High-speed adaptive optics line-scan OCT for cellular-resolution optoretinography

Abstract

Optoretinographythe non-invasive, optical imaging of light-induced functional activity in the retinastands to provide a critical biomarker for testing the safety and efficacy of new therapies as well as their rapid translation to the clinic. Optical phase change in response to light, as readily accessible in phaseresolved OCT, offers a path towards all-optical imaging of retinal function. However, typical human eye motion adversely affects phase stability and precludes the recording of fast light-induced retinal events.Here we introduce a high-speed line-scan spectral domain OCT with adaptive optics (AO), aimed at volumetric imaging and phase-resolved acquisition of retinal responses to light. By virtue of parallel acquisition of an entire retinal cross-section (B-scan) in a single high-speed camera frame, depth-resolved tomograms at speeds up to 16 kHz were achieved with high sensitivity and phase stability. To optimize spectral and spatial resolution, an anamorphic detection paradigm was introduced enabling improved light collection efficiency and signal roll-off compared to traditional methods. The benefits in speed, resolution and sensitivity were exemplified in imaging nanometer-millisecond scale light-induced optical path length changes in cone photoreceptor outer segments. With 660 nm stimuli, individual cone responses readily segregated into three clusters, corresponding to long, middle and short-wavelength cones. Recording such optoretinograms on spatial scales ranging from individual cones, to 100 µm-wide retinal patches offers a robust and sensitive biomarker for cone function in health and disease. Furthermore, incorporating this capability into an easy-to-use and ubiquitous diagnostic platform of OCT enables its widespread application to patient care and drug development.

Short-term assessment of subfoveal injection of AAV2-hCHM gene augmentation in choroideremia using adaptive optics ophthalmoscopy

“…non-invasive visualization of the cellular targets of such interventions, particularly in disease states, such as neurodegenerations, where biopsies or other biologic markers of treatment effects are not available. Further, techniques such as optoretinography [64][65][66][67][68] and AO microperimetry 30,[69][70][71] have complemented AO imaging by allowing the direct or indirect evaluation of photoreceptor visual function at the cellular level. The emergence of these tools may prove impactful for assessing the short-and long-term safety and efficacy of gene therapies for blinding diseases.…”

Mechanisms of Light-Induced Deformations in Photoreceptors

“…It enables sub-millisecond time resolution of axial deformations across a field of view containing tens of photoreceptors. This system is described in detail in (11,12), in which recordings made in the living human eye via pOCT demonstrated significant OPL changes in the outer segments of photoreceptors in response to light stimuli, as shown in Fig. 1.…”

Interferometric imaging of thermal expansion for temperature control in retinal laser therapy

“…The optical layout (Fig. 1) followed the design by Pandiyan et al [22] for high-speed line-scan OCT imaging. We here summarize the main components of the design; further details on the optical system can be found in Ref.…”

“…We here summarize the main components of the design; further details on the optical system can be found in Ref. [22]. The illumination is provided by a fiber-coupled superluminescent diode (M-T-850-HP-I, Superlum, 9-mW power) with a center wavelength of 840 nm and a bandwidth of 130 nm, providing an axial resolution of 2.4 μm in air.…”