Disc Parameters and Onset of Glaucomatous Field Loss
Optic
I. Methods and Alfred
Progressive Changes
Sommer, MD; Irvin Pollack, MD; A. Edward Maumenee,
\s=b\ Serial stereoscopic fundus photographs taken in known relationship to the onset of glaucomatous visual field loss on
12 eyes were intermixed with those from 206 age- and race-matched controls and analyzed in randomized masked fashion. Progressive changes in the size, shape, or contour of the disc, and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were readily apparent by the time of onset of glaucomatous field loss in all but two abnormal eyes (one case). In the latter instance, direct comparison of stereophotos indicated progressive pallor of the remaining disc tissue. Serial stereophotographs appear superior to fundus drawings for anticipating glaucomatous field loss.
(Arch Ophthalmol 97:1444-1448, 1979)
TXTith the failure of tonometry, to"
nography,
and other
measure¬
ments of aqueous
dynamics
ment of visual field
loss, clinicians are
to
accu¬
rately predict the eventual develop¬ increasingly reluctant to diagnose glaucoma and initiate therapy until observing definite evidence of neu¬ ronal damage (usually glaucomatous field
loss). As
an
earlier
means
of
diagnosis, investigators have sug¬ gested a variety of criteria supposedly sensitive and specific for the glauco¬ eg, size of the cup and of the remaining disc rim,' vertical ovalness of the cup,2 ' matous
disc,
narrowness
peripapillary pigmentary alterations,' and progressive changes in the cup. How early and with what regularity these and other criteria develop awaits analysis of fundus parameters at known temporal relationship to the -7
onset of
glaucomatous field loss. Previously, we published just such an analysis for a single parameter, 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).
in Disc
Morphology
MD
defects in the nerve fiber layer, which appears to be a sensitive and specific sign of impending field loss." In the present communication companion study (see 1449) we undertake a similar analysis of more conventional fundus parameters: the first article deals with changes in individual discs over time; the second, with the sensi¬ tivity and specificity of static screen¬ ing criteria. METHODS
Selection of patients and controls has been described in detail.'- In summary, by June 1976, classical glaucomatous field abnormalities (repeatable Seidel's scotoma, elongation of the blind spot of >60°, arcuate
scotoma, paracentral scotoma,
or
nasal step > 10°) on routine kinetic perime¬ try had developed in 24 eyes of 136 patients with ocular hypertension observed annual¬ ly in the Glaucoma Clinic of the Wilmer Institute. Stereoscopic fundus photographs preceding onset of visual field loss were available for 15, but only for 14 were they of sufficient clarity to permit analysis. Serial photos necessary for determining changes in the disc over time were avail¬ able for 12 eyes, and these constitute the abnormal cases reported in this study. Roughly, five age- and race-matched controls, individuals observed in identical fashion but with intraocular pressures consistently below 21 mm Hg and normal fields, were selected for each abnormal case.
All slides available on abnormal cases and matched controls were assigned ran¬ dom numbers, serially arranged, and examined by one of us (A.S.) in masked fashion. Limits of the physical and color cup were recorded on a ten-square-diame¬ ter grid in a modification of the technique of Shaffer et al." The geographic center of the disc was located on the grid and the cup drawn as a series of radii in the four cardinal directions, their bisectors, and points of particular narrowing of the remaining disc rim. These points were then connected in approximate shape of the cup and results tabulated in terms of the tensquare grid pattern, each representing one tenth of a disc diameter (DD). Solid lines define the boundary of the physical cup; dashed lines, the color cup; and small round circles, presence of "lamina dots." Absence of dashed lines indicates that the bounda¬ ries of the physical and color cups are identical. The shape of the cup was record¬ ed in cross section in at least one plane (the
Downloaded From: http://archopht.jamanetwork.com/ by a UQ Library User on 06/13/2015
horizontal meridian), solid lines indicating contour of the cup walls, and interruption of the solid lines by dashed lines, an inner, semitransparent cup wall. Additional characteristics of potential significance were also recorded: apparent thickness of the nerve fiber layer as it crossed the rim of the cup, illustrated in Fig 1 (graded E, thick or "elevated"; F, thinned or "flattened"; or L, completely flat or "lost"); orientation and location of the major retinal vessels in their course from the base of the cup to the temporal rim; visibility of the lamina "dots"; and
peripapillary pigmentary changes. As a measure of reproducibility, 40 slides were randomly chosen and reread without knowledge of their previous analysis. After all photos were read, the sketches were coded for diagnosis and temporal relationship to the development of visual field loss.
