Optic
Disc Parameters and
Onset of Glaucomatous Field Loss II. Static
Screening Criteria
Alfred Sommer, MD; Irvin Pollack, MD; A. Edward Maumenee, MD
\s=b\ Stereoscopic fundus photographs of 17 abnormal eyes, taken in known temporal relationship to the onset of glaucomatous visual field loss, and 206 eyes of ageand race-matched controls were examined in randomized masked fashion. Width of the narrowest remaining disc rim, size of the vertical and horizontal physical cups, contour of the temporal and nasal slopes (vertical ovalness), and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were all useful for distinguishing patients with impending or established visual field loss. None, however, was as effective as defects in the nerve fiber layer, the only parameter displaying sufficient promise as a clinical screening tool to warrant initiation of large-scale prospective evaluation.
(Arch Ophthalmol 97:1449-1454, 1979)
variety of fundus criteria have been proposed for detecting pa¬ tients with established or impending glaucomatous visual field loss.15 Un¬ fortunately, little data exist on the "f*
Accepted
for publication Oct 19, 1978. From the Wilmer Institute, Johns Hopkins Baltimore Hospital, (Drs Sommer, Pollack, and Maumenee), and Helen Keller International, New York (Dr Sommer). Reprint requests to Wilmer Institute, Johns Hopkins Hospital, 601 N Broadway, Baltimore, MD 21205 (Dr Sommer).
actual sensitivity and specificity of these criteria in known temporal rela¬ tionship to the development of such field loss. Our review of serial stereoscopic fundus photographs taken in known relationship to the onset of glaucoma¬ tous field loss (see page 1444) demon¬ strated that readily apparent changes in the size, shape, or contour of the cup, or color of the remaining disc tissue always occurred by the time field loss first appeared. But serial examination imposes a waiting period and delay in diagnosis and treatment during which the patient may suffer further neuronal damage or even become unavailable for follow-up. In the present article we assess the sensitivity and specificity of these same disc parameters as "single-look" screening criteria, to determine which, if any, warrant further investi¬
gation.
BACKGROUND
Reasonably clear stereoscopic fun¬ photographs available on 17 hypertensive eyes in which classical glaucomatous field loss (repeatable Seidel's scotoma, elongation of the dus
blind spot
>
60°,
arcuate
scotoma,
paracentral scotoma, or nasal step > 10°) eventually developed and 206 eyes of age- and race-matched con¬ trols (intraocular pressure consistent-
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21 mm Hg and normal fields) examined by one of us (A.S.) in masked fashion, and a variety of disc parameters assessed. All individuals had been followed up at the Wilmer Institute with annual tonometry, tonography, kinetic perimetry, and di¬ lated fundus examination. Stereoscop¬ ic color fundus photography of se¬ lected optic discs began in 1966, and the discs of all individuals were photo¬ graphed at least once, beginning in 1968. Limits of the physical cup, area of pallor ("color cup"), and exposed lamina dots were drawn to scale on a ten-square grid in modification of the method of Shaffer et al." Horizontal cross sections of the discs were sketched, indicating the thickness of the nerve fiber layer as it crossed the temporal ridge, and the transparency and contour of the temporal and nasal slopes. After all photos had been drawn and analyzed, they were reas¬ sembled in their original order and the temporal relationship between vari¬ ous parameters and onset of glauco¬ matous field loss in each abnormal eye tabulated. Forty randomly chosen slides re¬ read for reproducibility indicated per¬ fect agreement on the contour of the slopes, near-perfect agreement on the thickness of the nerve fiber layer, .and a mean variation of estimates of the physical cup/disc ratio of between 0.60
ly
—4
—3
—2
-1
0
7
2
2
5
3
11
3
4
5
8
8
11
—5s
+1
+2
11
1113
+3
'Includes two eyes with photos available only at this time. One has a diameter of 6.0 tenths DD, the other 8.0 tenths DD—both, therefore, screening positive. tExcludes patient 8 (eyes 9 and 10). iA total of 17 eyes were available (including patient 8: eyes 9 and 10).
Table 3.—Vertical Cup/Disc, Tenths of
a
Disc Diameter
No. of
Cup/Disc
Ratio: Controls %
Eyes
Cumulative %
0.0-1.75_83_40_
2.0-2.75_33_16_56 3.0-3.75_26_13_69 4.0-4.75_25_12_81 5.0-5.25_15_7_88 5.5-5.75_11_5_94 6.0-6.25_7_3_97 6.5-6.75_2_1_98 7.0-7.25_2_1_99 7.5-7.75_1_0_05_
8.0_1_0_05_100 206 Total
of two independent measurements, each of which may be changing at different rates (asymmetry of the two eyes and vertical ovalness of the cup). The proportion of cumulative and inter¬ val positive eyes provide a rough estimate of the sensitivity of the screening parame¬ ter. The cumulative proportion positive makes maximum use of all available photos, but underestimates the sensitivity achieved at each interval, since some eyes, already positive by the time their first photos were available, might well have screened positive earlier; while others, negative early in their course, lacked addi¬ tional photos. The proportion of eyes avail¬ able at each interval that were positive
(interval proportion positive) provides feeling for the higher sensitivity that might have been achieved at that interval,
some
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but is handicapped by the fewer eyes avail¬ able for comparison and whatever bias the lack of photos for the other eyes entails. Between them, these two techniques provide sufficient data to indicate which, if any, screening parameters deserve further
investigation.
One unusual, abnormal case (case 8) deserves mention. Both eyes (eyes 9 and 10) maintained a small, funnel-shaped cup throughout their course, repeated skull x-ray films and neurologic examination findings being unremarkable. In no instance would either eye have screened positive by any of the parameters investi¬ gated. Being unusual, and consistently screening normal, patient 8 is removed from the number of "available" and "posi¬ tive" photos at each interval, but it should be kept in mind that the apparent interval
Table 4.—Vertical
Cup/Disc
Table 5.—Width of Narrowest Disc Rim: Controls
Ratio: Abnormal Patients
Remaining
Years to Visual Field Loss
Cup/Disc
a 6.0 Tenths
Disc Diameter (DD) No. of eyes with available
-
a-5*
-
-4
-2
-3
-1
0
+1
+2
Width,
+3
Tenths of a Disc Diameter
photos No. of eyes
2
positivef Cumulative number posi¬
2
tive!
