A Framework for Detecting Glaucomatous Progression in the Optic Nerve Head of an Eye Using Proper Orthogonal Decomposition

Glaucoma is the second leading cause of blindness worldwide. Often, the optic nerve head (ONH) glaucomatous damage and ONH changes occur prior to visual field loss and are observable in vivo. Thus, digital image analysis is a promising choice for detecting the onset and/or progression of glaucoma. In this paper, we present a new framework for detecting glaucomatous changes in the ONH of an eye using the method of proper orthogonal decomposition (POD). A baseline topograph subspace was constructed for each eye to describe the structure of the ONH of the eye at a reference/baseline condition using POD. Any glaucomatous changes in the ONH of the eye present during a follow-up exam were estimated by comparing the follow-up ONH topography with its baseline topograph subspace representation. Image correspondence measures of L-1-norm and L-2-norm, correlation, and image Euclidean distance (IMED) were used to quantify the ONH changes. An ONH topographic library built from the Louisiana State University Experimental Glaucoma study was used to evaluate the performance of the proposed method. The area under the receiver operating characteristic curves (AUCs) was used to compare the diagnostic performance of the POD-induced parameters with the parameters of the topographic change analysis (TCA) method. The IMED and L-2-norm parameters in the POD framework provided the highest AUC of 0.94 at 10 degrees. field of imaging and 0.91 at 15 degrees. field of imaging compared to the TCA parameters with an AUC of 0.86 and 0.88, respectively. The proposed POD framework captures the instrument measurement variability and inherent structure variability and shows promise for improving our ability to detect glaucomatous change over time in glaucoma management.

Eye-view: A retinal image acquisition system

This paper presents a low cost but high resolution retinal image acquisition system of the human eye. The images acquired by a CMOS image sensor are communicated through the Universal Serial Bus (USB) interface to a personal computer for viewing and further processing. The image acquisition time was estimated to be 2.5 seconds. This system can also be used in telemedicine applications.

Eye-View: A retinal image capture system

This paper presents a low cost but high resolution retinal image acquisition system of the human eye. The images acquired by a CMOS image sensor are communicated through the Universal Serial Bus (USB) interface to a personal computer for viewing and further processing. The image acquisition time was estimated to be 2.5 seconds. This system can also be used in telemedicine applications.

Trans-saccadic processing of visual and motor planning during sequential eye movements

How the brain maintains perceptual continuity across eye movements that yield discontinuous snapshots of the world is still poorly understood. In this study, we adapted a framework from the dual-task paradigm, well suited to reveal bottlenecks in mental processing, to study how information is processed across sequential saccades. The pattern of RTs allowed us to distinguish among three forms of trans-saccadic processing (no trans-saccadic processing, trans-saccadic visual processing and trans-saccadic visual processing and saccade planning models). Using a cued double-step saccade task, we show that even though saccade execution is a processing bottleneck, limiting access to incoming visual information, partial visual and motor processing that occur prior to saccade execution is used to guide the next eye movement. These results provide insights into how the oculomotor system is designed to process information across multiple fixations that occur during natural scanning.

Understanding How the Brain Changes Its Mind: Microstimulation in the Macaque Frontal Eye Field Reveals How Saccade Plans Are Changed

Accumulator models that integrate incoming sensory information into motor plans provide a robust framework to understand decision making. However, their applicability to situations that demand a change of plan raises an interesting problem for the brain. This is because interruption of the current motor plan must occur by a competing motor plan, which is necessarily weaker in strength. To understand how changes of mind get expressed in behavior, we used a version of the double-step task called the redirect task, in which monkeys were trained to modify a saccade plan. We microstimulated the frontal eye fields during redirect behavior and systematically measured the deviation of the evoked saccade from the response field to causally track the changing saccade plan. Further, to identify the underlying mechanisms, eight different computational models of redirect behavior were assessed. It was observed that the model that included an independent, spatially specific inhibitory process, in addition to the two accumulators representing the preparatory processes of initial and final motor plans, best predicted the performance and the pattern of saccade deviation profile in the task. Such an inhibitory process suppressed the preparation of the initial motor plan, allowing the final motor plan to proceed unhindered. Thus, changes of mind are consistent with the notion of a spatially specific, inhibitory process that inhibits the current inappropriate plan, allowing expression of the new plan.

