PURPOSE. We identified candidate optical coherence tomography (OCT) markers for early glaucoma diagnosis. Time variation of retinal nerve fiber layer (RNFL) thickness, phase retardation, birefringence, and reflectance using polarization sensitive optical coherence tomography (PS-OCT) were measured in three non-human primates with induced glaucoma in one eye. We characterized time variation of RNFL thickness, phase retardation, birefringence, and reflectance with elevated intraocular pressure (IOP). METHODS.One eye of each of three non-human primates was laser treated to increase IOP. Each primate was followed for a 30-week period. PS-OCT measurements were recorded at weekly intervals. Reflectance index (RI) is introduced to characterize RNFL reflectance. Associations between elevated IOP and RNFL thickness, phase retardation, birefringence, and reflectance were characterized in seven regions (entire retina, inner and outer rings, and nasal, temporal, superior and inferior quadrants) by linear and non-linear mixed-effects models.RESULTS. Elevated IOP was achieved in three non-human primate eyes with an average increase of 13 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in the nasal region (P ¼ 0.0002), decreased RNFL phase retardation in the superior (P ¼ 0.046) and inferior (P ¼ 0.021) regions, decreased RNFL birefringence in the nasal (P ¼ 0.002) and inferior (P ¼ 0.029) regions, and loss of RNFL reflectance in the outer rings (P ¼ 0.018). When averaged over the entire retinal area, only RNFL reflectance showed a significant decrease (P ¼ 0.028).CONCLUSIONS. Of the measured parameters, decreased RNFL reflectance was the most robust correlate with glaucomatous damage. Candidate cellular mechanisms are considered for decreased RNFL reflectance, including mitochondrial dysfunction and retinal ganglion cell apoptosis. (Invest Ophthalmol Vis Sci. 2012;53:4380-4395) DOI:10.1167/iovs.11-9130 G laucoma is an optic neuropathy characterized by the progressive death of retinal ganglion cells and loss of associated axons in the retinal nerve fiber layer (RNFL). Without early diagnosis and therapeutic intervention, glaucoma eventually results in visual field abnormalities and vision loss. Studies indicate that as many as 40% of the axons may die before the visual field is affected, 1 suggesting an opportunity for the development of diagnostic tools that can prevent visual field loss in conjunction with application of neuroprotective strategies. As axons in the RNFL are lost, an associated RNFL thinning is observed. 2-4Optical coherence tomography (OCT) is an imaging modality that provides high-resolution (2-15 lm) cross-sectional images of the retina at video rate, and can quantify macroscopic changes in the optic nerve head (ONH) and RNFL. Inasmuch as previous studies have demonstrated a link between decreased RNFL thickness measured with OCT and glaucoma, 3 OCT measurements of RNFL thickness have become a routine component of glaucoma screening, diagnosis, and monitoring protocols...

A Swept Source Polarization-Sensitive Optical Coherence Tomography (SS-PS-OCT) instrument has been designed, constructed, and verified to provide high sensitivity depth-resolved birefringence and phase retardation measurements of the retinal nerve fiber layer. The swept-source laser had a center wavelength of 1059 nm, a full-width-half-max spectral bandwidth of 58 nm and an A-line scan rate of 34 KHz. Power incident on the cornea was 440 µW and measured axial resolution was 17 µm in air. A multiple polarization state nonlinear fitting algorithm was used to measure retinal birefringence with low uncertainty. Maps of RNFL phase retardation in a subject measured with SS-PS-OCT compare well with those generated using a commercial scanning laser polarimetry instrument. Peak-to-valley variation of RNFL birefringence given here is less than values previously reported at 840nm.

Background and Objectives The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two-channel two-photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta-based macrophages using plasmonic gold nanorose as an imaging contrast agent. Study Design/Materials and Methods Nanorose uptake by macrophages was identified by TPL microscopy in macrophage cell culture. Ex vivo aorta segments (8 × 8 × 2 mm3) rich in macrophages from a rabbit model of aorta inflammation were imaged by TPL microscopy in combination with OCT. Aorta histological sections (5 µm in thickness) were also imaged by TPL microscopy. Results Merged two-channel TPL images showed the lateral and depth distribution of nanorose-loaded macrophages (confirmed by RAM-11 stain) and other aorta components (e.g., elastin fiber and lipid droplet), suggesting that nanorose-loaded macrophages are diffusively distributed and mostly detected superficially within 20 µm from the luminal surface of the aorta. Moreover, OCT images depicted detailed surface structure of the diseased aorta. Conclusions Results suggest that TPL microscopy combined with OCT can simultaneously reveal macrophage distribution with respect to aorta surface structure, which has the potential to detect vulnerable plaques and monitor plaque-based macrophages overtime during cardiovascular interventions.

A low-resolution path-length-multiplexed scattering angle diverse optical coherence tomography (PM-SAD-OCT) is constructed to investigate the scattering properties of the retinal nerve fiber layer (RNFL). Low-resolution PM-SADOCT retinal images acquired from a healthy human subject show the variation of RNFL scattering properties at retinal locations around the optic nerve head. The results are consistent with known retinal ganglion cell neural anatomy and principles of light scattering. Application of PM-SAD-OCT may provide potentially valuable diagnostic information for clinical retinal imaging.