Improving our understanding, and detection, of glaucomatous damage: An approach based upon optical coherence tomography (OCT)

Abstract

Although ophthalmologists are becoming increasingly reliant upon optical coherence tomography (OCT), clinicians who care for glaucoma patients are not taking full advantage of the potential of this powerful technology. First, we ask, how would one describe the nature of glaucomatous damage if only OCT scans were available? In particular, a schematic model of glaucomatous damage is developed in section 2, and the nature of glaucomatous damage seen on OCT scans described in the context of this model in section 3. In particular, we illustrate that local thinning of the circumpapillary retinal nerve fiber layer (cpRNFL) around the optic disc can vary in location, depth, and/or width, as well as homogeneity of damage. Second, we seek to better understand the relationship between the thinning of the cpRNFL and the various patterns of sensitivity loss seen on visual fields obtained with standard automated perimetry. In sections 4 and 5, we illustrate why one should expect a wide range of visual field patterns, and iilustrate why they should not be placed into discrete categories. Finally, section 6 describes how the clinician can take better advantage of the information in OCT scans. The approach is summarized in a single-page report, which can be generated from a single wide-field scan. The superiority of this approach, as opposed to the typical reliance on summary metrics, is described.

Keywords: Glaucoma; Macula; OCT; Optical coherence tomography; Retinal ganglion cell; Retinal nerve fiber layer; Visual field.

Fig. 1

A schematic model of the macula relating retinal ganglion cell (RGCs) axons locations to circumpapillary retinal nerve fiber (cpRNFL) locations. (A) The borders of the superior (magenta) and inferior (light blue) regions of the macula supplying RNF input to the disc are superimposed on RNFL tracings modified from Fig. 2A in Jansonius et al. (2012), with permission. (B) The cpRNFL thickness plot is shown in the typical temporal (N) to superior (S) to nasal (N) to inferior (I) to temporal (N) orientation. The regions of the cpRNFL associated with macula (±8°) are shown by the magenta and light blue horizontal lines and arrows. (C) Same as (B) but with the cpRNFL thickness plot shown in the NSTIN orientation.

Fig. 2

A schematic model relating RGC axons locations to cpRNFL locations of the temporal half of the disc. (A) The borders of the superior (red) and inferior (blue) regions of the retina supplying RNF input to the temporal half of the disc are superimposed on RNFL tracings modified from Fig. 2A in Jansonius et al. (2012), with permission. (B) The cpRNFL thickness plot is shown in the TSNIT orientation. The regions of the cpRNFL associated with the central retinal region (±15°+nasal step region) are shown by the red and blue horizontal lines and arrows. (C) Same as in panel (B) but the cpRNFL thickness plot shown in the NSTIN orientation.

Fig. 3

A schematic model showing the regions (orange, gray, and green) of the disc most vulnerable to local glaucomatous damage as reported by Hood et al. (2013b). (A) The temporal half of the disc has two vulnerable regions, the superior vulnerability zone (SVZ) and the inferior vulnerability zone (IVZ). The IVZ (green) overlaps the region of the cpRNFL (light blue) associated with the inferior macular retinal region. This region of overlap (black) is the macula vulnerability zone (MVZ). The SVZ (orange) does not overlap the region of the disc (magenta) associated with the superior macular retinal region. (B) The NSTIN cpRNFL thickness plot showing the regions around the disc associated with the temporal half of the disc (red and blue), with the macula (magenta and light blue), and the SVZ (orange), IVZ (green) and MVZ (black) indicated with horizontal lines.

