The effect of image resolution of display types on accommodative microfluctuations.

PURPOSE: To determine whether accommodative microfluctuations (AMFs) are affected by the image resolution of the display type being observed. The effect of refractive error is also examined. METHODS: Twenty participants, (10 myopes and 10 emmetropes) observed a target on four different displays: paper, smartphone, e-reader and visual display unit screen (VDU), whilst their accommodative responses were measured using a continuous recording infrared autorefractor. The accommodative response and AMF measures comprising low frequency components (LFC), high frequency components (HFC) and the root mean square (RMS) of the AMFs were analysed. RESULTS: A significant increase in LFC power was observed for the paper stimulus when compared to the VDU and smartphone conditions. Myopes demonstrated a significantly higher LFC and mean accommodative response compared to emmetropes across the four displays. A significant difference in the mean AR between the displays with the lowest and highest resolution was found. A higher mean AR was found with higher resolution of the image. The HFC and RMS accommodation were not affected by display type. CONCLUSION: The mean accommodative response and the mean LFC power appear to respond differently depending on the type of display in use. Higher resolution devices showed a reduced lag of accommodation to the accommodative demand; however, this may cause a lead of accommodation in myopes for higher resolution display types.

Wavefront-sensorless adaptive optics with a laser-free spinning disk confocal microscope.

Adaptive optics is being applied widely to a range of microscopies in order to improve imaging quality in the presence of specimen-induced aberrations. We present here the first implementation of wavefront-sensorless adaptive optics for a laser-free, aperture correlation, spinning disk microscope. This widefield method provides confocal-like optical sectioning through use of a patterned disk in the illumination and detection paths. Like other high-resolution microscopes, its operation is compromised by aberrations due to refractive index mismatch and variations within the specimen. Correction of such aberrations shows improved signal level, contrast and resolution.

Adaptive optics visual simulators: a review of recent optical designs and applications [Invited].

In their pioneering work demonstrating measurement and full correction of the eye's optical aberrations, Liang, Williams and Miller, [JOSA A14, 2884 (1997)10.1364/JOSAA.14.002884] showed improvement in visual performance using adaptive optics (AO). Since then, AO visual simulators have been developed to explore the spatial limits to human vision and as platforms to test non-invasively optical corrections for presbyopia, myopia, or corneal irregularities. These applications have allowed new psychophysics bypassing the optics of the eye, ranging from studying the impact of the interactions of monochromatic and chromatic aberrations on vision to neural adaptation. Other applications address new paradigms of lens designs and corrections of ocular errors. The current paper describes a series of AO visual simulators developed in laboratories around the world, key applications, and current trends and challenges. As the field moves into its second quarter century, new available technologies and a solid reception by the clinical community promise a vigorous and expanding use of AO simulation in years to come.

Adaptive optics for high-resolution imaging.

Adaptive optics (AO) is a technique that corrects for optical aberrations. It was originally proposed to correct for the blurring effect of atmospheric turbulence on images in ground-based telescopes and was instrumental in the work that resulted in the Nobel prize-winning discovery of a supermassive compact object at the centre of our galaxy. When AO is used to correct for the eye's imperfect optics, retinal changes at the cellular level can be detected, allowing us to study the operation of the visual system and to assess ocular health in the microscopic domain. By correcting for sample-induced blur in microscopy, AO has pushed the boundaries of imaging in thick tissue specimens, such as when observing neuronal processes in the brain. In this primer, we focus on the application of AO for high-resolution imaging in astronomy, vision science and microscopy. We begin with an overview of the general principles of AO and its main components, which include methods to measure the aberrations, devices for aberration correction, and how these components are linked in operation. We present results and applications from each field along with reproducibility considerations and limitations. Finally, we discuss future directions.

Compact and contactless reflectance confocal microscope for neurosurgery.

