Optic Disc Margin Anatomy inPatients with Glaucoma and NormalControls with Spectral Domain OpticalCoherence Tomography

Alexandre S.C. Reis, MD,1,2 Glen P. Sharpe, MSc,1 Hongli Yang, PhD,3 Marcelo T. Nicolela, MD,1

Claude F. Burgoyne, MD,3 Balwantray C. Chauhan, PhD1

Objective: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin withspectral domain-optical coherence tomography (SD-OCT).

Design: Cross-sectional study.Participants: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and

age-matched normal controls.Methods: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour.

For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique,or nonoblique) and the presence of Bruch’s membrane overhanging the border tissue. Optic disc stereophoto-graphs were co-localized to SD-OCT data with customized software. The frequency with which the disc marginidentified in stereophotographs coincided with (1) Bruch’s membrane opening (BMO), defined as the innermostedge of Bruch’s membrane; (2) Bruch’s membrane/border tissue, defined as any aspect of either outside BMOor border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computedat each clock hour.

Main Outcome Measures: The SD-OCT structures coinciding with the disc margin in stereophotographs.Results: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range)

age of 68.1 (42–86) years and 63.5 (42–77) years, respectively. Although 28 patients (93%) had 2 or more bordertissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, fre-quently with Bruch’s membrane overhang. Externally oblique border tissue was less frequent, observed mostlyinferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc.Although the configurations were not statistically different between patients and controls, they were among the3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin wassome aspect of Bruch’s membrane and border tissue external to BMO. Bruch’s membrane overhang wasregionally present in the majority of patients with glaucoma and controls; however, in most cases it was notvisible as the disc margin.

Conclusions: The clinically perceived disc margin is most likely not the innermost edge of Bruch’s mem-brane detected by SD-OCT. These findings have important implications for the automated detection of the discmargin and estimates of the neuroretinal rim.

Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.Ophthalmology 2011;xx:xxx © 2011 by the American Academy of Ophthalmology.

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The optic nerve head (ONH) comprises retinal ganglion cell(RGC) axons, blood vessels, glia, and connective tissue. It isthought to be the primary site of damage in glaucoma.1–3

The optic disc margin is a clinical construct for structuresthat encompass the neural tissue within the ONH. Its accu-rate clinical identification is central to the quantitative esti-mate of cup:disc ratio and the foundation of all quantitativeassessments of the neuroretinal rim by modern imagingtechniques. However, histologically, what the clinician sees

as the disc margin has been a source of controversy, with the c

© 2011 by the American Academy of OphthalmologyPublished by Elsevier Inc.

ossibility that structures that most accurately define theuter boundary of the ONH neural tissue are not alwaysisible by clinical examination techniques. Furthermore,ssessments of optic disc size vary according to examina-ion technique.4,5

The border tissue of Elschnig (Fig 1) is fibrous tissue thatises up from the anterior edge of the sclera to fuse withruch’s membrane to separate the choroid from RGC axonss they pass through the anterior portion of the neural

anal.6,7 Border tissue is highly relevant to the optic disc

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Ophthalmology Volume xx, Number x, Month 2011

margin because its anatomy relative to the anterior edge ofthe sclera determines whether or not it is visible to theclinician and what structure is perceived as the edge ofthe optic disc. Recent advances in 3-dimensional histo-morphometric reconstructions of postmortem tissues8,9

allow a better understanding of optic disc margin anat-omy, and spectral domain optical coherence tomography(SD-OCT)10,11 permits in vivo detection of these struc-tures,12,13 thereby providing an opportunity to determinewhat the clinician perceives as the disc margin and towhat degree SD-OCT– detected structures that clearlydefine the outer border of the neural tissues are clinicallyvisible.

Border tissue anatomy is regionally variable within in-dividual ONHs and can be characterized as internally orexternally oblique relative to the underlying sclera.13,14 In-ternally oblique border tissue extends internal to the anteriorscleral opening to fuse with Bruch’s membrane such that theunderlying sclera is not clinically visible (Fig 1). Externallyoblique border tissue extends external to the anterior scleralopening to fuse with Bruch’s membrane such that a portionof border tissue, and sometimes the underlying sclera, isclinically visible. Finally, as regions of internally obliqueborder tissue transition to externally oblique within an in-dividual ONH, there can be regions of vertical or non-oblique border tissue, perpendicular to the clinical plane ofview.

