Thickness, phase retardation, birefringence, and reflectance of the retinal nerve fiber layer : implications for glaucoma diagnosis

Glaucoma is the second leading cause of blindness worldwide after cataract. Retinal nerve fiber layer thickness (RNFLT), phase retardation, and birefringence measured by Polarization Sensitive Optical Coherence Tomography (PS-OCT) have been used for glaucoma diagnosis. We first investigated two different image registration algorithms, a mutual information (MI) based algorithm and a log-polar transform cross-correlation (LPCC) based algorithm, on both human and non-human primate models. We evaluated the effects of image registration on longitudinal analysis of RNFLT in non-human primates using PS-OCT. Then, we investigated thickness, phase retardation, birefringence, and reflectance of the retinal nerve fiber layer as measured by PS-OCT in normal and glaucomatous non-human primates in a longitudinal study. We defined a new Reflectance Index (RI) and demonstrated that it might be an earlier indicator of glaucoma onset than RNFLT, phase retardation, or birefringence. Finally, we validated this finding on cross-sectional clinical study on human eyes measured by PS-OCT and RTVue OCT. For the data measured by PS-OCT, we showed that for distinguishing between glaucomatous and healthy eyes, as well as for distinguishing between glaucoma suspect and healthy eyes, our new normalized RNFL reflectance index (NRRI) performs significantly better than phase retardation and birefringence. The performances of NRRI and RNFL thickness in both conditions were statistically indistinguishable in this study, which is likely due to the limited sample size. For the data measured by RTVue OCT, the performances of NRRI and RNFL thickness were statistically indistinguishable for distinguishing between glaucomatous and healthy eyes. NRRI performs significantly better than RNFL thickness for distinguishing between glaucoma suspect and healthy eyes. NRRI also performs significantly better than temporal, superior, nasal, inferior and temporal (TSNIT) average and nerve fiber indicator (NFI) from GDx VCC for distinguishing between glaucoma suspect and healthy eyes. NRRI is a promising parameter for distinguishing glaucoma suspect and healthy eyes and may indicate disease in the pre-perimetric stage.