Amniotic membrane is applied to the diseased ocular surface to stimulate wound healing and tissue repair, because it releases supportive growth factors and cytokines. These effects fade within about a week after application, necessitating repeated application. Generally, amniotic membrane is fixed with sutures to the ocular surface, but surgical intervention at the inflamed or diseased site can be detrimental. Therefore, we have developed a system for the mounting of amniotic membrane between two rings for application to a diseased ocular surface without surgical intervention (sutureless amniotic membrane transplantation). With this system, AmnioClip, amniotic membrane can be applied like a large contact lens. First prototypes were tested in an experiment on oneself for wearing comfort. The final system was tested on 7 patients in a pilot study. A possible influence of the ring system on the biological effects of amniotic membrane was analyzed by histochemistry and by analyzing the expression of vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF 2) and pigment epithelium-derived factor (PEDF) from amniotic membranes before and after therapeutic application. The final product, AmnioClip, showed good tolerance and did not impair the biological effects of amniotic membrane. VEGF-A and PEDF mRNA was expressed in amniotic membrane after storage and mounting before transplantation, but was undetectable after a 7-day application period. Consequently, transplantation of amniotic membranes with AmnioClip provides a sutureless and hence improved therapeutic strategy for corneal surface disorders.Trial Registration:ClinicalTrials.gov NCT02168790

To compare the ocular counter-roll (OCR) measured using iris images during binocular fixation and head tilt with OCR measured via fundus photography.

Advances in imaging have made it increasingly common to study soft tissues without first embedding them in plastic or paraffin and without using labels or stains. The process, however, usually still involves fixation and cryosectioning, which could deform the tissues. Our goal was to quantify the morphological changes of ocular tissues caused by formalin fixation and cryosectioning. From each of 6 porcine eyes, 4 regions were obtained: cornea, equatorial and posterior sclera, and posterior pole containing the optic nerve head. Samples were imaged using visible light microscopy fresh, 1-minute and 24-hours post-fixation, and post-cryosectioning. Effects were assessed by 14 parameters representing sample size and shape. Overall, formalin fixation and sectioning caused only minimal changes to the ocular tissues, with average percentage parameter differences of 0.1%, 1%, and 1.2% between fresh and post-fixing by 1 minute, 24 hours, and post-cryosectioning, respectively. Parameter changes were not directional, and were only weakly dependent on the duration of fixation and the region of the eye. These results demonstrate that formalin fixation and cryosectioning are good choices for studying ocular tissue morphology and structure, as they do not cause the large tissue shrinkage or distortions typically associated with other, more complicated, techniques.

To develop a new method of manufacturing contact lens-shaped crosslinked amniotic membranes (AMs) using glutaraldehyde (GA) and dialdehyde starch (DAS) as crosslinking agents.

During periods of steady fixation, we make small-amplitude ocular movements, termed microsaccades, at a rate of 1-2 every second. Early studies provided evidence that visual sensitivity is reduced during microsaccades-akin to the well-established suppression associated with larger saccades. However, the results of more recent work suggest that microsaccades may alter retinal input in a manner that enhances visual sensitivity to some stimuli. Here we parametrically varied the spatial frequency of a stimulus during a detection task and tracked contrast sensitivity as a function of time relative to microsaccades. Our data reveal two distinct modulations of sensitivity: suppression during the eye movement itself and facilitation after the eye has stopped moving. The magnitude of suppression and facilitation of visual sensitivity is related to the spatial content of the stimulus: suppression is greatest for low spatial frequencies, while sensitivity is enhanced most for stimuli of 1-2 cycles/°, spatial frequencies at which we are already most sensitive in the absence of eye movements. We present a model in which the tuning of suppression and facilitation is explained by delayed lateral inhibition between spatial frequency channels. Our data show that eye movements actively modulate visual sensitivity even during fixation: the detectability of images at different spatial scales can be increased or decreased depending on when the image occurs relative to a microsaccade. NEW & NOTEWORTHY Given the frequency with which we make microsaccades during periods of fixation, it is vital that we understand how they affect visual processing. We demonstrate two selective modulations of contrast sensitivity that are time-locked to the occurrence of a microsaccade: suppression of low spatial frequencies during each eye movement and enhancement of higher spatial frequencies after the eye has stopped moving. These complementary changes may arise naturally because of sluggish gain control between spatial channels.