Mutual inhibition and capacity sharing during parallel preparation of serial eye movements

Many common activities, like reading, scanning scenes, or searching for an inconspicuous item in a cluttered environment, entail serial movements of the eyes that shift the gaze from one object to another. Previous studies have shown that the primate brain is capable of programming sequential saccadic eye movements in parallel. Given that the onset of saccades directed to a target are unpredictable in individual trials, what prevents a saccade during parallel programming from being executed in the direction of the second target before execution of another saccade in the direction of the first target remains unclear. Using a computational model, here we demonstrate that sequential saccades inhibit each other and share the brain's limited processing resources (capacity) so that the planning of a saccade in the direction of the first target always finishes first. In this framework, the latency of a saccade increases linearly with the fraction of capacity allocated to the other saccade in the sequence, and exponentially with the duration of capacity sharing. Our study establishes a link between the dual-task paradigm and the ramp-to-threshold model of response time to identify a physiologically viable mechanism that preserves the serial order of saccades without compromising the speed of performance.

A Chemodosimetric Probe Based on a Conjugated Oxidized Bis-Indolyl System for Selective Naked-Eye Sensing of Cyanide Ions in Water

A new bis-indolyl-based colorimetric probe has been synthesized. This allows a Michael-type adduct formation for the detection of cyanide ions. The probe shows a remarkable color change from red to colorless upon addition of the cyanide ions in pure water. The cyanide ion reacts with the probe and removes the conjugation of the bis-indolyl moiety of the probe with that of the 4-substituted aromatic ring. This renders the probe colorless. The mechanism of the reaction of the probe with the cyanide ion was established by using 1H and 13C NMR spectroscopy, mass spectrometry, and kinetic studies.

Lacrimal Proline Rich 4 (LPRR4) Protein in the Tear Fluid Is a Potential Biomarker of Dry Eye Syndrome

Dry eye syndrome (DES) is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4). LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA). LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.

Proactive control of sequential saccades in the human supplementary eye field

Our ability to regulate behavior based on past experience has thus far been examined using single movements. However, natural behavior typically involves a sequence of movements. Here, we examined the effect of previous trial type on the concurrent planning of sequential saccades using a unique paradigm. The task consisted of two trial types: no-shift trials, which implicitly encouraged the concurrent preparation of the second saccade in a subsequent trial; and target-shift trials, which implicitly discouraged the same in the next trial. Using the intersaccadic interval as an index of concurrent planning, we found evidence for context-based preparation of sequential saccades. We also used functional MRI-guided, single-pulse, transcranial magnetic stimulation on human subjects to test the role of the supplementary eye field (SEF) in the proactive control of sequential eye movements. Results showed that (i) stimulating the SEF in the previous trial disrupted the previous trial type-based preparation of the second saccade in the nonstimulated current trial, (ii) stimulating the SEF in the current trial rectified the disruptive effect caused by stimulation in the previous trial, and (iii) stimulating the SEF facilitated the preparation of second saccades based on previous trial type even when the previous trial was not stimulated. Taken together, we show how the human SEF is causally involved in proactive preparation of sequential saccades.

Structural Integrity of the Greek Key Motif in beta gamma-Crystallins Is Vital for Central Eye Lens Transparency