Visual guidance at the cellular level during neurosurgical procedures is essential for complete tumour resection. We present a compact reflectance confocal microscope with a 20 mm working distance that provided <1.2 µm spatial resolution over a 600 µm × 600 µm field of view in the near-infrared region. A physical footprint of 200 mm × 550 mm was achieved using only standard off-the-shelf components. Theoretical performance of the optical design was first evaluated via commercial Zemax software. Then three specimens from rodents: fixed brain, frozen calvaria and live hippocampal slices, were used to experimentally assess system capability and robustness. Results show great potential for the proposed system to be translated into use as a next generation label-free and contactless neurosurgical microscope.

High precision automated alignment procedure for two-mirror telescopes.

A significant challenge in the production of Earth observation satellites is the precise alignment of the telescope optical components. We have developed a strategy to perform automated alignment of two-mirror telescopes for use in a realistic factory-based setting. A Ritchey-Chrétien telescope was used as an example. The secondary mirror was mounted on a high precision hexapod and its misalignment inferred from the Zernike coefficients for tilt, defocus, and coma, as measured by a phase-shifting interferometer. The required corrections to the position of the secondary mirror were implemented using an integral controller and alignment was achieved within minutes, compared to within days when using a manual alignment process. The Zernike coefficient for each aberration was reduced to within one standard deviation of the fluctuations due to residual instability (48 nm).

Cognitive Demand and Accommodative Microfluctuations.

Previous studies have shown cognition to have an influence on accommodation. Temporal variation in the accommodative response occurs during the fixation on a stationary target. This constantly shifting response has been called accommodative micro-fluctuations (AMFs). The aim of this study is to determine the effects of increasing task cognitive demand on the ocular accommodation response. AMFs for 12 myopes and 12 emmetropes were measured under three conditions of varying cognitive demand and comprising reading of numbers (Num), simple arithmetic (SA), and complex arithmetic (CA). Fast Fourier transforms were used to analyze the different frequency band components of the AMFs. Other aspects of AMFs including root mean square accommodation values and chaos analysis was applied. A repeated measures ANOVA revealed a significant main effect of cognition in the mean power of the high frequency component (HFC) (F2,44 = 10.03, p < 0.005). Pairwise analyses revealed that these differences exist between SA and CA tasks (p < 0.005) and the Num and CA (p < 0.005) tasks with the HFC power being the highest for the CA condition. It appears that the difficulty of a task does affect active accommodation but to a lesser extent than other factors affecting accommodation.

Sensitivity of Chaos Measures in Detecting Stress in the Focusing Control Mechanism of the Short-Sighted Eye.

When fixating on a stationary object, the power of the eye's lens fluctuates. Studies have suggested that changes in these so-called microfluctuations in accommodation may be a factor in the onset and progression of short-sightedness. Like many physiological signals, the fluctuations in the power of the lens exhibit chaotic behaviour. A breakdown or reduction in chaos in physiological systems indicates stress to the system or pathology. The purpose of this study was to determine whether the chaos in fluctuations of the power of the lens changes with refractive error, i.e. how short-sighted a subject is, and/or accommodative demand, i.e. the effective distance of the object that is being viewed. Six emmetropes (EMMs, non-short-sighted), six early-onset myopes (EOMs, onset of short-sightedness before the age of 15), and six late-onset myopes (LOMs, onset of short-sightedness after the age of 15) took part in the study. Accommodative microfluctuations were measured at 22 Hz using an SRW-5000 autorefractor at accommodative demands of 1 D (dioptres), 2 D, and 3 D. Chaos theory analysis was used to determine the embedding lag, embedding dimension, limit of predictability, and Lyapunov exponent. Topological transitivity was also tested for. For comparison, the power spectrum and standard deviation were calculated for each time record. The EMMs had a statistically significant higher Lyapunov exponent than the LOMs ([Formula: see text] vs. [Formula: see text]) and a lower embedding dimension than the LOMs ([Formula: see text] vs. [Formula: see text]). There was insufficient evidence (non-significant p value) of a difference between EOMs and EMMs or EOMs and LOMs. The majority of time records were topologically transitive. There was insufficient evidence of accommodative demand having an effect. Power spectrum analysis and assessment of the standard deviation of the fluctuations failed to discern differences based on refractive error. Chaos differences in accommodation microfluctuations indicate that the control system for LOMs is under stress in comparison to EMMs. Chaos theory analysis is a more sensitive marker of changes in accommodation microfluctuations than traditional analysis methods.