1
2
5 8
4
3
3 8
10
4~Ö
12
3.0-3.75 2.0-2.75
12
1213
Table 6.—Width of Narrowest Rim Width s 1.0 Tenths
Disc Diameter (DD) No. of eyes with available
photos
Remaining -4
-3
t_7_2
No. of eyes
positivet Cumulative number posi¬ tivet
2
2
0.75
5
-2
—1
0
+1
+2
5_3
11 4 5 4 38354
9
10
-5t -4 -3 -2 -1
Ratio of
12
12
14
12
0
+1
+2
+3
+4 +5
when
10
available from the same sitting. Eye with the earlier or worst initial visual field defect is the denominator. Three eyes had indeterminate ratios: 0.75/0, 1.25/0, 2.25/0. Since one rim was already "0" (by our earlier rim criteria must have established or impending visual field defect) and asymmetry existed, these were considered positive. tlncludes two pairs for which further photos were unavailable. One ratio was 4.0, hence positive,
the other 1.0, hence negative. tExcludes patient 8 (eyes 9 and 10). §A total of 13 pairs of eyes were available for comparison (including patient 8: eyes 9 and 10). ||One, still negative at + 3 years, had a ratio of 0.25/0.25. By + 5 years it was 0.0/0.0 (by our earlier rim criteria must have established or impending visual field defect), hence called positive.
RESULTS
Cup/Disc Ratio acceptable level of speci¬ ficity, 92%, occurs at a cup size of six tenths DD (Table 1). At this level (Table 2), almost half the eyes were already identified by —2 years, although the cumulative sensitivity at Horizontal
The first
99 100
7~.
...
0 years was still only 65%. years all eyes ever to screen
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Cumulalive
Eyes 56
58
1.2-1.3 1.4-1.5
11
1.6-1.9 2.0-2.9
8 5
11 10 8
3.0-3.9 4.0-4.9
3 1
No. of
10
% 70 80 89 94
5 3
2
1
97 98
2
100
96
Cup/Disc
Ratio
The first acceptable screening level and its sensitivity and specificity are similar to those for the horizontal cup/disc ratio (Tables 3 and 4). Any narrowing of the screening level, however, to 6.5 tenth's DD, results in a precipitous fall in sensitivity (two cases positive at the 6.0 tenths DD level would screen negative if the screening level were 6.5 tenths DD).
By +3 positive
(13/17) had already done so. The cumulative sensitivity is reduced, by an unknown degree, by two eyes still screening negative at the time of their last available photos, at —3 and 0 years, respectively, though at the time they were still rather far from the screening level (5.0 and 3.25 tenths DD). The interval sensitivity ap¬ proached 100% by + 2 years (excluding both eyes of patient 8, which would have screened negative). Narrowing of the screening level to 6.5 tenths DD raises the specificity to 96% without any loss in sensitivity. Further narrowing, however, causes a fall in sensitivity.
%
Smaller Rim 0.0-1.1
Vertical 11
paired photos
sensitivity might well be less than shown. For comparison these two eyes are included in the "total available eyes" in the cumulative column. A minus sign indicates the number of years preceding visual field loss; a plus sign, years following such loss; and a zero, the year visual field loss first occurred. All abnormal eyes had at least one photograph taken at or before 0 years, and all but two at or after 0 years as well.
1
...
•Includes only those individuals with paired photos taken at the same sitting.
available:): positive}:
'Comparisons made only
99
Posifive
to
5.0 Total
No.
1
1
7.—Asymmetry of the Remaining Rim in the Two Eyes*: Controls
Years to Visual Field Loss
1
206
57
20_77 18_96 2_98
Narrowest
Table 8.—Asymmetry of the Narrowest Remaining Rim in the Two Eyes*: Abnormal Patients
Cumulative number positives
2
.;.
Table
+3
Includes two eyes with photos available only at this time. Both screened positive. tExcludes the two eyes of patient 8 (eyes 9 and 10). JA total of 17 eyes were available (including patient 8: eyes 9 and 10).
Ratio a 3.0 No. of cases with paired photos
3 0
0.50 0.25 Total
Larger
3
38
% 39 18
Disc Rim: Abnormal Patients
125
2
41
1.0_5
Years to Visual Field Loss ,-*-> -5s
Eyes 80 37
1.25-1.75
•Includes two eyes with photos available only at this time. One with diameter of 4.5 tenths DD, thus at this level, the other 8.0 tenths DD, thus positive. tExcludes patient 8. tA total of 17 eyes were available (including patient 8: eyes 9 and 10)
negative
Cumulative %
No. of
Width of the Narrowest Remaining Rim
At the minimal acceptable screen¬ ing level ('< one tenth DD) the sensi¬ tivity and specificity are slightly better than for either of the preceding
parameters (Tables 5 and 6). The
specificity
was
abnormal eyes
96%. Nine of the 17
were
already positive
—2 years, 12 by 0 years, and 14 by + 3 years. Of the remaining three eyes, two belonged to patient 8 (eyes 9 and 10), and the other had a rim that decreased from four tenths DD at —5 years, to 1.25 tenths DD by 0 years, the last available photo. It is reason¬ able to assume this eye would likely have screened positive by +3 years,
by
Table 9.—Vertical Ovalness of the
Table 10.—Thickness of the Nerve Fiber Layer: Controls
Cup: Abnormal Patients
Years to Visual Field Loss
No. of
Concave Slopes* No. of eyes with available photos§ No. of eyes positives Cumulative number positive| Concave slopes plus cup/disc cri¬ terion 1 No. of eyes with available photos§ No. of eyes positives Cumulative number
>
positive|j
_5t -4
-3t
-1
-2
+1
+2
+4
11 10
Elevated Flattened
10
11
11
12
1
1
1
6
one
met the
slope criterion, the
previously meeting both criteria now meets only the slope criterion. positive column for both criteria. SExcludes patient 8 (eyes 9 and 10). ||A total of 17 eyes were available (including patient 8: eyes 9 and 10). I Concave temporal and nasal slopes plus a cup/disc ratio > 0.5 tenths DD greater case
other
It remains in
cumulative
in the vertical than horizontal direction. ff Two cases previously positive now negative because cup too large to permit vertical/horizontal disparity. They remain positive in the cumulative column. "'One case previously positive now has larger cup in the horizontal than vertical meridian. It remains positive in the cumulative column.
Table 11.—Thickness of Nerve Fiber
Layer:
Abnormal Patients
Years to Visual Field Loss -4 Flat
Lost No. of eyes with available No. positivet
-3
-1
-2
Of
-1
-2
+3t
14
14
11
11
or
10 10 13
photosf
Cumulative number positives Lost No. of eyes with available photosj No. positivet Cumulative number positives
10 10
0
ni
*Of the two eyes with photos available only for this interval, one was normal thickness, the other flat. fThe border of one eye was out of focus and could not be read; this is excluded from both the number available and the number positive. tExcludes patient 8 (eyes 9 and 10). SA total of 17 eyes were available (including patient 8: eyes 9 and 10). ||Those missed, read as flat, were previously read as lost, indicating limited variability. Of the eyes, one had subsequent photos, all of which were read as lost once again. 1 The additional case is the one that could not be read at 0 years.
leaving only the
two eyes of case 8 undetected. Interval sensitivities were similar to those for the cup-/disc parame¬
ters.
