This PDF file contains the front matter associated with SPIE Proceedings Volume 11941, including the Title Page, Copyright information, Table of Contents, and Conference Committee listings.

A high-speed spectral-domain optical coherence tomography (SD-OCT) system was developed for ophthalmic applications. The system utilizes a supercontinuum laser to achieve ~1 µm axial and ~2µm lateral resolution in biological tissue at a 400 kHz image acquisition rate. This system can be used for in-vivo, non-contact imaging of the cellular structure of the human retina and cornea.

Hyalocytes are resident macrophages residing in the vitreous cortex of the eye. They help maintain optical clarity, manage immunological threats, and respond to vascular insults. Recently, Castanos et al 2020 reported the ability to image these cells using clinical OCT and Hammer et al 2020 demonstrated their appearance using AO OCT. In this study we demonstrate the use of quad detection AO SLO imaging combined with clinical en face OCT in healthy human subjects to observe the dynamic morphological changes and the variable motility of these cells above the retinal surface over extended time intervals.

Delayed dark adaptation due to homeostatic imbalances in the retina is a subclinical symptom of retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), the leading cause of irreversible vision loss. Thus, objective measurement of dark adaptation can facilitate the early diagnosis of various retinal diseases. However, there is a lack of noninvasive methods capable of simultaneous assessment of both anatomical arrangement and functional interactions among retinal cells. Here we demonstrate intrinsic signal optoretinography (ORG) of dark adaptation in the C57BL/6J mouse retina. Optical coherence tomography (OCT) imaging for ORG was continuously performed during dark adaptation at every 5 min interval for 30 minutes, and the spatiotemporal relationship of retinal activities was examined. We observed three imaging features in the retina under different light conditions. First, it was notable that dark adaptation caused a reduction in outer retinal thickness. Second, in the light-adapted retina, the 3rd band of the outer retina was distinguished, which was absent in the dark-adapted retina, and a hypo-reflective band between the 3rd and 4th band was only observed in the light-adapted retina. Third, OCT intensity of the 2nd outer retinal band markedly decreased in the dark-adapted retina. A strong positive correlation between morphophysiological activities was also confirmed. OCT-based ORG enables the measurement of dynamic progress of dark adaptation in a quantitative way with layer-specificity, which can aid in diagnosing early-stage retinal diseases.

Adaptive optics (AO) has enabled microscopic views of retinal neurons and assessment of their function in living eyes when combined with different imaging modalities, such as scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). Here, we present a novel design of a multimodal AO imaging system, based on Fourier domain mode-locked (FDML) laser technology. The design allows simultaneous and registered collection of AO-SLO images and AO-OCT volumes at near video rates (13.4 Hz). In addition to the multimodal optical design, the system also features an additional stimulus port and software algorithms to provide multiple functional modes with which to investigate living human retinal cells. The optical system was designed in Zemax with spherical mirrors placed in an out-of-plane configuration to reduce system astigmatism. The system was found to achieve diffraction limited image quality across a 4.5° × 4.5° scanning field. The measured AO-OCT system axial resolution is 8.7 μm in the eye, sensitivity was measured at 88 dB with ~7 dB roll-off over the first ~2 mm. The multimodal system performance was demonstrated by imaging various retinal cells and vessels with co-registered AO-OCT and AO-SLO images. The multifunctional feature was demonstrated by measuring the light-induced phase change of the cone outer segment. The methods will enable development of more sensitive AO-based cellular biomarkers for improved retinal disease diagnosis and treatment.

Currently available clinical devices cannot provide localized maps of corneal stiffness. We present a phase-sensitive method of compressional optical coherence elastography (OCE) for mapping corneal stiffness. In situ measurements showed that the strain, ε, slightly decreased as a function of IOP and CXL significantly decreased the strain (P<0.001). The change in pressure in the eye-globe, ΔIOP, was also measured during compression. We quantified the elasticity, E, of the cornea by E=ΔIOP/ε. In contrast to the strain, there was a significant effect of the baseline IOP on the stiffness (P<0.001). After CXL, there was a ~85% increase in stiffness, which was significant (P<0.001). In addition to the whole sample CXL, partial CXL was performed where only one half of the cornea was treated. The strain in the untreated region was significantly greater (P=0.030) than the strain in the CXL region, and the elasticity was significantly greater in the CXL region (P=0.030). Next, in vivo measurements were performed in an anesthetized rabbit. The strain decreased by ~75% after CXL, which was significant (P<0.001). Partial CXL was performed on another animal, where only half the cornea was treated. The strain in the untreated region was significantly less (P<0.001) than the strain in the CXL region. Our results show the capability of compression-based OCE to measure changes in corneal biomechanical properties in 4 different scenarios (in situ traditional CXL, in situ partial CXL, in vivo traditional CXL, in vivo partial CXL).