Vision science and adaptive optics, the state of the field.

Adaptive optics is a relatively new field, yet it is spreading rapidly and allows new questions to be asked about how the visual system is organized. The editors of this feature issue have posed a series of question to scientists involved in using adaptive optics in vision science. The questions are focused on three main areas. In the first we investigate the use of adaptive optics for psychophysical measurements of visual system function and for improving the optics of the eye. In the second, we look at the applications and impact of adaptive optics on retinal imaging and its promise for basic and applied research. In the third, we explore how adaptive optics is being used to improve our understanding of the neurophysiology of the visual system.

BMP2 repression and optimized culture conditions promote human bone marrow-derived mesenchymal stem cell isolation.

AIM: Human mesenchymal stem cells (hMSC) are multipotent progenitor cells. We propose the optimization of hMSC isolation and recovery using the application of a controlled hypoxic environment. MATERIALS & METHODS: We evaluated oxygen, glucose and serum in the recovery of hMSC from bone marrow (BMhMSC). Colony forming units-fibroblastic, cell numbers, tri-lineage differentiation, immunofluorescence and microarray were used to confirm and characterize BMhMSC. RESULTS: In an optimized (2% O(2), 4.5 g/l glucose and 5% serum) environment both colony forming units-fibroblastic (p = 0.01) and cell numbers (p = 0.0001) were enhanced over standard conditions. Transcriptional analysis identified differential expression of bone morphogenetic protein 2 (BMP2) and, putatively, chemokine (C-X-C motif) receptor 2 (CXCR2) signaling pathways. CONCLUSION: We have detailed a potential milestone in the process of refinement of the BMhMSC isolation process.

Effect of correction of aberration dynamics on chaos in human ocular accommodation.

We used adaptive optics to determine the effect of monochromatic aberration dynamics on the level of chaos in the accommodation control system. Four participants viewed a stationary target while the dynamics of their aberrations were either left uncorrected, defocus was corrected, or all aberrations except defocus were corrected. Chaos theory analysis was used to discern changes in the accommodative microfluctuations. We found a statistically significant reduction in the chaotic nature of the accommodation microfluctuations during correction of defocus, but not when all aberrations except defocus were corrected. The Lyapunov exponent decreased from 0.71 ± 0.07 D/s (baseline) to 0.55 ± 0.03 D/s (correction of defocus fluctuations). As the reduction of chaos in physiological signals is indicative of stress to the system, the results indicate that for the participants included in this study, fluctuations in defocus have a more profound effect than those of the other aberrations. There were no changes in the power spectrum between experimental conditions. Hence chaos theory analysis is a more subtle marker of changes in the accommodation control system and will be of value in the study of myopia onset and progression.

Processing blur of conflicting stimuli during the latency and onset of accommodation.

The accommodative response (AR) to changes in dioptric accommodative stimulus (AS) during the latency period and onset of accommodation was investigated. Participants monocularly observed one period of a square wave in AS, with a 2-D baseline and mean, and amplitude 1 D or 2 D; the period of the square wave ranged from 0.10 s to 1.00 s; both increases and decreases were used for the first step in AS. At periods of 0.30s and longer, accommodation was found to respond to both levels of the stimulus. Rapid retinal monitoring appeared to be taking place for such stimuli. The amplitudes of peaks in AR did not usually depend on whether a particular level of AS occurred first or second, but for 8/40 conditions, a significant difference was found, with a stronger response when the level of AS occurred second. Null or incorrect responses were also observed in many trials, possibly linked with the natural microfluctuations of accommodation. Minimum response times to the changes in AS were observed, which increased with decreasing period of the AS. The time interval between peaks in the AR decreased with decreasing period of the AS. The findings were consistent with a parallel processing model previously proposed for saccades, where input from a later change in stimulus may enter an element of the control system when that element has finished processing an earlier change. More than one change in stimulus may therefore be passing through the multi-element control system at a time.

