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2010 Scott Gradingof Papilledemaand OCT
2010 Scott Gradingof Papilledemaand OCT
Objectives: To compare and contrast 2 methods of quan- tographs correlated well (R=0.85). OCT total retinal thick-
titating papilledema, namely, optical coherence tomog- ness and MFS grade from photographs had a similar cor-
raphy (OCT) and Modified Frisén Scale (MFS). relation of 0.87. Comparing OCT RNFL thickness with
OCT total retinal thickness, a slope of 1.64 suggests a
Methods: Digital optic disc photographs and OCT fast greater degree of papilledema thickness change when
retinal nerve fiber layer (RNFL) thickness, fast RNFL map, using the latter.
total retinal thickness, and fast disc images were ob-
tained in 36 patients with papilledema. Digital optic disc Conclusions: For lower-grade abnormalities, OCT com-
photographs were randomized and graded by 4 masked pares favorably with clinical staging of optic nerve pho-
expert reviewers using the MFS. We performed Spear- tographs. With higher grades, OCT RNFL thickness pro-
man rank correlations of OCT RNFL thickness, OCT total cessing algorithms often fail, with OCT total retinal
retinal thickness, and MFS grade from photographs. thickness performing more favorably.
Results: OCT RNFL thickness and MFS grade from pho- Arch Ophthalmol. 2010;128(6):705-711
P
APILLEDEMA, OR OPTIC DISC patient fixation stability during imaging
swelling due to raised intra- without eye tracking and the failure of seg-
cranial pressure, has been mentation algorithms for defining RNFL
graded using the Frisén thickness and total retinal thickness in eyes
Scale.1 This scale uses visual with severe papilledema.
features of the optic disc and peripapil- Although fundus photographs require
lary retina to stage optic disc edema. Its subjective interpretation, they show de-
reproducibility has been validated,1 but it tailed topographic relationships of optic
is limited by use of an ordinal scale. disc edema that may be difficult to quan-
Optical coherence tomography (OCT) tify and document on clinical examina-
is a potential tool to quantify changes in the tion. Unlike OCT, photographic artifacts
Author Affiliations: degree of papilledema and to monitor the (eg, defocus or incorrect light exposure)
Department of Ophthalmology efficacy of treatment interventions. First de- that could interfere with interpretation are
and Visual Sciences, Carver scribed in 1991 by Huang et al,2 OCT is a usually obvious.
School of Medicine, University
cross-sectional imaging technique that OCT is useful in evaluating various oph-
of Iowa, and Veterans Affairs
Hospital, Iowa City (Drs Scott, quantitatively assesses multiple layers of the thalmic disorders such as band atrophy,
Kardon, Lee, and Wall); and retina, allowing measurement of the reti- glaucoma, diabetic retinopathy, cystoid
Institute of Neuroscience and nal nerve fiber layer (RNFL) with a reso- macular edema, central serous retinopa-
Physiology, Department of lution of approximately 10 µm using time- thy, macular hole formation, optic nerve
Clinical Neurosciences, domain variables.3-5 Direct measurements head pits, and ischemic optic neuropa-
Sahlgrenska Academy, are calculated by a computer algorithm to thy.12-18 Most of these conditions involve
University of Gothenburg, quantify the nerve fiber layer and total reti- RNFL thinning. Few studies evaluated the
Gothenburg, Sweden nal thickness. OCT offers several advan- use of OCT in measuring RNFL or total reti-
(Dr Frisén). Dr Lee is now with tages over conventional photographic nal thickening due to papilledema. A 2007
the Department of
imaging such as use with small pupil sizes study19 compared the findings of OCT vs
Ophthalmology, The Methodist
Hospital and the Departments and nuclear cataracts. OCT findings are rea- disc photographs in children with idio-
of Ophthalmology, Neurology, sonably reproducible on successive mea- pathic intracranial hypertension. Another
and Neurosurgery, Weill Cornell surements in normal eyes and in eyes with study20 assessed the importance of RNFL
Medical College New York, glaucoma.6-11 Despite these advantages, limi- thickness analysis in intracranial hyperten-
New York. tations of OCT include the requirement for sion using imaging laser polarimetry. In pa-
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dopapilledema but did not directly compare OCT vs fundus
photograph grades. To our knowledge, this is the first study
to compare OCT RNFL thickness and OCT total retinal
thickness with fundus disc photographs in adults having
raised intracranial pressure. Our objectives were to com-
pare and contrast OCT and Modified Frisén Scale (MFS)
grading with the peripapillary RNFL in quantifying optic
disc edema.
