Age-related changes in geometry and transparency of human crystalline lens revealed by optical signal discontinuity zones in swept-source OCT images.

BACKGROUND: The shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function. METHODS: OCT images of the anterior segment of 49 eyes of subjects (9-78 years) were acquired, and the OSD zones (nucleus, C1-C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye's optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed. RESULTS: The increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (- 0.053 mm/year, - 0.013 mm/year and - 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1ß, and the highest increase in density was in the C2-C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function. CONCLUSIONS: OCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure-function relationship of the ageing lens and offer insights into both pathological and aging alterations.

Increased crystalline lens coverage in optical coherence tomography with oblique scanning and volume stitching.

A three-dimensional optical coherence tomography (OCT) crystalline lens imaging method based on oblique scanning and image stitching is presented. The method was designed to increase OCT imaging volume of crystalline lens in vivo. A long-range swept-source (SS)-OCT imaging system, which can measure the entire anterior segment of eye in a single acquisition, is used to acquire one central volume and 4 extra volumes with different angles between optical axis of OCT instrument and the pupillary axis. The volumes are then stitched automatically by developed software. To show its effectiveness and verify its validity, we scanned the subjects before and after pupil dilation drops and compared the experimental results. By determining the number of voxels representing the signal from the crystalline lens in 3-D OCT images, our method can provide around 17% additional volumetric lens coverage compared with a regular imaging procedure. The proposed approach could be used clinically in early diagnosis of cortical cataract. Wider field of view offered by this method may facilitate more accurate lens biometry in its peripheral zones, which potentially contributes to understanding of lens shape modifications of the accommodating eye.

Volumetric Optical Imaging and Quantitative Analysis of Age-Related Changes in Anterior Human Vitreous.

Purpose: The purpose of this study was to characterize age-related changes in anterior human vitreous with 3-D swept source optical coherence tomography (SS-OCT) and evaluate associations with axial length (AL) and contrast sensitivity function (CSF). Methods: There were 49 phakic eyes in 49 patients (40.0 ± 19.3 years) had 3-D volumetric scanning of the lens and retrolental vitreous with SS-OCT at 1050 nm. OCT-derived indices of vitreous optical density (VOD), vitreous opacification ratio (VOR), and lens optical density (LOD) were correlated with AL and double-pass assessment of retinal point spread function (Objective Scatter Index [OSI]). CSF was measured using an adaptive-optics visual simulator (area under log-log contrast sensitivity function [AULCSF]). Results: Vitreous SS-OCT detected gel vitreous, liquefied lacunae, Berger's space, retrolental laminae, and fibrous opacifications. VOD, VOR, and LOD showed high reproducibility (intraclass correlation coefficients 0.968, 0.975, and 0.998, respectively). VOD was highly correlated with VOR (Pearson's R = 0.96, P < 0.000001). VOD, VOR, and LOD correlated with age (R = 0.48, 0.58, and 0.85, P < 0.001 for each). VOR and LOD correlated with OSI (R = 0.36, P = 0.0094, and R = 0.36, P = 0.0096, respectively). VOR correlated negatively with AULCSF (R = -0.53, P < 0.00009), which was related to OSI. Myopic eyes had higher OSI than nonmyopic eyes (P = 0.0121), consistent with correlation between OSI and AL (R = 0.37, P = 0.0091). Multivariable regression confirmed these findings. Conclusions: SS-OCT visualized microstructural features of anterior human vitreous, where opacification is associated with increased light scattering and CSF degradation. SS-OCT enables high-resolution optical evaluation of vitreous opacities.

In vivo SS-OCT imaging of crystalline lens sutures.

We demonstrate in vivo three-dimensional (3-D) visualization of crystalline lens sutures in healthy eyes using swept source optical coherence tomography (SS-OCT). Volumetric data sets of the crystalline lenses were acquired and processed to obtain enhanced contrast projection images and to extract suture patterns in both anterior and posterior lens. The results presented different types of the sutures including Y-sutures, simple and complex star sutures. Age-related changes in suture arrangement were characterized quantitatively. Crystalline lens suture imaging with SS-OCT might be a useful tool in fundamental studies on development and ageing of human lens.

Two-photon microperimetry: sensitivity of human photoreceptors to infrared light.

Microperimetry is a subjective ophthalmologic test used to assess retinal function at various specific and focal locations of the visual field. Historically, visible light has been described as ranging from 400 to 720 nm. However, we previously demonstrated that infra-red light can initiate visual transduction in rod photoreceptors by a mechanism of two-photon absorption by visual pigments. Here we introduce a newly designed and constructed two-photon microperimeter. We provide for the first time evidence of the presence of a nonlinear process occurring in the human retina based on psychophysical tests using newly developed instrumentation. Since infra-red light penetrates the aged front of the eye better than visible light, it has the potential for improved functional diagnostics in patients with age-related visual disorders.

Two-photon imaging of the mammalian retina with ultrafast pulsing laser.

Noninvasive imaging of visual system components in vivo is critical for understanding the causal mechanisms of retinal diseases and for developing therapies for their treatment. However, ultraviolet light needed to excite endogenous fluorophores that participate in metabolic processes of the retina is highly attenuated by the anterior segment of the human eye. In contrast, 2-photon excitation fluorescence imaging with pulsed infrared light overcomes this obstacle. Reducing retinal exposure to laser radiation remains a major barrier in advancing this technology to studies in humans. To increase fluorescence intensity and reduce the requisite laser power, we modulated ultrashort laser pulses with high-order dispersion compensation and applied sensorless adaptive optics and custom image recovery software and observed an over 300% increase in fluorescence of endogenous retinal fluorophores when laser pulses were shortened from 75 fs to 20 fs. No functional or structural changes to the retina were detected after exposure to 2-photon excitation imaging light with 20-fs pulses. Moreover, wide bandwidth associated with short pulses enables excitation of multiple fluorophores with different absorption spectra and thus can provide information about their relative changes and intracellular distribution. These data constitute a substantial advancement for safe 2-photon fluorescence imaging of the human eye.

OCT angiography by absolute intensity difference applied to normal and diseased human retinas.

We compare four optical coherence tomography techniques for noninvasive visualization of microcapillary network in the human retina and murine cortex. We perform phantom studies to investigate contrast-to-noise ratio for angiographic images obtained with each of the algorithm. We show that the computationally simplest absolute intensity difference angiographic OCT algorithm that bases only on two cross-sectional intensity images may be successfully used in clinical study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein occlusion.

Multi-parametric imaging of murine brain using spectral and time domain optical coherence tomography.

Examination of brain functions in small animal models may help improve the diagnosis and treatment of neurological conditions. Transcranial imaging of small rodents' brains poses a major challenge for optical microscopy. Another challenge is to reduce the measurement time. We describe methods and algorithms for three-dimensional assessment of blood flow in the brains of small animals, through the intact skull, using spectral and time domain optical coherence tomography. By introducing a resonant scanner to the optical setup of the optical coherence tomography (OCT) system, we have developed and applied a high-speed spectral OCT technique that allows us to vary the imaging range of flow and to shorten measurement time. Multi-parameter signal analysis enables us to obtain both qualitative and quantitative information about flow velocity from the same set of data.