Correspondence of chaos in binocular aberration dynamics.

We used a binocular Shack-Hartmann sensor to measure the aberration dynamics of six participants at a rate of 21 Hz. Chaos theory analysis was used to determine the Lyapunov exponent for the time evolution of the rms wavefront error, accommodation, and each individual Zernike coefficient up to and including the fifth radial order. In all cases there was no statistically significant difference between the Lyapunov exponents between the two eyes, suggesting that the level of chaos is common between them. The mean Lyapunov exponent averaged across both eyes of all participants was 0.42±0.14 µm/s for the rms wavefront error, 0.37±0.06 D/s for accommodation, and 0.32±0.09 µm/s averaged across Zernike coefficients. We found no statistically significant correlation per se between the eyes, except for horizontal coma. The correlation may be masked by the impact of differing tear film dynamics. Understanding the nature of aberration dynamics has utility in optimizing the performance of adaptive optics systems for the human eye.

Chaos in ocular aberration dynamics of the human eye.

Since the characterization of the eye's monochromatic aberration fluctuations in 2001, the power spectrum has remained the most widely used method for analyzing their dynamics. However, the power spectrum does not capture the complexities of the fluctuations. We measured the monochromatic aberration dynamics of six subjects using a Shack-Hartmann sensor sampling at 21 Hz. We characterized the dynamics using techniques from chaos theory. We found that the attractor embedding dimension for all aberrations, for all subjects, was equal to three. The embedding lag averaged across aberrations and subjects was 0.31 ± 0.07 s. The Lyapunov exponent of the rms wavefront error was positive for each subject, with an average value of 0.44 ± 0.15 µm/s. This indicates that the aberration dynamics are chaotic. Implications for future modeling are discussed.

Multifractal nature of ocular aberration dynamics of the human eye.

Ocular monochromatic aberrations display dynamic behavior even when the eye is fixating on a stationary stimulus. The fluctuations are commonly characterized in the frequency domain using the power spectrum obtained via the Fourier transform. In this paper we used a wavelet-based multifractal analytical approach to provide a more in depth analysis of the nature of the aberration fluctuations. The aberrations of five subjects were measured at 21 Hz using an open-view Shack-Hartmann sensor. We show that the aberration dynamics are multifractal. The most frequently occurring Hölder exponent for the rms wavefront error, averaged across the five subjects, was 0.31 ± 0.10. This suggests that the time course of the aberration fluctuations is antipersistant. Future applications of multifractal analysis are discussed.

Effect of temporal location of correction of monochromatic aberrations on the dynamic accommodation response.

Dynamic correction of monochromatic aberrations of the eye is known to affect the accommodation response to a step change in stimulus vergence. We used an adaptive optics system to determine how the temporal location of the correction affects the response. The system consists of a Shack-Hartmann sensor sampling at 20 Hz and a 37-actuator piezoelectric deformable mirror. An extra sensing channel allows for an independent measure of the accommodation level of the eye. The accommodation response of four subjects was measured during a +/- 0.5 D step change in stimulus vergence whilst aberrations were corrected at various time locations. We found that continued correction of aberrations after the step change decreased the gain for disaccommodation, but increased the gain for accommodation. These results could be explained based on the initial lag of accommodation to the stimulus and changes in the level of aberrations before and after the stimulus step change. Future considerations for investigations of the effect of monochromatic aberrations on the dynamic accommodation response are discussed.

One-step recovery of marrow stromal cells on nanofibers.

