Multivariate Longitudinal Modeling of Macular Ganglion Cell Complex: Spatiotemporal Correlations and Patterns of Longitudinal Change

PURPOSE: To investigate spatiotemporal correlations among ganglion cell complex (GCC) superpixel thickness measurements and explore underlying patterns of longitudinal change across the macular region. DESIGN: Longitudinal cohort study. SUBJECTS: One hundred eleven eyes from 111 subjects from the Advanced Glaucoma Progression Study with ≥ 4 visits and ≥ 2 years of follow-up. METHODS: We further developed our proposed Bayesian hierarchical model for studying longitudinal GCC thickness changes across macular superpixels in a cohort of glaucoma patients. Global priors were introduced for macular superpixel parameters to combine data across superpixels and better estimate population slopes and intercepts. MAIN OUTCOME MEASURES: Bayesian residual analysis to inspect cross-superpixel correlations for subject random effects and residuals. Principal component analysis (PCA) to explore underlying patterns of longitudinal macular change. RESULTS: Average (standard deviation [SD]) follow-up and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and −8.9 (5.9) dB, respectively. Superpixel-level random effects and residuals had the greatest correlations with nearest neighbors; correlations were higher in the superior than in the inferior region and strongest among random intercepts, followed by random slopes, residuals, and residual SDs. PCA of random intercepts showed a first large principal component (PC) across superpixels that approximated a global intercept, a second PC that contrasted the superior and inferior macula, and a third PC, contrasting inner and nasal superpixels with temporal and peripheral superpixels. PCs for slopes, residual SDs, and residuals were remarkably similar to those of random intercepts. CONCLUSIONS: Introduction of cross-superpixel random intercepts and slopes is expected to improve estimation of population and subject parameters. Further model enhancement may be possible by including cross-superpixel random effects and correlations to address spatiotemporal relationships in longitudinal data sets.