METHODS
Digital optic disc photographs of the right or left eye were se-
lected for review if corresponding OCT images of the RNFL were
Grade 0 Grade 1 available and if photographs and OCT images were of sufficient
quality. For OCT analysis, the circular image had to be cen-
tered on the nerve, the signal strength had to be at least 5 (range,
1[lowest]-10 [highest]), and the proprietary algorithm used by
the manufacturer (OCT3; Zeiss Meditech, Dublin, California)
had to successfully delineate the borders of the RNFL on manual
inspection of the images. The proprietary algorithm creates a best-
fit estimate of the inner and outer borders of the RNFL and the
total retinal thickness to calculate the mean thickness, as dem-
onstrated by the overlayed white lines of the B-scan in Figure 1.
Algorithm failure occurred when the borders of the retinal lay-
ers delineated by the software were qualitatively incompatible
with the borders inferred by experts (C.J.S. and R.H.K.). For fun-
dus photographs, the optic nerve had to be in focus to allow evalu-
ation of the RNFL at the disc border. Analysis was monocular
rather than binocular because of some poor photographic qual-
ity or failure to capture the entire extent of the z-axis by OCT
Grade 2 Grade 3 due to peripapillary elevation and cropping of the B-scan in 1 of
2 eyes. Furthermore, use of both eyes would violate a principle
of parametric statistics, as the results of one eye are not inde-
pendent of the other eye. Although the relationship between eyes
could be accounted for with nested analysis of variance, using
both eyes in some patients would have complicated our statis-
tical analysis. Patients retrospectively identified as having raised
intracranial pressure at some point in their clinical course from
January 2004 to March 2008 were included in the study, and the
imaging studies chosen were from the patient’s first presenta-
tion to our clinic for evaluation. While most cases were idio-
pathic, the specific etiology was not addressed, as the pathogen-
esis of disc edema pathogenesis of papilledema was secondary
to raised intercranial pressure in all cases is static and should not
affect comparison of disc appearance with OCT values. No other
cause of visual loss or optic disc edema was present such as op-
tic nerve compression, inflammatory optic neuropathy, or is-
Grade 4 Grade 5
chemic optic neuropathy. Monocular digital photographs were
randomized and graded by 4 masked expert reviewer neuro-
Figure 1. Representative fundus photographs of each Modified Frisén Scale ophthalmologists (3 from the University of Iowa and 1 from the
grade as summarized in Table 1. A representative optical coherence University of Gothenburg, Sweden). Photographs were viewed
tomography image is below each disc grade. Overlayed white lines of the
optical coherence tomography image represent borders of the retinal nerve
at 1600⫻1200 resolution (SyncMaster 213T; Samsung, Ridge-
fiber layer thickness (upper and middle lines) and the total retinal thickness field Park, New Jersey).