We examined the spontaneous association between numbers and space by documenting attention deployment and the time course of associated spatial-numerical mapping with and without overt oculomotor responses. In Experiment 1, participants maintained central fixation while listening to number names. In Experiment 2, they made horizontal target-direct saccades following auditory number presentation. In both experiments, we continuously measured spontaneous ocular drift in horizontal space during and after number presentation. Experiment 2 also measured visual-probe-directed saccades following number presentation. Reliable ocular drift congruent with a horizontal mental number line emerged during and after number presentation in both experiments. Our results provide new evidence for the implicit and automatic nature of the oculomotor resonance effect associated with the horizontal spatial-numerical mapping mechanism.

We evaluated the effects of strabismus repair on fixational eye movements (FEMs) and stereopsis recovery in patients with fusion maldevelopment nystagmus (FMN) and patients without nystagmus. Twenty-one patients with strabismus, twelve with FMN and nine without nystagmus, were tested before and after strabismus repair. Eye-movements were recorded during a gaze-holding task under monocular viewing conditions. Fast (fixational saccades and quick phases of nystagmus) and slow (inter-saccadic drifts and slow phases of nystagmus) FEMs and bivariate contour ellipse area (BCEA) were analyzed in the viewing and non-viewing eye. Strabismus repair improved the angle of strabismus in subjects with and without FMN, however patients without nystagmus were more likely to have improvement in stereoacuity. The fixational saccade amplitudes and intersaccadic drift velocities in both eyes decreased after strabismus repair in subjects without nystagmus. The slow phase velocities were higher in patients with FMN compared to inter-saccadic drifts in patients without nystagmus. There was no change in the BCEA after surgery in either group. In patients without nystagmus, the improvement of the binocular function (stereopsis), as well as decreased fixational saccade amplitude and intersaccadic drift velocity, could be due, at least partially, to central adaptive mechanisms rendered possible by surgical realignment of the eyes. The absence of improvement in patients with FMN post strabismus repair likely suggests the lack of such adaptive mechanisms in patients with early onset infantile strabismus. Assessment of fixation eye movement characteristics can be a useful tool to predict functional improvement post strabismus repair.

The aim of this cross-sectional study was to use standard automated perimetry to compare fixation variability among the dominant eye fixation, non-dominant eye fixation, and binocular fixation conditions. Thirty-five eyes of 35 healthy young participants underwent standard automated perimetry (Humphrey 24-2 SITA-Standard) in dominant eye fixation, non-dominant eye fixation, and binocular fixation conditions. Fixation variability during foveal threshold and visual field measurement, which was recorded using a wearable eye-tracking glass and calculated using the bivariate contour ellipse area (deg2), was compared among the three fixation conditions. Further, the association of bivariate contour ellipse area with ocular position and fusional amplitude during binocular fixation was analysed. There were no significant differences in bivariate contour ellipse area during foveal threshold measurement among the dominant eye fixation (1.75 deg2), non-dominant eye fixation (1.45 deg2), and binocular fixation (1.62 deg2) conditions. In contrast, the bivariate contour ellipse area during visual field measurement in binocular fixation (2.85 deg2) was significantly lower than the bivariate contour ellipse area in dominant eye fixation (4.62 deg2; p = 0.0227) and non-dominant eye fixation (5.24 deg2; p = 0.0006) conditions. There was no significant difference in bivariate contour ellipse area during visual field measurement between dominant eye fixation and non-dominant eye fixation conditions. There was no significant correlation between bivariate contour ellipse area and either ocular position or fusional amplitude during both foveal threshold and visual field measurements. Thus, fixation variability might be improved in binocular fixation conditions during a long-duration test, such as visual field measurement.

