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. Author manuscript; available in PMC: 2019 Jun 1.
Published in final edited form as: Acta Ophthalmol. 2018 Jun;96(4):e493–e502. doi: 10.1111/aos.13657

Protruded Retinal Layers Within the Optic Nerve Head Neuroretinal Rim

Lucas A Torres 1, Jayme R Vianna 1, Faisal Jarrar 1, Glen P Sharpe 1, Makoto Araie 2, Joseph Caprioli 3, Shaban Demirel 4, Christopher A Girkin 5, Masanori Hangai 6, Aiko Iwase 7, Jeffrey M Liebmann 8,*, Christian Y Mardin 9, Toru Nakazawa 10, Harry A Quigley 11, Alexander F Scheuerle 12, Kazuhisa Sugiyama 13, Hidenobu Tanihara 14, Goji Tomita 15, Yasuo Yanagi 16,*, Claude F Burgoyne 4, Balwantray C Chauhan 1
PMCID: PMC6093290  NIHMSID: NIHMS919068  PMID: 30105788

Abstract

Purpose

To determine the frequency with which retinal tissues other than the nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a component of optical coherence tomography (OCT) neuroretinal rim measurements.

Methods

Ninety healthy (30 White, Black and Japanese, respectively) subjects were included in the study. A radial scan pattern (24 B-scans centred on Bruch’s membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW) measurement points, we determined whether PRL were present, absent or indeterminate. When present, the proportion of PRL within the MRW was quantified.

Results

PRL were present in 503 (11.6%), absent in 3805 (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%) subjects had ≥1 points with PRL, with White subjects having the highest frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; P < 0.01). PRL were present in one-third of points in the temporal sector, but ≤ 5% in other sectors. When present, the median PRL thickness was 53.0 (interquartile range [IQR]: 33.0 to 78.5) μm, representing 20.6 (IQR: 13.0 to 28.5)% of MRW. Globally, the median PRL thickness comprised 1.3 (IQR: 0.2 to 3.5)% of the MRW, however, in the temporal sector, it exceeded 30% of MRW in some subjects.

Conclusions

PRL are a component of MRW measurements in most normal subjects, occurring in almost 12% of all measurement points analyzed. There were racial variations in the presence of PRL and a significantly higher frequency of PRL in the temporal sector.

Introduction

Advances in optical coherence tomography (OCT) have allowed a detailed appraisal of optic nerve head anatomy, leading to new concepts for the acquisition, analysis and interpretation of OCT data. For example, OCT has revealed that the clinically visible optic disc margin is not a consistent anatomical structure from which the neuroretinal rim can be assessed (Chauhan & Burgoyne 2013, Reis et al. 2012, Strouthidis et al. 2009). Many investigators have now proposed that Bruch’s membrane opening (BMO), which is readily identified with OCT, but not always with funduscopic examination, is a consistent outer border of the rim that should be used as a reference point for its measurement (Reis et al. 2012, Strouthidis et al. 2009, Strouthidis et al. 2009). Furthermore, unlike classical rim measurements, which are made in the fixed plane of the disc margin, newer research supports measurement of the minimum width from BMO to the internal limiting membrane. This parameter is termed minimum rim width (MRW), and allows the direction, or MRW vector, to vary according to the orientation of the rim tissue (Chen 2009, Gardiner et al. 2014, Povazay et al. 2007, Reis et al. 2012, Strouthidis et al. 2011). These new principles have led to increased diagnostic accuracy for glaucoma (Chauhan et al. 2013) and a better alignment of these structural parameters to visual field findings (Danthurebandara et al. 2014, Pollet-Villard et al. 2014).

In addition to axons of retinal ganglion cells, the neuroretinal rim contains other elements, such as blood vessels and glial tissue (Varela & Hernandez 1997, Wang et al. 2002), likely contributing to the sub-optimal relationship between rim measurements and the visual field, or even retinal nerve fibre layer (RNFL) thickness. While this sub-optimal relationship is perceived to problematic, it is also reasonable to propose that identifying the non-axonal components of the rim may improve our understanding of their behaviour in glaucoma.