(upper and lower lines) estimated using the algorithm (OCT3; Zeiss We used an adaptation of a clinical staging scale initially de-
Meditech, Dublin, California). Modified Frisén Scale key features (Table 1) are scribed by one of us (L.F.) (Table 1 and Figure 1).1 The first 2
well demonstrated. grades are primarily dependent on changes surrounding the op-
tic disc such as decreased translucency and opacification of the
tients with retinal vein occlusions and inflammatory op- peripapillary nerve fiber layer (the term blurring is avoided be-
tic neuropathies, Menke et al21 found that OCT RNFL cause it has many meanings, including lack of image focus). Grade
0 represents no optic disc edema, and grades 1 through 5 rep-
thickness was increased compared with that in control sub- resent increasing severity of optic disc edema. We modified the
jects. Hoye et al22 used OCT to demonstrate subretinal Frisén Scale by identifying a key feature for each grade, with the
macular edema in papilledema, and OCT has been used other criteria considered minor. For grade 1, the key feature is
to measure RNFL thickness in patients with optic neuri- the presence of a C-shaped halo of opacification of the RNFL at
tis.23,24 Other studies25-27 compared OCT (as well as auto- the region of the optic disc border; a gap remained at the loca-
mated perimetry) RNFL thickness in papilledema and pseu- tion of the maculopapular bundle. Rarely, a thin smooth-edged,
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ring-shaped peripapillary light reflex may be present in normal
anatomy; when present, it is a continuous reflex. Therefore, patho- Table 1. Modified Frisén Scale
logic designation requires irregularity and breakup of any ring-
shaped peripapillary reflex (grade 1 in Figure 1). Grade 2 is char- Papilledema Grade
acterized by a circumferential halo with decreased translucency 0 (Normal Optic Disc)
(opacification of the RNFL), with complete visualization of each Prominence of the retinal nerve fiber layer at the nasal, superior, and
major retinal artery and vein along its length as it courses over inferior poles in inverse proportion to disc diameter
the optic disc and its border. Grade 3 has loss of visualization Radial nerve fiber layer striations, without tortuosity
(discontinuity) along a segment of at least 1 major vessel as it
1 (Minimal Degree of Edema)
courses over the optic disc margin but continues in the center
C-shaped halo that is subtle and grayish with a temporal gap; obscures
of the optic nerve. Grade 4 is characterized primarily by discon- underlying retinal details a
tinuity due to opacification of at least 1 but not all major vessels Disruption of normal radial nerve fiber layer arrangement striations
on the optic disc. Temporal disc margin normal
In the original description by Frisén, grade 5 is classified as
follows: “Anterior expansion of the nerve head now dominates 2 (Low Degree of Edema)
Circumferential halo a
over sideways expansion. The nerve head assumes a relatively
Elevation (nasal border)
smooth, dome-shaped protrusion, with a narrow and smoothly
No major vessel obscuration
demarcated halo. The major retinal vessels climb steeply over
the dome surface. Segments of these vessels may or may not be 3 (Moderate Degree of Edema)
totally obscured by overlying swollen tissue.”1(p16) Because this Obscuration of ⱖ1 segment of major blood vessels leaving disc a
grade did not have a clear-cut primary feature, we added one in Circumferential halo
which grade 5 is reached when there is obscuration of all major Elevation (all borders)
vessels on the optic disc. We excluded grade 5 cases from our Halo (irregular outer fringe with finger-like extensions)
analysis because the few examples did not have OCT images in 4 (Marked Degree of Edema)
which the algorithm did not fail. Total obscuration on the disc of a segment of a major blood vessel on
Corresponding OCT images of each grade are shown in the disc a
Figure 1. Compared with OCT RNFL thickness, OCT total reti- Elevation (whole nerve head, including the cup)
nal thickness borders may demonstrate a greater degree of neu- Border obscuration (complete)
rosensory detachment with increasing edema, but the soft- Halo (complete)
ware algorithm can fail at severe papilledema levels, with borders Grade 5 (Severe Degree of Edema)
appearing beyond the range of visualization by reviewers. For Obscuration of all vessels on the disc and leaving the disc a
MFS grading of the optic disc photographs, if there was un-
certainty in assigning a grade between 2 increments, the lesser a Key features (major findings) for each grade.