In most monkey eyes, there is overhang of Bruch’s

Figure 1. Schematic representation of border tissue (BT) configurationborder tissue/scleral junction to fuse with Bruch’s membrane (BM). B,Border tissue extends externally from the posterior border tissue/scleraperpendicular relative to the scleral opening. For simplicity, the retinBruch’s membrane opening.

membrane extending beyond the innermost termination of c

2

order tissue (Fig 1B). Strouthidis et al12 recently comparedlinical, histomorphometric, and SD-OCT optic disc marginnatomy in monkey eyes. They proposed that what thelinician recognizes as the disc margin depends mainly onhe 3-dimensional architecture of Bruch’s membrane andnderlying border tissue, rather than a single structure.urthermore, they observed that where Bruch’s membranextended beyond border tissue, the extension was clinicallyisible and represented the optic disc margin in most re-ions of most monkey eyes.13

In humans, even though the anatomy underlying theptic disc margin is well described,6,15 there is no system-tic characterization of SD-OCT disc margin anatomy. Inarticular, the frequency of Bruch’s membrane overhangnd whether it is visible as the clinical disc margin inlaucomatous and healthy eyes is not known.

In this study, we co-localized SD-OCT data sets to opticisc stereophotographs of patients with glaucoma with aariety of optic disc appearances and normal controls fromhich the clinical optic disc margin was determined. Wead 3 objectives: (1) to characterize border tissue orienta-ion; (2) to identify the deep ONH structures detected withD-OCT that co-localize with the clinically visible opticisc margin; and (3) to determine the frequency of SD-CT–detected Bruch’s membrane extending beyond the

linically visible disc margin. The latter has implications forhe accuracy with which neuroretinal rim assessments, suchs cup:disc ratio and automated neuroretinal rim area, are

Internally oblique: Border tissue extends internally from the posteriorally oblique with Bruch’s membrane overhang. C, Externally oblique:tion to fuse with Bruch’s membrane. D, Nonoblique: Border tissue isment epithelium overlying Bruch’s membrane is not shown. BMO �

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Reis et al � Optic Disc Margin Anatomy in Glaucoma

Materials and Methods

Participants

Thirty patients with open-angle glaucoma with early to moder-ate visual field loss and 10 healthy age-matched normal controlsubjects were recruited from 2 prospective longitudinal obser-vational studies being conducted at the Eye Care Centre, QueenElizabeth II Health Sciences, Halifax, Nova Scotia, Canada. Toinclude a range of optic disc appearances in glaucoma, patientswith focal, diffuse, or sclerotic optic disc damage were re-cruited. These forms of optic disc damage have been describedin detail16 –18 with evidence that recognizing these appearanceshas clinical importance.19 Briefly, in focal damage there is asuperior or inferior notch, with the remaining neuroretinal rimrelatively well preserved. In diffuse damage, there is concentriccup enlargement and no localized areas of loss or pallor. Insclerotic damage the cupping is shallow, with marked areas ofperipapillary atrophy and choroidal sclerosis.

If both eyes were eligible, 1 eye was randomly selected as thestudy eye. For the present study, 10 patients representing eachoptic disc damage group were randomly selected, in addition to 10age-matched control subjects. In accordance with the Declarationof Helsinki, all subjects gave informed consent to participate, andthe ethics review board of the Queen Elizabeth II Health SciencesCentre approved the study.