Asymmetry of the Two Eyes The clearest demonstration
asymmetry between
a
patient's
of two
the ratio of the widths of eyes their narrowest remaining rims. A ratio permits maintenance of a large difference even as the rims become smaller and the potential for an abso¬ lute difference decreases. In some instances of abnormal eyes, however, the ratio was indeterminate (the denominator being zero). Since, by our was
preceding analysis,
zero
_Eyes
remaining
rim indicates an eye is almost sure to have established or impending visual
field loss, these were considered posi¬ tive. The minimal acceptable screening level occurred at 3.0 or above (Table 7), a specificity of 94%. The sensitivity remained very low until 0 years, by which time nine of the 13 cases had already screened positive (Table 8). By + 5 years, 11 of the 13 cases were positive. Interval sensitivities were not as high as for the preceding
parameters.
Any narrowing of the criteria a drop in sensitivity. At 4.0 or above, two cases positive at 0 years resulted in
and tive.
one
at +5 years become nega¬
Cup We analyzed two definitions of "vertical ovalness": concave temporal Vertical Ovalness of the
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187 15
Cumulative
%_% 91_
Lost_4
Total
'Concave temporal and nasal slopes. tOf the two eyes with photos available only for this interval, met neither criteria for positivity.
JOne
+3
206
7_98 2_100
and nasal slopes with a cup/disc ratio of at least 0.5 tenths DD greater in the vertical than horizontal meridian, and the slope criterion by itself. Concave nasal and temporal slopes were pres¬ ent in only 8% (17 eyes) of controls, and in 0.5% (one eye) was this asso¬ ciated with the additional cup/disc meridional criterion. The sensitivity of both criteria are presented in Ta¬ ble 9. The specificity for the less strin¬ gent slope criterion is 92%, within the acceptable range. Ten of the 17 eyes already were positive at 0 years, the two remaining eyes becoming positive at + 4 years. Two of the five negative eyes did not have photos taken at + 4 years. Had they been available, the
cumulative sensitivity might have been higher. As expected, the specific¬ ity of the more stringent criterion was much higher (99.5%), but the sensitivi¬ ty much lower. Less than half the eyes were already positive by the time visual field loss first occurred (0 years), and only one additional case became positive at + 4 years. In fact, the cumulative sensitivity is some¬ what misleading. Keeping with our earlier practice, once an eye screened positive it remained in the cumulative positive column. But several patients eventually lost their meridional crite¬ rion as the horizontal cup expanded faster than the vertical, eventually surpassing it in size. Therefore, what was originally a positive case might, if screened later in its course, be nega¬
tive.
Interval sensitivities for either cri¬ terion were lower than for the cup/ disc criteria or width of the remaining disc rim. Thickness of the Nerve Fiber Layer
article (see demonstrated progressive thinning of the nerve fiber layer during the course of the disease. After sketching the actual thickness ob¬ served in three dimensions we catego¬ rized the thickness as normal (E, or elevated), thinned (F, or flattened), or lost (L, completely flat, without any thickness at all). Masked reproducibility trials indicated near-perfect In
1444)
our
we
companion
agreement, with only occasional pho¬ tos being reread in adjacent catego¬ ries (E-F, F-L). The broader criterion, flattened or
which to base a diagnosis and initiate therapy. The question is whether it is
sufficiently more common among glaucomatous patients than normal individuals to serve as a distinguish¬ ing characteristic. Similarly, indicat¬ ing the diagnosis was correct 86% of the times is equally unrevealing. We do not know what proportion of patients with glaucoma were missed (resulting in false-negatives) and what proportion without glaucoma were mistakenly diagnosed as having it (resulting in false-positives). This is especially problematic in glaucoma, where only a very small proportion of the population has the disease and where the actual mix of patients with glaucoma and normal patients may
lost, has an acceptable specificity of 91% (Table 10). The sensitivity was quite high, almost half the eyes posi¬
tive at —2 years, and 13 of the 17 positive by the time of onset of glau¬ comatous field loss (Table 11). Maxi¬ mum sensitivity, 14 of 17 eyes posi¬ tive, was achieved by +1 years. In fact, all 14 positive eyes were probably recognizable as such by 0 years. The
single case added at +1 year (L, completely lost) was out of focus and
could not be read at 0 years. It is reasonable to suppose that, had the 0-year photo been in focus, it would at least have been flattened at that time. Of the three eyes that never screened
positive,
two
belonged
to
vary from series to series. For exam¬ ple, surveys commonly show that 0.4% of the adult population have glauco¬ matous field loss and that one half to two thirds of those with such field loss, but only 9% of the population as a whole, have a single screening pres¬ sure over 21 mm Hg. Therefore, pres¬ sures over 21 mm Hg "suggest" glau¬ comatous field loss; they result in only nine false-positives and 0.2 falsenegatives for every 100 individuals screened, and they provide the correct diagnosis "91% of the time." But this is not nearly as meaningful as know¬ ing the sensitivity is only 65%» (more than one third of all patients with established field loss would be missed by simple tonometric screening), and that the specificity is 91% (9% of all normal individuals will be thought to be abnormal) regardless of the actual proportion of normal and abnormal subjects in the group studied. An "ideal" screening test would have a sensitivity and specificity of 100%, something rarely achieved. In practice, we attempt to strike a
patient 8,
and the third had a thick nerve fiber layer at —5 years, the only photo avail¬ able. Interval sensitivities were higher than for any other criterion. Excluding case 8, it reached 100% by 0 years. The specificity of the narrower criterion, lost, was far higher (98%), but the sensitivity was reduced and the diagnosis delayed. Half the eyes were not screened positive until between —1 and 0 years, though 11 of the 17 eyes were positive by +1 years. One additional case became positive at + 5 years (not shown in Table 11). Two of the five eyes that never screened positive were from patient 8, while two others negative at —5 years lacked additional photos. Other Criteria
Presence of peripapillary pigmenta¬ tion, visible laminar dots covering an
of at least 2x2 tenths DD, concave and "beanpot" contours of the temporal slope were all present in too large a propor¬ tion of controls to serve as useful area
transparency, and
screening parameters. COMMENT
A variety of disc parameters have been advocated to help distinguish patients with impending or estab¬ lished visual field loss. Unfortunately, we are rarely provided with the sensi¬ tivity and specificity of these criteria, and almost all comparisons are be¬ tween patients with and without established field loss, precluding any assessment of when, in the course of the disease, those parameters first become positive. Some investigators simply state a particular criterion "suggests" true glaucoma, insufficient information on
'
balance between maximum sensitivi¬ ty, since we do not wish to overlook cases requiring treatment, while keeping the specificity within man¬ ageable limits. This is especially diffi¬ cult in glaucoma screening, where the prevalence of true disease is so low. For example, since 9% of a population over age 40 will have screening pres¬ sures over 21 mm Hg, but only 3% of these hypertensive patients will have established field loss (a useful criteri¬ on of true glaucoma), 32 normal patients screen positive for every one abnormal patient detected, a wholly inadequate ratio. Admittedly, glauco¬ matous field loss will develop in some of these ocular hypertensive patients, but at a rate so low (estimated at one to five per 1,000 per yr) as to limit its value. Raising the pressure criterion
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will improve the specificity and reduce the number of false-positives, but also lowers the sensitivity, in¬ creasing the number of false-nega¬ tives (patients with true glaucoma thought not to have it). In the present study we attempted to arrive at an estimate of the true sensitivity and specificity of the most promising fundus parameters at vari¬ ous stages in the course of the disease. Since stereoscopic fundus photo¬ graphs were not taken at regular annual intervals, our methods admit¬ tedly are inexact. Definitive investi¬ gation would require annual examina¬ tion of hundreds of ocular hyperten¬ sive patients over a period of ten to 15 years. Before embarking on so expen¬ sive and laborious a task, it is reason¬ able to avail ourselves of all available data to determine which, if any, pa¬ rameters are worthy of such investi¬ gation. Our study provides sufficient information on which to base this decision. None of the parameters investi¬ gated really proved satisfactory. Of those with promise, the specificities varied from 92% to 98%—acceptable levels—but the sensitivities were quite low, at least until rather late in the course of the disease. For example, one of the highest sensitivities was recorded by screening for remaining disc rim at its narrowest point of one tenth DD or less. While nine of 17 eyes
already positive at —2 years, only 12 of 17 were positive at the onset of glaucomatous visual field loss (0 years), and the maximum sensitivity, were
14 to 15 of 17 was not achieved until three years later. The sensitivities for flattening of the nerve fiber layer as it crossed the temporal rim were comparable, while those for vertical ovalness (in its broader, less specific, sense), and horizontal and vertical cup/disc ratios were somewhat low¬ er.
