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Shields Gray Crescents Masquerading as


Glaucomatous Cupping of the Optic Nerve
Head
Mohamed S. Sayed, MD,1,* Michael Margolis, MD,1,2,* Jessica L. Chen, MD,1,3 Giovanni Gregori, PhD,1
Richard K. Lee, MD, PhD1

Purpose: Gray crescents characterized by darkly pigmented regions on the optic nerve head could make
assessment of cupping difficult by obscuring the true anatomic disc border. On slit-lamp examination, 2
morphologically distinct types of gray crescents at the curved disc boundary exist. The in vivo histologic char-
acteristics differentiating these 2 types are described using spectral-domain (SD) OCT.
Methods: A prospective interventional case series in a single tertiary referral center. Sixteen eyes of 10
patients with gray crescents determined through clinical examination and fundus photography underwent cross-
sectional optic nerve head and parapapillary imaging using high-resolution SD OCT. In vivo histology of gray
crescents was characterized.
Results: In SD OCT images across the areas of gray crescent, type A gray crescents represent regions where
the retinal pigment epithelium (RPE)-Bruch’s membrane complex is absent and the dark underlying choroid is
directly visible. In contrast, type B gray crescents represent regions of the retina where the RPE is clumped or
thickened, typically appearing to be folded upon itself, revealing the embryonic continuity of the RPE and
neuroretina.
Conclusions: Shields type A and B gray crescents appear different clinically because histologically they
represent differences in RPE. Type A grey crescents lack RPE, whereas type B crescents have thickened, folded
RPE. Gray crescents can obscure the true disc border and result in pseudo-cupping of the optic nerve head.
Identification of gray crescents is clinically important because failure to recognize pseudo-cupping can contribute
to overdiagnosis of glaucoma. Ophthalmology Glaucoma 2018;1:99-107 ª 2018 by the American Academy of
Ophthalmology

The intrapapillary and parapapillary regions of the optic in the prevalence of gray crescents in glaucomatous
nerve head have variable morphologic configurations compared with nonglaucomatous eyes apparently exists.2
throughout the population. This variability has been attrib- However, these gray crescents are clinically important
uted to ethnicity, refractive status, and conditions affecting because they may be mistaken for parapapillary
the optic nerve head (e.g., glaucoma) among other factors. pigmentation,3 obscure the neuroretinal rim tissue, and
Pigmentation within or in the vicinity of the optic nerve give a false impression of neural retinal rim loss due to
head is an important clinical feature that, together with other glaucomatous damage (i.e., pseudo-cupping). This is of
optic disc morphologic features, helps clinicians distinguish particular importance when assessing cup-to-disc ratio in
different clinical entities that involve the optic nerve head. African American patients, who have a higher prevalence of
Gray pigmented crescents within the optic disc border are both glaucoma and gray crescents.3
clinically apparent in many eyes. Shields subsequently found it necessary to distinguish his
In 1980, Bruce Shields1 termed a pigmented crescent initially described gray crescent from a different type of dark
located within the disc margin of the optic nerve head a tissue found at the curved disc boundarydthe latter previ-
“gray crescent.” The gray crescent is typically a slate-gray ously termed conus pigmentosusddescribed as a darker,
crescentic pigmentation of the neuroretinal rim, commonly more irregular and stereoscopically more superficial area of
located in the temporal or inferotemporal periphery, and retinal pigment epithelium (RPE) hypertrophy that may
considered to be a normal anatomic variant. The gray cover the parapapillary scleral crescent and appears to enter
crescent is distinct from different variants of parapapillary the intrapapillary disc region.3 Other investigators, seeking
pigmentation observed outside of the disc margin. The to understand the epidemiologic characteristics of the gray
exact cause of this gray crescent is not known but was crescent, had unwittingly lumped the 2 categories
thought to possibly represent areas where melanin or together, because the histologic nature of the 2 gray
melanocytes have accumulated on or within the crescents was not determined.2,4 For the purpose of
neuroretinal rim tissue of the nerve head.2 No difference in vivo histologic OCT evaluation, we have designated the

