Purpose The lamina cribrosa (LC) is a leading target for initial glaucomatous damage. We investigated the in vivo microstructural deformation within the LC volume in response to acute IOP modulation while maintaining fixed intracranial pressure (ICP). Methods In vivo optic nerve head (ONH) spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) were obtained from eight eyes of healthy adult rhesus macaques (7 animals; ages = 7.9–14.4 years) in different IOP settings and fixed ICP (8–12 mm Hg). IOP and ICP were controlled by cannulation of the anterior chamber and the lateral ventricle of the brain, respectively, connected to a gravity-controlled reservoir. ONH images were acquired at baseline IOP, 30 mm Hg (H1-IOP), and 40 to 50 mm Hg (H2-IOP). Scans were registered in 3D, and LC microstructure measurements were obtained from shared regions and depths. Results Only half of the eyes exhibited LC beam-to-pore ratio (BPR) and microstructure deformations. The maximal BPR change location within the LC volume varied between eyes. BPR deformer eyes had a significantly higher baseline connective tissue volume fraction (CTVF) and lower pore aspect ratio ( P = 0.03 and P = 0.04, respectively) compared to BPR non-deformer. In all eyes, the magnitude of BPR changes in the anterior surface was significantly different (either larger or smaller) from the maximal change within the LC (H1-IOP: P = 0.02 and H2-IOP: P = 0.004). Conclusions The LC deforms unevenly throughout its depth in response to IOP modulation at fixed ICP. Therefore, analysis of merely the anterior LC surface microstructure will not fully capture the microstructure deformations within the LC. BPR deformer eyes have higher CTVF than BPR non-deformer eyes.

Purpose: Broken stick analysis is a useful approach to detect the unknown breakpoints where association between measurements change. Currently, most longitudinal studies aggregate measurements obtained from all visits without considering the repeated measurements from a given eye so that segmented linear models can be applied to such "compressed" cross-sectional data. The purpose of this study is to introduce an advanced robust segmented mixed model (RSMM) which accommodates longitudinal measurements from both eyes, and is robust to outliers. Methods: The model setup and parameter estimation algorithm of RSMM was introduced. The performance of all competing methods were assessed via comprehensive simulation studies and application to a longitudinal ophthalmic study with 216 eyes (145 subjects) followed for 3.7±1.3 years to examine the longitudinal association between structural and functional measurements. Results: In the simulation studies, the breakpoint estimates of RSMM exhibit smallest bias and mean squared error (MSE), with empirical coverage probability closest to the nominal level for scenarios with and without outlier data points. In the application to the longitudinal ophthalmic study, results of RSMM indicated the existence of two breakpoints between visual field mean deviation (MD) and retinal nerve fiber layer thickness (RNFL) and one breakpoint between MD and cup to disc ratio (CDR) while the cross-sectional analysis approach only detected one and none, respectively. Conclusions: RSMM improves the estimation accuracy of breakpoints for longitudinal ophthalmic studies. The conventional cross-sectional analysis approach is not recommended for future studies.