Fig. 4

Retinal ganglion cell plus inner plexiform thickness (RGC+) and glaucomatous damage seen with spectral domain (sd) OCT. (A) The average RGC+ thickness map for 54 healthy controls shown in pseudo-color. (B) The average RGC+ thickness map for 23 patients with moderate glaucoma [i.e., 24-2 visual field mean deviation (MD) worse than −5.5 dB] shown in pseudo-color. (C) A difference map generated by subtracting the RGC+ thickness map for the age-similar controls in panel (A) from the RGC+ thickness map in panel (C). The color indicates the degree of thinning. (D) The schematic model of the macula from Figs. 1 and 3 is superimposed upon the central ±8° of panel C to indicate the relationship of the thinned region in panel C to the region projecting to the MVZ. The circles represent groups of RGCs and the associated black lines bundles of axons. The axon bundles with solid black lines feed into the temporal quadrant, while those with the interrupted black lines project to the SVZ (upper dotted), the MVZ of the IVZ (dashed) and IVZ outside the MVZ (lower dotted). (E) The regions from panel D are shown with the more and less vulnerable regions labelled. Panels A, B and C are modified from (Hood et al., 2012).

Fig. 5

The sdOCT results for an eye with a relatively local, but relatively deep cpRNFL defect. (A) An image from a circumpapillary scan along with the region within the red rectangle showed enlarged to the right. The white arrows point to the defect. (B) The cpRNFL thickness plot (black, magenta, and light blue curve) obtained from the disc cube scan (solid) in panel (C, left panel) and the circle scan (dashed) in panel (A) and shown in NSTIN orientation as in Fig. 1C. (C) The RNFL thickness map from the sdOCT cube scan of the macula (left) and disc (right). (D) The RGC+ thickness map from the sdOCT cube scan of the macula. (E) The RNFL probability maps based upon the thickness maps in panel (C). (F) The RGC+ probability map based upon the thickness maps in panel (D). The black circles in panels (E) and (F) show the borders (±8°) of the macula. The arrows in all panels show the abnormal regions associated with the superior (black) and inferior (red) defects.

Fig. 6

The retinal regions of 3 hypothetical deep cpRNRL defects of the IVZ (A) and SVZ (B). Each region is associated with a 15° segment of the IVZ or SVZ. These regions were approximated from the RNFL tracings of Jansonius et al (2012), shown as the faint tracings.

Fig. 7

The RNFL and RGC+ probability maps predicted by the schematic model for 3 hypothetical IVZ defects that are relatively narrow, but deep. (A) A cpRNFL thickness plot as in Fig. 1C and 2C showing the location of 3 hypothetical defects (black, blue and green regions). (B)(C)(D) The predicted RNFL probability maps for the 3 defects. (E)(F)(G) The predicted RGC+ probability maps for the 3 defects. In panels (B–G), green and red indicate within normal limits and significantly abnormal, respectively, while yellow indicates a thinned RGC+ region that may or may not be obvious on the RGC+ plot as the RGC+ layer outside the macula (black circle) is relatively thin, even when healthy.

Fig. 8

The RNFL and RGC+ probability maps predicted by the schematic model for 3 hypothetical SVZ defects that are relatively narrow, but deep. (A)–(G) Same as corresponding panels in Fig. 7, but for 3 hypothetical SVZ defects.

Fig. 9

The sdOCT results for an eye with a relatively local and relatively shallow cpRNFL defect. (A)–(F) Same as corresponding panels in Fig. 5. The red arrows in all panels show the abnormal regions.

Fig. 10

The sdOCT results for an eye with a relatively wide and relatively deep cpRNFL defect. (A)–(F) Same as corresponding panels in Fig. 5. In panel (A), the arrows point to locations of the defect with little or no RNFL remaining (white) and with some RNFL remaining (yellow). The green horizontal line indicates the extent of the IVZ in panels (A–C). In panel (B), the black arrow indicates the approximate point on the disc corresponding to the midline of the macula.

Fig. 11

The sdOCT and AO-SLO results for an eye with a relatively wide and relatively heterogeneous cpRNFL defect. (A) An image from a circumpapillary scan. (B) The cpRNFL thickness plot (black, magenta, and light blue curve). (C) Enlarged view of the portion of the cpRNFL scan within the red rectangle in panel (A) shown with (upper) and without (lower) the segmentation of the cpRNFL shown. (D) An AO-SLO image. (E) An en-face image of a wide-field scan of this eye with the region within the green rectangle enlarged in the lower right corner. This region corresponds to the region within the AO-SLO image in panel D. The arrows in panels (C–E) correspond to the same locations with largely missing RNFL bundles (white) and with some preservation of RNF bundles (yellow). Panels (D) and (E) are modified from Fig. 4A, B in Hood et al. (2015B).