Fortune and colleagues (Fortune et al. 2016) recently reported in monkeys that MRW measurements could contain not just the RNFL, but portions of the outer and middle retinal layers. Indeed, they argued that the presence of these ‘protruded’ retinal layers in the rim measurement could be another reason why the observed correlation between MRW and actual axonal counts in monkey was not as strong as the correlation between RNFL thickness and axon counts.

To determine the potential importance of protruded retinal layers (PRL) in humans, we performed this study to assess their frequency and magnitude within the MRW of healthy subjects. As previous studies with OCT showed variation in optic nerve head (ONH) anatomy, for example in cup-disc ratio (Knight et al. 2012), optic disc area (Girkin et al. 2011, Knight et al. 2012), and laminar depth (Rhodes et al. 2014), according to different races, we report data in White, Black and Japanese normal subjects. We also investigated whether orientation of the border tissue of Elschnig (Anderson & Hoyt 1969) had an influence on the presence and extent of PRL in MRW measurements.

Methods

Participants

Data were acquired from a larger series of multi-centre studies characterising the ONH, RNFL and macula in normal subjects. The subjects in this report comprised a sub-sample of 30 individuals each in three groups that self-identified as White, Black or Japanese. Each participating institution received approval from its Ethics Review Board. In accordance with the Declaration of Helsinki, all participants provided informed consent.

Subjects were included if all the following criteria were met: (1) normal eye examination without vitreoretinal or choroidal disease or prior intraocular surgery (except cataract or refractive surgery), (2) intraocular pressure of 21 mmHg or less, (3) best-corrected visual acuity of 20/40 or better, (4) refractive spherical error within 6 diopter (D) and cylinder error within 2D, and (5) normal visual field, defined by a normal glaucoma hemifield test and mean deviation within normal limits. Subjects were excluded if either of the following were found: (1) unreliable visual field examination results based on the reliability indices and the perimetrist’s notes, or (2) OCT images of insufficient quality (truncated B-scans where the internal limiting membrane could not be segmented and/or image quality score < 20). When both eyes were eligible, only one randomly selected eye was used for the analysis.

The 30 subjects per race group were determined as follows. We first computed the maximum number of subjects that would allow the same sample size for each race in each of the 6 decade groups. To maintain the same number of subjects per decade group and race, the sample size was dictated by the minimum number of subjects in each decade group, which in this case was 5 (among those aged 70–80 years). We then randomly selected 5 subjects per race in each of the other decade groups.

OCT Imaging

The ONH was imaged with OCT (Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany) with software version VV (Heyex, Heidelberg Engineering). The scan pattern consisted of 24 radially equidistant B-scans, each subtending 15°, and was aligned and acquired according to the subject’s own fovea-to-BMO centre axis (Chauhan et al. 2015). Each B-scan contained 768 A-scans and was derived from an average of 25 individual scans. Each B-scan contained 2 BMO points (180° apart), hence there were 2 MRW measurements per scan and 48 per eye. At each measurement point, the MRW angle represented the angle between the MRW plane of measurement and the BMO reference line, which connects the two BMO points of each scan.

Image segmentation

At each MRW measurement point, PRL, defined as any retinal layer besides the RNFL included within the MRW based on layer contrast in unenhanced B-scans (Fig. 1), were classified as being present, absent or indeterminate. The latter category occurred typically when there were shadows cast by overlying blood vessels at the point of measurement or when it was uncertain whether outer retinal layers were or were not within the MRW. When PRL were present, their width was measured with the calliper tool of the software along the MRW vector (Fig. 1).

Figure 1.

Figure 1

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Protruded retinal layers (PRL) in the neuroretinal rim in two radial B-scans (top and bottom) obtained with optical coherence tomography of the optic nerve head and peripapillary retina. In both images, PRL were present at the temporal measurement point but absent at the nasal point (insets). Bottom image shows PRL thickness (black bar with caps) as a proportion of the minimum rim width (MRW, blue arrow, inset). In this case, the PRL thickness (102 μm) corresponds to 44% of the measured MRW. Red lines show the internal limiting membrane and red dots show Bruch’s membrane opening.