 2018 by the American Academy of Ophthalmology https://doi.org/10.1016/j.ogla.2018.08.001 99


Published by Elsevier Inc. ISSN 2589-4196/18
Ophthalmology Glaucoma Volume 1, Number 2, September/October 2018

former as a Shields type A gray crescent and the latter as a provides RNFL thickness from 4 B-scan circles, and each includes
Shields type B gray crescent. 1024 A-scans. Imaging was acquired in 0.15 seconds. Standard
The histologic equivalent of the gray crescent has been colored optic nerve head photographs were taken for all patients.
suggested to be melanocyte accumulation or intrapapillary Three examiners (M.M., M.S.S., and R.K.L.) examined all images.
RPE-Bruch’s membrane extension, with some OCT support
demonstrating the possibility of Bruch’s membrane to Results
extend beyond the optic disc border into the substance of the
optic nerve head.1,4-6 Jonas et al7 have characterized the Ten eyes were found to have type A gray crescents (lighter, slate
zones of parapapillary atrophy (PPA) histomorphologically gray; Fig 1) and 6 eyes were found to have type B grey crescents
and by OCT.8 However, to our knowledge, the histologic (darker ledge of black tissue; Fig 2) by SD OCT. In 1 patient, the
nature of the gray crescent is yet to be determined. In this right eye had a type B gray crescent and the left eye had a type A
study, we compared gray crescent photographs with gray crescent. Seven of the 10 eyes with type A gray crescents also
spectral-domain (SD) OCT for in vivo histologic charac- had PPA, whereas only 1 eye with type B gray crescent had
terization of eyes with gray crescents. concomitant PPA. All 3 examiners agreed on the classification of
Our results demonstrate 2 distinct anatomic variants of all eyes. A standard RNFL analysis was performed in 7 patients
gray crescents that can be characterized histologically using Cirrus (6 eyes with type A and 4 eyes with type B gray
in vivo using SD OCT: type A gray crescent and type B crescents). The RNFL thickness as measured with Cirrus
gray crescent of the optic nerve head. Gray crescents have correlated with the degree of glaucomatous damage, and not with
significant implications for the clinical assessment of the the presence or type of gray crescent. Figure 3 demonstrates that
optic disc. Spectral-domain OCT can help identify gray in a typical optic nerve with a type A gray crescent, nerve fiber
crescents and provide a more accurate measurement of the layer thickness is normal, although the optic nerve head has a
cup-to-disc ratio. Erroneous identification of the optic disc pseudo-cupped appearance.
border as obscured by gray crescents can lead to a false The RNFL thickness measured by the RTVue RNFL 3.45 scan
assessment of the cup-to-disc ratio and to pseudo-cupping, was concordant with the glaucomatous damage that would be ex-
which can result in overdiagnosis or misdiagnosis of pected in an optic disc with only the actual amount of cupping,
glaucoma. rather than the perceived pseudo-cupping caused by the gray
crescent. The RNFL thickness ratios as measured by the RTVue
RNFL 3.45 scan correlated with those measured with Cirrus. The
Methods Cirrus values were, on average, lower as demonstrated in Figure 4,
which demonstrates borderline temporal RNFL thickness in the
The study was approved by the Institutional Review Board of the
right eye of a patient with a type A gray crescent, correlating
University of Miami Miller School of Medicine and adhered to the
tenants of the Declaration of Helsinki. Informed consent was ob- with actual, rather than the perceived, cup-to-disc ratio.
tained from the subjects after explanation of the nature and possible
consequences of the study. All participants underwent a full Discussion
ophthalmologic evaluation including visual acuity assessment,
intraocular pressure measurement, slit-lamp biomicroscopy, and
fundus examination. The inclusion criterion was a clearly identi- The Elschnig’s ring, comprising the border tissue of
fiable optic nerve head gray crescent on clinical examination. Elschnig, which is a collagenous tissue arising from the
Exclusion criteria were any optic nerve disease apart from glau- sclera, enclosing the choroid, and joining Bruch’s mem-
coma (e.g., melanocytoma of the optic nerve head) and previous brane, is widely believed to give rise to the fundoscopic
retinal laser treatment or surgery. appearance of the perceived disc margin.9,10 In cross-
Sixteen eyes of 10 consecutive patients with a gray crescent sectional OCT images, the termination of the Bruch’s
were identified through clinical examination and imaged with the membrane, where the neural canal comprising retinal
RTVue high-resolution SD OCT (Optovue, Fremont, CA) and ganglion cells begins at the Bruch’s membrane opening and
fundus photography. A 6-mm-long retinal line scan transecting the
extends through the choroid and sclera, is believed to
optic nerve head at the area of predetermined gray crescent was
taken for each eye using the RTVue SD OCT, with a default represent the optic disc margin.11,12 Because the resolution
orientation angle of 0 (left-to-right horizontal line). Each line scan of SD OCT does not allow the distinct isolation of Bruch’s
automatically averages 16 high-definition B-scan register frames membrane from the overlying RPE, it is acceptable to use
(each includes 1024 A-scans of a 0.039-second duration each) at the RPE-Bruch’s membrane complex termination as a
the same location in 0.63 seconds to improve signal. The RTVue surrogate for Bruch’s membrane opening.13
OCT only averages frames with good yield and correlation if eye However, such definition of the border tissue architecture
movement or blinking occurred during scanning. Four images with is mostly applicable in cases in which the optic nerve head is
at least 10 valid frames each were taken for every eye to increase free of confounding anatomic features. Earlier OCT studies
diagnostic precision. have shown that what clinicians perceive as the disc margin
A standard retinal nerve fiber layer (RNFL) analysis was per-
is not a single anatomic structure, but rather variable in ul-
formed as clinically indicated in 7 patients (6 eyes with type A and
4 eyes with type B gray crescents) (Cirrus; Carl Zeiss Meditec Inc., trastructural terms, and can comprise border tissue, Bruch’s
Dublin, CA). Cirrus was used for RNFL analysis because this is the membrane opening, or anterior scleral opening.14 With the
standard of care in our institution. The RNFL thickness was also use of the current technology, these landmarks can be
measured using RTVue RNFL 3.45 scan in 2 patients. The RNFL highly variable and at times difficult to accurately identify,
3.45 scan is a circular 3.45-mm scan centered on the optic disc that such as in cases of high myopia. Moreover, studies also

