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At least 91 records · Page 5

2022 Prentice Award Lecture: Advancing Retinal Imaging and Visual Function in Patient Management and Disease Mechanisms

Patient-based research plays a key role in probing basic visual mechanisms. Less-well recognized is the role of patient-based retinal imaging and visual function studies in elucidating disease mechanisms, which are accelerated by advances in imaging and function techniques and are most powerful when combined with the results from histology and animal models. A patient's visual complaints can be one key to patient management, but human data are also key to understanding disease mechanisms. Unfortunately, pathological changes can be difficult to detect. Before advanced retinal imaging, the measurement of visual function indicated the presence of pathological changes that were undetectable with existing clinical examination. Over the past few decades, advances in retinal imaging have increasingly revealed the unseen. This has led to great strides in the management of many diseases, particularly diabetic retinopathy and macular edema, and age-related macular degeneration. It is likely widely accepted that patient-based research, as in clinical trials, led to such positive outcomes. Both visual function measures and advanced retinal imaging have clearly demonstrated differences among retinal diseases. Contrary to initial thinking, sight-threatening damage in diabetes occurs to the outer retina and not only to the inner retina. This has been clearly indicated in patient results but has only gradually entered the clinical classifications and understanding of disease etiology. There is strikingly different pathophysiology for age-related macular degeneration compared with photoreceptor and retinal pigment epithelial genetic defects, yet research models and even some treatments confuse these. It is important to recognize the role that patient-based research plays in probing basic visual mechanisms and elucidating disease mechanisms, combining these findings with the concepts from histology and animal models. Thus, this article combines sample instrumentation from my laboratory and progress in the fields of retinal imaging and visual function.

60 APPLIED LIFE SCIENCES↗

Cadmium-Free QD Building Blocks for Human Centric Lighting

This project developed Cd-free quantum dot (QD) downconverters for efficacious human-centric lighting (HCL) light emitting diode (LED) devices. Solid state HCL devices address the lack of light in the cyan wavelength region (460-490 nm) in white LEDs by enhancing the melanopic daylight efficacy ratio (MDER) value. MDER is a metric that indicates the degree to which artificial lighting stimulates nonvisual biological processes in the retina responsible for regulating circadian rhythms compared with natural lighting. The peak sensitivity of melanopsin in the retina is at 479 nm, therefore artificial lighting which can fill the well-known “cyan gap” may improve human health. Due to the Restriction of Hazardous Substances (RoHS) regulations, cadmium-free core/shell/shell QDs are the primary targets for low toxicity, tunable downconverters. Cyan- and red-emitting core/shell/shell QDs were implemented in LED devices toward achieving a brightness of 210 lm/W at 4000 K, CRI 90, and MDER > 0.7. Synthetic development of Cd-free materials yielded cyan InP/ZnS QDs with a photoluminescence quantum yield (PLQY) of ~60% between 480-490 nm, and red InP/ZnSe/(ZnSeS)/ZnS QDs reaching ~80% PLQY at 620-630 nm. We successfully demonstrated that the inclusion of cyan QDs increased the MDER value to ≥0.7, but the brightness of the HCL LED devices was hindered due to low PLQY values. However, upon substitution of the Cd-free cyan QD with a low-Cd QD with >90% PLQY, brightness improved by 25% over the Cd-free device to 179 lm/W. Despite the technical obstacles remaining toward improving emission characteristics and stability of QDs under high flux, we have confirmed the promise of narrow, tunable QD emitters in SSL packages toward the goal of healthy, human-centric lighting.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy

The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving putative synaptic structures and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions with sub-capillary details in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high-resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

Sensory, Decision and Control Systems: April to July 1966

The quarter reported here for the NASA contract, and the longer period reported for the Air Force contract, saw the development of two system concepts for the transmission of video data from a remote location to Earth. In the simpler system, a stereoscopic outline together with other data such as reflectance and possibly the texture of objects will be transmitted to Earth. The objects considered are those larger than a predetermined size and within a predetermined range. From the stereoscopic outlines presented to the operator on Earth he will decide what objects he would like pictured in full TV frames and order these transmitted. In the more elaborate system, TV cameras will be carried on a vehicle and the direction in which the vehicle moves will be chosen by an onboard decision computer. Perceptual decisions may also be made to identify objects whose characteristics have been reported to Earth and whose value to the Earth observer has been communicated back to the perceptual computer. The assembly of cameras, perceptual computer, decision computer and vehicle is called a robot. Photosensors for this robot are television cameras, the first models of which have been tested under computer control. A model of both the perceptual computer and the decision computer has been simulated. It consists of 12 modules, each of which makes an initial guess as to what the response to incoming data should be. Each takes the data from all other modules and combines it in a nonlinear fashion with the data coming directly into it to arrive at a mixed guess as to what act should be performed. When 60% of the modules vote 0. 5 probability for one act, that act is performed. Convergence to a satisfactory decision took from 5 to 25 time steps. The model of the frog's retina previously reported is here extended to that part of the brain, called the tectum, where the frog begins to respond to objects detected by the retina.