Border tissue obliqueness (Reis et al. 2012, Strouthidis et al. 2009, Strouthidis et al. 2009) was measured for each of the two measurement points within each B-scan. A straight line that best approximated the border tissue and scleral canal was drawn first, starting at BMO. Next, a reference line connecting the two BMO points was determined. The angle between the border tissue plane and the BMO reference line was defined as border tissue angle (Vianna et al. 2016), with internally oblique border tissue (Reis et al. 2012, Strouthidis et al. 2009, Strouthidis et al. 2009) configurations having an angle greater than 90° and externally oblique (Reis et al. 2012, Strouthidis et al. 2009, Strouthidis et al. 2009) configurations having an angle less than 90° (Fig. 2). The orientation of the MRW vector relative to the BMO reference plane was also computed at each MRW measurement point and defined as MRW angle, with MRW angle increasing as the MRW vector was oriented further from BMO centre (Fig. 3).

Figure 2.

Figure 2

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Border tissue angle segmentation in B-scans of two optic nerve head radial B-scans subjects (left and right images, respectively). Top images: unmarked images. Middle images: from each Bruch’s membrane opening (BMO) point (red dots), the border tissue is traced with a straight line (yellow line). Bottom images: the border tissue angle at each measurement point is calculated with relative to the BMO reference plane (red dotted line). The B-scan of one subject (left images) has one point with an externally oblique angle (52°) and another with an internally oblique angle (136°). The other subject (right images) has internally oblique angles at both measurement points (153° and 125°).

Figure 3.

Figure 3

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Minimum rim width (MRW) vector orientation in each of the 2 measurement points in a B-scan. The MRW angles are measured from the Bruch’s membrane opening (red dots) reference plane (dotted red line).

Image segmentation for the first 12 (13%) subjects was performed together by 3 examiners (LT, FJ and BCC) to discuss and ensure agreement on how to judge and segment the images. Thereafter, a single examiner (FJ) segmented the images for all remaining 78 (87%) subjects. All image segmentations were then reviewed by two examiners (LT and FJ) and corrected when necessary.

Reproducibility of image segmentations

The intra-individual agreement for assessing the presence and extent of PRL as well as in the assessment of border tissue angle was determined for one observer (FJ), who segmented most of the images. OCT images were obtained in the same manner as described above for an independent group of 15 White healthy subjects, which were used to perform the reproducibility analysis. The examiner segmented the OCT images twice, on different days.

Statistical analysis

Data were summarised with median and interquartile range (IQR) values. Comparisons of continuous variables among the three races were performed with the Kruskal-Wallis test, while the comparisons of categorical values utilized the chi-squared test. Kappa statistics were used for the reproducibility study.

The number of MRW measurement points with PRL was calculated globally and in each of 6 ONH sectors as described previously (Garway-Heath et al. 2000). From the 48 points evaluated in each subject, 15 were located in the nasal sector, 13 in the temporal and 5 in each of the others sectors (supero-nasal, supero-temporal, infero-nasal and infero-temporal).

For each measurement point in which PRL were present, an adjusted MRW was calculated by subtracting the PRL thickness from the total or unadjusted MRW. The global unadjusted and adjusted MRW were calculated as averages for each subject. For this calculation, measurement points where the presence of PRL was classified as absent or indeterminate were given a PRL thickness value of 0.0 μm.

Linear regression was used to estimate the correlation between BMO area and the number of MRW measurement points with PRL per eye. The influence of border tissue angle at each point on the presence of PRL was evaluated with a mixed-effects logistic model. Mixed effect models were used to account for the correlation between multiple observations (i.e., measurement points) from each subject. Data analysis was performed with the open-source software R (version 3.3.1), and package lmer4 (version 1.1–12).

