Wide-field Trend-based Progression Analysis of Combined Retinal Nerve Fiber Layer and Ganglion Cell Inner Plexiform Layer Thickness

Objective Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. Design Prospective, longitudinal study. Participants A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. Methods OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. Main Outcome Measures Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. Results More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%–33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%–20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%–8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%–92.4%), 94.9% (95% CI: 90.6%–99.2%), and 96.9% (95% CI: 93.5%–100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2–5.0) or likely (HR: 4.6, 95% CI: 1.5–14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. Conclusions Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients. Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. Prospective, longitudinal study. A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%–33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%–20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%–8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%–92.4%), 94.9% (95% CI: 90.6%–99.2%), and 96.9% (95% CI: 93.5%–100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2–5.0) or likely (HR: 4.6, 95% CI: 1.5–14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.