Purpose: To use optical coherence tomography (OCT) to identify the specific retinal layers and macular regions damaged in glaucoma. Design: Observational cross-sectional study. Participants: One hundred forty-nine participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: normal (N) perimetric glaucoma (PG), and glaucoma suspect and preperimetric glaucoma (GSPPG) with 44, 73, and 29 persons, respectively. Methods: The Zeiss Stratus OCT system (Carl Zeiss Meditec, Inc., Dublin, CA) was used to map the macula over a 6-mm diameter and to scan the circumpapillary nerve fiber layer (cpNFL). The macular OCT images were exported for automatic segmentation using software developed by the authors. The thickness of the macular nerve fiber layer (mNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL), inner nuclear layer (mINL), outer retinal layer (mORL), and total retinal thickness were measured. Thickness measurements of GSPPG and PG eyes were compared with those of N eyes. The ability to differentiate between GSPPG and PG eyes against N eyes was assessed by fractional loss, standardized deviation, and the area under the receiver operating characteristic curve. Main Outcome Measures: Area-weighted average thicknesses of retinal sublayers in the macula. Results: The mNFL, mGCL, mIPL, and mINL were significantly (P<0.001) thinner in both the GSPPG and PG eyes than in the N eyes. In PG eyes, mNFL, mGCL, and mIPL thinning was most severe (approximately 20%), mINL thinning was intermediate (7%), and mORL thinning was minimal (3%). The repeatability (coefficient of variation and intraclass correlation) of thickness measurements was improved by combining the mNFL, mGCL, and mIPL measurements as the inner retinal layer (mIRL). The mIRL was the best macular parameter for glaucoma diagnosis and had discriminant power comparable with that of the cpNFL. The fractional loss of mIRL thickness was most severe in the inferior perifoveal region for both the PG and GSPPG groups. Conclusions: Glaucoma leads to thinning of the mNFL, mGCL, mIPL, and mINL, even before detectable visual field changes occur. A combination of the 3 innermost layers seems to provide optimal glaucoma detection. Increasing the sampling of peripheral macula with a new OCT scan pattern may improve glaucoma diagnosis further.
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