Results

Key characteristics of the study subjects are shown in Table 1. There were some differences among the groups: Black subjects were the most myopic; Japanese subjects had the largest BMO area and the thinnest global unadjusted MRW (all P < 0.01).

Table 1.

Summary of subject characteristics*

All White Black Japanese P
Age (years) 49.5
(36.6 to 63.5)		 49.5
(36.6 to 62.6)		 49.3
(36.6 to 63.5)		 49.9
(35.3 to 64.2)		 0.42
Refraction (D) 0.0
(−1.2 to 0.6)		 0.1
(−0.5 to 0.6)		 −0.6
(−1.5 to 0.0)		 −0.1
(−1.0 to 1.1)		 <0.01
BMO area (mm1) 1.9
(1.6 to 2.2)		 1.9
(1.5 to 2.1)		 1.8
(1.5 to 2.1)		 2.1
(1.9 to 2.4)		 <0.01
Global unadjusted
MRW (μm)		 320.0
(282.3 to 356.5)		 337.4
(302.1 to 382.9)		 325.1
(300.6 to 356.5)		 288.6
(262.1 to 329.2)		 <0.01
Global adjusted
MRW (μm)		 310.7
(276.4 – 350.5)		 330.0
(287.1 – 365.8)		 317.1
(291.7 – 355.6)		 287.6
(261.8 – 328.8)		 <0.01
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*

Median and interquartile range

BMO = Bruch’s membrane opening

MRW = Minimum rim width

In the reproducibility study, the kappa statistic for intra-individual agreement for categorising the presence or absence of PRL was 0.82, classified as ‘almost perfect’ according to Landis and Koch (Landis & Koch 1977). The median difference between the two evaluations of PRL thickness was 0 (IQR: −12 to 4.5) μm, while the corresponding figure for border tissue angle was 0.1 (IQR: −5.8 to 5.0) °.

With 24 B-scans (48 MRW measurement points) per subject, there were a total of 4320 points analyzed. PRL were present in 503 (11.6%) points, absent in 3805 (88.1%) and labeled as indeterminate in 12 (0.3%) points. Overall, 69 (76.6%) subjects had ≥1 points with PRL within MRW (Table 2): the frequency was highest in White subjects (29 [97%]), then Black subjects (22 [73%]) and lowest in Japanese subjects (18 [60%]). The temporal sector had the highest number of MRW measurement points with PRL: 391 (33.4%) of 1170 points; while the frequencies in the other sectors were: 13 (2.8%) of 450 points in the infero-temporal sector, 23 (5.1%) of 450 in the supero-temporal sector, 64 (4.7%) of 1350 in the nasal sector, 6 (1.3%) of 450 in the infero-nasal sector and 6 (1.3%) out of 450 in the supero-nasal sector (Fig. 4).

Table 2.

Frequency of protruded retinal layers

All White Black Japanese P
Subjects with PRL 69
(76.6%)		 29
(96.6%)		 22
(73.3%)		 18
(60.0%)		 <0.01
Total number of positions with PRL 503
(11.6%)		 218
(15.1%)		 181
(12.6%)		 104
(7.2%)		 <0.01
Percentage of positions with PRL per subject* 10.4%
(2.1 to 18.8%)		 12.5%
(8.3 to 23.0%)		 10.4%
(0.5 to 18.8%)		 2.1%
(2.1 to 10.4%)		 <0.01
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*

Median and interquartile range

PRL = protruded retinal layers

Figure 4.

Figure 4

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Polar plot (in right eye format) showing the frequency of protruded retinal layers (PRL) in each of the 48 optic nerve head neuroretinal rim measurement points evaluated. The black dotted lines separate the 6 sectors. T = Temporal, ST = supero-temporal, SN = supero-nasal, N = nasal, IN = infero-nasal, IT = infero-temporal.