This study demonstrates the feasibility of using OCT to quantify microfluctuations in ocular biometry at steady-state accommodation. The preliminary results confirm the presence of two main frequency components in mechanical fluctuations of the lens consistent with prior studies on microfluctuations of optical accommodation (LFC: ≤ 0.6Hz and HFC: 1.0Hz – 2.5Hz). Both frequency components increased with accommodation. This study also measured axial eye length (AEL) fluctuations and found a peak around 2.5-3 Hz. The fluctuations in AEL may be caused by eye movements such as saccades.

While previously published work demonstrated the overall sensitivity of phase decorrelation optical coherence tomography (PhD-OCT) to crosslinking (CXL) in the cornea, it did not capitalize on the depth-resolving capability of PhD-OCT. Here, PhD-OCT was used to observe the depth-dependent differences in accelerated crosslinking efficiency with and without supplemental oxygen. Traditional crosslinking showed good crosslink formation in the anterior stroma. For accelerated CXL with supplemental oxygen, a significant stiffening effect was seen throughout the stroma. No stiffening was observed in accelerated CXL without supplemental oxygen or sham treatment. Thus, PhD-OCT may observe depth-dependent, protocol-specific changes in corneal tissue due to crosslinking.

We demonstrated a handheld swept-source optical coherence tomography (OCT) imaging system with a 400 kHz vertical-cavity surface-emitting laser (VCSEL) light source, a non-contact approach, and an unprecedented 105° field of view (FOV) that was capable of obtaining images from the posterior pole to peripheral retina in a single shot. A spiral scanning pattern allowing real-time visualization was also implemented here to improve the sampling efficiency. To the best of our knowledge, this is the widest FOV for a portable non-contact OCT retinal imaging system to date. Improvements to the FOV allow detection of peripheral pathology and aid better understanding of the role of peripheral pathology in retinal diseases.

The incorporation of adaptive optics (AO) technology into ophthalmic imaging systems has enhanced the understanding of retinal structure and function and the progression of various retinal diseases in adults by allowing for the dynamic correction of ocular and/or system aberrations. However, the in vivo visualization of important human retinal microanatomy, including cone photoreceptors, has been largely limited to fully cooperative subjects who are able to fixate and/or sit upright for extended imaging sessions in large tabletop AO systems. Previously, we developed the first handheld AO scanning laser ophthalmoscope capable of 2-D imaging of cone photoreceptors in supine adults and infants. In this work, we present the design and fabrication of the first handheld AO optical coherence tomography (HAOOCT) probe capable of collecting high-resolution volumetric images of the human retina. We designed custom optomechanics to build a spectral domain OCT system with a compact form factor of 22 cm × 18 cm × 5.2 cm and a total weight of 630 grams. The OCT imaging channel has a theoretical lateral resolution of 2.26 μm over a 1.0° × 1.0° field of view and an axial resolution of 4.01 μm. Stabilized imaging of healthy human adult volunteers revealed the 3-D photoreceptor structure and retinal pigment epithelium cells. HAOOCT was then deployed in handheld operation to image photoreceptors in upright and recumbent adults, indicating its potential to extend AO-OCT to previously excluded patient populations.

Ophthalmic devices, such as contact lenses (CLs), or intraocular lenses (IOLs) require a clear lens with minimal glistening for optimal retinal image quality. Glistenings, which are scattering centers in ophthalmic lenses, induce light scatter and can degrade visual performance. To better understand the visual impact of lens glistening, an optical model was developed to quantitatively investigate the optical performance of an ophthalmic device with different magnitudes of glistening. Scattering centers, with different sizes and density, were incorporated into a phantom ophthalmic lens to simulate overall lens-eye system optical modulation transfer function (MTF). Blur images, due to ophthalmic device glistering, were simulated. To understand the interactions among MTF value reduction, simulated retinal image degradation and patient’s subjective response, Just Noticeable Difference (JND), which is the amount of change in vision that is just noticeable when compared with the prior state, is employed to quantify patient’s subjective response to blur images. As an example, with a 0.25% volume density of 10-μm scattering centner, a 3JND patient’s visual perception degradation was computed for a 4-mm pupil size comparing with a scattering-free case.

Van Herick technique is a qualitative tool for assessing the anterior chamber angle and can be exploited as a simple screening alternative to gonioscopy. In our previous papers, we presented a novel instrument able to automatically perform the Van Herick manoeuvre. Therefore, to fully automate the screening method from the acquired images, it is still necessary to automatically determine the Van Herick grade. In this paper, we present a deep learning algorithm for automatically determining the Van Herick grade. In particular, the performances of three different Convolutional Neural Networks have been verified by acquiring the eye images of 80 patients. All the networks return the Van Herick grade classification with sufficient accuracy for a screening system and, after proper training, can offer a real-time response.