Despite the disappointing nature of results, they are more encourag¬ ing than those recently reported by
our
Kitazawa and associates.1' For reasons of asym¬ metry of the two discs differs from theirs, and the results are not directly comparable. The lower specificity of the cup/disc ratio criterion in their study is probably attributable to at least two factors: they used an "ac¬ cepted" screening level of five tenths DD, while we purposely adjusted the level to achieve a minimal specificity of 91%; their "controls" were "ocular hypertensive patients," in some of whom visual field loss might have been on the verge of developing, while
already given, our definition
normotensive patients, a group under these circumstances.1" Their lower sensitivi¬ ours were more
appropriate
ty represents
single determination, subject entered the study, unadjusted for
presumably
a
at the time each
duration to visual field loss. In our study, sensitivity was recalculated at annual intervals adjusted for duration to field loss. A combination of criteria does not improve the situation appreciably: eyes with the narrowest rims tended to be the ones with flattened nerve fiber layers, vertical ovalness and large cups. In contrast, we recently demonstrated that defects in the nerve fiber layer of the retina correct¬ ly identified all abnormal patients within one year of onset of visual field loss, including patient 8 (eyes 9 and 10), which could not be identified by any of the above criteria.10 Regression analysis suggested that nerve fiber layer defects were likely to be visible in the vast majority of cases years before the onset of visual field loss.
It is hardly surprising that defects in the nerve fiber layer are more sensitive and specific indices of impending field loss than various cup/ disc relationships. Defects in both the nerve fiber layer and visual fields are direct consequences of neuronal dam¬ age. Disc parameters, however, repre¬ sent a complex mixture of normal variation and damage of both nerve elements and glial supporting struc¬ tures, primarily the latter. The significance of visible defects in the nerve fiber layer deserves fullscale, definitive, prospective evalua¬ tion. The additional cost and effort of evaluating these other, admittedly less promising, disc parameters at the same time should be minimal and might well be warranted. Asymmetry of the two eyes, peripa¬
pillary pigmentary abnormalities,
of transparency and abnormal temporal slope, and visibility of the lamina dots were insufficiently sensitive and specific to serve as useful screening tools. area
contours of the
We do not wish to imply that a valid clinical sign must also be a useful screening tool. A screening tool must have a high sensitivity and specificity. But by narrowing the criteria one may raise the specificity dramatically, to a point that any patient fulfilling the criteria has a very high likelihood of having true glaucoma. For example, none of the controls had a narrowest rim of less than 0.25 tenths DD, a vertical or horizontal cup/disc ratio greater than 8.0 tenths DD, or asym¬ metry of the remaining rim in the two eyes of greater than 5.0 tenths DD, while only 0.5% met our strictest defi¬ nition (contour and cup/disc ratio) of vertical ovalness. Patients fulfilling any of these criteria deserve imme¬ diate and thorough investigation and perhaps therapy as well, regardless of whether or not glaucomatous field loss already has occurred. Of course, this
heightened specificity implies a sharp loss in sensitivity, and many patients with impending or established field loss will not satisfy these criteria.
References 1. Fishman RS: Optic disc asymmetry. Arch Ophthalmol 84:590-594, 1970. 2. Primrose J: Early signs of the glaucomatous disc. Br J Ophthalmol 55:820-825, 1971. 3. Kirsch RE, Anderson DR: Clinical recognition of glaucomatous cupping. Am J Ophthalmol
75:442-454, 1973. 4. Spaeth GL, Hitchings RA, Sivalingam E: The optic disc in glaucoma: Pathogenetic correlation of five patterns of cupping in chronic open-
angle glaucoma.
Trans Am Acad
Ophthalmol
Otolaryngol 81:217-223, 1976. 5. Portney GL: Photogrammetric analysis
of the three-dimensional geometry of normal and glaucomatous optic cups. Trans Am Acad Ophthalmol Otolaryngol 81:239-246, 1976. 6. Shaffer RN, Ridgway WL, Brown R, et al: The use of diagrams to record changes in glaucomatous disc. Am J Ophthalmol 80:460-464, 1975. 7. Hollows FC, Graham PA: Intraocular pressure, glaucoma, and glaucoma suspects in a defined population. Br J Ophthalmol 50:570-586,
1966. 8. Drance SM: Correlation between optic disc changes and visual field defects in chronic openangle glaucoma. Trans Am Acad Ophthalmol Otolaryngol 81:224-226, 1976. 9. Kitazawa Y, Horie T, Aoki S, et al: Untreated ocular hypertension. Arch Ophthalmol 95:1180-1184, 1977. 10. Sommer A, Miller NR, Pollack I, et al: The nerve fiber layer in the diagnosis of glaucoma. Arch Ophthalmol 95:2149-2156, 1977.