grade was given an additional “⫹” symbol. For example, if it
was difficult to determine whether there was a C-shaped halo
or a 360° circumferential halo, the disc would be graded as 1⫹. rate cohort of 101 patients was randomly selected from a database
Because the first sign of papilledema in an experimental mon- of 224 patients with known papilledema at initial presenta-
key model was optic disc elevation,28 grade 0⫹ was used to char- tion from the University of Iowa using the same Stratus OCT3
acterize elevation that exceeded grade 0 but lacked the char- to determine if borders were captured accurately. The image
acteristics of grade 1. passed if the OCT algorithm followed the expected borders of
OCT fast RNFL, fast RNFL map, and fast optic disc images RNFL thickness and total retinal thickness on the B-scan as
were obtained at the time of digital color photography (Stra- evaluated by one of us (C.J.S.). The image failed if the algo-
tus OCT3, Zeiss Meditech). The mean RNFL thickness and total rithm did not follow the expected borders. The respective disc
retinal thickness were obtained if the proprietary algorithm photograph for each OCT image was evaluated and excluded
seemed to follow the expected borders in their entirety on the if of insufficient quality. Digital photographs were reviewed and
displayed B-scan and if the circular image seemed to be cen- graded by one of us (C.J.S.) using the MFS as previously de-
tered on the video display. Most RNFL circular image data rep- scribed. The failure rate was calculated for each photographic
resented 3 trials of each eye, for which the data were averaged. MFS grade similarly as for each OCT image.
The trial with the most accurately appearing fit for RNFL bor-
ders along with the highest signal strength was chosen for fur- RESULTS
ther analysis. OCT data with low signal strength (⬍5) or for
which no trials had adequate RNFL border tracing over 360°
of the circular image were excluded and tabulated. Among 36 patients with papilledema, 7 (19%) had grade
Disc grade for each patient was based on majority rule among 0, 7 (19%) had grade 1, 10 (28%) had grade 2, 4 had grade
3 of us (R.H.K., A.G.L., and M.W.) using the same computer 3 (11%), and 8 (22%) had grade 4 disc edema using ma-
monitor for evaluation. If all 3 reviewers were not in agreement, jority rule. The 3 reviewers agreed on grade most of the
grading by 2 reviewers was used, with the third reviewer’s grade time, and only once was there more than a 1-grade differ-
excluded. To evaluate possible higher correlation, 2 of us (R.H.K. ence by 1 reviewer compared with the other 2 reviewers
and M.W.) arranged the photographs in ranked order from low- (Figure 2A). One-grade differences occurred between all
est to highest amount of disc edema. As a cross-check, grading grades, and differences exceeding 1 grade occurred be-
was performed by one of us (L.F.) and correlated with OCT find- tween grades 2 and 4 (Figure 2B). If the “⫹” notation was
ings independent of the 3 reviewers. We performed Spearman
added to a grade, it was omitted to establish a numeric
rank correlations of OCT RNFL thickness, OCT total retinal thick-
ness, and MFS grade from photographs. scheme for further quantitative analysis. OCT RNFL thick-
Because the Stratus OCT3 was not specifically designed to ness and total retinal thickness showed significant corre-
measure papilledema, the software failure rate of the algo- lation with the MFS grade from photographs.
rithm for determining RFNL thickness and total retinal thick- In grading papilledema, we found strong correlation
ness was assessed as a function of papilledema grade. A sepa- between the MFS and OCT findings. When OCT RNFL
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A B
Difference of 6
>1 grade 2.8 Expert 1
Expert 2
5 Expert 3
Expert 4
3
Difference of
1 grade 41.7%
Equal grading 2
55.5%
0
0 5 10 15 20 25 30 35 40
Ranked Order of Modified Frisén Scale Grade
Figure 2. Papilledema grading differences in 36 patients. A, Among 3 reviewers using the Modified Frisén Scale. B, Between 2 reviewers using the Modified Frisén
Scale and 1 reviewer using ranked order of Modified Frisén Scale grade. The y-axis is slightly offset to delineate each expert’s grade. Note the good concordance
among reviewers.
