Retinal imaging with adaptive optics full-field OCT

A Full-Field OCT (FFOCT) setup coupled to a compact transmissive liquid crystal spatial light modulator (LCSLM) is used to induce or correct aberrations and simulate eye examinations. To reduce the system complexity, strict pupil conjugation was abandoned. During our work on quantifying the effect of geometrical aberrations on FFOCT images, we found that the image resolution is almost insensitive to aberrations. Indeed if the object channel PSF is distorted, its interference with the reference channel conserves the main feature of an unperturbed PSF with only a reduction of the signal level. This unique behavior is specific to the use of a spatially incoherent illumination. Based on this, the FFOCT image intensity was used as the metric for our wavefront sensorless correction. Aberration correction was first conducted on an USAF resolution target with the LSCLM as both aberration generator and corrector. A random aberration mask was induced, and the low-order Zernike Modes were corrected sequentially according to the intensity metric function optimization. A Ficus leaf and a fixed mouse brain tissue slice were also imaged to demonstrate the correction of sample self-induced wavefront distortions. After optimization, more structured information appears for the leaf imaging. And the high-signal fiber-like myelin fiber structures were resolved much more clearly after the whole correction process for mouse brain imaging. Our experiment shows the potential of this compact AO-FFOCT system for aberration correction imaging. This preliminary approach that simulates eyes aberrations correction also opens the path to a simple implementation of FFOCT adaptive optics for retinal examinations.

The adaptive optics (AO) technique is widely used to compensate for ocular aberrations and improve imaging resolution. However, when affected by intraocular scatter, speckle noise, and other factors, the quality of the retinal image will be degraded. To effectively improve the image quality without increasing the imaging system's complexity, the post-processing method of image deblurring is adopted. In this study, we proposed a conditional adversarial network-based method for directly learning an end-to-end mapping between blurry and restored AO retinal images. The proposed model was validated on synthetically generated AO retinal images and real retinal images. The restoration results of synthetic images were evaluated with the metrics of peak signal-to-noise ratio (PSNR), structural similarity (SSIM), perceptual distance, and error rate of cone counting. Moreover, the blind image quality index (BIQI) was used as the no-reference image quality assessment (NR-IQA) algorithm to evaluate the restoration results on real AO retinal images. The experimental results indicate that the images restored by the proposed method have sharper quality and higher signal-to-noise ratio (SNR) when compared with other state-of-the-art methods, which has great practical significance for clinical research and analysis.

Aim: The objective of this project was to evaluate high resolution images from an adaptive optics retinal imager through comparisons with standard film-based and standard digital fundus imagers. Methods: A clinical prototype adaptive optics fundus imager (AOFI) was used to collect retinal images from subjects with various forms of retinopathy to determine whether improved visibility into the disease could be provided to the clinician. The AOFI achieves low-order correction of aberrations through a closed-loop wavefront sensor and an adaptive optics system. The remaining high-order aberrations are removed by direct deconvolution using the point spread function (PSF) or by blind deconvolution when the PSF is not available. An ophthalmologist compared the AOFI images with standard fundus images and provided a clinical evaluation of all the modalities and processing techniques. All images were also analyzed using a quantitative image quality index. Results: This system has been tested on three human subjects (one normal and two with retinopathy). In the diabetic patient vascular abnormalities were detected with the AOFI that cannot be resolved with the standard fundus camera. Very small features, such as the fine vascular structures on the optic disc and the individual nerve fiber bundles are easily resolved by the AOFI. Conclusion: This project demonstrated that adaptive optic images have great potential in providing clinically significant detail of anatomical and pathological structures to the ophthalmologist.