RESULTS
As others have already indicated, analysis of the size and shape of the cup is frequently a difficult and all too subjective task. Contours of the physi¬ cal cup can assume a variety of forms (Fig 2), and decisions of where the cup begins often necessarily are arbitrary. Statements that it begins where the
contour passes below the level of the
retina,7 if taken literally, would result
in a large proportion of normal indi¬ viduals with enormous cups. Instead, the examiner chose the point where the slope first developed a definite inward deflection. As will be seen, though generally sound, this defini¬ tion raised difficulties in one abnor¬ mal case (case 8, eyes 9 and 10). Anoth¬ er difficulty arises in stereoscopic
viewing: one can frequently see two slopes—a superficial, thin, transparent one, presumably the equivalent of the outer limiting membrane, and an opaque deeper one, often of very different contour (Fig 2, bottom left). Except where the superficial slope was extraordinarily thin and gossa¬ mer-like, it defined the
cup.
The color cup, read monoscopically, was even more evasive. In some instances there was a rather sharp transition between pale gray cup and normal pink rim. Often, however,
Fig 1.—System
center, thinned
of
grading
or
thickness of
nerve
fiber
flattened; right, completely flat
as it crosses lost. Dashed line
layer
or
temporal disc rim. Left, Thick represents retinal surface.
or
elevated;
Fig 2.—Examples of wide variety of cup-slopes encountered, complicating determi¬ nation of exactly where cup "began." Top left, Symmetrical, gradual, convex slopes; top center, steeper, less symmetrical, more concave slopes; top right, "bean-pot" slope temporally; bottom left, double layered wall; inner, dashed line represents semitransparent tissue often carrying vessels; solid line, deeper, opaque cup walls.
these blended
imperceptibly, again requiring subjective appraisal. In oth¬ er
instances there
were
three differ¬
ent color zones: a central, chalky white zone; a gray "intermediate zone"; and a pink outer zone. Invariably, stereo¬
scopic analysis indicated the gray zone to represent thin, semitransparent membrane overlying a deeper opaque cup of different contour. All analyses of cup size in this study are limited to the physical cup. Reproducibility Fourteen of the 40 eyes reread had small physical cups (radii equal to or less than one tenth DD in all direc¬ tions). Each was reread in exactly the same fashion. As would be expected, greater variability existed in the remaining 26 eyes with large cup/disc ratios (Table 1). For comparison with other series, the limits of variability are presented in Table 2. Since vari¬ ability in the cardinal directions was often additive, the magnitude of vari¬ ation of the total horizontal and verti¬ cal cup/disc diameters is greater than for the cardinal radii. Horizontally, 33 were within one tenth DD; six between one and two tenths DD, and one between two and three tenths DD of one another. The latter was from an
case with a large, dark, pigmented patch straddling the tem¬ poral disc margin for one to two tenths DD; one reading apparently was taken to the inner edge of the pigmented area, the other estimated the true disc edge as falling 1.5 tenths DD more peripheral, in keeping with the nonpigmented margin. These re¬ sults compare favorably with those reported by others."1" The temporal and nasal slopes of all 40 eyes were drawn with exactly the same shape on both readings. Repeat estimations of the thickness of the nerve fiber layer passing over the temporal rim was the same in 36 eyes. In the four others they differed by only an adjacent reading (ie, E-F,
abnormal
or
F-L).