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In Vivo Imaging of Shields Gray Crescents

Figure 1. A and B, Type A gray crescent. The colored optic disc photographs show the true edge of the disc as seen clinically, as well as the pseudo-disc
margin constituted by the edge of the type A gray crescent. Note the gradual thinning followed by cessation of the retinal pigment epithelium (RPE)-Bruch’s
membrane complex, causing an enhancement of signal at the choroid level on spectral-domain (SD) OCT and resulting in clinical gray crescent. The white
arrow shows the termination of the RPE-Bruch’s membrane complex, and the yellow arrow points the edge of the type A gray crescent, marking the end of
the choroidal hyper-reflectivity zone. Type A gray crescent falls between the white and the yellow arrows on the OCT cross-section.

have shown that the clinically or colored fundus Shields gray crescents represent a deviation from the
photographyeidentified disc border and the disc margin as normal anatomy, and the subjective location of the clinical
delineated by SD OCT can poorly correlate.15,16 In addition, and OCT landmarks can be highly variable. In the present
there are cases in which Bruch’s membrane extends into the study, however, we demonstrate a highly consistent ultra-
substance of the optic nerve head.6 structural pattern in gray crescents using SD OCT.

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Figure 2. A and B, Type B gray crescent. Note the clumping of the retinal pigment epithelium (RPE)-Bruch’s membrane complex that appears folded upon
itself on spectral-domain (SD) OCT, resulting in a clinical gray crescent. The white arrowheads define the edges of the folded/clumped segment of RPE-
Bruch’s membrane complex underlying the clinically identifiable type B gray crescent. A, Temporal type B gray crescent showing clumping of the RPE-
Bruch’s membrane complex on SD OCT (white circle) in association with parapapillary atrophy (PPA) with thinning of the RPE-Bruch’s membrane complex
and choroidal hyperreflectivity (green circle). Note that in the colored photograph, the true disc margin is obscured and difficult to identify because of the
presence of both the type B gray crescent and PPA. B, Type B gray crescent. The colored photograph shows the true edge of the disc as clinically seen and
the edge of the type B gray crescent.