Inclusion criteria was diagnosis of open-angle glaucoma,including primary, pseudoexfoliative, or pigmentary glaucomawith glaucomatous visual field loss with standard automatedperimetry and glaucomatous optic disc damage. The visual fieldwas tested with the Swedish Interactive Thresholding Algo-rithm20 program 24-2 of the Humphrey Field Analyzer (CarlZeiss Meditec, Dublin, CA). Glaucomatous visual field loss wasdefined with an abnormal Glaucoma Hemifield Test result.21

Exclusion criteria were concomitant ocular disease and sys-temic medication known to affect the visual field. Normalcontrols had a normal eye examination with an intraocularpressure less than 21 mmHg and a normal visual field defined asa Glaucoma Hemifield Test, mean deviation, and pattern stan-dard deviation within normal limits. Additional inclusion cri-teria for all subjects were best-corrected visual acuity �0.3(20/40) logarithm minimum angle of resolution in the studyeye, refraction within �6.00 diopters sphere, and �3.00 di-opters astigmatism.

Imaging

Optic disc stereophotographs were acquired with a fundus cam-era (FF3, Carl Zeiss Jena GmbH, Jena, Germany) with an Allenseparator. The images were captured on 35-mm slide film,which was developed and processed into color slides. Stereo-photograph slides were digitized at a resolution of 4800 dpiusing a color-calibrated slide scanner (Nikon LS-5000 ED,Nikon Corporation, Tokyo, Japan). Each subject had the studyeye imaged with a commercially available SD-OCT device(Spectralis, Heidelberg Engineering GmbH, Heidelberg, Ger-many). A radially equidistant scanning pattern centered on theoptic disc was used (24 high-resolution 15-degree radial scans,each averaged from 30 B-scans, with 768 A-scans per B-scan),with a scanning speed of 40 000 A-scans per second. Optic discphotographs and SD-OCT scans were acquired on the same day

or within 3 months of each other. s

o-localization of Spectral Domain Opticaloherence Tomography Volumes and Optic Dischotographs

n infrared image was extracted from the SD-OCT raw data forach subject. Depending on a subjective determination of theest-quality photograph, with clear focus at the disc margin, eitherhe right or left side of the stereophotograph pair was selected forach eye and rescaled to 1536�1536 pixels. By using an automaticub-pixel registration algorithm,22 each selected photographsource image) was aligned and matched to its correspondingnfrared image (target image) to generate a registered photograph.he registration was performed with public domain software

ImageJ, version 1.43u, TurboReg plug-in, National Institutes ofealth, Bethesda, MD). To test the alignment, a 65% transparent

egistered photograph was superimposed on the correspondingnfrared image (Adobe Photoshop CS3; Adobe Systems, San Jose,A) and saved as a 2-layer image file. Co-localization required theutline of the central retinal vessels and their bifurcations to beatched between the infrared OCT image and the photograph. If

resent, misalignments between the 2 images were corrected byhifting, scaling, and rotating the registered image. A singlebserver (A.S.C.R.) performed all the co-localizations. Theo-localization process is illustrated in Figure 2 (available atttp://aaojournal.org).

Because the infrared and disc photographs are 2-dimensionalrojections of 3-dimensional surfaces, the accuracy of the reg-stration process was evaluated to determine whether there wereifferences in projection between the 2 imaging modalities. Theistance between 2 approximately horizontal landmarks and 2pproximately vertical landmarks in the infrared image wasomputed in all 40 subjects. Landmarks were clear vesselifurcations. The procedure was repeated with the correspond-ng landmarks in the aligned disc photograph. The horizontal:ertical ratio was computed for the 2 image types, and annalysis of the differences was performed. The median modulusf the difference in ratios was 0.009 or 0.9% (95% confidencenterval, 0.008 – 0.020, or 0.8%–2.0%), indicating that the reg-stration process was accurate and did not induce meaningfulrojection errors.

ptic Disc Margin Assessment

ne observer (A.S.C.R.) demarcated all the optic disc marginsn the registered photographs by placing a line along the discargin using commercial software (Adobe Photoshop CS3).he observer also had access to the original stereophotographlides that were viewed on a light table with a stereo-viewer toccurately identify the disc margin. The disc margin was de-ned as the innermost border of reflective tissue that was

nternal to any pigmented tissue and within which only neuralissue was present. If there was no clear reflective tissue pres-nt, then the disc margin was defined as the innermost termi-ation of pigmented tissue. Thereafter, he and 3 additionalbservers (M.T.N., C.F.B., and B.C.C.) reviewed all optic discsnd concurred on the location of the optic disc margin. For eachubject, the observers had access to digitized stereophotographairs on a computer monitor with a Screen-Vu stereoscope (PSfg., Portland, OR) and the original stereo slides. The regis-

ered image with the demarcated optic disc margin was saved asn image file.