Improved understanding of the mechanisms underlying inherited retinal degenerations has created the possibility of developing much needed treatments for these relentless, blinding diseases. However, standard clinical indicators of retinal health (such as visual acuity and visual field sensitivity) are insensitive measures of photoreceptor survival. In many retinal degenerations, significant photoreceptor loss must occur before measurable differences in visual function are observed. Thus, there is a recognized need for more sensitive outcome measures to assess therapeutic efficacy as numerous clinical trials are getting underway. Adaptive optics (AO) retinal imaging techniques correct for the monochromatic aberrations of the eye and can be used to provide nearly diffraction-limited images of the retina. Many groups routinely are using AO imaging tools to obtain in vivo images of the rod and cone photoreceptor mosaic, and it now is possible to monitor photoreceptor structure over time with single cell resolution. Highlighting recent work using AO scanning light ophthalmoscopy (AOSLO) across a range of patient populations, we review the development of photoreceptor-based metrics (e.g., density/geometry, reflectivity, and size) as candidate biomarkers. Going forward, there is a need for further development of automated tools and normative databases, with the latter facilitating the comparison of data sets across research groups and devices. Ongoing and future clinical trials for inherited retinal diseases will benefit from the improved resolution and sensitivity that multimodal AO retinal imaging affords to evaluate safety and efficacy of emerging therapies.

To correct wave front distortion, a phased only Liquid Crystal Spatial Light Modulator (LCSLM) is used. LCSLM can modulate the phase of the incident beam by changing the electric field applied to the transparent electrodes of a liquid crystal cell. The voltage change causes the refractive index of the liquid crystal change, so a phase shift produces. The distortion of a wave front can be measured by using a wave front interferometer. Since each pixel of SLM may be addressed and controlled independently, so proper voltage is supplied to each pixel to compensate the phase corresponding to the distortion. Before wave front correction, the LCSLM is tested and corrected by employing a Twyman-Green interferometer, which shows the relationship between the applied voltage and the phase value of each pixel. Experiment result shows that after error compensation of LCSLM, the wave front distortion correction accuracy reaches 0.06 λ.

The change in ocular wavefront aberrations with visual angle determines the isoplanatic patch, defined as the largest field of view over which diffraction-limited retinal imaging can be achieved. Here, we study how the isoplanatic patch at the foveal center varies across 32 schematic eyes, each individualized with optical biometry estimates of corneal and crystalline lens surface topography, assuming a homogeneous refractive index for the crystalline lens. The foveal isoplanatic patches were calculated using real ray tracing through 2, 4, 6 and 8 mm pupil diameters for wavelengths of 400-1200 nm, simulating five adaptive optics (AO) strategies. Three of these strategies, used in flood illumination, point-scanning, and line-scanning ophthalmoscopes, apply the same wavefront correction across the entire field of view, resulting in almost identical isoplanatic patches. Two time-division multiplexing (TDM) strategies are proposed to increase the isoplanatic patch of AO scanning ophthalmoscopes through field-varying wavefront correction. Results revealed substantial variation in isoplanatic patch size across eyes (40-500%), indicating that the field of view in AO ophthalmoscopes should be adjusted for each eye. The median isoplanatic patch size decreases with increasing pupil diameter, coarsely following a power law. No statistically significant correlations were found between isoplanatic patch size and axial length. The foveal isoplanatic patch increases linearly with wavelength, primarily due to its wavelength-dependent definition (wavefront root-mean-squared, RMS <λ/14), rather than aberration chromatism. Additionally, ray tracing reveals that in strongly ametropic eyes, induced aberrations can result in wavefront RMS errors as large as λ/3 for an 8-mm pupil, with implications for wavefront sensing, open-loop ophthalmic AO, spectacle prescription and refractive surgery.

Using the liquid crystal spatial light modulator (LC-SLM) as the wavefront corrector, an open-loop adaptive optics (AO) system for fundus imaging in vivo is constructed. Compared with the LC-SLM closed-loop AO system, the light energy efficiency is increased by a factor of 2, which is helpful for the safety of fundus illumination in vivo. In our experiment, the subjective accommodation method is used to precorrect the defocus aberration, and three subjects with different myopia 0, -3, and -5 D are tested. Although the residual wavefront error after correction cannot to detected, the fundus images adequately demonstrate that the imaging system reaches the resolution of a single photoreceptor cell through the open-loop correction. Without dilating and cyclopleging the eye, the continuous imaging for 8 s is recorded for one of the subjects.