Examining B-scan images across the areas of gray cres- crescents appeared lighter (slate gray) and more sloped at
cent in the optic discs of 16 eyes with gray crescents, dif- the temporal disc border (Fig 1A and B), whereas type B
ferences in the RPE-Bruch’s membrane complex of the gray crescents appeared darker and had a more sharply
retina explain the 2 clinically identified types of gray cres- delineated, almost overhanging ledge of black tissue at the
cents. Although clinically subtle by stereo slit-lamp bio- internal temporal disc border when viewed in stereo (Fig
microscopy and often difficult to distinguish, type A gray 2A and B). The different types of gray crescents were

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In Vivo Imaging of Shields Gray Crescents

Figure 3. A and B, Normal nerve fiber layer assessment in gray crescent. A, Note the difference between the perceived optic disc border (green arrows) and the
actual optic disc border (black arrows) in the left eye of a patient with a temporal type A gray crescent, adding a pseudo-cupping component to the cup-to-disc
ratio. Also note the presence of parapapillary atrophy (PPA) outside the actual optic disc border. The PPA appears lighter in color compared with the adjacent
temporal gray crescent. B, Standard retinal nerve fiber layer (RNFL) analysis (Cirrus; Carl Zeiss Meditec Inc., Dublin, CA) demonstrating normal average RNFL
thickness and normal RNFL thickness in the temporal quadrant of left eye, corresponding to the location of the gray crescent, despite suspicious thinning of
superior RNFL on the quadratic map. Left eye analyses demarcated by black line; temporal RNFL demarcated by red line in RNFL thickness map.

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Figure 4. AeC, The retinal nerve fiber layer (RNFL) thickness as measured by RTVue (Optovue, Fremont, CA) RNFL 3.45 scan and Cirrus RNFL
analysis. A, Temporal type A gray crescent in the right eye, with a gradual thinning of the RPE-Bruch’s membrane complex and enhancement of signal at
the choroid level on spectral-domain (SD) OCT and resulting in clinical gray crescent. Note the difference between the perceived optic disc border (green
arrows) and the actual optic disc border (black arrows). B, RTVue RNFL 3.45 scan showing only borderline temporal thinning on the RNFL, less than would
be expected in the apparent degree of cupping implied by the gray crescent. C, Cirrus RNFL analysis showing temporal borderline RNFL thickness,
correlating with the measurement obtained by the RTVue RNFL 3.45 scan. Note the lower values of the Cirrus RNFL analysis. Right eye analyses marked by
black line on Cirrus printout.

much easier to differentiate with in vivo histologic Type A gray crescents, which appear slate gray, dark
assessment using SD OCT. Clinically, both types of gray areas around the temporal portion of the optic nerve disc on
crescents give the appearance of pseudo-cupping because color photographs (Fig 1A and B), represent regions where
they obscure a significant portion of the neuroretinal rim, the RPE and Bruch’s membrane are absent and where light
thereby increasing the amount of perceived cupping as the penetrates readily through that region of the optic nerve
inner rim of the gray crescent is mistaken to be the true disc head border. This is similar in microstructure to the OCT
margin. morphology of the gamma zone of PPA as demonstrated

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Figure 4. (contiued).