Many eye diseases, such as diabetic retinopathy (DR) and retinopathy of prematurity (ROP), can cause abnormalities at both central and peripheral regions of the fundus. Therefore, a wide field fundus imaging is desirable for screening, diagnosis, and treatment evaluation of eye diseases. The traditional fundus imaging device which uses trans-pupillary illumination has 30° to 60° field of view. In the trans-pupillary illumination, illumination path and observing path are typically separated by using different portions of the pupil to minimize the effect of reflectance artifact. Therefore, transpupillary illumination limits the field of view because only the central part can be used for imaging purpose. Transpalpebral illumination has been explored as an alternative approach to deliver light to the interior of the eye through the pars-plana, which enables capturing a wide portion of the fundus. Without the need of pharmacologic pupil dilation, a 150° visual angle fundus image was achieved. Previous studies implemented trans-palpebral illumination using a broadband LED. As it is well known that the transmission of long wavelength light is much higher than the short wavelength. Therefore, trans-palpebral illumination based fundus images are red oriented, with compromised image quality for visualizing retinal vasculatures. We have demonstrated the trans-palpebral illumination for the ultra-wide field fundus imaging. We report here the feasibility of using independent green and red illumination power controls to compensate for the difference of spectral efficiency. The color balanced trans-pars-planar illumination significantly increased dynamic range of the fundus camera.

Glaucoma is a global disease that leads to blindness due to pathological loss of retinal ganglion cell axons in the optic nerve head (ONH). The presented project aims at improving a computational algorithm for estimating the thickness and surface area of the waist of the nerve fiber layer in the ONH. Our currently developed deep learning AI algorithm meets the need for a morphometric parameter that detects glaucomatous change earlier than current clinical follow-up methods. In 3D OCT image volumes, two different AI algorithms identify the Optic nerve head Pigment epithelium Central Limit (OPCL) and the Inner limit of the Retina Closest Point (IRCP) in a 3D grid. Our computational algorithm includes the undulating surface area of the waist of the ONH, as well as waist thickness. In 16 eyes of 16 non-glaucomatous subjects aged [20;30] years, the mean difference in minimal thickness of the waist of the nerve fiber layer between our previous and the current post-processing strategies was estimated as CI_μ(0.95) 0 ±1 μm (D.f. 15). The mean surface area of the waist of the nerve fiber layer in the optic nerve head was 1.97 ± 0.19 mm². Our computational algorithm results in slightly higher values for surface areas compared to published work, but as expected, this may be due to surface undulations of the waist being considered. Estimates of the thickness of the waist of the ONH yields estimates of the same order as our previous computational algorithm.

The three classes of photoreceptors cones, rods, and intrinsically photosensitive retinal ganglion cells (ipRGCs) contribute to the pupillary light reflex (PLR). The Silent Substitution technique has been proposed to analyze the contribution of individual photoreceptor to PLR. Through the usage of properly selected pairs of light stimuli, this approach allows stimulating a single class of photoreceptors while keeping the activation of all the others constant. In this way, it is possible to understand the single photoreceptors class effect on both image-forming and non-image-forming functions of the human eyes. In this work, a simple approach to perform the Silent Substitution technique is presented and tested. The instrumentation has been designed with four primaries RGBY fiber-coupled LEDs and a double lens system to achieve a Maxwellian-View like optical system. Preliminary tests were conducted on three volunteers in which the PLRs induced by melanopic and chloropic stimulation were measured. The preliminary results confirm the expectations, the light-adapted pupil diameter is principally regulated by the activation level of the melanopsin-expressing ipRGCs photoreceptors, while conedriven induced pupil responses to peak in color contrast are transitory, reverting to the light-adapted baseline pupil diameter more rapidly in respect to melanopsin counterpart.

The purpose of this study is to use optical coherence tomography (OCT) to characterize the reflectance profiles of retinal blood vessels and to use these features for artery-vein classification in OCT angiography (OCTA). The retinal arteries and veins show unique features in the depth-resolved OCT. Both the upper and lower side of the retinal arteries have hyperreflective boundaries. However, retinal veins reveal only hyper-reflective boundary at the upper side. In both small and large arteries, relatively uniform lumen intensity was observed. On the other hand, the vein lumen intensity was dependent on the vessel size; the bottom half of the lumen of small veins show a hyper-reflective zone while the bottom half of the lumen of big veins a hypo-reflective zone.