Fig. 12

The sdOCT results for an eye with widespread cpRNFL damage. (A) An image from a circumpapillary scan. (B) The cpRNFL thickness plot (black, magenta, and light blue curve). (C) The RGC+ probability plot. (D) The RNFL probability plot.

Fig. 13

The schematic model with the location of the VF test points. (A) The schematic model from Fig. 2A with the location of the 24-2 VF test points. The solid black curve represents axons coming from RGCs in the region of one of the 24-2 VF test points, while the dashed black curve represents axons from from RGCs outside the 24-2 VF. (B) The schematic model from Fig. 1A with the location of the 10-2 VF test points. (C) A fundus view with the RGC+ thinning map from Fig. 5C along with the location of the 24-2 VF test points. In all panels, the VF locations are adjusted to account for the displacement of RGCs near the fovea (Hood et al, 2011). Panel C modified from Hood et al. (2013a).

Fig. 14

A comparison of abnormal regions on the VFs and OCT RNFL and RGC+ probability maps for the eye in Fig. 9. (A) 24-2 VF probability maps. (B) 10-2 VF probability maps with an abnormal region enclosed within the black border. (C) The RNFL probability map from Fig. 9E flipped to be in field view and with the 24-2 VF locations from Fig. 13A superimposed. (D) The RGC+ probability map from Fig. 9F flipped to be in field view with the 10-2 VF locations from Fig. 13B superimposed. The 10-2 points within the black border are the same as in panel (B).

Fig. 15

A comparison of abnormal regions on the VFs and OCT RNFL and RGC+ probability maps for the eye in Fig. 19. (A) 24-2 VF total deviation (TD) probability map (left) and TD values (right) with an abnormal region enclosed within the red border. The gray arrow indicates an area of the VF with relatively good TD values. (B) 10-2 VF total deviation (TD) probability map (left) and TD values (right) with an abnormal region enclosed within the black border. (C) The RNFL probability map from Fig. 10E flipped to be in field view and with the 24-2 VF locations from Fig. 13A superimposed. The 24-2 points within the red border are the same as in panel (B). (D) The RGC+ probability map from Fig. 10F flipped to be in field view with the 10-2 VF locations from Fig. 13B superimposed. The 10-2 points within the black border are the same as in panel (B).

Fig. 16

A comparison of abnormal regions on the VFs and OCT RNFL and RGC+ probability maps for the eye in Fig. 5. (A) 24-2 VF probability maps with abnormal regions enclosed within the pink (upper VF) and red (lower VF) borders. (B) 10-2 VF probability maps with an abnormal region enclosed within the gray (upper VF) and black (lower VF) borders. (C) The RNFL probability map from Fig. 5E flipped to be in field view and with the 24-2 VF locations from Fig. 13A superimposed. The 24-2 points within the pink and red borders are the same as in panel (A). (D) The RGC+ probability map from Fig. 5F flipped to be in field view with the 10-2 VF locations from Fig. 13B superimposed. The 10-2 points within the gray and black borders are the same as in panel (B).

Fig. 17

A comparison of abnormal regions on the VFs and OCT RNFL and RGC+ probability maps for an eye with an “atypical” VF pattern. (A) 24-2 VF probability maps with abnormal regions enclosed within the red and black borders. (B) 10-2 VF probability maps with an abnormal region enclosed within the red and black borders. (C) The RNFL probability map in VF view with the 24-2 VF locations from Fig. 13A superimposed. The 24-2 points within the red and black borders are the same as in panel (A). (D) The RGC+ probability in VF view with the 10-2 VF locations from Fig. 13B superimposed. The 10-2 points within the red and black borders are the same as in panel (B).