Fifteen (50%) of the glaucoma patients were clinically exam-ned by two glaucoma specialists (M.T.N and C.F.B) to confirmhe location of the disc margin. Optic discs were examined stereo-

copically with a slit lamp biomicroscope at low and high magni-

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fication with 78 and 90 diopter lenses under white and red-freedirect and oblique illumination.

Segmentation of Optic Disc Margin Structures inSpectral Domain Optical Coherence TomographyImages

The SD-OCT raw data were imported into customized softwareenabling 3-dimensional visualization and manual segmentation ofSD-OCT structures. The software is based on the VisualizationToolkit (VTK, Clifton Park, NY)12,13 and allows segmentation ofstructures in the SD-OCT B-scan with simultaneous correspondingprojection in the 2-dimensional infrared image (extracted from theSD-OCT data) and registered photograph. After loading the reg-istered photograph with a line demarcating the optic disc margin,1 operator (A.S.C.R.) identified and manually segmented the SD-OCT structure coinciding with the optic disc margin in all radial

Figure 3. Registered photograph with the optic disc margin demarcatiorientation) acquired in the positions indicated by black dashed lines. The gr(SD-OCT) structure corresponding to the clinical visible disc margin.

B-scans. b

4

dentification of Optic Disc Margin Structures inpectral Domain Optical Coherence Tomographymages

ll eyes were transformed to right-eye format. The SD-OCT scansere categorized in terms of border tissue obliqueness, presence ofruch’s membrane overhang, and the SD-OCT structure coincid-

ng with the optic disc margin demarcated in the photographs.lthough the analysis was performed on all 24 radial scans, for this

eport, only data for the 12 clock hour positions are presentedFig 3).

Border tissue was classified at each clock hour into 3 categories ofbliqueness: (1) internally oblique, where border tissue extends inter-al to the anterior scleral opening (Fig 1A, B); (2) externally oblique,here border tissue extends external to the anterior scleral opening

Fig 1C); and (3) nonoblique, where border tissue is perpendicularelative to scleral opening (Fig 1D). The presence of Bruch’s mem-

reen dots) and 12-clock hour radial B-scans (displayed with the samets on the B-scans show the spectral domain optical coherence tomography

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rane overhang (Fig 1B) was also quantified. Border tissue classifi-

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Reis et al � Optic Disc Margin Anatomy in Glaucoma

cation was initially made by 1 observer (ASCR) and then reviewedand verified by 3 additional observers (M.T.N., C.F.B., and B.C.C.).

The SD-OCT structure coinciding with the optic disc margin,identified in the optic disc stereophotograph, was classified at eachclock hour into 3 categories: (1) Bruch’s membrane opening(BMO), when the clinically identified disc margin co-localizedwith the innermost edge of Bruch’s membrane, with or withoutoverlying retinal pigment epithelium, in the SD-OCT image (Fig4A); (2) Bruch’s membrane/border tissue, when the disc marginco-localized with Bruch’s membrane and border tissue and whenthe innermost edges of Bruch’s membrane and border tissue didnot coincide (Fig 4B); and (3) border tissue alone, when the discmargin co-localized with border tissue alone (Fig 4C).

Figure 4. Schematic representation and spectral domain optical coherence(white arrows) in the B-scans indicate the SD-OCT structure correspondin(BMO) corresponding to the optic disc margin when BMO was coincidentor when there was a Bruch’s membrane overhang (A3). B, Bruch’s membedges of Bruch’s membrane and border tissue did not coincide. C, Border

Table 1. Characteristics of Patients

Glaucoma

Age (yrs) 68.1 (42–86)Gender (M/F) 16/14Mean deviation (dB) �2.9 (�13.0 to �

dB � decibels.