The absence of perfect reproducibil¬ ity explains occasional variation in analysis of sequential photos. Direct immediate comparisons of a patient's photos would have eliminated much of the variability but would have intro¬ duced an immeasurable and potential¬ ly large degree of observer bias.
Peripapillary pigment alterations, changes in location and direction of the major vessels crossing the tempo¬ ral ridge, and presence of "bean-pot" shaped slopes were found in a large
Downloaded From: http://archopht.jamanetwork.com/ by a UQ Library User on 06/13/2015
of normal eyes be discussed further.
proportion
so
will not
Subjects
In ten of the 12 eyes, progressive changes in disc morphology would have been apparent from stereoscopic fundus photographs or drawings by the time glaucomatous field loss first appeared. Table 3 indicates the rela¬ tionship between onset of field loss in each eye and changes in those disc parameters found to have the highest screening potential. A minus sign indicates the number of years preced¬ ing visual field loss; a plus sign, years following such loss; and a zero, the year field loss first appeared. Greatest growth in horizontal and vertical cup/disc ratios and loss of disc rim occurs between —5 and —2 years, the period of maximum restructuring and potential for change. After that time, usually little disc rim remains to be altered. Nonetheless, obvious changes (>0.75 tenths DD) in at least one
of these three parameters is
usually apparent for the overall inter¬ val —2 to 0 years, though not always at
each individual annual increment. Vertical ovalness where present, was an early finding and rarely repre¬ sented a change during the period of observation. Though lamina dots were
f Fig 3.—Case 1, eye 1 (OS). In this and all subsequent diagrams, cup/disc relationships are presented in frontal plane and (horizontal) cross section, both interpreted from stereophotos. In frontal plane, solid line represents boundary of physical cup; dashed line, boundary of color cup; multiple small circles, visible lamina dots (though not necessarily drawn to scale). In cross section, solid line represents opaque walls of cup and its surroundings (retinal pigment epithelium, choroid, or sclera, depending on status of peripapillary tissue); dashed lines interrupting solid line, as at left, area of semitransparent cup wall (superficial to deeper opaque wall); and anterior dashed lines passing over solid disc rim, height of retinal surface (thickness of nerve fiber layer). Progressive enlargement of cup, flattening of nerve fiber layer, and concavity of temporal slope are evident (left) four years prior to onset of glaucomatous visual field defects (—4 years), through —1 year (center), and at time of onset of field defect (0 years) (right).
Table
1.—Variability
of
Repeated Estimations of Cup Width'1
Difference Between
(N
Nasal
Superior Inferior
Horizontal
0.27 0.50
Vertical
0.39
"Values
are
JExcludes
also area
40f)
expressed in tenths
those with
of
Readings
Difference Between
(N SD 0.40 0.48
Mean 0.31 0.27 0.19
Temporal
tAII eyes.
=
0.22 0.34 0.64 0.53 a
cup/disc ratios
disc diameter
=
26J)
Readings
time.
Thinning of the nerve fiber layer as it crossed the temporal rim also became apparent rather early in the course of glaucomatous damage, but sufficient additional alteration oc¬ curred so that a change in thickness was usually observed between -2 and 0 years.
More difficult to quantitate, but no less useful, were progressive changes in the contours of the disc, as demon¬ strated in the illustrative cases be¬ low. Case 1, Eye 1.-Between -8 and -4 years
there was only a slight increase in temporal cupping and decrease in the convexity of the transparent temporal slope. Between —4 (Fig 3, left) and 0 (Fig 3, center) years there was far more dramatic progression: the physical cup enlarged in all directions, the inferotemporal rim being reduced, by year 0, to less than 0.25 tenths DD. Increas¬ ing concavity of the temporal slope, with thinning and flattening in the depths of the cup, exposed ever larger amounts of bare, dotted, lamina cribrosa. There was no longer any thickness to the neural tissue as it passed over the temporal rim (lost). By + 2 years (Fig 3, right), the temporal slope
1 38 40 39 40 33 35
Optic
I. Methods and Alfred
Progressive Changes
Sommer, MD; Irvin Pollack, MD; A. Edward Maumenee,
\s=b\ Serial stereoscopic fundus photographs taken in known relationship to the onset of glaucomatous visual field loss on
12 eyes were intermixed with those from 206 age- and race-matched controls and analyzed in randomized masked fashion. Progressive changes in the size, shape, or contour of the disc, and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were readily apparent by the time of onset of glaucomatous field loss in all but two abnormal eyes (one case). In the latter instance, direct comparison of stereophotos indicated progressive pallor of the remaining disc tissue. Serial stereophotographs appear superior to fundus drawings for anticipating glaucomatous field loss.
