age, Sex, and Family History of Glaucoma, Arch 8. Armaly, M.F.; Monstavicius, B.F.; and Sayegh,
Ophthal 73:11-18 (Jan) 1965. R.E.: Ocular Pressure and Aqueous Outflow Facility
4. Armaly, M.F.: The Des Moines Population in Siblings, Arch Ophthal 80:354-360 (Sept) 1968.
Study of Glaucoma, Invest Ophthal 1:618-628 (Oct) 9. Allen, L., et al: Instant Positive Photographs
1962. and Stereograms of Ocular Fundus Fluorescence,
5. Becker, B., and Shaffer, R.N.: Diagnosis and Arch Ophthal 75:192-198 (Feb) 1966.
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