Assessing Ganglion Cell Layer Topography in Human Albinism Using Optical Coherence Tomography

Abstract

Purpose: To test whether ganglion cell layer (GCL) and inner plexiform layer (IPL) topography is altered in albinism.

Methods: Optical coherence tomography scans were analyzed in 30 participants with albinism and 25 control participants. Horizontal and vertical line scans were acquired at the fovea, then strip registered and averaged. The Duke Optical Coherence Tomography Retinal Analysis Program was used to automatically segment the combined GCL and IPL and total retinal thickness, followed by program-assisted manual segmentation of the boundary between the GCL and IPL. Layer thickness and area under the curve (AUC) were calculated within 2.5 mm of the fovea. Nasal-temporal and superior-inferior asymmetry were calculated as an AUC ratio in each quadrant.

Results: GCL and IPL topography varied between participants. The summed AUC in all quadrants was similar between groups for both the GCL (P = 0.84) and IPL (P = 0.08). Both groups showed nasal-temporal asymmetry in the GCL, but only participants with albinism had nasal-temporal asymmetry in the IPL. Nasal-temporal asymmetry was greater in albinism for both the GCL (P < 0.0001) and the IPL (P = 0.0006). The GCL usually comprised a greater percentage of the combined GCL and IPL in controls than in albinism.

Conclusions: The GCL and IPL have greater structural variability than previously reported. GCL and IPL topography are significantly altered in albinism, which suggests differences in the spatial distribution of retinal ganglion cells. This finding provides insight into foveal development and structure-function relationships in foveal hypoplasia.

Figure 1.

The GCL and IPL can be clearly delimited in processed OCT scans. An example processed image from a participant with albinism, JC_11430 (A), is shown with segmentation contours (B) for the ILM (red), RNFL/GCL boundary (orange), GCL/IPL boundary (yellow), IPL/INL boundary (light blue), and RPE (dark blue). Scale bars = 200 µm.

Figure 2.

Manual GCL segmentation is repeatable. Bland-Altman plots show repeatability of GCL thickness for control participants in the horizontal (A) and vertical (B) directions, as well as for participants with albinism in the horizontal (C) and vertical (D) directions. Each point is a single thickness measurement at a single eccentricity, with 51 measurements per participant per scan. Circles show right eye measurements and crosses show left eye measurements. Solid lines show bias, dashed lines show limits of agreement, and gray boxes show 95% confidence intervals.

Figure 3.

GCL and IPL topography is unique in albinism. GCL and IPL thickness for controls is shown in the horizontal (A) and vertical (B) directions, as well as for participants with albinism in the horizontal (C) and vertical (D) directions. The proportional contribution of the GCL to the combined GCIPL is shown for controls and participants with albinism in the horizontal (E) and vertical (F) directions. Eccentricity directions are labeled temporal (T), nasal (N), inferior (I), or superior (S). Error bars show ± 1 SD.

Figure 4.

GCL and IPL thickness topography varies among control participants. Some participants, such as JC_0878 (A), have GCL thickness that exceeds IPL thickness at the foveal rim in the nasal quadrant (arrow), although this may not be the case in the temporal quadrant. This is present in the inferior quadrant in all but seven control eyes, and in the superior quadrant in all but two control eyes. Other participants, such as JC_10549 (B), show a pronounced lateral separation between the maximum GCL thickness and maximum IPL thickness, particularly in the inferior quadrant (arrowheads). Finally, some participants, such as JC_11350 (C), show much greater maximum GCL thickness relative to maximum IPL thickness that is evident in all quadrants. Eccentricity directions are labeled temporal (T), nasal (N), inferior (I), or superior (S).

Figure 5.

The distribution of GCL and IPL area is unique in albinism. The summed AUC of all four quadrants (temporal, nasal, inferior, and superior) of the GCL and IPL is not different between groups, although the IPL AUC trended toward being greater in albinism (A). Both the GCL and IPL show greater nasal-temporal asymmetry in albinism (B). The GCL shows greater superior-inferior asymmetry in controls, while the IPL is relatively symmetric in the vertical direction in both groups (C).

Figure 6.

The spectrum of GCL and IPL topography among participants with albinism reflects variability in foveal maturity. Participants with less developed foveae, such as AD_11897 (A), show little evidence of a foveal depression. Other participants, such as JC_10508 (B) show a depression in the GCIPL (filled arrowhead) only in the vertical direction, while participants with slightly more developed foveae, such as JC_0492 (C), also show this depression in the TRT (open arrowhead). Participants with the most developed foveae, such as JC_0456 (D), also show depressions in the GCIPL and TRT in the horizontal direction. Scale bars on OCT images = 200 µm.