Control system↗

Automatic optometer operates with infrared test pattern

Refractive strength of human eye is monitored by optometer that automatically and continuously images infrared test pattern onto the retina. Condition of focus of the eye at any instant is determined from optometer settings needed to maintain focus of the pattern on the retina.

Cornsweet, T. N.↗

Human visual response to nuclear particle exposures

Experiments with accelerated helium ions were performed in an effort to localize the site of initial radiation interactions in the eye that lead to light flash observations by astronauts during spaceflight. The character and efficiency of helium ion induction of visual sensations depended on the state of dark adaptation of the retina; also, the same events were seen with different efficiencies and details when particle flux density changed. It was concluded that fast particles cause interactions in the retina, particularly in the receptor layer, and thus give rise to the sensations of light flashes, streaks, and supernovae.

Tobias, C. A.↗

System and method for character recognition

A character recognition system is disclosed in which each character in a retina, defining a scanning raster, is scanned with random lines uniformly distributed over the retina. For each type of character to be recognized the system stores a probability density function (PDF) of the random line intersection lengths and/or a PDF of the random line number of intersections. As an unknown character is scanned, the random line intersection lengths and/or the random line number of intersections are accumulated and based on a comparison with the prestored PDFs a classification of the unknown character is performed.

Hong, J. P.↗

Photographic Screening for Eye Defects

Images of retinas examined for characteristic patterns. Color photographs of retinas taken. Proper alinement of eye obtained by asking subject to gaze at light-emitting diode. "Red-eye" patterns in resulting color photographs examined by trained observers for signs of ocular defects. System used to check power of contact lenses and eyeglasses by taking photographs with these items in place.

Richardson, J.↗

Generation-V dual-Purkinje-image eyetracker

Major advances characterize the Generation-V dual-Purkinje-image eyetracker compared with the Generation-III version previously described. These advances include a large reduction in size, major improvements in frequency response and noise level, automatic alignment to a subject, and automatic adjustment for different separation between the visual and optic axes, which can vary considerably from subject to subject. In a number of applications described in the paper, the eyetracker is coupled with other highly specialized optical devices. These applications include accurately stabilizing an image on a subject's retina; accurately simulating a visually dead retinal region (i.e., a scotoma) of arbitrary shape, size, and position; and, for clinical purposes, stabilizing the position of a laser coagulator beam on a patient's retina so that the point of contact is unaffected by the patient's own eye movements.

Crane, H. D.↗

Optical correlator use at Johnson Space Center

For automation and robotics in the Space Station era, NASA's Johnson Space Center is pursuing several means of synthetic vision. The optical correlator is one such means. The deformable mirror device will form the basis of the first correlator in this project. In-house and contracted effort is being used. Initial in-house activities will concentrate on an impulse deconvolution technique and on a programmable retina for spatial remappings of an image prior to correlation. The retina will permit a form of edge extraction and other primitive operations. Additionally, it will be used as a research tool for assisting persons with low vision.

Juday, Richard D.↗

Spatial vision within egocentric and exocentric frames of reference

It is remarkable that we are able to perceive a stable visual world and judge the directions, orientations, and movements of visual objects given that images move on the retina, the eyes move in the head, the head moves on the body, and the body moves in space. An understanding of the mechanisms underlying perceptual stability and spatial judgements requires precise definitions of relevant coordinate systems. An egocentric frame of reference is defined with respect to some part of the observer. There are four principal egocentric frames of reference, a station-point frame associated with the nodal point of the eye, an retinocentric frame associated with the retina, a headcentric frame associated with the head, and a bodycentric frame (torsocentric) associated with the torso. Additional egocentric frames can be identified with respect to any segment of the body. An egocentric task is one in which the position, orientation, or motion of an object is judged with respect to an egocentric frame of reference. A proprioceptive is a special kind of egocentric task in which the object being judged is also part of the body. An example of a proprioceptive task is that of directing the gaze toward the seen or unseen toe. An exocentric frame of reference is external to the observer. Geographical coordinates and the direction of gravity are examples of exocentric frames of reference. These various frames are listed in tabular form, together with examples of judgements of each type.