CORRECTION Error in Tabulation.\p=m-\In the article entitled
"Scaling of Visual Acuity Measurements,"
published in the February issue of the Archives (97:327-330, 1979), the tabulation at the top of the first column on page 328 should have appeared as follows: a
1
2 y
100%
(minutes of arc)
=
visual
83.6%
3
4
efficiency 69.9%
58.4%
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Disc Parameters and
Onset of Glaucomatous Field Loss II. Static
Screening Criteria
Alfred Sommer, MD; Irvin Pollack, MD; A. Edward Maumenee, MD
\s=b\ Stereoscopic fundus photographs of 17 abnormal eyes, taken in known temporal relationship to the onset of glaucomatous visual field loss, and 206 eyes of ageand race-matched controls were examined in randomized masked fashion. Width of the narrowest remaining disc rim, size of the vertical and horizontal physical cups, contour of the temporal and nasal slopes (vertical ovalness), and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were all useful for distinguishing patients with impending or established visual field loss. None, however, was as effective as defects in the nerve fiber layer, the only parameter displaying sufficient promise as a clinical screening tool to warrant initiation of large-scale prospective evaluation.
(Arch Ophthalmol 97:1449-1454, 1979)
variety of fundus criteria have been proposed for detecting pa¬ tients with established or impending glaucomatous visual field loss.15 Un¬ fortunately, little data exist on the "f*
Accepted
for publication Oct 19, 1978. From the Wilmer Institute, Johns Hopkins Baltimore Hospital, (Drs Sommer, Pollack, and Maumenee), and Helen Keller International, New York (Dr Sommer). Reprint requests to Wilmer Institute, Johns Hopkins Hospital, 601 N Broadway, Baltimore, MD 21205 (Dr Sommer).
actual sensitivity and specificity of these criteria in known temporal rela¬ tionship to the development of such field loss. Our review of serial stereoscopic fundus photographs taken in known relationship to the onset of glaucoma¬ tous field loss (see page 1444) demon¬ strated that readily apparent changes in the size, shape, or contour of the cup, or color of the remaining disc tissue always occurred by the time field loss first appeared. But serial examination imposes a waiting period and delay in diagnosis and treatment during which the patient may suffer further neuronal damage or even become unavailable for follow-up. In the present article we assess the sensitivity and specificity of these same disc parameters as "single-look" screening criteria, to determine which, if any, warrant further investi¬
gation.
BACKGROUND
Reasonably clear stereoscopic fun¬ photographs available on 17 hypertensive eyes in which classical glaucomatous field loss (repeatable Seidel's scotoma, elongation of the dus
blind spot
>
60°,
arcuate
scotoma,
paracentral scotoma, or nasal step > 10°) eventually developed and 206 eyes of age- and race-matched con¬ trols (intraocular pressure consistent-
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21 mm Hg and normal fields) examined by one of us (A.S.) in masked fashion, and a variety of disc parameters assessed. All individuals had been followed up at the Wilmer Institute with annual tonometry, tonography, kinetic perimetry, and di¬ lated fundus examination. Stereoscop¬ ic color fundus photography of se¬ lected optic discs began in 1966, and the discs of all individuals were photo¬ graphed at least once, beginning in 1968. Limits of the physical cup, area of pallor ("color cup"), and exposed lamina dots were drawn to scale on a ten-square grid in modification of the method of Shaffer et al." Horizontal cross sections of the discs were sketched, indicating the thickness of the nerve fiber layer as it crossed the temporal ridge, and the transparency and contour of the temporal and nasal slopes. After all photos had been drawn and analyzed, they were reas¬ sembled in their original order and the temporal relationship between vari¬ ous parameters and onset of glauco¬ matous field loss in each abnormal eye tabulated. Forty randomly chosen slides re¬ read for reproducibility indicated per¬ fect agreement on the contour of the slopes, near-perfect agreement on the thickness of the nerve fiber layer, .and a mean variation of estimates of the physical cup/disc ratio of between 0.60
ly
—4
—3
—2
-1
0
7
2
2
5
3
11
3
4
5
8
8
11
—5s
+1
+2
11
1113
+3
'Includes two eyes with photos available only at this time. One has a diameter of 6.0 tenths DD, the other 8.0 tenths DD—both, therefore, screening positive. tExcludes patient 8 (eyes 9 and 10). iA total of 17 eyes were available (including patient 8: eyes 9 and 10).
Table 3.—Vertical Cup/Disc, Tenths of
a
Disc Diameter
No. of
Cup/Disc
Ratio: Controls %
Eyes
Cumulative %
0.0-1.75_83_40_
2.0-2.75_33_16_56 3.0-3.75_26_13_69 4.0-4.75_25_12_81 5.0-5.25_15_7_88 5.5-5.75_11_5_94 6.0-6.25_7_3_97 6.5-6.75_2_1_98 7.0-7.25_2_1_99 7.5-7.75_1_0_05_
8.0_1_0_05_100 206 Total
of two independent measurements, each of which may be changing at different rates (asymmetry of the two eyes and vertical ovalness of the cup). The proportion of cumulative and inter¬ val positive eyes provide a rough estimate of the sensitivity of the screening parame¬ ter. The cumulative proportion positive makes maximum use of all available photos, but underestimates the sensitivity achieved at each interval, since some eyes, already positive by the time their first photos were available, might well have screened positive earlier; while others, negative early in their course, lacked addi¬ tional photos. The proportion of eyes avail¬ able at each interval that were positive
(interval proportion positive) provides feeling for the higher sensitivity that might have been achieved at that interval,
some
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but is handicapped by the fewer eyes avail¬ able for comparison and whatever bias the lack of photos for the other eyes entails. Between them, these two techniques provide sufficient data to indicate which, if any, screening parameters deserve further
investigation.
One unusual, abnormal case (case 8) deserves mention. Both eyes (eyes 9 and 10) maintained a small, funnel-shaped cup throughout their course, repeated skull x-ray films and neurologic examination findings being unremarkable. In no instance would either eye have screened positive by any of the parameters investi¬ gated. Being unusual, and consistently screening normal, patient 8 is removed from the number of "available" and "posi¬ tive" photos at each interval, but it should be kept in mind that the apparent interval
Table 4.—Vertical
Cup/Disc
Table 5.—Width of Narrowest Disc Rim: Controls
Ratio: Abnormal Patients
Remaining
Years to Visual Field Loss
Cup/Disc
a 6.0 Tenths
Disc Diameter (DD) No. of eyes with available
-
a-5*
-
-4
-2
-3
-1
0
+1
+2
Width,
+3
Tenths of a Disc Diameter
photos No. of eyes
2
positivef Cumulative number posi¬
2
tive!
