In vivo imaging of inner plexiform layer lamination in humans with visible light OCT
Vivek J. Srinivasana,b aBiomedical Engineering Department, University of California Davis, Davis, California, USA 95616 bDepartment of Ophthalmology and Vision Science, University of California Davis School of Medicine, Sacramento, California, USA 95817 *[email protected] Need for predictive glaucoma diagnostics
• Glaucoma is characterized by retinal ganglion cell death
But how do retinal ganglion cells degenerate before death?
Liu et al., PNAS, 2017 New insight into early glaucoma from animal studies
• Early changes of RGC dendrites in off sublamina of inner plexiform layer (IPL) precede somatic changes in mice
Microbead injection model Laser photocoagulation model
Feng et al., IOVS, 2013; Santina et al., J Neurosci, 2013; El-Danaf and Huberman, J Neurosci, 2015; Ou et al., J Neurosci, 2016; Puyang et al., Exp Eye Res, 2017 …… Inner plexiform layer lamination • The inner plexiform layer (IPL) is a layer of synapses between the bipolar, ganglion and amacrine cells • The IPL is divided functionally into ‘on’ and ‘off’ sublaminae
G: Ganglion cell B: Bipolar cell A: Amacrine cell Modified from Soto et al., Front Cell Neurosci, 2015 Inner plexiform layer lamination • The inner plexiform layer (IPL) is a layer of synapses between the bipolar, ganglion and amacrine cells • IPL is divided functionally into ‘on’ and ‘off’ sublaminae
Tanna et al., British Journal of Ophthalmology 2010 Inner plexiform layer lamination • The inner plexiform layer (IPL) is a layer of synapses between the bipolar, ganglion and amacrine cells • IPL is divided functionally into ‘on’ and ‘off’ sublaminae • The organization of the IPL is a potential biomarker for retinal diseases and glaucoma Motivations for visible light OCT • Achieve ultrahigh axial resolution (< 2 μm in air) • Resolve fine retinal layers (Povazay et al., Opt Lett, 2001; Chong et al., Biomed Opt Express, 2017)
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• Can also measure and quantify intrinsic chromophores (Yi et al., Opt Lett, 2013; Robles et al., Nat Photonics, 2011) Human visible light OCT system
GLV-SLM
Fig. 1. (A) Fiber-based visible light spectral / Fourier domain OCT system for imaging the human retina (M: mirror, AL: achromatizing lens, RC: reflective collimator, L: lens, FLInnovative: focusing lens, DG: diffractionengineeringgrating, LSC: linesolutions-scan camera, NDFto : accountneutral density filter,for DMtechnical: dichroic mirror, MTS: Motorized translational stage). (B) Zero- power triplet achromatizing lens (AL) used in the sample arm. (B) The axial resolution in air and sensitivity roll-off of the visible light@ByersOCT system Eye Institute at Stanford University challenges of visible light Outer retinal imaging with visible light OCT
• A fiber-based spectral / Fourier domain visible light OCT system with longitudinal chromatic aberration (LCA) correction • Bruch’s membrane (BM) is well-separated from the retinal pigment epithelium (RPE) across the entire 6.5 mm (~22°) field-of-view in a single B-scan. ELM IS / OS ELM COST ROST RPE IS / OS BM COST RPE BM CC
Chong et al., Biomed Opt Express, 2018 Inner plexiform layer lamination
GCL IPL
INL
G: Ganglion cell B: Bipolar cell A: Amacrine cell Modified from Soto et al., Front Cell Neurosci, 2015
2.6 mm (~8.2º) Inner plexiform layer lamination analysis
GCL IPL
INL
2.6 mm (~8.2º) Inner plexiform layer lamination analysis
On sublamina has deeper troughs Pattern persists as IPL thickness changes and (typically) better contrast. Peaks and troughs spaced evenly.
GCL IPL INL Possible explanations for 5-band IPL reflectance pattern • Variations in synapse density and type as well as neurite type and orientation across sublaminae are all possible contributors to the observed IPL reflectance pattern.
Nelson et al., J Neurophysiol, 1978
Koontz & Hendrickson., The Journal of Comparative Neurology, 1987 • Studies in glaucoma are underway Acknowledgements Lab Website: http://www.bme.ucdavis.edu/srinivasanlab/ Lab Members (Current): Collaborator: Former Lab Members: Aaron Kho Prof. James Boggan Marcel Bernucci Oybek Kholiqov Prof. Bruce Lyeth Dr. Dawid Borycki Dr. Vivek Srinivasan Prof. Ryan M Martin Dr. Aaron Chan Tingwei Zhang Prof. Ben Waldau Dr. Shau Poh Chong Dr. Wenjun Zhou Prof. Lara L Zimmermann Dr. Conor Leahy Jun Zhu Prof. Alfredo Dubra Dr. Conrad Merkle Prof. Jeffrey Goldberg Harsha Radhakrishnan
FUNDING AGENCIES National Institutes of Health: R01NS094681, R03EB023591, R21NS105043, and R01EY028287 Glaucoma Research Foundation Catalyst for a Cure Contact: Thanks [email protected]