A B
450 800
600
300
500
250
400
200
300
150
200
100
R = 0.85 100 R = 0.87
50
P<.001 P<.001
0 0
0 1 2 3 4 5 0 1 2 3 4 5
Modified Frisén Scale Grade Modified Frisén Scale Grade
Figure 3. Papilledema grading differences in 36 patients among reviewers. A, Using optical coherence tomography (OCT) retinal nerve fiber layer (RNFL)
thickness vs using Modified Frisén Scale grade. B, Using OCT total retinal thickness vs using Modified Frisén Scale grade.
thickness was compared with MFS grade from photo- RNFL thickness. When comparing OCT RNFL thickness
graphs (using majority rule), Spearman rank correlation with OCT total retinal thickness, a strong linear relation-
was 0.85 (P⬍.001). When OCT total retinal thickness ship was observed at R2 =0.90 (y=1.64x⫹105.5) (P⬍.001)
was compared with MFS grade from photographs, Spear- (Figure 5). The slope of 1.64 suggests a greater degree of
man rank correlation was 0.87 (P ⬍.001) (Figure 3). papilledema thickness change when using OCT total reti-
In cross-check grading by one of us (L.F.), Spearman rank nal thickness. Among 199 eyes in 101 patients evaluated
correlations were 0.79 (P ⬍.001) and 0.83 (P ⬍.001) for to analyze whether the algorithm was able to capture ex-
the latter. pected borders of the RNFL and total retinal thickness, the
Two of us (R.H.K. and M.W.) also ranked photo- highest failure rates were seen with higher grades of disc
graphs based on lowest to highest amount of disc edema. edema (Figure 6). Higher failure rates were found with
This was done to increase stratification of the data to dem- OCT RNFL thickness than with OCT total retinal thick-
onstrate potential higher correlation when using a finer scale. ness. All photographs were of sufficient quality to assign
Spearman rank correlation increased to 0.88 (P⬍.001) an MSF grade without failure, as most patients had sev-
when OCT RNFL thickness was compared with ranked or- eral photographs taken at the same time and the highest-
der of MFS grade (range, 1-36) (Figure 4). Spearman rank quality photograph was used for assessment.
correlation increased to 0.90 (P⬍.001) when OCT total
retinal thickness was compared with ranked order of MFS
COMMENT
grade. Interobserver Spearman rank correlation between
the 2 reviewers was highly significant at 0.87. In majority
rule when comparing MFS grading from photographs, OCT We found strong Spearman rank correlation between OCT
total retinal thickness had higher correlation than OCT RNFL thickness, OCT total retinal thickness, and MFS
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A B
450 800
400 700
300
500
250
400
200
300
150
200
100
R = 0.88 100 R = 0.90
50
P<.001 P<.001
0 0
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Ranked Order of Modified Frisén Scale Grade Ranked Order of Modified Frisén Scale Grade
Figure 4. Papilledema grading differences in 36 patients. A, Using optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness vs using ranked
order of Modified Frisén Scale grade. B, Using OCT total retinal thickness vs using ranked order of Modified Frisén Scale grade.
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A B
80 80
Fail
70 70 Pass
60 60
50 50
No. of Eyes
No. of Eyes
40 40
30 30
20 20
10 10
0 0
0 1 2 3 4 0 1 2 3 4
Modified Frisén Scale Grade Modified Frisén Scale Grade
Figure 6. Pass rates and fail rates using optical coherence tomography (OCT) measurements vs Modified Frisén Scale grade. A total of 199 eyes were evaluated in
101 patients. A, Using retinal nerve fiber layer (RNFL) thickness. B, Using total retinal thickness.
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associated maculopathy using optical coherence tomography. Arch Ophthalmol.
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