Fig. 18

A comparison of abnormal regions on the VFs and OCT RNFL and RGC+ probability maps for an eye with nasal step defects. (A) 24-2 VF total deviation probability map with abnormal regions enclosed within the red and black borders. (B) The RNFL probability map in VF view with the 24-2 VF locations from Fig. 13A superimposed. The 24-2 points within the red borders are the same as in panel (A). (C) The circumpapillary scan for this eye with the corresponding abnormal cpRNFL region (yellow arrow) between the dashed red vertical lines. (D) The cpRNFL thickness plot for this eye. The abnormal region is between the dashed red vertical lines. (E) The model with 24-2 points from Fig. 13A with the regions of abnormal points from panel (A) enclosed within the black and red borders. The dashed bold blue line shows the location of the raphe in this eye.

Fig. 19

The sdOCT results for an eye with widespread cpRNFL damage. (A) An image from a circumpapillary scan. (B) The cpRNFL thickness plot (black, magenta, and light blue curve). The SVZ is shown as the green line. (C) The 24-2 VF total deviation (TD) probability map (left) and TD values (right) with the inferior abnormal region enclosed within the red border. (D)) The 10-2 VF total deviation (TD) probability map (left) and TD values (right) with the inferior abnormal region enclosed within the black border. The corresponding regions of the cpRNFL are indicated by the red and black lines with arrows in panels A and B. (E) An en-face slab image of the 9×12mm scan. (F) An en-face slab image of a 3×3mm scan of disc. (G) AO-SLO image. The yellow and white arrows are approximately the same locations in panels (E), (F), and (G). Modified from Fig. 6A, B in Hood et al. (2015B).

Fig. 20

A one-page OCT report for the eye in Fig. 5. (A) An image from a circumpapillary scan. (B) The cpRNFL thickness plot (black) obtained from the disc cube scan (solid) in panel (C, left panel) and the circle scan (dashed) in panel (A) and shown in NSTIN orientation as in Fig. 1C. (C) The RNFL thickness map from the sdOCT cube scan of the macula (left) and disc (right). (D) The RGC+ thickness map from the sdOCT cube scan of the macula. (E) The RNFL probability maps based upon the thickness maps in panel (C) shown in VF view with the 24-2 VF locations from Fig. 13A superimposed. (F) The RGC+ probability map based upon the thickness maps in panel (D) with the 10-2 VF locations from Fig. 13B superimposed. The black circles in panels (E) and (F) show the borders (±8°) of the macula and, the color bar to the right shows the probability for both the OCT thickness. Designed by Hood and Raza (2014).

Fig. 21

A one-page OCT report for the eye in Fig. 20 without VF probabilities.

Fig. 22

A one-page commercial report for the eye in Fig. 5 based upon a single wide-field (9×12mm) swept-source OCT cube scan [9.30beta (Atlantis) and v1.16beta (IMAGEnet6), Topcon Inc, Tokyo, Japan]. (A) An image derived from the wide-field scan. (B) The cpRNFL thickness plot (black) obtained from the disc cube scan and shown in NSTIN orientation as in Fig. 1C. (C) The RNFL thickness map from the sdOCT cube scan of the macula (left) and disc (right). (D) The RGC+ thickness map from the wide-field cube scan. (E) The RNFL probability maps based upon the thickness maps in panel (C) shown in VF view with the 24-2 and 10-2 VF locations from Fig. 13A.B superimposed. (F) The RGC+ probability map based upon the thickness maps in panel (D) with the 10-2 VF locations from Fig. 13B superimposed. The circles in panels (E) and (F) show the borders (±8°) of the macula and, the color bar to the right indicates the probability for the OCT thickness. G. An en-face slab image as described in Hood et al (2015b). (H) Pie charts showing the thickness values and probabilities for quadrants (top) and clock hours (bottom). Green, yellow and red indicate within normal limits, p≤0.05 and p≤0.01. See Hood et al (2016).

Fig. 23

An eye with local damage of the RNFL and RGC+ layer due to a vitelliform macular detachment (VMD). (A)–(H) as in Fig. 22. (J) The b-scan (right) along the green line on the en-face image in panel I. The red arrow shows the same location in panels (C, D, G, I and J).