*Values shown are median (range).

tatistical Analysisategoric variables were analyzed with the chi-square test, andontinuous variables were analyzed with the Mann–Whitney testith commercial software (PASW Statistics v. 18, SPSS Inc.,hicago, IL).

esults

he subjects comprised 20 men (50%) and 20 women (50%) ofuropean ancestry. Table 1 summarizes the age, gender, and visualeld mean deviation statistics. There were no group differences in

ography (SD-OCT) examples of optic nerve head delineations. Black dotse clinically visible optic disc margin. A, The Bruch’s membrane openingthe innermost edge of Bruch’s membrane and border tissue (A1 and A2)

border tissue corresponding to the optic disc margin when the innermoste alone corresponding to the optic disc margin.

Glaucoma and Healthy Controls*

Controls P

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Ophthalmology Volume xx, Number x, Month 2011

age or gender distribution; however, the mean deviation wassignificantly worse in patients than in controls.

Overall, the most frequent border tissue configuration wasinternally oblique in patients with glaucoma (Fig 5, available athttp://aaojournal.org). It was the most frequent configuration su-perior temporal to inferior nasal (from the 10 to 5 o’clock posi-tions). In the remaining sectors (from the 6 to 9 o’clock positions),the most frequent border tissue orientation was externally oblique,although not as preponderant as the internally oblique configura-tion in the remaining sectors. In normal controls, the most frequentconfiguration was internally oblique around the whole optic disc(Fig 5, available at http://aaojournal.org), although, as in patientswith glaucoma, it was substantially more frequent temporally toinferior nasally (from the 9 to 5 o’clock positions). The border tissueconfigurations were not statistically different between patients andcontrols (P�0.08, across all clock hours). Nineteen patients (63%)showed all 3 border tissue configurations, 9 patients (30%) showed 2border tissue configurations, and 2 patients (7%) showed the sameconfiguration throughout the disc. The corresponding figures in con-trols were 4 (40%), 2 (20%), and 4 (40%), respectively.

Patients with glaucoma with focal damage had a predominantlyinternally oblique border tissue configuration in the superior andnasal quadrants, and an externally oblique configuration in theinferior and temporal quadrants (Fig 6, available at http://aaojournal.org). Although patients with diffuse damage had a similar pattern ofinternally oblique configuration, there was an almost complete ab-sence of externally oblique border tissue (Fig 6, available at http://aaojournal.org). Patients with sclerotic damage had an internallyoblique configuration around the optic disc except inferiorly (at the 6and 7 o’clock positions; Fig 6, available at http://aaojournal.org).These configurations were statistically different among the glaucomagroups inferior temporally to superior temporally (from the 7 to 10o’clock positions; P � 0.05) but not in the other sectors.

The SD-OCT structure most commonly coinciding with theclinically identified disc margin in patients with glaucoma andcontrols was a location on Bruch’s membrane with border tissuebeneath (Fig 7). This pattern was most obvious inferior temporallyto superior nasally in both patients (from the 8 to 1 o’clockpositions) and controls (from the 8 to 2 o’clock positions). At otherlocations, BMO and, less frequently, border tissue alone corre-sponded to the clinical disc margin (Fig 7). There were no statis-tical differences between patients and controls in the frequency ofSD-OCT structures identified as the disc margin (P�0.10 at all

Figure 7. Polar plots with connected points showing the frequency of specto the optic disc margin by clock hour for all patients with glaucoma (n �each clock hour represents the frequency of each SD-OCT structure analy

clock hours); however, there were statistically significant differ- fi

6

nces among the 3 glaucoma groups inferior temporally to superioremporally (from the 7 to 10 o’clock positions, P�0.05). Theseifferences were due to the focal and sclerotic disc damage groupsaving relatively more cases where the disc margin correspondedo border tissue alone, which was not observed in any eyes withiffuse damage. Within the same disc in 14 patients (47%), all 3D-OCT structures individually corresponded to the disc margin;

n 14 patients (47%), 2 structures corresponded to the disc margin,hereas a single structure only corresponded to the disc margin inpatients (7%). These figures in controls were 4 (40%), 5 (50%),

