Integrating Macular Ganglion Cell Inner Plexiform Layer and Parapapillary Retinal Nerve Fiber Layer Measurements to Detect Glaucoma Progression

Abstract

Purpose: To investigate the temporal relationship among progressive macular ganglion cell inner plexiform layer (GCIPL) thinning, progressive parapapillary retinal nerve fiber layer (RNFL) thinning, and visual field (VF) progression in patients with primary open-angle glaucoma (POAG). Design: Prospective study. Participants: One hundred thirty-six POAG patients (231 eyes) followed up for ≥5 years. Methods: OCT imaging of the macular GCIPL and parapapillary RNFL and perimetry were performed at ∼ 4-month intervals. Progressive GCIPL and RNFL thinning were determined by Guided Progression Analysis (GPA) of serial GCIPL and RNFL thickness maps. The specificities of GPA were calculated from the proportions of eyes with progressive GCIPL or RNFL thinning in 67 eyes of 36 healthy individuals followed up for ≥5 years. Visual field progression (likely or possible) was determined by the Early Manifest Glaucoma Trial criteria. Main Outcome Measures: Hazard ratios for VF progression, progressive RNFL thinning, and progressive GCIPL thinning, as determined by time-varying Cox models. Results: GPA detected 57 eyes (24.7%) with progressive GCIPL thinning and 66 eyes (28.6%) with progressive RNFL thinning at a specificity of 95.5% and 91.0%, respectively. Thirty-five eyes (15.2%) demonstrated progressive RNFL and GCIPL thinning, whereas 53 eyes (22.9%) demonstrated progressive RNFL or GCIPL thinning. Eyes with progressive GCIPL thinning had a higher risk for progressive RNFL thinning (HR, 5.27; 95% confidence interval [CI], 2.89–9.62), whereas eyes with progressive RNFL thinning were also at a higher risk for progressive GCIPL thinning (HR, 2.99; 95% CI, 1.48–6.02), after adjusting for baseline covariates. The HRs for likely and possible VF progression were 3.48 (95% CI, 1.51–8.01) and 2.74 (95% CI, 1.26–5.98), respectively, on detection of progressive GCIPL thinning and 3.66 (95% CI, 1.68–7.97) and 2.54 (95% CI, 1.23–5.21), respectively, on detection of progressive RNFL thinning after adjusting for baseline covariates. Eyes with VF progression were not at risk of progressive RNFL or GCIPL thinning (P ≥ 0.493). Conclusions: Progressive macular GCIPL thinning and progressive parapapillary RNFL thinning are mutually predictive. Because progressive RNFL thinning and progressive GCIPL thinning are both indicative of VF progression, integrating macular GCIPL and parapapillary RNFL measurements is relevant to facilitate early detection of disease deterioration in glaucoma patients.