For the measurement points in which PRL were present, the median PRL thickness and PRL thickness, relative to unadjusted MRW, was 53.0 (IQR: 33.0 to 78.5) μm and 20.6 (IQR: 13.0 to 28.5)%, respectively (Fig. 5). The global and sectoral distributions of PRL thickness and the PRL thickness relative to unadjusted MRW are shown in Figure 6. Globally, the median PRL thickness was 4.1 (IQR: 0.5 to 10.3) μm, comprising 1.3 (IQR: 0.2 to 3.5)% of the unadjusted MRW. The temporal sector had the largest median PRL thickness with a median of 13.0 (IQR: 0.0 to 30.1) μm, comprising 5.5 (IQR: 0.0 to 13.7)% of the unadjusted MRW. In the other sectors, the median PRL thickness was 0.0 μm (Fig. 6).

Figure 5.

Figure 5

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Histograms showing the distribution of protruded retinal layers (PRL) thickness (left plot) and PRL thickness relative to the unadjusted minimum rim width (MRW, right plot) in those measurement points where PRL were present. The median values of PRL thickness and PRL thickness relative to the unadjusted MRW are 53.0 μm and 20.6%, respectively.

Figure 6.

Figure 6

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Box plots showing the global and sectoral distribution of the protruded retinal layers (PRL) thickness (left plot) and the PRL thickness proportion relative to the MRW (computed PRL thickness/unadjusted MRW, right plot). The data points above or below the box plots represent values outside the interquartile range. MRW = minimum rim width, G = global, T = temporal, ST = supero-temporal, SN = supero-nasal, N = nasal, IN = infero-nasal, IT = infero-temporal.

The median MRW angle nasally was close to 90°, indicating a close to vertical MRW vector compared to temporally, superiorly or inferiorly, which had a more horizontal MRW vector towards to the BMO centre (Figs. 3 and 7). In measurement points with PRL, the corresponding MRW angle was generally greater than the median for all points, indicating a MRW vector more external to the BMO centre (Fig. 7).

Figure 7.

Figure 7

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Minimum rim width (MRW) angle distribution. Median and interquartile ranges of all measurement points in all subjects are represented by bold lines and gray shading, respectively. MRW angle in points with protruded retinal layers (PRL, blue dots). A median of 66.7 (interquartile range: 49.5 to 100.0)% of the blue dots were above the bold line, indicating that the MRW angles for the points with PRL are generally greater than the MRW angles in all points. T = temporal, ST = supero-temporal, SN = supero-nasal, N = nasal, IN = infero-nasal, IT = infero-temporal.

The lowest values of border tissue angle, indicating more externally oblique border tissue configuration, occurred in the temporal and infero-temporal sectors, while the highest values, indicating more internally oblique border tissue configuration, occurred more frequently in the nasal and supero-nasal sectors (Fig. 8). There was a negative association between the proportion of measurement points with PRL and border tissue angle (odds ratio for frequency of PRL = 0.84 (CI: 0.82 - 0.87) for each 10° of increase in border tissue angle, P < 0.01; Fig. 9) indicating that there was a lesser likelihood of PRL with increasingly internally oblique border tissue angle. The proportion of MRW measurement points with PRL was particularly high in extreme externally oblique border tissue configurations (angles ≤ 30°). There was a poor relationship between BMO area and the number of measurement points with PRL (adjusted R2 = 0.00, P = 0.68; Fig. 10).

Figure 8.

Figure 8

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Border tissue angle distribution in the optic nerve head. Median and interquartile ranges are represented by the bold line and gray shading, respectively. The dashed horizontal line separates border tissue angles corresponding to internally oblique configuration (> 90°) and externally oblique configuration (< 90°). T = temporal, ST = supero-temporal, SN = supero-nasal, N = nasal, IN = infero-nasal, IT = infero-temporal.

Figure 9.

Figure 9

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Scatterplot showing the influence of each 10° change in border tissue angle on the frequency of protruded retinal layers (PRL). The red line, generated by a logistic mixed effect model, represents the predicted relationship. The dashed vertical line separates border tissue angles corresponding to internally oblique configuration (> 90°) and externally oblique configuration (< 90°).

Figure 10.

Figure 10

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Scatterplot showing the association between Bruch’s membrane opening (BMO) area and the number of measurement points with protruded retinal layers (PRL).

