Nripun Sredar

Reproducibility of Measuring Lamina Cribrosa Pore Geometry in Human and Nonhuman Primates with In Vivo Adaptive Optics Imaging

PURPOSE The ability to consistently resolve lamina cribrosa pores in vivo has applications in the study of optic nerve head and retinal disease mechanisms. Repeatability was assessed in imaging laminar pores in normal living eyes with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). METHODS Reflectance images (840 nm) of the anterior lamina cribrosa were acquired using the AOSLO in four or more different sessions in two normal rhesus monkey eyes and three normal human eyes. Laminar pore areas, elongations (ratio of major to minor axes of the best-fit ellipse) and nearest neighbor distances were calculated for each session. Measurement repeatability was assessed across sessions. RESULTS Pore areas ranged from 90 to 4365 μm(2) in monkeys and 154 to 6637 μm(2) in humans. Mean variabilities in measuring pore area and elongation (i.e., mean of the standard deviation of measurements made across sessions for the same pores) were 50 μm(2) (6.1%) and 0.13 (6.7%), respectively, in monkeys and 113 μm(2) (8.3%) and 0.17 (7.7%), respectively, in humans. Mean variabilities in measuring nearest neighbor distances were 1.93 μm (5.2%) in monkeys and 2.79 μm (4.1%) in humans. There were no statistically significant differences in any pore parameters across sessions (ANOVA, P > 0.05). CONCLUSIONS The anterior lamina cribrosa was consistently imaged in vivo in normal monkey and human eyes. The small intersession variability in normal pore geometry suggests that AOSLO imaging could be used to measure and track changes in laminar pores in vivo during glaucomatous progression.

Wavefront sensorless adaptive optics ophthalmoscopy in the human eye

Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor ‘beacon’ can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains.

3D modeling to characterize lamina cribrosa surface and pore geometries using in vivo images from normal and glaucomatous eyes

En face adaptive optics scanning laser ophthalmoscope (AOSLO) images of the anterior lamina cribrosa surface (ALCS) represent a 2D projected view of a 3D laminar surface. Using spectral domain optical coherence tomography images acquired in living monkey eyes, a thin plate spline was used to model the ALCS in 3D. The 2D AOSLO images were registered and projected onto the 3D surface that was then tessellated into a triangular mesh to characterize differences in pore geometry between 2D and 3D images. Following 3D transformation of the anterior laminar surface in 11 normal eyes, mean pore area increased by 5.1 ± 2.0% with a minimal change in pore elongation (mean change = 0.0 ± 0.2%). These small changes were due to the relatively flat laminar surfaces inherent in normal eyes (mean radius of curvature = 3.0 ± 0.5 mm). The mean increase in pore area was larger following 3D transformation in 4 glaucomatous eyes (16.2 ± 6.0%) due to their more steeply curved laminar surfaces (mean radius of curvature = 1.3 ± 0.1 mm), while the change in pore elongation was comparable to that in normal eyes (−0.2 ± 2.0%). This 3D transformation and tessellation method can be used to better characterize and track 3D changes in laminar pore and surface geometries in glaucoma.

A correction algorithm to simultaneously control dual deformable mirrors in a woofer-tweeter adaptive optics system

We present a direct slope-based correction algorithm to simultaneously control two deformable mirrors (DMs) in a woofer-tweeter adaptive optics system. A global response matrix was derived from the response matrices of each deformable mirror and the voltages for both deformable mirrors were calculated simultaneously. This control algorithm was tested and compared with a 2-step sequential control method in five normal human eyes using an adaptive optics scanning laser ophthalmoscope. The mean residual total root-mean-square (RMS) wavefront errors across subjects after adaptive optics (AO) correction were 0.128 ± 0.025 μm and 0.107 ± 0.033 μm for simultaneous and 2-step control, respectively (7.75-mm pupil). The mean intensity of reflectance images acquired after AO convergence was slightly higher for 2-step control. Radially-averaged power spectra calculated from registered reflectance images were nearly identical for all subjects using simultaneous or 2-step control. The correction performance of our new simultaneous dual DM control algorithm is comparable to 2-step control, but is more efficient. This method can be applied to any woofer-tweeter AO system.

In Vivo Changes in Lamina Cribrosa Microarchitecture and Optic Nerve Head Structure in Early Experimental Glaucoma

The lamina cribrosa likely plays an important role in retinal ganglion cell axon injury in glaucoma. We sought to (1) better understand optic nerve head (ONH) structure and anterior lamina cribrosa surface (ALCS) microarchitecture between fellow eyes of living, normal non-human primates and (2) characterize the time-course of in vivo structural changes in the ONH, ALCS microarchitecture, and retinal nerve fiber layer thickness (RNFLT) in non-human primate eyes with early experimental glaucoma (EG). Spectral domain optical coherence tomography (SDOCT) images of the ONH were acquired cross-sectionally in six bilaterally normal rhesus monkeys, and before and approximately every two weeks after inducing unilateral EG in seven rhesus monkeys. ONH parameters and RNFLT were quantified from segmented SDOCT images. Mean ALCS pore area, elongation and nearest neighbor distance (NND) were quantified globally, in sectors and regionally from adaptive optics scanning laser ophthalmoscope images. In bilaterally normal monkeys, ONH parameters were similar between fellow eyes with few inter-eye differences in ALCS pore parameters. In EG monkeys, an increase in mean ALCS Depth (ALCSD) was the first structural change measured in 6 of 7 EG eyes. A decrease in mean minimum rim width (MRW) simultaneously accompanied this early change in 4 of 6 EG eyes and was the first structural change in the 7th EG eye. Mean ALCS pore parameters were among the first or second changes measured in 4 EG eyes. Mean ALCS pore area and NND increased in superotemporal and temporal sectors and in central and peripheral regions at the first time-point of change in ALCS pore geometry. RNFLT and/or mean ALCS radius of curvature were typically the last parameters to initially change. Survival analyses found mean ALCSD was the only parameter to significantly show an initial change prior to the first measured loss in RNFLT across EG eyes.