nd 1 (10%), respectively.There was Bruch’s membrane overhang in the majority of

atients with glaucoma and controls around the optic disc (exceptor the 6 and 7 o’clock positions in patients and 7 o’clock positionn controls; Fig 8). The proportion of patients with Bruch’s mem-rane overhang in whom BMO was identified as the clinical discargin ranged from 5 of 26 (19%) at 12 o’clock to 13 of 24 (54%)

t 3 o’clock (Fig 8). In controls, the respective figures were 0 of 80%) at 9 o’clock to 4 of 5 (80%) at 7 o’clock (Fig 8). Thus, in theajority of patients and controls with Bruch’s membrane over-

ang, it was not clinically visible. These findings were confirmedy clinical examination where in none of the cases was the SD-CT-detected Bruch’s membrane overhang clinically visible. A

linical case illustrating Bruch’s membrane overhang identified byD-OCT but invisible by disc photography is shown in Figure 9.

iscussion

haracterizing the anatomic variations of structures that definehe optic disc margin may more accurately describe the clinicalonstruct we currently recognize as the disc margin. To theest of our knowledge, this is the first published study to useD-OCT ONH data co-localized to clinical photographs to

dentify structures that underlie optic disc margin appearancen patients with glaucoma and normal controls. The patientsere selected to represent the broad appearances of the opticisc observed in patients with glaucoma.

In this study, we found that the obliqueness of borderissue varied according to location in the optic disc, withost patients and controls showing 2 or all 3 of the con-

omain optical coherence tomography (SD-OCT) structure correspondingand healthy control subjects (n � 10). The distance from the origin atclock hour. SD-OCT � spectral domain optical coherence tomography.

tral d30)

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Reis et al � Optic Disc Margin Anatomy in Glaucoma

tion was internally oblique, most often observed in thesuperior and nasal quadrants, frequently accompanied withBruch’s membrane overhang. The externally oblique con-figuration was less common, observed most often in theinferior and temporal quadrants, and infrequently accompa-nied with Bruch’s membrane overhang. The SD-OCT struc-ture identified most frequently as the optic disc margin inthe disc stereophotographs was some aspect of Bruch’smembrane and border tissue. At these locations, the termi-nation of Bruch’s membrane was internal to the bordertissue and not visible as the disc margin. Thus, in most caseswhat the clinician sees as the disc margin is not a discern-able junction or edge of an anatomical structure. The BMOcorresponded to the disc margin in some locations of afewer number of subjects, whereas border tissue alone ac-counted for the disc margin in a minority of eyes. What theclinician identifies as the margin in a single optic disc israrely a single structure; most commonly, 2 or all 3 of theSD-OCT structures corresponded to the disc margin.

The border tissue configurations described by Strouthidiset al13,14 in monkey eyes are similar to the present findings.In both patients and controls, border tissue most frequentlyhad an internally oblique configuration from the superiortemporal to inferior nasal (from the 10 o’clock to 5 o’clockpositions) aspect of the disc. Although not statistically dif-ferent, there was a tendency for the glaucomatous eyes tohave relatively more externally oblique border tissue infero-temporally compared with controls. These distinct bordertissue configurations may correspond with the obliquecourse of RGC axons through the sclera.23,24

The various forms of optic disc damage in glaucoma16–18

indicate differential susceptibility to further progression19

and may be important to recognize clinically. There weresignificant differences in the frequency of border tissueorientation among the 3 types of disc damage (Fig 7).Patients with focal damage had more prevalent externallyoblique border tissue configuration, especially in the infero-temporal sector compared with the other 2 groups. Theinferotemporal sector is the first to present neuroretinal rim

Figure 8. Polar plots with connected points showing the frequency of Br(n � 30) and healthy control subjects (n � 10). The external areas (lighinternal areas (dark grey) show the frequency of Bruch’s membrane openmembrane overhang. The distance from the origin at each clock hour re

loss in glaucoma25 and has been shown to have the highest a

ate of neuroretinal rim deterioration.26,27 Finally, patientsith focal damage appear to have the highest rate of visualeld and optic disc progression than other forms of dam-ge.19 The potential correspondence between a specific bor-er tissue configuration and susceptibility to damage may bemportant to investigate in future research.