1
2
5 8
4
3
3 8
10
4~Ö
12
3.0-3.75 2.0-2.75
12
1213
Table 6.—Width of Narrowest Rim Width s 1.0 Tenths
Disc Diameter (DD) No. of eyes with available
photos
Remaining -4
-3
t_7_2
No. of eyes
positivet Cumulative number posi¬ tivet
2
2
0.75
5
-2
—1
0
+1
+2
5_3
11 4 5 4 38354
9
10
-5t -4 -3 -2 -1
Ratio of
12
12
14
12
0
+1
+2
+3
+4 +5
when
10
available from the same sitting. Eye with the earlier or worst initial visual field defect is the denominator. Three eyes had indeterminate ratios: 0.75/0, 1.25/0, 2.25/0. Since one rim was already "0" (by our earlier rim criteria must have established or impending visual field defect) and asymmetry existed, these were considered positive. tlncludes two pairs for which further photos were unavailable. One ratio was 4.0, hence positive,
the other 1.0, hence negative. tExcludes patient 8 (eyes 9 and 10). §A total of 13 pairs of eyes were available for comparison (including patient 8: eyes 9 and 10). ||One, still negative at + 3 years, had a ratio of 0.25/0.25. By + 5 years it was 0.0/0.0 (by our earlier rim criteria must have established or impending visual field defect), hence called positive.
RESULTS
Cup/Disc Ratio acceptable level of speci¬ ficity, 92%, occurs at a cup size of six tenths DD (Table 1). At this level (Table 2), almost half the eyes were already identified by —2 years, although the cumulative sensitivity at Horizontal
The first
99 100
7~.
...
0 years was still only 65%. years all eyes ever to screen
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Cumulalive
Eyes 56
58
1.2-1.3 1.4-1.5
11
1.6-1.9 2.0-2.9
8 5
11 10 8
3.0-3.9 4.0-4.9
3 1
No. of
10
% 70 80 89 94
5 3
2
1
97 98
2
100
96
Cup/Disc
Ratio
The first acceptable screening level and its sensitivity and specificity are similar to those for the horizontal cup/disc ratio (Tables 3 and 4). Any narrowing of the screening level, however, to 6.5 tenth's DD, results in a precipitous fall in sensitivity (two cases positive at the 6.0 tenths DD level would screen negative if the screening level were 6.5 tenths DD).
By +3 positive
(13/17) had already done so. The cumulative sensitivity is reduced, by an unknown degree, by two eyes still screening negative at the time of their last available photos, at —3 and 0 years, respectively, though at the time they were still rather far from the screening level (5.0 and 3.25 tenths DD). The interval sensitivity ap¬ proached 100% by + 2 years (excluding both eyes of patient 8, which would have screened negative). Narrowing of the screening level to 6.5 tenths DD raises the specificity to 96% without any loss in sensitivity. Further narrowing, however, causes a fall in sensitivity.
%
Smaller Rim 0.0-1.1
Vertical 11
paired photos
sensitivity might well be less than shown. For comparison these two eyes are included in the "total available eyes" in the cumulative column. A minus sign indicates the number of years preceding visual field loss; a plus sign, years following such loss; and a zero, the year visual field loss first occurred. All abnormal eyes had at least one photograph taken at or before 0 years, and all but two at or after 0 years as well.
1
...
•Includes only those individuals with paired photos taken at the same sitting.
available:): positive}:
'Comparisons made only
99
Posifive
to
5.0 Total
No.
1
1
7.—Asymmetry of the Remaining Rim in the Two Eyes*: Controls
Years to Visual Field Loss
1
206
57
20_77 18_96 2_98
Narrowest
Table 8.—Asymmetry of the Narrowest Remaining Rim in the Two Eyes*: Abnormal Patients
Cumulative number positives
2
.;.
Table
+3
Includes two eyes with photos available only at this time. Both screened positive. tExcludes the two eyes of patient 8 (eyes 9 and 10). JA total of 17 eyes were available (including patient 8: eyes 9 and 10).
Ratio a 3.0 No. of cases with paired photos
3 0
0.50 0.25 Total
Larger
3
38
% 39 18
Disc Rim: Abnormal Patients
125
2
41
1.0_5
Years to Visual Field Loss ,-*-> -5s
Eyes 80 37
1.25-1.75
•Includes two eyes with photos available only at this time. One with diameter of 4.5 tenths DD, thus at this level, the other 8.0 tenths DD, thus positive. tExcludes patient 8. tA total of 17 eyes were available (including patient 8: eyes 9 and 10)
negative
Cumulative %
No. of
Width of the Narrowest Remaining Rim
At the minimal acceptable screen¬ ing level ('< one tenth DD) the sensi¬ tivity and specificity are slightly better than for either of the preceding
parameters (Tables 5 and 6). The
specificity
was
abnormal eyes
96%. Nine of the 17
were
already positive
—2 years, 12 by 0 years, and 14 by + 3 years. Of the remaining three eyes, two belonged to patient 8 (eyes 9 and 10), and the other had a rim that decreased from four tenths DD at —5 years, to 1.25 tenths DD by 0 years, the last available photo. It is reason¬ able to assume this eye would likely have screened positive by +3 years,
by
Table 9.—Vertical Ovalness of the
Table 10.—Thickness of the Nerve Fiber Layer: Controls
Cup: Abnormal Patients
Years to Visual Field Loss
No. of
Concave Slopes* No. of eyes with available photos§ No. of eyes positives Cumulative number positive| Concave slopes plus cup/disc cri¬ terion 1 No. of eyes with available photos§ No. of eyes positives Cumulative number
>
positive|j
_5t -4
-3t
-1
-2
+1
+2
+4
11 10
Elevated Flattened
10
11
11
12
1
1
1
6
one
met the
slope criterion, the
previously meeting both criteria now meets only the slope criterion. positive column for both criteria. SExcludes patient 8 (eyes 9 and 10). ||A total of 17 eyes were available (including patient 8: eyes 9 and 10). I Concave temporal and nasal slopes plus a cup/disc ratio > 0.5 tenths DD greater case
other
It remains in
cumulative
in the vertical than horizontal direction. ff Two cases previously positive now negative because cup too large to permit vertical/horizontal disparity. They remain positive in the cumulative column. "'One case previously positive now has larger cup in the horizontal than vertical meridian. It remains positive in the cumulative column.
Table 11.—Thickness of Nerve Fiber
Layer:
Abnormal Patients
Years to Visual Field Loss -4 Flat
Lost No. of eyes with available No. positivet
-3
-1
-2
Of
-1
-2
+3t
14
14
11
11
or
10 10 13
photosf
Cumulative number positives Lost No. of eyes with available photosj No. positivet Cumulative number positives
10 10
0
ni
*Of the two eyes with photos available only for this interval, one was normal thickness, the other flat. fThe border of one eye was out of focus and could not be read; this is excluded from both the number available and the number positive. tExcludes patient 8 (eyes 9 and 10). SA total of 17 eyes were available (including patient 8: eyes 9 and 10). ||Those missed, read as flat, were previously read as lost, indicating limited variability. Of the eyes, one had subsequent photos, all of which were read as lost once again. 1 The additional case is the one that could not be read at 0 years.
leaving only the
two eyes of case 8 undetected. Interval sensitivities were similar to those for the cup-/disc parame¬
ters.