Chlamydia (C.) suis can often be isolated from conjunctival swab specimens from pigs with conjunctivitis or keratoconjunctivitis. In the field, it is assumed to be a multifactorial disease triggered by immunosuppressing factors. This is the first experimental study to provoke clinical signs of conjunctivitis in pigs after C. suis primary mono-infection. Five six-week-old male piglets, free of ocular chlamydia shedding and seronegative for Chlamydia, were conjunctivally infected with the C. suis-type strain S45 (1 × 109 inclusion forming units), while four piglets served as negative controls. The infection group developed clinical signs of conjunctivitis with a peak in the first week post-infection. Immunohistochemical evaluation revealed the presence of Chlamydia not only in the conjunctival epithelium, but also in the enlarged lacrimal glands, lungs, and intestine. No circulating antibodies could be detected during the whole study period of three weeks, although three different test systems were applied as follows: the complement fixation test, MOMP-based Chlamydiaceae ELISA, and PmpC-based C. suis ELISA. Meanwhile, high numbers of IFN-γ-producing lymphocytes within PBMC were seen after C. suis re-stimulation 14 days post-infection. Hence, these data suggest that entry via the eye may not elicit immunological responses comparable to other routes of chlamydial infections.

To introduce a modified technique for primary/secondary intraocular lens (IOL) fixation without corneal incision in vitrectomized eyes.

This study aimed to compare modified knotless transscleral suture fixation of intraocular lens (IOL) with traditional transscleral suture fixation for adolescents and young patients with congenital ectopia lentis (CEL).

The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain.

Recording synchronous data from EEG and eye-tracking provides a unique methodological approach for measuring the sensory and cognitive processes of overt visual search. Using this approach we obtained fixation related potentials (FRPs) during a guided visual search task specifically focusing on the lambda and P3 components. An outstanding question is whether the lambda and P3 FRP components are influenced by concurrent task demands. We addressed this question by obtaining simultaneous eye-movement and electroencephalographic (EEG) measures during a guided visual search task while parametrically modulating working memory load using an auditory N-back task. Participants performed the guided search task alone, while ignoring binaurally presented digits, or while using the auditory information in a 0, 1, or 2-back task. The results showed increased reaction time and decreased accuracy in both the visual search and N-back tasks as a function of auditory load. Moreover, high auditory task demands increased the P3 but not the lambda latency while the amplitude of both lambda and P3 was reduced during high auditory task demands. The results show that both early and late stages of visual processing indexed by FRPs are significantly affected by concurrent task demands imposed by auditory working memory.

Ocular accommodation is the process of adjusting the eye's crystalline lens so as to bring the retinal image into sharp focus. The major stimulus to accommodation is therefore retinal defocus, and in essence, the job of accommodative control is to send a signal to the ciliary muscle which will minimize the magnitude of defocus. In this article, we first provide a tutorial introduction to control theory to aid vision scientists without this background. We then present a unified model of accommodative control that explains properties of the accommodative response for a wide range of accommodative stimuli. Following previous work, we conclude that most aspects of accommodation are well explained by dual integral control, with a "fast" or "phasic" integrator enabling response to rapid changes in demand, which hands over control to a "slow" or "tonic" integrator which maintains the response to steady demand. Control is complicated by the sensorimotor latencies within the system, which delay both information about defocus and the accommodation changes made in response, and by the sluggish response of the motor plant. These can be overcome by incorporating a Smith predictor, whereby the system predicts the delayed sensory consequences of its own motor actions. For the first time, we show that critically-damped dual integral control with a Smith predictor accounts for adaptation effects as well as for the gain and phase for sinusoidal oscillations in demand. In addition, we propose a novel proportional-control signal to account for the power spectrum of accommodative microfluctuations during steady fixation, which may be important in hunting for optimal focus, and for the nonlinear resonance observed for low-amplitude, high-frequency input. Complete Matlab/Simulink code implementing the model is provided at https://doi.org/10.25405/data.ncl.14945550.