This study describes the one-step isolation and expansion of marrow stromal cells (MSCs) directly onto the implantable nanofibrous scaffolds. Coverslips were first coated with either aligned or random configurations of poly L,D lactic acid, poly lactic-glycolic acid, and poly-epsilon-caprolactone and then seeded with fresh bone marrow aspirate. Colony-forming units were quantified and the differentiation capacities of the recovered cells were explored. Further optimization was provided by exploring the impact of hyperoxic (21% O(2)) and physiologically approximate (2% O(2)) on cell recovery. Aligned nanofibers in 2% O(2) were identified as being superior for isolation of MSCs. Isolated cells formed colonies following the direction of nanofibers, indicating potential for guided tissue regeneration. The isolated MSCs demonstrated retention of multipotency. These findings offer a rapid, cost-effective method of producing a stem-cell-seeded scaffold for regeneration of multiple tissue types.

Effect of correction of ocular aberration dynamics on the accommodation response to a sinusoidally moving stimulus.

We used an adaptive optics system to correct the aberration dynamics of five subjects while they fixated on a monochromatic stimulus undergoing sinusoidal vergence changes between 1.5 and 2.5 D, at a temporal frequency of 0.2 Hz. The aberrations were measured at 20 Hz using a Shack-Hartmann sensor and corrected using a 37-actuator deformable mirror. The accommodation response (AR) was analyzed in terms of the gain and phase lag. Manipulation of aberrations significantly affected the gain of the AR for only one subject when the odd-order aberrations were corrected. The predictability of the sinusoidal stimulus could account for the lack of an effect in the remaining subjects and conditions.

Dual wavefront sensing channel monocular adaptive optics system for accommodation studies.

Manipulation of the eye's aberrations using adaptive optics (AO) has shown that optical imperfections can affect the dynamic accommodation response. A limitation of current system designs used for such studies is an inability to make direct measurements of the eye's aberrations during the experiment. We present an AO system which has a dual wavefront sensing channel. The corrective device is a 37-actuator piezoelectric deformable mirror. The measurements used to control the mirror, and direct measurements of the eye's aberrations, are captured on a single Shack-Hartmann sensor. Other features of the system include stroke amplification of the deformable mirror and a rotating diffuser to reduce speckle.We demonstrate the utility of the system by investigating the impact of aberration dynamics on the control of steady-state accommodation on four subjects.

Role of ocular aberrations in dynamic accommodation control.

BACKGROUND: Accommodation control is mediated by a number of cues, including blur,chromatic aberration and target proximity. Data from wavefront measurements have shown clear shifts in ocular aberrations during increasing accommodative demand, most notably a negative shift in spherical aberration. Work in adaptive optics, where aberrations have been corrected, has suggested a role for aberrations in the control of accommodation for some individuals. This study aimed to determine the relative effects of aberration correction and inversion on closed-loop stepwise accommodation responses to small increases and decreases in stimulus vergence. METHODS: An adaptive optics system was used to modify ocular aberrations, while five participants viewed a high contrast target stepping 0.5 D in an inward or outward direction. Aberrations were variously unchanged, corrected or inverted following the step change in stimulus vergence. A Shack-Hartmann wavefront sensor was used to record accommodative responses to the stepwise changes in stimulus vergence. Accommodative response data were analysed using a curve fitting method to calculate the gain,latency and response time. RESULTS: Correction of aberrations failed to have a significant effect on dynamic accommodative responses. Inversion of even-order aberration terms produced a significant reduction in accommodative response gain for outward steps in stimulus vergence.Additionally, an increase in the number of accommodative responses in the wrong direction was seen following aberration inversion. Inward steps were not altered significantly by aberration inversion. CONCLUSION: Accommodation in humans appears to derive a cue from the even-order aberrations of the eye to help guide the initial direction of responses to reductions in stimulus vergence (that is, disaccommodation). With all aberrations and even-order aberrations inverted, the number of incorrect directional responses to outward moving stimuli increases, suggesting that aberrations are important in determining the initial path of stepwise accommodative responses.