Howard, Ian P.↗

Visualization and modeling of factors influencing visibility in computer-aided crewstation design

We have developed two modules for use in computer-aided design (CAD) of crewstation environments that enhance the designer's appreciation of factors influencing the pilot's vision and visual processing capacity. The Binocular Optics Module (BOM) is an interactive tool for visualizing geometric aspects of (1) how retinal imagery of the environment changes on the pilot's retinas under conditions of eye and object motion, and (2) how visual capabilities that can be modeled as regions or contours on the retinas, affect spatial perception of the environment. The Visual Performance Module (VPM) contains a signal processing model of human visual discrimination that quantitatively predicts visual discrimination performance. The outputs of the VPM are retinal contours that represent performance probabilities. These contours may be used as inputs to the BOM for visualizing those volumes of space within the crewstation that bound different levels of the pilot's of visual discrimination capability. Used together, the BOM and VPM provide the designer with the opportunity to interactively explore relationships between environmental retinal imagery and visual function, and the ability to factor the pilot's visual capabilities into the earliest phases of crewstation CAD.

Arditi, Aries↗

Image remapping strategies applied as protheses for the visually impaired

Maculopathy and retinitis pigmentosa (rp) are two vision defects which render the afflicted person with impaired ability to read and recognize visual patterns. For some time there has been interest and work on the use of image remapping techniques to provide a visual aid for individuals with these impairments. The basic concept is to remap an image according to some mathematical transformation such that the image is warped around a maculopathic defect (scotoma) or within the rp foveal region of retinal sensitivity. NASA/JSC has been pursuing this research using angle invariant transformations with testing of the resulting remapping using subjects and facilities of the University of Houston, College of Optometry. Testing is facilitated by use of a hardware device, the Programmable Remapper, to provide the remapping of video images. This report presents the results of studies of alternative remapping transformations with the objective of improving subject reading rates and pattern recognition. In particular a form of conformal transformation was developed which provides for a smooth warping of an image around a scotoma. In such a case it is shown that distortion of characters and lines of characters is minimized which should lead to enhanced character recognition. In addition studies were made of alternative transformations which, although not conformal, provide for similar low character distortion remapping. A second, non-conformal transformation was studied for remapping of images to aid rp impairments. In this case a transformation was investigated which allows remapping of a vision field into a circular area representing the foveal retina region. The size and spatial representation of the image are selectable. It is shown that parametric adjustments allow for a wide variation of how a visual field is presented to the sensitive retina. This study also presents some preliminary considerations of how a prosthetic device could be implemented in a practical sense, vis-a-vis, size, weight and portability.

Johnson, Curtis D.↗

Ocular hazards of light

The eye is protected against bright light by the natural aversion response to viewing bright light sources. The aversion response normally protects the eye against injury from viewing bright light sources such as the sun, arc lamps and welding arcs, since this aversion limits the duration of exposure to a fraction of a second (about 0.25 s). The principal retinal hazard resulting from viewing bright light sources is photoretinitis, e.g., solar retinitis with an accompanying scotoma which results from staring at the sun. Solar retinitis was once referred to as 'eclipse blindness' and associated 'retinal burn'. Only in recent years has it become clear that photoretinitis results from a photochemical injury mechanism following exposure of the retina to shorter wavelengths in the visible spectrum, i.e., violet and blue light. Prior to conclusive animal experiments at that time, it was thought to be a thermal injury mechanism. However, it has been shown conclusively that an intense exposure to short-wavelength light (hereafter referred to as 'blue light') can cause retinal injury. The product of the dose-rate and the exposure duration always must result in the same exposure dose (in joules-per-square centimeter at the retina) to produce a threshold injury. Blue-light retinal injury (photoretinitis) can result from viewing either an extremely bright light for a short time, or a less bright light for longer exposure periods. This characteristic of photochemical injury mechanisms is termed reciprocity and helps to distinguish these effects from thermal burns, where heat conduction requires a very intense exposure within seconds to cause a retinal coagulation otherwise, surrounding tissue conducts the heat away from the retinal image. Injury thresholds for acute injury in experimental animals for both corneal and retinal effects have been corroborated for the human eye from accident data. Occupational safety limits for exposure to UVR and bright light are based upon this knowledge. As with any photochemical injury mechanism must consider the action spectrum, which describes the relative effectiveness of different wavelengths in causing a photobiological effect. The action spectrum for photochemical retinal injury peaks at approximately 440 nm.