Discussion

Fortune et al (Fortune et al. 2016) previously identified PRL in OCT images of monkey ONHs and speculated that the PRL could be one of the reasons for the weaker correlation between rim parameters and axons counts compared to that between peripapillary RNFL thickness and axons counts. In the present study we assessed the frequency with which PRL were detected within the neuroretinal rim and the impact they had on MRW measurements in a multiracial sample of healthy subjects. PRL were identified in at least one B-scan in 69 (76.6%) subjects and in 503 (11.6%) MRW measurement points examined, over one-third of which were in the temporal sector. When present, the median PRL thickness in the temporal sector was 53 μm, corresponding to 20.6% of the unadjusted MRW. In the temporal sector, the PRL thickness made up 5.5% of the unadjusted MRW, however, in some subjects this proportion exceeded 30% (Fig. 6). Globally, PRL accounted for 1.3% of the MRW and in no subject did it exceed 10%.

Although OCT is now a well-established tool to help clinicians assess structural glaucomatous damage with objective measurements of the ONH rim, peripapillary RNFL and the macular ganglion cell layer, there are potential limitations of these parameters and questions regarding what precisely they measure. If the goal of these parameters is to relate to retinal ganglion cell function, then they should specifically provide an estimate of functional ganglion cell components, and not include non-neural components such as blood vessels, connective or glial tissue. Current technology does not allow subtraction of all non-neural components from the width, area or volume measurements currently in use, however, attempts to account for blood vessels, suggested by some authors (Knighton et al. 2012, Patel et al. 2014, Ye et al. 2016) to adjust rim measurements for the PRL could help in this regard. However, it is important to recognize that also glaucoma affects non-neural tissues also (Yang et al. 2015, Yang et al. 2017, Yang et al. 2011) and that while the inclusion of these components may result in a less than perfect alignment with functional loss, it does not mean that diagnostic accuracy for glaucoma is adversely affected.

In addition to documenting the frequency of PRL and its magnitude within the neuroretinal rim, we also addressed factors related to the presence of PRL. Although our study was limited by a relatively small sample size, we found a consistent difference in PRL frequency among races, with the Japanese having the lowest frequency. Racial differences among structural measurements have already been shown in parameters of the ONH, for example, in the cup-disc ratio (Knight et al. 2012), optic disc area (Girkin et al. 2011, Knight et al. 2012), laminar depth (Rhodes et al. 2014) and BMO area (Rhodes et al. 2015, Rhodes et al. 2017). The clinical relevance of these inter-racial differences in ONH parameters are still not clear (Knight et al. 2012, Rao et al. 2010, Zelefsky et al. 2006). Although race-specific normative databases may be an alternative to deal with these differences (Zelefsky et al. 2006), the large within-race variability of these parameters indicates there would be little benefit of accounting for race in diagnostic tests for glaucoma (Rhodes et al. 2017). The MRW adjustment for PRL thickness would lead to a smaller inter-racial difference of MRW, as White and Black subjects, who had thicker MRW, also had a higher frequency of PRL compared to Japanese subjects, in whom the BMO area was largest. Therefore, even if future studies demonstrated that adjusting MRW for PRL thickness is clinically beneficial, it will be unlikely that specific normative databases for each race would be necessary.

We observed that PRL were more frequently found in the temporal sector, where there also was a higher likelihood of the border tissues having an externally oblique configuration. In our study we assumed that the border tissues and the anterior scleral canal were continuous to define neural canal obliqueness, however, this assumption may not be valid, as we did not separately segment these two structures. Nonetheless how border tissue or neural canal obliqueness could influence the presence of PRL is not clear. We also showed that the presence of PRL was related to the orientation of MRW: most points with PRL had a MRW vector that was oriented further from the BMO centre than the corresponding one for the entire population. However, it is interesting to note that although nasal points had a higher median MRW angle compared to temporal points (indicating that MRW was oriented more externally relative to the BMO centre), it was rare to observe PRL nasally compared to temporally where PRL were more frequently present. This observation suggests that the retinal layers protruding within the rim might be closer to BMO temporally compared to nasally. The higher density of photoreceptors (Curcio et al. 1990) and retinal ganglion cells (Curcio & Allen 1990) temporal to the ONH and the centrifugal displacement of the inner retinal layers at the fovea (Springer & Hendrickson 2004, Springer & Hendrickson 2004, Springer & Hendrickson 2005) support our findings, though we did not measure the proximity of the retinal layers to BMO.