Asymmetry of the Two Eyes The clearest demonstration
asymmetry between
a
patient's
of two
the ratio of the widths of eyes their narrowest remaining rims. A ratio permits maintenance of a large difference even as the rims become smaller and the potential for an abso¬ lute difference decreases. In some instances of abnormal eyes, however, the ratio was indeterminate (the denominator being zero). Since, by our was
preceding analysis,
zero
_Eyes
remaining
rim indicates an eye is almost sure to have established or impending visual
field loss, these were considered posi¬ tive. The minimal acceptable screening level occurred at 3.0 or above (Table 7), a specificity of 94%. The sensitivity remained very low until 0 years, by which time nine of the 13 cases had already screened positive (Table 8). By + 5 years, 11 of the 13 cases were positive. Interval sensitivities were not as high as for the preceding
parameters.
Any narrowing of the criteria a drop in sensitivity. At 4.0 or above, two cases positive at 0 years resulted in
and tive.
one
at +5 years become nega¬
Cup We analyzed two definitions of "vertical ovalness": concave temporal Vertical Ovalness of the
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187 15
Cumulative
%_% 91_
Lost_4
Total
'Concave temporal and nasal slopes. tOf the two eyes with photos available only for this interval, met neither criteria for positivity.
JOne
+3
206
7_98 2_100
and nasal slopes with a cup/disc ratio of at least 0.5 tenths DD greater in the vertical than horizontal meridian, and the slope criterion by itself. Concave nasal and temporal slopes were pres¬ ent in only 8% (17 eyes) of controls, and in 0.5% (one eye) was this asso¬ ciated with the additional cup/disc meridional criterion. The sensitivity of both criteria are presented in Ta¬ ble 9. The specificity for the less strin¬ gent slope criterion is 92%, within the acceptable range. Ten of the 17 eyes already were positive at 0 years, the two remaining eyes becoming positive at + 4 years. Two of the five negative eyes did not have photos taken at + 4 years. Had they been available, the
cumulative sensitivity might have been higher. As expected, the specific¬ ity of the more stringent criterion was much higher (99.5%), but the sensitivi¬ ty much lower. Less than half the eyes were already positive by the time visual field loss first occurred (0 years), and only one additional case became positive at + 4 years. In fact, the cumulative sensitivity is some¬ what misleading. Keeping with our earlier practice, once an eye screened positive it remained in the cumulative positive column. But several patients eventually lost their meridional crite¬ rion as the horizontal cup expanded faster than the vertical, eventually surpassing it in size. Therefore, what was originally a positive case might, if screened later in its course, be nega¬
tive.
Interval sensitivities for either cri¬ terion were lower than for the cup/ disc criteria or width of the remaining disc rim. Thickness of the Nerve Fiber Layer
article (see demonstrated progressive thinning of the nerve fiber layer during the course of the disease. After sketching the actual thickness ob¬ served in three dimensions we catego¬ rized the thickness as normal (E, or elevated), thinned (F, or flattened), or lost (L, completely flat, without any thickness at all). Masked reproducibility trials indicated near-perfect In
1444)
our
we
companion
agreement, with only occasional pho¬ tos being reread in adjacent catego¬ ries (E-F, F-L). The broader criterion, flattened or
which to base a diagnosis and initiate therapy. The question is whether it is
sufficiently more common among glaucomatous patients than normal individuals to serve as a distinguish¬ ing characteristic. Similarly, indicat¬ ing the diagnosis was correct 86% of the times is equally unrevealing. We do not know what proportion of patients with glaucoma were missed (resulting in false-negatives) and what proportion without glaucoma were mistakenly diagnosed as having it (resulting in false-positives). This is especially problematic in glaucoma, where only a very small proportion of the population has the disease and where the actual mix of patients with glaucoma and normal patients may
lost, has an acceptable specificity of 91% (Table 10). The sensitivity was quite high, almost half the eyes posi¬
tive at —2 years, and 13 of the 17 positive by the time of onset of glau¬ comatous field loss (Table 11). Maxi¬ mum sensitivity, 14 of 17 eyes posi¬ tive, was achieved by +1 years. In fact, all 14 positive eyes were probably recognizable as such by 0 years. The
single case added at +1 year (L, completely lost) was out of focus and
could not be read at 0 years. It is reasonable to suppose that, had the 0-year photo been in focus, it would at least have been flattened at that time. Of the three eyes that never screened
positive,
two
belonged
to
vary from series to series. For exam¬ ple, surveys commonly show that 0.4% of the adult population have glauco¬ matous field loss and that one half to two thirds of those with such field loss, but only 9% of the population as a whole, have a single screening pres¬ sure over 21 mm Hg. Therefore, pres¬ sures over 21 mm Hg "suggest" glau¬ comatous field loss; they result in only nine false-positives and 0.2 falsenegatives for every 100 individuals screened, and they provide the correct diagnosis "91% of the time." But this is not nearly as meaningful as know¬ ing the sensitivity is only 65%» (more than one third of all patients with established field loss would be missed by simple tonometric screening), and that the specificity is 91% (9% of all normal individuals will be thought to be abnormal) regardless of the actual proportion of normal and abnormal subjects in the group studied. An "ideal" screening test would have a sensitivity and specificity of 100%, something rarely achieved. In practice, we attempt to strike a
patient 8,
and the third had a thick nerve fiber layer at —5 years, the only photo avail¬ able. Interval sensitivities were higher than for any other criterion. Excluding case 8, it reached 100% by 0 years. The specificity of the narrower criterion, lost, was far higher (98%), but the sensitivity was reduced and the diagnosis delayed. Half the eyes were not screened positive until between —1 and 0 years, though 11 of the 17 eyes were positive by +1 years. One additional case became positive at + 5 years (not shown in Table 11). Two of the five eyes that never screened positive were from patient 8, while two others negative at —5 years lacked additional photos. Other Criteria
Presence of peripapillary pigmenta¬ tion, visible laminar dots covering an
of at least 2x2 tenths DD, concave and "beanpot" contours of the temporal slope were all present in too large a propor¬ tion of controls to serve as useful area
transparency, and
screening parameters. COMMENT
A variety of disc parameters have been advocated to help distinguish patients with impending or estab¬ lished visual field loss. Unfortunately, we are rarely provided with the sensi¬ tivity and specificity of these criteria, and almost all comparisons are be¬ tween patients with and without established field loss, precluding any assessment of when, in the course of the disease, those parameters first become positive. Some investigators simply state a particular criterion "suggests" true glaucoma, insufficient information on
'
balance between maximum sensitivi¬ ty, since we do not wish to overlook cases requiring treatment, while keeping the specificity within man¬ ageable limits. This is especially diffi¬ cult in glaucoma screening, where the prevalence of true disease is so low. For example, since 9% of a population over age 40 will have screening pres¬ sures over 21 mm Hg, but only 3% of these hypertensive patients will have established field loss (a useful criteri¬ on of true glaucoma), 32 normal patients screen positive for every one abnormal patient detected, a wholly inadequate ratio. Admittedly, glauco¬ matous field loss will develop in some of these ocular hypertensive patients, but at a rate so low (estimated at one to five per 1,000 per yr) as to limit its value. Raising the pressure criterion
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will improve the specificity and reduce the number of false-positives, but also lowers the sensitivity, in¬ creasing the number of false-nega¬ tives (patients with true glaucoma thought not to have it). In the present study we attempted to arrive at an estimate of the true sensitivity and specificity of the most promising fundus parameters at vari¬ ous stages in the course of the disease. Since stereoscopic fundus photo¬ graphs were not taken at regular annual intervals, our methods admit¬ tedly are inexact. Definitive investi¬ gation would require annual examina¬ tion of hundreds of ocular hyperten¬ sive patients over a period of ten to 15 years. Before embarking on so expen¬ sive and laborious a task, it is reason¬ able to avail ourselves of all available data to determine which, if any, pa¬ rameters are worthy of such investi¬ gation. Our study provides sufficient information on which to base this decision. None of the parameters investi¬ gated really proved satisfactory. Of those with promise, the specificities varied from 92% to 98%—acceptable levels—but the sensitivities were quite low, at least until rather late in the course of the disease. For example, one of the highest sensitivities was recorded by screening for remaining disc rim at its narrowest point of one tenth DD or less. While nine of 17 eyes
already positive at —2 years, only 12 of 17 were positive at the onset of glaucomatous visual field loss (0 years), and the maximum sensitivity, were
14 to 15 of 17 was not achieved until three years later. The sensitivities for flattening of the nerve fiber layer as it crossed the temporal rim were comparable, while those for vertical ovalness (in its broader, less specific, sense), and horizontal and vertical cup/disc ratios were somewhat low¬ er.