Sliney, David H.↗

In Search of an Optoretinogram

A sensitive apparatus was constructed to measure the infrared reflectance of human retinas in vivo. Changes in the light scattering properties of rod outer segments have been observed both in excised retinas and photoreceptor suspensions, motivating the present work. Unlike results of vitro studies, no visually evoked changes were observed, despite a very low noise level. Methods for improving the technique using modem developments in CCD cameras are discussed.

Mulligan, Jeffrey B.↗

Quantification of rat retinal growth and vascular population changes after single and split doses of proton irradiation: translational study using stereology methods

This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.

NASA Discipline Radiation Health↗

Bioinspired engineering of exploration systems for NASA and DoD

A new approach called bioinspired engineering of exploration systems (BEES) and its value for solving pressing NASA and DoD needs are described. Insects (for example honeybees and dragonflies) cope remarkably well with their world, despite possessing a brain containing less than 0.01% as many neurons as the human brain. Although most insects have immobile eyes with fixed focus optics and lack stereo vision, they use a number of ingenious, computationally simple strategies for perceiving their world in three dimensions and navigating successfully within it. We are distilling selected insect-inspired strategies to obtain novel solutions for navigation, hazard avoidance, altitude hold, stable flight, terrain following, and gentle deployment of payload. Such functionality provides potential solutions for future autonomous robotic space and planetary explorers. A BEES approach to developing lightweight low-power autonomous flight systems should be useful for flight control of such biomorphic flyers for both NASA and DoD needs. Recent biological studies of mammalian retinas confirm that representations of multiple features of the visual world are systematically parsed and processed in parallel. Features are mapped to a stack of cellular strata within the retina. Each of these representations can be efficiently modeled in semiconductor cellular nonlinear network (CNN) chips. We describe recent breakthroughs in exploring the feasibility of the unique blending of insect strategies of navigation with mammalian visual search, pattern recognition, and image understanding into hybrid biomorphic flyers for future planetary and terrestrial applications. We describe a few future mission scenarios for Mars exploration, uniquely enabled by these newly developed biomorphic flyers.

Space Flight↗

Role of the flocculus of the cerebellum in motor learning of the vestibulo-ocular reflex

Structure-function studies at the systems level are an effective method for understanding the relationship of the central nervous system to behavior. Motor learning or adaptation of the vestibulo-ocular reflex is a clear example wherein this approach has been productive. During a vestibulo-ocular reflex the brain converts a head velocity signal, transduced through the vestibular semicircular canals, into an eye movement command delivered to the extraocular muscles. If the viewed target remains on the fovea of the retina, the reflex is compensatory, and its gain, eye velocity/head velocity, is one. When the image of the viewed object slips across the retina, visual acuity decreases, and the gain of the reflex, which is no longer one, is plastically adapted or adjusted until retinal stability is restored. The anatomic substrate for this plasticity thus involves brain structures in which visual-vestibular interaction can potentially occur, as well as vestibular and visual sensory and oculomotor motor structures. Further, it has been known for many years that removal of the flocculus of the cerebellum permanently precludes further vestibulo-ocular reflex adaptation, demonstrating the involvement of the cerebellum in this behavior. Maekawa and Simpson (J Neurophysiol 1973;36: 649-66) discovered that one visual input to the flocculus involved the accessory optic system and the inferior olive. Ensuing work has demonstrated that the visual signals used to adapt the vestibulo-ocular reflex are transmitted by this accessory optic system to the flocculus and subsequently to brain stem structures involved in vestibulo-ocular reflex plasticity. Presently the inclusive list of anatomic sites involved in vestibulo-ocular reflex circuitry and its adaptive plasticity is small. Our laboratory continues to believe that this behavior should be caused by interactions within this small class of neurons. By studying each class of identified neuron and its interactions with others within the list, we hope to ultimately understand the mechanisms used by the brain in the expression of this behavior.

Non-NASA Center↗