Because our study included only healthy subjects, we cannot yet speculate on the clinical implications of our findings. How glaucoma disease severity influences the presence of PRL and the clinical implications of these findings require additional studies, now in progress, that are beyond the scope of this report. The differences in the frequency, magnitude and especially sectoral variation in the presence of PRL among healthy subjects may suggest that adjusting MRW for PRL thickness could impact diagnostic accuracy.

There is considerable controversy in the literature as to whether retinal layers distal to the inner plexiform layer are affected in glaucoma. Histological studies in both experimental monkey glaucoma and human glaucoma eyes indicate either modest (Fan et al. 2011, Lei et al. 2008, Werner et al. 2011, Wygnanski et al. 1995) or no (Hasegawa et al. 2016, Ishikawa et al. 2005, Kendell et al. 1995, Kotowski et al. 2012) photoreceptor layer loss. Retinal ganglion cells have their somas in the ganglion cell layer, their axons in the RNFL and their dendrites in the inner plexiform layer. Thus it is expected that in addition to the RNFL loss, there is thinning of the ganglion cell layer (Ishikawa et al. 2005, Na et al. 2012, Tan et al. 2008, Wilsey et al. 2016), and the inner plexiform layer (Wilsey et al. 2016) in glaucoma that is readily detectable with OCT. We did not perform manual segmentation of each retinal layer (except the RNFL) within the PRL and therefore cannot speculate whether, in single examinations, potential damage to the other retinal layers in glaucoma could impact diagnostic accuracy of MRW. If there were no progressive loss of the outer retina in glaucoma, the presence of PRL would not be expected to impact the value of MRW for monitoring serial changes in the neuroretinal rim. In a possible scenario of progressive PRL thinning, the rate of MRW change would be amplified by the inclusion of PRL in the MRW measurements.

In the present study, one-third of the MRW measurement points in the temporal sector had PRL. This finding may be one of several reasons to explain why the temporal sector has the weakest diagnostic accuracy for glaucoma compared to other sectors (Chauhan et al. 2013). Development of automated algorithms to segment the RNFL only within the rim may be necessary and have clinical benefit if future studies were to demonstrate improved diagnostic accuracy of adjusted MRW measurements.

In summary, we demonstrated that most normal subjects had at least one MRW measurement point within radial ONH scans in which retinal layers in addition to the RNFL are included in the measurement of MRW. These PRL were measured as part of the MRW in almost 12% of the total number of measurement points. The clinical relevance of these findings and whether PRL have any impact on the diagnosis and follow-up of glaucoma remain to be determined.

Acknowledgments

Funding/Support: Dalhousie Medical Research Foundation, Halifax, NS, Canada (BCC), National Eye Institute, National Institutes of Health, Bethesda MD (grant no. EY021281, CFB), Center for Disease Control, Atlanta, GA (CAG), Heidelberg Engineering, Heidelberg, Germany (JC, SD, CAG, MH, AI, JML, CYM, TN, HAQ, AFS, KS, HT, GT, YY, CFB, BCC)

Financial disclosures: Commercial Relationships: Heidelberg Engineering, MA, JC, SD, CAG, MH, AI, JML, CYM, TN, HAQ, AFS, KS, HT, GT, YY, CFB, BCC (F)

Footnotes

DR. LUCAS A. TORRES (Orcid ID : 0000-0003-4136-7362)

DR. TORU NAKAZAWA (Orcid ID : 0000-0002-5591-4155)

DR. BALWANTRAY CHAUHAN (Orcid ID : 0000-0002-7936-6907)

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