Optical coherence tomography (OCT) is a well-established, non-invasive, high-resolution retinal imaging modality that is gaining widespread popularity in the clinic to assess pathological changes in the anterior segment, such as corneal edema, fibrosis, and neovascularization. We examined the potential of anterior segment (AS-OCT) as a quantitative and qualitative tool for grading ocular injury following chemical exposure. Current clinical ocular toxicity assessment primarily evaluates ocular surface changes, neglecting any deeper damage, and is largely incapable of gauging the depth of damage, a key prognostic determinant. In this work, we demonstrate the capability of AS-OCT to visualize ocular changes, such as Descemet’s membrane detachment, corneal swelling, epithelial keratinization, and iris damage. Furthermore, we show consistent differences in the progression of corneal damage following chemical exposure at mild, moderate, and severe dose levels and attempt to quantify some of these changes, such as corneal thickness and neovascularization. In conclusion, AS-OCT combined with OCT angiography (OCTA) is a powerful non-invasive imaging tool for monitoring changes in the eye and provides an improved understanding of the concentration-dependent progression of chemical injury. As such, AS-OCT can guide the clinical management of ocular chemical exposures, as well as advance eye irritation safety testing.

Early detection of diabetic retinopathy (DR) is an essential step to prevent vision losses. This study is to conduct comparative optical coherence tomography (OCT) and OCT-Angiography (OCTA) analysis, and to identify quantitative features for robust detection of early DR. Five quantitative OCT features were derived to analyze the outer retinal band intensity in the central fovea, parafovea and perifovea regions. Similarly, eight quantitative OCTA features were established to analyze the superficial and deep vascular plexuses. OCT and OCTA images of 21 eyes from healthy control subjects, 20 eyes from diabetic patients without retinopathy (NoDR), and 21 eyes from mild DR patients were used for this study. Comparative analysis revealed that quantitative OCT features related to the Inner Segment ellipsoid (ISe) has the best sensitivity for objective differentiation of all cohorts.

An intact blood-retinal barrier is critical to maintaining the function of the retina. Many diseases of the eye have been directly associated with impairment in vascular permeability, and methods to measure vascular permeability could offer a window into early detection of disease; however, there exist no direct measures of vascular permeability that have be translated to the clinic. This work details a complete clinical workflow to quantify vascular permeability and volumetric blood flow from fluorescein videoangiography data, with validation through realistic simulations. For optimizing the protocol, this study carried on frame rate of fluorescein videoangiography to generate a high-resolution image while minimizing the error.

The foveal avascular zone (FAZ), as visualized by optical coherence tomography angiography (OCTA), has distinct parametric characteristics. These metrics can help us understand FAZ variations in various ophthalmic conditions such as diabetic retina, retinopathy of prematurity, glaucoma, and pathological myopia. One of the several factors that influence the accuracy of these measures is the eye's axial length (AXL). Even though the OCTA is designed to image the retina with a standard AXL of 23.95 mm, there is considerable variation even in normal healthy eyes; for example, the average Indian's AXL is 23.34 ± 1.12 mm, which would result in retinal image magnification changes It has been reported that, if the FAZ area is not corrected for AXL, there can be up to a 51.0 % deviation in the measured parameters. Bennett's correction (and variations) are commonly employed to determine axial magnification. This study compares the effects of magnification in emmetropic Indian eyes with and without Bennett's correction. The FAZ dimensions were measured in healthy normal Indian subjects with a mean ± SD of 27.38 ± 11.62 years, AXL 23.40 ± 0.88 mm, and mean spherical equivalent of 0.08 ± 0.24 D using a newly designed automated image processing approach. Our results indicate no need to correct axial length variations over a 23.18 to 24.01 mm range in emmetropic eyes. This implies that any AXL longer than 24.01 mm and smaller than 23.18 mm may require axial magnification correction to precisely measure FAZ parameters.

Optic disc tilt (ODT), increased ovality, peripapillary atrophy, and abnormally large or small optic discs are the earliest known reported changes in myopic eyes. Studies of these early changes may lead to a better understanding of the pathophysiology of myopia progression. The study aims to investigate if there is a relationship between the ODT and ovality in myopes. ODT. The ovality index was quantified in myopic eyes (n=33) and compared with 21 emmetropic eyes. The myopic OCT images were labelled based on a severity scale as low-moderate (between -0.50 D to -6.00 D SE) and high-myopia (worse than -6.00 D SE) using standard myopia classifications. From segmented OCT images of the optic nerve head, the optic disc boundary was extracted by traversing all the pixels of the image and selecting only those pixels with an intensity value lower than 30 in all 3 color channels. Then, an ellipse was fit to the extracted optic disc boundaries using an automated image processing method. From these the long and short axes of the ellipses were measured. Using this measurement ODT and ovality were calculated. Higher ODT was observed with the shorter axis in low-moderate myopic eyes 18.15 (IQR 15.83 – 23.81) and smaller ODT was observed in the high-myopic eye’s longer axis 11.83 (IQR 7.20 – 14.39). A significantly altered ovality index was observed with increase in degree of myopia.