Effect of Subthreshold Nanosecond Laser on Loss of OCT Outer Retinal Bands in Age-Related Macular Degeneration: A LEAD Study Report

Abstract

Purpose: To evaluate the effect of subthreshold nanosecond laser (SNL) treatment on the rate of loss of the OCT outer retinal bands in intermediate age-related macular degeneration (AMD).

Design: Post hoc analysis of the Laser Intervention in the Early Stages of AMD (LEAD) study.

Participants: A subset of 285 of 292 individuals in the LEAD study with bilateral large drusen without signs of multimodal imaging-defined late AMD at baseline, seen at 1 follow-up visit where neovascular AMD (nAMD) was absent.

Methods: Participants were randomized to receive SNL or sham treatment in 1 study eye at 6-monthly intervals and were reviewed for up to 36 months. OCT scans from all visits without nAMD were automatically segmented to examine between-group differences in the rate of change in external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE) loss in the entire central 5-mm diameter region, or only nondrusen areas in this region.

Main outcome measures: Between-group differences in the rate of ELM, EZ, and RPE loss.

Results: Overall, there was no significant between-group difference in the rate of change in the loss of all OCT outer retinal band parameters (P ≥ 0.206). However, there was evidence of significant treatment effect modification based on the coexistence of reticular pseudodrusen (RPD) in the study eye when evaluating the rate of RPE loss in the entire central 5-mm diameter region, and for the rate of ELM, EZ, and RPE loss when considering only nondrusen areas in this region (P ≤ 0.006). In eyes without coexistent RPD, there was a significant slowing of the loss of all OCT outer retinal band parameters with SNL treatment (P ≤ 0.038 for all), whereas there was no significant between-group difference in all parameters in eyes with coexistent RPD (P ≥ 0.153 for all).

Conclusions: Subthreshold nanosecond laser treatment slowed the progressive loss of the OCT outer retinal bands in intermediate AMD in eyes without coexistent RPD. This study also showed for the first time the responsiveness of these novel outcome measures to treatment.

Financial disclosure: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Age-related macular degeneration; Drusen; Ellipsoid zone; Geographic atrophy; Subthreshold nanosecond laser.

Figure 1

Two examples – (A) and (B) – of the external limiting membrane (ELM), ellipsoid zone (EZ), retinal pigment epithelium (RPE), and drusen thickness maps (top row) derived from using the retinal layer segmentation model on the OCT volume scans. Regions of ELM, EZ, or RPE loss (based on A-scans where the thickness was ≤5 μm) in nondrusen and drusen areas are shown as white and gray regions, respectively (as indicated in the legend, shown on the top right). This study evaluated the total area of loss of these OCT outer retinal bands in the entire central 5-mm diameter region (including both drusen and nondrusen areas), or in only nondrusen areas in this region. Two selected OCT B-scans taken through the locations indicated by the black triangles (#1 corresponding to the OCT scan in the middle row, and #2 corresponding to the OCT scan in the bottom row) are shown, with the layer segmentation lines overlaid. The legend of the 8 layers and 4 pathological features that could be segmented is shown on the right (RNFL = retinal nerve fiber layer; GCL+IPL = ganglion cell layer and inner plexiform layer; INL+OPL = inner nuclear layer and outer plexiform layer; MZ = myoid zone; EZ+OPR+IZ = EZ, outer photoreceptor segment, and interdigitation zone; CC+CS = choriocapillaris and choroidal stroma; AM = amorphous material; IRF = intraretinal fluid; SRF = subretinal fluid; PED = pigment epithelial detachment. Note that the MZ and EZ+OPR+IZ layers were referred to as the layers where the ELM and EZ bands were present in this study). The color of the segmentation lines overlaid on each OCT B-scan corresponds to the upper boundary of the 8 retinal layers shown in the legend on the right, with the exception of the CC+CS where the segmentation lines of both the upper and lower boundaries are shown. Note also that the color of the shaded masks on each OCT B-scan also corresponds to the 4 pathological features shown in the legend.

Figure 2

Subgroup analyses of study eyes without coexistent reticular pseudodrusen at baseline, when evaluating the mean change from baseline of the extent of loss of the OCT outer retinal bands (external limiting membrane [ELM; left column], ellipsoid zone [EZ; middle column], and retinal pigment epithelium [RPE; right column]), shown separately for the subthreshold nanosecond laser (SNL; black) and sham (gray) groups. ^# = when considering the entire central 5-mm diameter region (top row) or only nondrusen areas in this region (bottom row). Only visits where neovascular age-related macular degeneration was absent were included. Error bars represent 95% confidence of the mean, and asterisks indicate a statistically significant difference between the SNL and sham groups at P < 0.05.

Figure 3

Subgroup analyses of study eyes with coexistent reticular pseudodrusen at baseline when evaluating the mean change from baseline of the extent of loss of the OCT outer retinal bands (external limiting membrane [ELM; left column], ellipsoid zone [EZ; middle column], and retinal pigment epithelium [RPE; right column]), shown separately for the subthreshold nanosecond laser (SNL; black) and sham (gray) groups. ^# = when considering the entire central 5 mm diameter region (top row), or only nondrusen areas in this region (bottom row). Only visits where neovascular age-related macular degeneration was absent were included. Error bars represent 95% confidence of the mean. Note that no statistically significant difference between the SNL and sham groups at P < 0.05 were noted at any time point for all parameters evaluated.

Figure 4

Example of a study eye that was randomized to the sham treatment arm that developed atrophic age-related macular degeneration (AMD) at 24 months after baseline. Thickness maps for the external limiting membrane (ELM), ellipsoid zone (EZ), retinal pigment epithelium (RPE), and drusen, along with a selected OCT B-scan taken through the location shown on the black triangles on the left, are shown for each 6-monthly follow-up visit. Regions of ELM, EZ, or RPE loss (based on A-scans where the thickness was ≤5 μm) in nondrusen and drusen areas are shown as white and gray overlays. Plots of the total square root area of ELM, EZ, and RPE loss over time, separately for the entire central 5-mm diameter region (black; including both drusen and nondrusen areas) and for only nondrusen areas (gray), are shown on the bottom. Note in this example that there was some evidence of ELM and EZ loss before the development of atrophic AMD at 24 months when evaluating the entire central 5-mm diameter region. However, loss of all 3 OCT outer retinal bands in only nondrusen areas in this region developed and increased over time after the onset of atrophic AMD.

Figure 5

Example of a study eye that was randomized to the subthreshold nanosecond laser treatment arm that did not develop late age-related macular degeneration (AMD) over the follow-up period. Thickness maps for the external limiting membrane (ELM), ellipsoid zone (EZ), retinal pigment epithelium (RPE), and drusen, along with a selected OCT B-scan taken through the location shown on the black triangles on the left, are shown for each 6-monthly follow-up visit. Regions of ELM, EZ, or RPE loss (based on A-scans where the thickness was ≤5 μm) in nondrusen and drusen areas are shown as white and gray overlays. Plots of the total square root area of ELM, EZ, and RPE loss over time, separately for the entire central 5-mm diameter region (black; including drusen and nondrusen areas) and for only nondrusen areas (gray), are shown on the bottom. Note in this example that there was evidence of ELM and EZ loss in the entire central 5-mm diameter region across all the visits (which were present in different regions across different visits) but minimal evidence of ELM and EZ loss in only nondrusen areas in this region. There was no evidence of RPE loss over all visits.