We discuss the design and implementation of a low-cost, high-resolution adaptive optics test-bed for vision research. It is well known that high-order aberrations in the human eye reduce optical resolution and limit visual acuity. However, the effects of aberration-free eyesight on vision are only now beginning to be studied using adaptive optics to sense and correct the aberrations in the eye. We are developing a high-resolution adaptive optics system for this purpose using a Hamamatsu Parallel Aligned Nematic Liquid Crystal Spatial Light Modulator. Phase-wrapping is used to extend the effective stroke of the device, and the wavefront sensing and wavefront correction are done at different wavelengths. Issues associated with these techniques will be discussed.

Image restoration of the open-loop adaptive optics retinal imaging system based on optical transfer function analysis

To characterize the photoreceptors and choroidal morphology of heterozygous female carriers of choroideremia who typically do not have any visual defects but can have severe funduscopic changes. This was a clinical case series study. Detailed ophthalmic examinations were performed on six female carriers from four families with choroideremia. The subfoveal choroidal thickness (SFCT) was determined by spectral-domain optical coherence tomography (SD-OCT) and the cone photoreceptor density by adaptive optics (AO) retinal imaging. SFCT and cone densities of the carriers were compared to that of normal eyes of healthy subjects. The mean age of the carriers was 42.5 years. Fundus photographs showed diffuse, patchy depigmentation; however, the SFCT was within the normal limits. AO retinal imaging revealed preserved cone densities at temporal eccentricities from 2 to 8 angular degrees. The findings indicate that despite the presence of distinctive depigmentation of the retinal pigment epithelium in female carriers of choroideremia, their cone photoreceptor densities and SFCT are well-preserved. These observations may account for the good visual acuity and lack of an awareness of visual disturbances. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:76-85.].

Adaptive optics, in combination with multi-photon techniques, is a powerful approach to image deep into a specimen. Remarkably, virtually all adaptive optics schemes today rely on wavefront modulators that are reflective, diffractive or both. This, however, can pose a severe limitation for applications. Here, we present a fast and robust sensorless adaptive optics scheme adapted for transmissive wavefront modulators. We study our scheme in numerical simulations and in experiments with a novel, optofluidic wavefront shaping device that is transmissive, refractive, polarisation-independent, and broadband. We demonstrate scatter correction of two-photon-excited fluorescence images of microbeads as well as brain cells and benchmark our device against a liquid-crystal spatial light modulator. Our method and technology could open new routes for adaptive optics in scenarios where previously, the restriction to reflective and diffractive devices may have staggered innovation and progress.

Liquid crystal spatial light modulator (LC-SLM) has a series of attractive characteristics as a wave-front corrector of adaptive optical system such as compactness, high density integration, low cost and possibility of batch production. However, it also has some limitations such as effective only on polarized light, chromatic aberration and low response speed and limited phase stroke. In order to investigate these pros and cons in detail, a series of experiments and analyses have been conducted using a LC-SLM Model P256 of Boulder Nonlinear System. The nonlinear phase response to applied voltage was measured for 1 different wavelengths. The coupling between neighboring elements and response time were also measured. The error of phase wrapping for multi-wavelength wave-front of broad spectral band light was studied. The fitting capability to Zernike polynomials was demonstrated. An adaptive optical system with this LC-SLM and Shack-Hartmann sensor was close-looped. As a result, the applicability of LC-SLM for different applications will be evaluated and discussed.

This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD). We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. FEM were measured with high precision (RMS-S2S = 0.0015degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

We present an open-loop adaptive optics (AO) system based on two liquid-crystal spatial light modulators (LCSLMs) that profit from high precision wavefront generation and good repeatability. A wide optical bandwidth of 300 nm is designed for the system, and a new open-loop optical layout is invented to conveniently switch between the open and closed loop. The corresponding control algorithm is introduced with a loop frequency (the reciprocal of the total time delay of a correction loop) of 103 Hz. The system was mounted onto a 2.16 m telescope for vertical atmospheric turbulence correction. The full width at half-maximum of the image of the star α Boo reached 0.636 arc sec after the open-loop correction, while it was 2.12 arc sec before the correction. The result indicates that the open-loop AO system based on LCSLMs potentially has the ability to be used for general astronomical applications.

Author Index to volume 202