In Parkinson's disease, a precursor phenomenon to visual hallucinations presents as 'pareidolias' which make ambiguous forms appear meaningful. To evoke and detect pareidolias in patients, a noise pareidolia test was recently developed, although its task-dependent mechanisms are yet to be revealed. When subjected to this test, we hypothesized that patients exhibiting pareidolias would show altered top-down influence of visual processing allowing us to demonstrate the influence of pareidolic illusionary behaviour in Parkinson's disease patients. To that end, we evaluated eye-movement strategies and fixation-related presaccadic activity on scalp EEG when participants performed the test. Twelve healthy controls and 21 Parkinson's disease patients, evaluated for cognitive, visuo-spatial and executive functions, took a modified computer-based version of the noise pareidolia test in a free-viewing EEG eye-tracking experiment. Eye-tracking metrics (fixation-related durations and counts) documented the eye movement behaviour employed in correct responses (face/noise) and misperceptions (pareidolia/missed) during early and late visual search conditions. Simultaneously, EEG recorded the presaccadic activity in frontal and parietal areas of the brain. Based on the noise pareidolia test scores, we found certain Parkinson's disease patients exhibited pareidolias whereas others did not. ANOVA on eye-tracking data showed that patients dwelled significantly longer to detect faces and pareidolias which affected both global and local search dynamics depending on their visuo-perceptual status. Presaccadic activity in parietal electrodes for the groups was positive for faces and pareidolias, and negative for noise, though these results depended mainly on saccade size. However, patients sensitive to pareidolias showed a significantly higher presaccadic potential on frontal electrodes independent of saccade sizes, suggesting a stronger frontal activation for pareidolic stimuli. We concluded with the following interpretations (i) the noise pareidolia test specifically characterizes visuo-perceptual inadequacies in patients despite their wide range of cognitive scores, (ii) Parkinson's disease patients dwell longer to converge attention to pareidolic stimuli due to abnormal saccade generation proportional to their visuo-perceptual deficit during early search, and during late search, due to time-independent alteration of visual attentional network and (iii) patients with pareidolias show increased frontal activation reflecting the allocation of attention to irrelevant targets that express the pareidolic phenomenon. While the disease per se alters the visuo-perceptual and oculomotor dynamics, pareidolias occur in Parkinson's disease due to an abnormal top-down modulation of visual processing that affects visual attention and guidance to ambiguous stimuli.

In the absence of an optic chiasm, visual input to the right eye is represented in primary visual cortex (V1) in the right hemisphere, while visual input to the left eye activates V1 in the left hemisphere. Retinotopic mapping In V1 reveals that in each hemisphere left and right visual hemifield representations are overlaid (Hoffmann et al., 2012). To explain how overlapping hemifield representations in V1 do not impair vision, we tested the hypothesis that visual projections from nasal and temporal retina create interdigitated left and right visual hemifield representations in V1, similar to the ocular dominance columns observed in neurotypical subjects (Victor et al., 2000). We used high-resolution fMRI at 7T to measure the spatial distribution of responses to left- and right-hemifield stimulation in one achiasmic subject. T2-weighted 2D Spin Echo images were acquired at 0.8mm isotropic resolution. The left eye was occluded. To the right eye, a presentation of flickering checkerboards alternated between the left and right visual fields in a blocked stimulus design. The participant performed a demanding orientation-discrimination task at fixation. A general linear model was used to estimate the preference of voxels in V1 to left- and right-hemifield stimulation. The spatial distribution of voxels with significant preference for each hemifield showed interdigitated clusters which densely packed V1 in the right hemisphere. The spatial distribution of hemifield-preference voxels in the achiasmic subject was stable between two days of testing and comparable in scale to that of human ocular dominance columns. These results are the first in vivo evidence showing that visual hemifield representations interdigitate in achiasmic V1 following a similar developmental course to that of ocular dominance columns in V1 with intact optic chiasm.

Response inhibition, or the suppression of prepotent but contextually inappropriate behaviors, is essential to adaptive, flexible responding. Individuals with autism spectrum disorders (ASD) consistently show deficient response inhibition during antisaccades. In our prior functional MRI study, impaired antisaccade performance was accompanied by reduced functional connectivity between the frontal eye field (FEF) and dorsal anterior cingulate cortex (dACC), regions critical to volitional ocular motor control. Here we employed magnetoencephalography (MEG) to examine the spectral characteristics of this reduced connectivity. We focused on coherence between FEF and dACC during the preparatory period of antisaccade and prosaccade trials, which occurs after the presentation of the task cue and before the imperative stimulus. We found significant group differences in alpha band mediated coherence. Specifically, neurotypical participants showed significant alpha band coherence between the right inferior FEF and right dACC and between the left superior FEF and bilateral dACC across antisaccade, prosaccade, and fixation conditions. Relative to the neurotypical group, ASD participants showed reduced coherence between these regions in all three conditions. Moreover, while neurotypical participants showed increased coherence between the right inferior FEF and the right dACC in preparation for an antisaccade compared to a prosaccade or fixation, ASD participants failed to show a similar increase in preparation for the more demanding antisaccade. These findings demonstrate reduced long-range functional connectivity in ASD, specifically in the alpha band. The failure in the ASD group to increase alpha band coherence with increasing task demand may reflect deficient top-down recruitment of additional neural resources in preparation to perform a difficult task.