(Arch Ophthalmol 97:1444-1448, 1979)
TXTith the failure of tonometry, to"
nography,
and other
measure¬
ments of aqueous
dynamics
ment of visual field
loss, clinicians are
to
accu¬
rately predict the eventual develop¬ increasingly reluctant to diagnose glaucoma and initiate therapy until observing definite evidence of neu¬ ronal damage (usually glaucomatous field
loss). As
an
earlier
means
of
diagnosis, investigators have sug¬ gested a variety of criteria supposedly sensitive and specific for the glauco¬ eg, size of the cup and of the remaining disc rim,' vertical ovalness of the cup,2 ' matous
disc,
narrowness
peripapillary pigmentary alterations,' and progressive changes in the cup. How early and with what regularity these and other criteria develop awaits analysis of fundus parameters at known temporal relationship to the -7
onset of
glaucomatous field loss. Previously, we published just such an analysis for a single parameter, 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).
in Disc
Morphology
MD
defects in the nerve fiber layer, which appears to be a sensitive and specific sign of impending field loss." In the present communication companion study (see 1449) we undertake a similar analysis of more conventional fundus parameters: the first article deals with changes in individual discs over time; the second, with the sensi¬ tivity and specificity of static screen¬ ing criteria. METHODS
Selection of patients and controls has been described in detail.'- In summary, by June 1976, classical glaucomatous field abnormalities (repeatable Seidel's scotoma, elongation of the blind spot of >60°, arcuate
scotoma, paracentral scotoma,
or
nasal step > 10°) on routine kinetic perime¬ try had developed in 24 eyes of 136 patients with ocular hypertension observed annual¬ ly in the Glaucoma Clinic of the Wilmer Institute. Stereoscopic fundus photographs preceding onset of visual field loss were available for 15, but only for 14 were they of sufficient clarity to permit analysis. Serial photos necessary for determining changes in the disc over time were avail¬ able for 12 eyes, and these constitute the abnormal cases reported in this study. Roughly, five age- and race-matched controls, individuals observed in identical fashion but with intraocular pressures consistently below 21 mm Hg and normal fields, were selected for each abnormal case.
All slides available on abnormal cases and matched controls were assigned ran¬ dom numbers, serially arranged, and examined by one of us (A.S.) in masked fashion. Limits of the physical and color cup were recorded on a ten-square-diame¬ ter grid in a modification of the technique of Shaffer et al." The geographic center of the disc was located on the grid and the cup drawn as a series of radii in the four cardinal directions, their bisectors, and points of particular narrowing of the remaining disc rim. These points were then connected in approximate shape of the cup and results tabulated in terms of the tensquare grid pattern, each representing one tenth of a disc diameter (DD). Solid lines define the boundary of the physical cup; dashed lines, the color cup; and small round circles, presence of "lamina dots." Absence of dashed lines indicates that the bounda¬ ries of the physical and color cups are identical. The shape of the cup was record¬ ed in cross section in at least one plane (the
Downloaded From: http://archopht.jamanetwork.com/ by a UQ Library User on 06/13/2015
horizontal meridian), solid lines indicating contour of the cup walls, and interruption of the solid lines by dashed lines, an inner, semitransparent cup wall. Additional characteristics of potential significance were also recorded: apparent thickness of the nerve fiber layer as it crossed the rim of the cup, illustrated in Fig 1 (graded E, thick or "elevated"; F, thinned or "flattened"; or L, completely flat or "lost"); orientation and location of the major retinal vessels in their course from the base of the cup to the temporal rim; visibility of the lamina "dots"; and
peripapillary pigmentary changes. As a measure of reproducibility, 40 slides were randomly chosen and reread without knowledge of their previous analysis. After all photos were read, the sketches were coded for diagnosis and temporal relationship to the development of visual field loss.