Three-dimensional histomorphometric reconstructions inonkey eyes suggest that the SD-OCT–detected termina-

ion of Bruch’s membrane consistently co-localizes to theptic disc margin.14,24 In the present study, the SD-OCT–etected termination of Bruch’s membrane infrequently co-ocalized with the optic disc margin, highlighting importantifferences between monkey and human eyes. In addition topecies difference, these differences may be age-relatedecause the monkeys were relatively young and the humansere relatively old.With automated segmentation of Bruch’s membrane

ith SD-OCT, Hu et al28 concluded that BMO coincidedell with the disc margin. In the present study, Bruch’sembrane/border tissue or border tissue alone coincidedost frequently with the disc margin. Although in some

atients, BMO was coincident with the optic disc margin,ften there was identifiable border tissue underneath (Fig 4,1 and A2), making it difficult to assess whether it was theverlying BMO or border tissue that made the disc marginlinically visible. For practical purposes and maintaininghe terminology proposed by Strouthidis et al,12,13 we clas-ified these eyes as those in which BMO was identified ashe disc margin. The findings of this study strongly suggesthat the goal of automated disc margin segmentation shouldot be to detect the clinically defined disc margin because,t a given clock hour, it may not identify those clinicallynvisible anatomic structures that most accurately define themount of remaining neuroretinal rim tissue.

Our disc margin findings are in agreement with Fantesnd Anderson15 who performed clinical histologic correla-ions in 21 eyes enucleated for choroidal melanomas. Theyuggested that although Bruch’s membrane can overhanghe anterior scleral canal opening, it is not usually visible

membrane (BM) overhang by clock hour for all patients with glaucomashow the frequency of Bruch’s membrane overhang by clock hour. TheMO) identified as the optic disc margin in those subjects with Bruch’sts frequency.

uch’st grey)ing (B

lone or with overlying retinal pigment epithelium. In the

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Ophthalmology Volume xx, Number x, Month 2011

present study, we found that in the majority of patients inwhom Bruch’s membrane overhang was detected by SD-OCT, the clinically visible disc margin was not identified bythe termination of Bruch’s membrane. The ONH complex-ity and inter- and intra-individual variation in the clinicalvisibility of an overhanging Bruch’s membrane in humaneyes may explain the large discordance between the BMOand optic disc margin. The discordance between these 2landmarks may influence the accuracy of clinical neuroreti-

Figure 9. Right eye of a patient with glaucoma in whom the presence ocoherence tomography (SD-OCT) B-scans provides evidence that the SDinvisible by optic disc stereophotography. A, Optic disc photograph regi(broken white lines) showing the clinical disc margin determined with sdetermined with SD-OCT B-scans and co-localized to the disc photographThe line scan x (shown in C) is at a location where BM is intact, and thnot part of the study protocol and were obtained additionally (left to rightin A and B for clarity. BM is continuous in x and y (C and D), indicatinga break in z (E) verifying that the central locations of this scan are inside thmembrane in x and y (C and D) and curves around Bruch’s membrane ovisible in the photograph, it indicates that the temporal region of Bruch’this region is internal to the clinical disc margin and clinically invisibleneuroretinal rim tissue. BM � Bruch’s membrane; Cra � cilioretinal arte

nal rim tissue assessment. An analysis of the effects of a

8

ruch’s membrane visibility on clinical rim assessment iseyond the scope of this study; however, this work is underay and will be the focus of a separate report.Our study has some limitations. The sample was randomly

hosen from a selected cohort of patients with distinct forms oflaucomatous optic disc damage. Although it is likely that weave captured the range of deep ONH characteristics, they maye more heterogeneous in a general glaucomatous population.he delineations performed are laborious and time-consuming,

inically visible cilioretinal artery within vertical spectral domain optical–detected region of Bruch’s membrane (BM) overhang adjacent to it isto B, infrared image. Inset in A, Magnification of the rectangular area

