OCT-Defined Atrophic Age-Related Macular Degeneration Changes Associated with Deep Visual Sensitivity Losses: A Multicenter Study

Abstract

Purpose: To identify combination(s) of OCT changes that define atrophic age-related macular degeneration (AMD) lesions associated with repeatable deep visual sensitivity defects.

Design: Reader study.

Participants: One hundred seventy-one OCT scans from 60 eyes of 53 participants.

Methods: Participants underwent 2 high-density targeted microperimetry tests (Macular Integrity Assessment device with Goldmann Size III stimuli) per visit of a 3.5° (approximately 1000 μm) diameter region-of-interest that had evidence of at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA). OCT B-scans within the region sampled on microperimetry were annotated by 12 readers from 6 established reading centers for 7 different features related to RPE and outer retinal atrophy. The prevalence of the presence of a repeatable ≤10 decibel (dB) defect on microperimetry for lesions categorized by 18 different combinations of such features, or criteria, was determined.

Main outcome measures: The criteria for OCT-defined atrophic changes showing a ≥90% prevalence of a repeatable ≤10 dB defect, which has previously shown to be characteristic of regions with a truly nonresponding test location on microperimetry.

Results: Sixty percent of complete RPE and outer retinal atrophy (cRORA) lesions-based on the presence of hypertransmission and RPE abnormalities ≥250 μm in width, with evidence of overlying photoreceptor (PR) degeneration, on an OCT B-scan-had a repeatable ≤10 dB defect. However, between 92% and 98% of lesions with both hypertransmission and complete RPE loss ≥500 μm, and with evidence of any size of any feature of overlying PR degeneration, had a repeatable ≤10 dB defect, depending on the criteria considered. Between 92% and 95% of lesions with hypertransmission ≥500 μm and either overlying external limiting membrane disruption, or outer plexiform layer and inner nuclear layer subsidence, and/or hyporeflective wedge-shaped band(s) ≥500 μm, with or without RPE abnormalities, had a repeatable ≤10 dB defect.

Conclusions: This study identified various criteria for OCT-defined atrophic AMD lesions with functional characteristics that can be expected of regions with a truly nonresponding test location on high-density targeted microperimetry testing (i.e., having a ≥90% prevalence of a repeatable ≤10 dB defect). Such OCT-defined lesions could thus serve as functionally relevant clinical endpoints of end-stage atrophic AMD to facilitate preventative treatment trials.

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

Keywords: Age-related macular degeneration; Geographic atrophy; Microperimetry; Optical coherence tomography; cRORA.

Figure 1

OCT B-scan showing an example with the 7 features associated with atrophy annotated by 1 grader in this study, including: choroidal signal hypertransmission, RPE abnormalities, complete RPE loss, EZ disruption, ELM disruption, ONL thinning, and OPL+INL subsidence and/or hyporeflective wedge-shaped band (graded together as a single feature). ELM = external limiting membrane; EZ = ellipsoid zone; ONL = outer nuclear layer; OPL+INL = outer plexiform layer and inner nuclear layer; RPE = retinal pigment epithelium.

Figure 2

Two examples of lesions showing a repeatable ≤10 dB defect on high-density targeted microperimetry testing, with the number of readers considering atrophic AMD changes to be present based on 5 selected criteria, are shown. The dashed black box on the near-infrared reflectance image (middle column) indicates the location where the 2 microperimetry tests (left column) were performed and where the OCT B-scan (right column) was taken through. AMD = age-related macular degeneration; dB = decibel; ELM = external limiting membrane; hyporeflective wedge = hyporeflective wedge-shaped band(s) within Henle fiber layer; OPL+INL = outer plexiform layer and inner nuclear layer; PR = photoreceptor; RPE = retinal pigment epithelium.

Figure 3

Two examples of lesions without a repeatable ≤10 dB defect on high-density targeted microperimetry testing, with the number of readers considering atrophic AMD changes to be present based on 5 selected criteria, are shown. The dashed black box on the near-infared reflectance image (middle column) indicates the location where the 2 microperimetry tests (left column) were performed and where the OCT B-scan (right column) was taken through. AMD = age-related macular degeneration; dB = decibel; ELM = external limiting membrane; hyporeflective wedge = hyporeflective wedge-shaped band(s) within Henle fiber layer; OPL+INL = outer plexiform layer and inner nuclear layer; PR = photoreceptor; RPE = retinal pigment epithelium.