RESULTS
As others have already indicated, analysis of the size and shape of the cup is frequently a difficult and all too subjective task. Contours of the physi¬ cal cup can assume a variety of forms (Fig 2), and decisions of where the cup begins often necessarily are arbitrary. Statements that it begins where the
contour passes below the level of the
retina,7 if taken literally, would result
in a large proportion of normal indi¬ viduals with enormous cups. Instead, the examiner chose the point where the slope first developed a definite inward deflection. As will be seen, though generally sound, this defini¬ tion raised difficulties in one abnor¬ mal case (case 8, eyes 9 and 10). Anoth¬ er difficulty arises in stereoscopic
viewing: one can frequently see two slopes—a superficial, thin, transparent one, presumably the equivalent of the outer limiting membrane, and an opaque deeper one, often of very different contour (Fig 2, bottom left). Except where the superficial slope was extraordinarily thin and gossa¬ mer-like, it defined the
cup.
The color cup, read monoscopically, was even more evasive. In some instances there was a rather sharp transition between pale gray cup and normal pink rim. Often, however,
Fig 1.—System
center, thinned
of
grading
or
thickness of
nerve
fiber
flattened; right, completely flat
as it crosses lost. Dashed line
layer
or
temporal disc rim. Left, Thick represents retinal surface.
or
elevated;
Fig 2.—Examples of wide variety of cup-slopes encountered, complicating determi¬ nation of exactly where cup "began." Top left, Symmetrical, gradual, convex slopes; top center, steeper, less symmetrical, more concave slopes; top right, "bean-pot" slope temporally; bottom left, double layered wall; inner, dashed line represents semitransparent tissue often carrying vessels; solid line, deeper, opaque cup walls.
these blended
imperceptibly, again requiring subjective appraisal. In oth¬ er
instances there
were
three differ¬
ent color zones: a central, chalky white zone; a gray "intermediate zone"; and a pink outer zone. Invariably, stereo¬
scopic analysis indicated the gray zone to represent thin, semitransparent membrane overlying a deeper opaque cup of different contour. All analyses of cup size in this study are limited to the physical cup. Reproducibility Fourteen of the 40 eyes reread had small physical cups (radii equal to or less than one tenth DD in all direc¬ tions). Each was reread in exactly the same fashion. As would be expected, greater variability existed in the remaining 26 eyes with large cup/disc ratios (Table 1). For comparison with other series, the limits of variability are presented in Table 2. Since vari¬ ability in the cardinal directions was often additive, the magnitude of vari¬ ation of the total horizontal and verti¬ cal cup/disc diameters is greater than for the cardinal radii. Horizontally, 33 were within one tenth DD; six between one and two tenths DD, and one between two and three tenths DD of one another. The latter was from an
case with a large, dark, pigmented patch straddling the tem¬ poral disc margin for one to two tenths DD; one reading apparently was taken to the inner edge of the pigmented area, the other estimated the true disc edge as falling 1.5 tenths DD more peripheral, in keeping with the nonpigmented margin. These re¬ sults compare favorably with those reported by others."1" The temporal and nasal slopes of all 40 eyes were drawn with exactly the same shape on both readings. Repeat estimations of the thickness of the nerve fiber layer passing over the temporal rim was the same in 36 eyes. In the four others they differed by only an adjacent reading (ie, E-F,
abnormal
or
F-L).