-disc photography (green dots) and Bruch’s membrane opening (BMO)dots). C–E, Equidistant line B-scans (x, y, and z in A and B, respectively).scan z (shown in E) is at a location just inside BM. These B-scans were

sent bottom to top in A and B). The locations of only x and z are shownthe scan locations are outside the neural canal. Bruch’s membrane showsral canal. A cross-section of the cilioretinal artery appears beneath Bruch’sng in z (E). Because the cilioretinal artery beneath Bruch’s membrane isbrane overhang is clinically transparent and invisible. Because BMO inventional clinical examinations overestimate the amount of remaining

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Reis et al � Optic Disc Margin Anatomy in Glaucoma

limiting the possibility of extending the study beyond its de-scriptive nature. We expect that with automated delineations inthe future, larger samples could be analyzed. Finally, althoughthe analysis in this study indicates that SD-OCT–detected, butclinically invisible, extensions of Bruch’s membrane exist (Fig9), SD-OCT with a longer wavelength light source in humansmay capture a fuller extent of the extension that will requireconfirmation histologically. Thus, in the present study, BMOrefers to the SD-OCT–detected, and not necessarily the histo-logic, entity.

In conclusion, the anatomic basis for the human optic discmargin is complex and can be highly variable within individualeyes and between different eyes. We observed structural dif-ferences in tissues associated with the disc margin in patientswith distinct forms of optic disc damage. In addition, what theclinician perceives as the optic disc margin in an individual eyeis rarely a single structure; most frequently it is some aspect ofBruch’s membrane and border tissue and less frequently BMOor border tissue alone. Finally, clinically invisible SD-OCT–detected extensions of Bruch’s membrane beyond the clinicaldisc margin were regionally present in the majority of glauco-matous and normal eyes.

Because the location where Bruch’s membrane termi-nates is potentially the most consistent site from which toquantify the neuroretinal rim, current disc margin–basedclinical and confocal scanning laser tomography examina-tions may overestimate the amount of remaining rim inthose regions in which the full extent of Bruch’s membraneis detected by SD-OCT, but not clinically. Furthermore, asthe clinically visible disc margin seldom appears to repre-sent a single anatomic structure, our findings challenge thelong-standing paradigm of disc margin–based neuroretinalrim tissue assessment.

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Ophthalmology Volume xx, Number x, Month 2011

Footnotes and Financial Disclosures

FfFUtTTIsG

CBS

Originally received: March 24, 2011.Final revision: September 28, 2011.Accepted: September 28, 2011.Available online: ●●●. Manuscript no. 2011-480.1 Department of Ophthalmology and Visual Sciences, Dalhousie Univer-sity, Halifax, Nova Scotia, Canada.2 Department of Ophthalmology, University of Sao Paulo, Sao Paulo,Brazil.3 Devers Eye Institute, Portland, Oregon.

Financial Disclosure(s):The author(s) have made the following disclosure(s): B.C. Chauhan,Heidelberg Engineering (financial support). C.F. Burgoyne, Heidelberg

Engineering (financial support). H

10

inancial Support: Grants MOP11357 (B.C.C.) and MOP200309 (M.T.N.)rom the Canadian Institutes of Health Research, Ottawa, Ontario; Capesoundation, Ministry of Education of Brazil, Brasilia, Brazil (A.S.C.R.);nited States Public Health Service Grants R01EY011610 (C.F.B.) from

he National Eye Institute, National Institutes of Health, Bethesda, MD;he Legacy Good Samaritan Foundation (C.F.B.), Portland, OR; the Searsrust for Biomedical Research (C.F.B.), Mexico, MO; the Alcon Research

nstitute (C.F.B.), Fort Worth, TX; and equipment and unrestricted re-earch support from Heidelberg Engineering (B.C.C., C.F.B.), Heidelberg,ermany.

orrespondence:alwantray C. Chauhan, PhD, Department of Ophthalmology and Visualciences, Dalhousie University, 1276 South Park Street, 2W Victoria,

alifax, Nova Scotia, Canada B3H 2Y9. E-mail: bal@dal.ca.