by Dai et al8 (Fig 2A). However, the type A gray crescents neuroretina. The blocked light due to this thickened RPE
appear to lie well within the boundaries of the disc margin as gives the region its dark appearance, as RPE is a dark pig-
identified by a careful clinical fundoscopic examination, mented layer of the retina. This is supported by the previous
unlike the gamma zone of PPA, which lies outside the finding that Bruch’s membrane may on occasions extend
clinically identifiable disc border. This loss of RPE- into the substance of the optic nerve head6 and is consistent
Bruch’s membrane complex in the type A gray crescents with the previous stereoscopic observation suggesting that
allows increased penetration of light and greater conus pigmentosus (called “type B gray crescent”) is more
illumination of deeper tissue, which appears as brightness superficial than the type A gray crescent.3
on the B-scans and en face SD OCT optic nerve image, The demographic characteristics of gray crescents have
thereby revealing the underlying choroid. The area is been reported.2,3 Type A gray crescents were found to be
therefore dark on slit-lamp examination because the under- more prevalent among African Americans (27%) than
lying darker choroid is directly visible. among whites in one study (7.4%),3 whereas another study2
In contrast, type B gray crescents represent regions of the found the prevalence of gray crescents in an all-white
retina where the RPE-Bruch’s membrane complex is population to be significantly higher (22%), probably
clumped or thickened, typically appearing to be folded upon because no distinction between type A and type B gray
itself, revealing the embryonic continuity of the RPE and crescents was made in the latter, possibly attributing the

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difference to a higher prevalence of type B among the white In patients with glaucoma who also have a gray crescent,
population compared with type A gray crescents. These the amount of RNFL present is typically much greater than
studies demonstrate that although gray crescents were more expected based on clinical examination. Recognizing
common in women than in men, age, sex, refractive error, pseudo-cupping is of a particular importance in an era when
intraocular pressure, and unlike PPA,17 the degree of the reliance on imaging in the diagnosis and follow-up of
glaucomatous damage did not correlate with the prevalence patients with glaucoma has dramatically increased, because
of gray crescents. In our observation, the association of although routine RNFL analysis may reveal a normal RNFL
gray crescents with PPA seems to be common, contrary to thickness, cup-to-disc ratio assessment may still lie outside
findings of the Reykjavik Eye Study, which suggested that normal limits in red lettering or boxes in patients with
the prevalence of gray crescents is inversely related to the gray crescents, possibly contributing to overdiagnosis and
presence of PPA.2 Given the small number of participants overtreating these patients.18 The understanding of the
in our study, we did not evaluate demographic data. The ultrastructure of gray crescents adds a new dimension to
aim of our study is to characterize the histologic nature of our ability to interpret RNFL analyses in eyes with gray
gray crescents using in vivo high-resolution SD OCT. crescent, because commonly used OCT platforms use
Our study shows that Shields type A and B gray cres- automated algorithms that define the margin of the optic
cents appear different clinically because histologically they disc at the termination of Bruch’s membrane, and these
represent differences in the RPE-Bruch’s membrane layer. platforms may therefore underestimate the circumpapillary
Spectral-domain OCT is useful for identifying and charac- RNFL thickness in type A gray crescents in which an early
terizing in vivo the different anatomic variants of gray termination of Bruch’s membrane is present, as shown in
crescents that represent pseudo-cupping clinically at the slit our results, potentially missing RNFL that extends beyond
lamp. Along with the correlative use of color photos, SD Bruch’s membrane termination (Fig 1A). Moreover, SD
OCT may be useful to distinguish type A gray crescents OCT line scans transecting the optic nerve head may be an
from type B gray crescents. important modality for following patients with glaucoma
Bruce Shields1 initially described dark areas around the with gray crescents for progression, because pseudo-cupping
temporal areas of the optic nerve disc as a gray crescent, may make assessing true increases in the cup-to-disc ratio
now recognized to be a type A gray crescent. This type of difficult by serial slit-lamp examination of the optic nerve head.
gray crescent has a loss of the RPE-Bruch’s membrane In conclusion, SD OCT is a powerful new approach for
layer and appears slate gray on color photographs (Fig 1). viewing cross-sectional retinal ultrastructure in vivo.
This loss of RPE-Bruch’s membrane complex allows Spectral-domain OCT is useful for identifying and charac-
increased penetration of light and greater illumination of terizing in vivo the different anatomic variants of optic
deeper tissue, which appears as brightness on the B-scans nerve head gray crescents and, along with the correlative use
and en face SD OCT optic nerve image, thereby revealing of color photos, differentiating gray crescents as type A and
the underlying choroid. We are unsure which anatomic type B anatomic gray crescents based on differences in the
layer represents the gray area on the OCT en face optic RPE-Bruch’s membrane complex. Shields gray crescents
nerve head image. Stereoscopic views of the optic nerve may be mistaken clinically as an increased cup-to-disc ratio
head in patients who have the gray crescents demonstrate with the internal border of the gray crescent mistaken for the
sloping, which may provide a false impression of cupping disc border. Clinicians should be aware that the presence of
because the disc border is mistaken to be the edge of the these disc changes may alter the appearance of the optic
gray crescent. This “pseudo-cupping” may be misleading disc, making the optic nerve head appear rather more cup-
to the clinician as glaucomatous damage to the optic nerve ped than it truly is. Distinct ultrastructural patterns exist for
head. the 2 types of gray crescents identified. These patterns are
A different anatomic version of gray crescents previously not associated with corresponding RNFL thinning as would
termed conus pigmentosus has been described, now termed be expected of the more illusively cupped discs when the
the “type B gray crescent.” The RPE in type B gray cres- presence of the gray crescents is overlooked. Spectral-
cents appears to be thickened and possibly folded upon it- domain OCT is clinically helpful for differentiating true
self, revealing the embryonic continuity of the RPE and cupping from pseudo-cupping. In combination with quan-
neuroretina (Fig 2A and B). titative measurements of the nerve fiber layer with SD OCT
The clinical importance of the gray crescent, as pointed and performing retinal histology in vivo with OCT cross-
out by Shields,1 is its role in creating a pseudo-cupped sectional analysis of cupping, a physiologically normal
appearance to the optic nerve. This pseudo-cupping occurs optic nerve head with a gray crescent (pseudo-cupped) can
because the disc rim edge from the border tissue of Elschnig be distinguished from a glaucomatous optic nerve head with
to the interior rim of the cup may appear to be significantly nerve fiber loss.
reduced because the edge of the inner rim of the gray
crescent is mistaken to be the disc border. Spectral-domain
OCT not only can identify the type of gray crescent but also References
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gray crescents may decrease the incidence of overcalling an optic nerve grey crescent in the Reykjavik Eye Study. Br J
optic nerve as having glaucomatous cupping. Ophthalmol. 2005;89:36e39.