Glanders is an equine zoonosis caused by Burkholderia mallei that is responsible for considerable economic loss. Complement fixation testing (CFT) using warm or cold incubation are recommended by the OIE, but many routinely used detection tests may present misleading results. To increase accuracy of glanders diagnosis and establish an appropriate protocol in collaboration with the National Equine Health Program, seven horses positive for glanders kept in isolation in Brazil were examined fortnightly by CFT, microbiological screening, and molecular testing. Warm and cold serologies with USDA and c.c.Pro antigens, respectively, were performed on 132 samples using the US Department of Agriculture protocol. The warm and cold serologies showed, respectively,12.9% and 17.3% seroreactive, 85.7% and 65.2% non-reactive, 0.8% and 3% inconclusive, and 0% and 2.3% anticomplementary. The agreement of CFT protocols was moderate. Of 213 clinical samples submitted to selective culture (167 nasal swabs, 5 ocular swabs, 3 lymph node punctures, and 38 tissue samples from four horses that died), 1.9% tested positive for B. mallei. Fourteen samples and one nasal swab (7%) tested positive with PCR. Cold CFT with the USDA and c.c.Pro antigens, in combination with PCR to increase sensitivity, may be useful for diagnosis of chronic glanders.

We evaluated the feasibility and safety of nictitating membrane fixation to address reduced contact lens stability by the nictitating membrane in a rabbit model. Under general anesthesia, twelve animals received a horizontal mattress suture between the nictitating membrane and the upper eyelid of one eye. To assess the effects of this technique and secondary side effects, contact lens stability test, Schirmer tear test, tear break-up time measurement, eye tissue pathology and morphology were evaluated. Contact lens stability was increased after nictitating membrane fixation. The percentage of contact lens retention in the nictitating membrane fixed rabbit after 4 hours was 90% whereas that in the untreated rabbit was 42.5%. In addition, there were no significant differences in tear quantity and quality between the fixed and untreated eyes. Furthermore, no remarkable pathological lesions were found in gross observation during the 1-month time period or the following pathological examination. In this study, we demonstrated that nictitating membrane fixation increases contact lens stability without specific side effects using a rabbit model. This minimally invasive procedure could be useful when designing animal models for testing new contact lenses and has potential to apply to other biomaterial research on the ocular surface.

The aim of this study was to determine whether objective ocular torsion in intermittent exotropia (IXT) changes after recession surgery, and to evaluate the relationship between change in ocular torsion and clinical parameters in IXT. Sixty patients between 3 and 14 years of age underwent lateral rectus (LR) recession for IXT. Digital fundus photographs were obtained from both eyes of each subject and the disc-foveal angle (ocular torsion) was calculated using image software. We compared the preoperative and postoperative amount of ocular torsion, and analyzed the correlation between the difference in ocular torsion (DOC) and clinical parameters including age, duration of strabismus, stereoacuity, amount of preoperative exodeviation, and mean dose response. We categorized the patients according to DOC value: positive DOC value as group 1, and negative DOC value as group 2. A correlation between ocular torsion dominance and fixation preference was also investigated using the Kappa test. The mean ocular torsion was 15.8 ± 4.6 degrees preoperatively and 13.7 ± 5.1 degrees postoperatively. Compared with preoperative values, the mean ocular torsion showed a significant decrease after LR recession (p<0.001), and a greater preoperative ocular torsion was significantly associated with the amount of DOC (r = 0.37, p<0.001). Degree of stereopsis, mean dose-response, and postoperative exodeviation were significantly different between group 1 (positive DOC) and group 2 (negative DOC) (p<0.001, 0.030, and 0.001 respectively). The Kappa test showed that there was a significant correlation between the dominance of ocular torsion and fixation preference (p = 0.020). Therefore, change in ocular torsion after LR recession can be a useful supplementary indicator for evaluating the degree of fusional control and for predicting postoperative surgical response in IXT.