Background: We highlight an unrecognized physiological role for the Greek key motif, an evolutionarily conserved super-secondary structural topology of the beta gamma-crystallins. These proteins constitute the bulk of the human eye lens, packed at very high concentrations in a compact, globular, short-range order, generating transparency. Congenital cataract (affecting 400,000 newborns yearly worldwide), associated with 54 mutations in beta gamma-crystallins, occurs in two major phenotypes nuclear cataract, which blocks the central visual axis, hampering the development of the growing eye and demanding earliest intervention, and the milder peripheral progressive cataract where surgery can wait. In order to understand this phenotypic dichotomy at the molecular level, we have studied the structural and aggregation features of representative mutations. Methods: Wild type and several representative mutant proteins were cloned, expressed and purified and their secondary and tertiary structural details, as well as structural stability, were compared in solution, using spectroscopy. Their tendencies to aggregate in vitro and in cellulo were also compared. In addition, we analyzed their structural differences by molecular modeling in silico. Results: Based on their properties, mutants are seen to fall into two classes. Mutants A36P, L45PL54P, R140X, and G165fs display lowered solubility and structural stability, expose several buried residues to the surface, aggregate in vitro and in cellulo, and disturb/distort the Greek key motif. And they are associated with nuclear cataract. In contrast, mutants P24T and R77S, associated with peripheral cataract, behave quite similar to the wild type molecule, and do not affect the Greek key topology. Conclusion: When a mutation distorts even one of the four Greek key motifs, the protein readily self-aggregates and precipitates, consistent with the phenotype of nuclear cataract, while mutations not affecting the motif display `native state aggregation', leading to peripheral cataract, thus offering a protein structural rationale for the cataract phenotypic dichotomy ``distort motif, lose central vision''.

An Efficient Probe for Rapid Detection of Cyanide in Water at Parts per Billion Levels and Naked-Eye Detection of Endogenous Cyanide

A new molecular probe based on an oxidized bis-indolyl skeleton has been developed for rapid and sensitive visual detection of cyanide ions in water and also for the detection of endogenously bound cyanide. The probe allows the naked-eye detection of cyanide ions in water with a visual color change from red to yellow ((max)=80nm) with the immediate addition of the probe. It shows high selectivity towards the cyanide ion without any interference from other anions. The detection of cyanide by the probe is ratiometric, thus making the detection quantitative. A Michael-type addition reaction of the probe with the cyanide ion takes place during this chemodosimetric process. In water, the detection limit was found to be at the parts per million level, which improved drastically when a neutral micellar medium was employed, and it showed a parts-per-billion-level detection, which is even 25-fold lower than the permitted limits of cyanide in water. The probe could also efficiently detect the endogenously bound cyanide in cassava (a staple food) with a clear visual color change without requiring any sample pretreatment and/or any special reaction conditions such as pH or temperature. Thus the probe could serve as a practical naked-eye probe for in-field experiments without requiring any sophisticated instruments.

A common stochastic accumulator with effector-dependent noise can explain eye-hand coordination

The computational architecture that enables the flexible coupling between otherwise independent eye and hand effector systems is not understood. By using a drift diffusion framework, in which variability of the reaction time (RT) distribution scales with mean RT, we tested the ability of a common stochastic accumulator to explain eye-hand coordination. Using a combination of behavior, computational modeling and electromyography, we show how a single stochastic accumulator to threshold, followed by noisy effector-dependent delays, explains eye-hand RT distributions and their correlation, while an alternate independent, interactive eye and hand accumulator model does not. Interestingly, the common accumulator model did not explain the RT distributions of the same subjects when they made eye and hand movements in isolation. Taken together, these data suggest that a dedicated circuit underlies coordinated eye-hand planning.

Eye-hand coordination during a double-step task: evidence for a common stochastic accumulator

Many studies of reaching and pointing have shown significant spatial and temporal correlations between eye and hand movements. Nevertheless, it remains unclear whether these correlations are incidental, arising from common inputs (independent model); whether these correlations represent an interaction between otherwise independent eye and hand systems (interactive model); or whether these correlations arise from a single dedicated eye-hand system (common command model). Subjects were instructed to redirect gaze and pointing movements in a double-step task in an attempt to decouple eye-hand movements and causally distinguish between the three architectures. We used a drift-diffusion framework in the context of a race model, which has been previously used to explain redirect behavior for eye and hand movements separately, to predict the pattern of eye-hand decoupling. We found that the common command architecture could best explain the observed frequency of different eye and hand response patterns to the target step. A common stochastic accumulator for eye-hand coordination also predicts comparable variances, despite significant difference in the means of the eye and hand reaction time (RT) distributions, which we tested. Consistent with this prediction, we observed that the variances of the eye and hand RTs were similar, despite much larger hand RTs (similar to 90 ms). Moreover, changes in mean eye RTs, which also increased eye RT variance, produced a similar increase in mean and variance of the associated hand RT. Taken together, these data suggest that a dedicated circuit underlies coordinated eye-hand planning.