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In Vivo Imaging of Shields Gray Crescents

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Footnotes and Financial Disclosures


Originally received: May 4, 2018. HUMAN SUBJECTS: Human subjects were included in this study. The
Final revision: July 30, 2018. human ethics committees at the University of Miami Miller School of
Accepted: August 1, 2018. Medicine approved the study. All research adhered to the tenets of the
Available online: August 7, 2018. Manuscript no. 2018-12. Declaration of Helsinki. All participants provided informed consent.
1
Bascom Palmer Eye Institute, University of Miami Miller School of No animal subjects were used in this study.
Medicine, Miami, Florida. Author Contributions:
2
Fillmore Eye Clinic, Deming, New Mexico. Conception and design: Margolis, Sayed, Gregori, Lee
3 Data collection: Margolis, Sayed, Chen, Lee
Palo Alto Eye Group, Palo Alto, California.
Analysis and interpretation: Margolis, Sayed, Chen, Lee
*M.S.S. and M.M. share equal contribution (co-first authorship).
Obtained funding: N/A
Financial Disclosure(s):
The author(s) have made the following disclosure(s): G.G.: Consultant e Overall responsibility: Sayed, Lee
Carl Zeiss. Abbreviations and Acronyms:
R.K.L.: Support e Walter G. Ross foundation and was supported by NIH PPA ¼ parapapillary atrophy; RNFL ¼ retinal nerve fiber layer;
grant K08 EY016775. RPE ¼ retinal pigment epithelium; SD ¼ spectral domain.
The Bascom Palmer Eye Institute is supported by National Institutes of Correspondence:
Health (NIH) Center Grant P30-EY014801 and an unrestricted grant from Richard K. Lee, MD, PhD, Bascom Palmer Eye Institute, University of
Research to Prevent Blindness. The RTVue SD OCT (Optovue, Fremont, Miami Miller School of Medicine, 900 NW 17th St., Miami, FL 33136. E-
CA) used in this study was loaned by Optovue for research purposes. mail: rlee@med.miami.edu.

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