The absence of perfect reproducibil¬ ity explains occasional variation in analysis of sequential photos. Direct immediate comparisons of a patient's photos would have eliminated much of the variability but would have intro¬ duced an immeasurable and potential¬ ly large degree of observer bias.
Peripapillary pigment alterations, changes in location and direction of the major vessels crossing the tempo¬ ral ridge, and presence of "bean-pot" shaped slopes were found in a large
Downloaded From: http://archopht.jamanetwork.com/ by a UQ Library User on 06/13/2015
of normal eyes be discussed further.
proportion
so
will not
Subjects
In ten of the 12 eyes, progressive changes in disc morphology would have been apparent from stereoscopic fundus photographs or drawings by the time glaucomatous field loss first appeared. Table 3 indicates the rela¬ tionship between onset of field loss in each eye and changes in those disc parameters found to have the highest screening potential. A minus sign indicates the number of years preced¬ ing visual field loss; a plus sign, years following such loss; and a zero, the year field loss first appeared. Greatest growth in horizontal and vertical cup/disc ratios and loss of disc rim occurs between —5 and —2 years, the period of maximum restructuring and potential for change. After that time, usually little disc rim remains to be altered. Nonetheless, obvious changes (>0.75 tenths DD) in at least one
of these three parameters is
usually apparent for the overall inter¬ val —2 to 0 years, though not always at
each individual annual increment. Vertical ovalness where present, was an early finding and rarely repre¬ sented a change during the period of observation. Though lamina dots were
f Fig 3.—Case 1, eye 1 (OS). In this and all subsequent diagrams, cup/disc relationships are presented in frontal plane and (horizontal) cross section, both interpreted from stereophotos. In frontal plane, solid line represents boundary of physical cup; dashed line, boundary of color cup; multiple small circles, visible lamina dots (though not necessarily drawn to scale). In cross section, solid line represents opaque walls of cup and its surroundings (retinal pigment epithelium, choroid, or sclera, depending on status of peripapillary tissue); dashed lines interrupting solid line, as at left, area of semitransparent cup wall (superficial to deeper opaque wall); and anterior dashed lines passing over solid disc rim, height of retinal surface (thickness of nerve fiber layer). Progressive enlargement of cup, flattening of nerve fiber layer, and concavity of temporal slope are evident (left) four years prior to onset of glaucomatous visual field defects (—4 years), through —1 year (center), and at time of onset of field defect (0 years) (right).
Table
1.—Variability
of
Repeated Estimations of Cup Width'1
Difference Between
(N
Nasal
Superior Inferior
Horizontal
0.27 0.50
Vertical
0.39
"Values
are
JExcludes
also area
40f)
expressed in tenths
those with
of
Readings
Difference Between
(N SD 0.40 0.48
Mean 0.31 0.27 0.19
Temporal
tAII eyes.
=
0.22 0.34 0.64 0.53 a
cup/disc ratios
disc diameter
=
26J)
Readings
time.
Thinning of the nerve fiber layer as it crossed the temporal rim also became apparent rather early in the course of glaucomatous damage, but sufficient additional alteration oc¬ curred so that a change in thickness was usually observed between -2 and 0 years.
More difficult to quantitate, but no less useful, were progressive changes in the contours of the disc, as demon¬ strated in the illustrative cases be¬ low. Case 1, Eye 1.-Between -8 and -4 years
there was only a slight increase in temporal cupping and decrease in the convexity of the transparent temporal slope. Between —4 (Fig 3, left) and 0 (Fig 3, center) years there was far more dramatic progression: the physical cup enlarged in all directions, the inferotemporal rim being reduced, by year 0, to less than 0.25 tenths DD. Increas¬ ing concavity of the temporal slope, with thinning and flattening in the depths of the cup, exposed ever larger amounts of bare, dotted, lamina cribrosa. There was no longer any thickness to the neural tissue as it passed over the temporal rim (lost). By + 2 years (Fig 3, right), the temporal slope
1 38 40 39 40 33 35