Despite the disappointing nature of results, they are more encourag¬ ing than those recently reported by
our
Kitazawa and associates.1' For reasons of asym¬ metry of the two discs differs from theirs, and the results are not directly comparable. The lower specificity of the cup/disc ratio criterion in their study is probably attributable to at least two factors: they used an "ac¬ cepted" screening level of five tenths DD, while we purposely adjusted the level to achieve a minimal specificity of 91%; their "controls" were "ocular hypertensive patients," in some of whom visual field loss might have been on the verge of developing, while
already given, our definition
normotensive patients, a group under these circumstances.1" Their lower sensitivi¬ ours were more
appropriate
ty represents
single determination, subject entered the study, unadjusted for
presumably
a
at the time each
duration to visual field loss. In our study, sensitivity was recalculated at annual intervals adjusted for duration to field loss. A combination of criteria does not improve the situation appreciably: eyes with the narrowest rims tended to be the ones with flattened nerve fiber layers, vertical ovalness and large cups. In contrast, we recently demonstrated that defects in the nerve fiber layer of the retina correct¬ ly identified all abnormal patients within one year of onset of visual field loss, including patient 8 (eyes 9 and 10), which could not be identified by any of the above criteria.10 Regression analysis suggested that nerve fiber layer defects were likely to be visible in the vast majority of cases years before the onset of visual field loss.
It is hardly surprising that defects in the nerve fiber layer are more sensitive and specific indices of impending field loss than various cup/ disc relationships. Defects in both the nerve fiber layer and visual fields are direct consequences of neuronal dam¬ age. Disc parameters, however, repre¬ sent a complex mixture of normal variation and damage of both nerve elements and glial supporting struc¬ tures, primarily the latter. The significance of visible defects in the nerve fiber layer deserves fullscale, definitive, prospective evalua¬ tion. The additional cost and effort of evaluating these other, admittedly less promising, disc parameters at the same time should be minimal and might well be warranted. Asymmetry of the two eyes, peripa¬
pillary pigmentary abnormalities,
of transparency and abnormal temporal slope, and visibility of the lamina dots were insufficiently sensitive and specific to serve as useful screening tools. area
contours of the
We do not wish to imply that a valid clinical sign must also be a useful screening tool. A screening tool must have a high sensitivity and specificity. But by narrowing the criteria one may raise the specificity dramatically, to a point that any patient fulfilling the criteria has a very high likelihood of having true glaucoma. For example, none of the controls had a narrowest rim of less than 0.25 tenths DD, a vertical or horizontal cup/disc ratio greater than 8.0 tenths DD, or asym¬ metry of the remaining rim in the two eyes of greater than 5.0 tenths DD, while only 0.5% met our strictest defi¬ nition (contour and cup/disc ratio) of vertical ovalness. Patients fulfilling any of these criteria deserve imme¬ diate and thorough investigation and perhaps therapy as well, regardless of whether or not glaucomatous field loss already has occurred. Of course, this
heightened specificity implies a sharp loss in sensitivity, and many patients with impending or established field loss will not satisfy these criteria.
References 1. Fishman RS: Optic disc asymmetry. Arch Ophthalmol 84:590-594, 1970. 2. Primrose J: Early signs of the glaucomatous disc. Br J Ophthalmol 55:820-825, 1971. 3. Kirsch RE, Anderson DR: Clinical recognition of glaucomatous cupping. Am J Ophthalmol
75:442-454, 1973. 4. Spaeth GL, Hitchings RA, Sivalingam E: The optic disc in glaucoma: Pathogenetic correlation of five patterns of cupping in chronic open-
angle glaucoma.
Trans Am Acad
Ophthalmol
Otolaryngol 81:217-223, 1976. 5. Portney GL: Photogrammetric analysis
of the three-dimensional geometry of normal and glaucomatous optic cups. Trans Am Acad Ophthalmol Otolaryngol 81:239-246, 1976. 6. Shaffer RN, Ridgway WL, Brown R, et al: The use of diagrams to record changes in glaucomatous disc. Am J Ophthalmol 80:460-464, 1975. 7. Hollows FC, Graham PA: Intraocular pressure, glaucoma, and glaucoma suspects in a defined population. Br J Ophthalmol 50:570-586,
1966. 8. Drance SM: Correlation between optic disc changes and visual field defects in chronic openangle glaucoma. Trans Am Acad Ophthalmol Otolaryngol 81:224-226, 1976. 9. Kitazawa Y, Horie T, Aoki S, et al: Untreated ocular hypertension. Arch Ophthalmol 95:1180-1184, 1977. 10. Sommer A, Miller NR, Pollack I, et al: The nerve fiber layer in the diagnosis of glaucoma. Arch Ophthalmol 95:2149-2156, 1977.
CORRECTION Error in Tabulation.\p=m-\In the article entitled
"Scaling of Visual Acuity Measurements,"
published in the February issue of the Archives (97:327-330, 1979), the tabulation at the top of the first column on page 328 should have appeared as follows: a
1
2 y
100%
(minutes of arc)
=
visual
83.6%
3
4
efficiency 69.9%
58.4%
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