The variation in transparency of amniotic membrane used in ocular surface regeneration

Background/aims: Scant consideration has been given to the variation in structure of the human amniotic membrane (AM) at source or to the significance such differences might have on its clinical transparency. Therefore, we applied our experience of quantifying corneal transparency to AM. Methods: Following elective caesarean, AM from areas of the fetal sac distal and proximal (ie, adjacent) to the placenta was compared with freeze-dried AM. The transmission of light through the AM samples was quantified spectrophotometrically; also, tissue thickness was measured by light microscopy and refractive index by refractometry. Results: Freeze-dried and freeze-thawed AM samples distal and proximal to the placenta differed significantly in thickness, percentage transmission of visible light and refractive index. The thinnest tissue (freeze-dried AM) had the highest transmission spectra. The thickest tissue (freeze-thawed AM proximal to the placenta) had the highest refractive index. Using the direct summation of fields method to predict transparency from an equivalent thickness of corneal tissue, AM was found to be up to 85% as transparent as human cornea. Conclusion: When preparing AM for ocular surface reconstruction within the visual field, consideration should be given to its original location from within the fetal sac and its method of preservation, as either can influence corneal transparency.

Hypo-accommodation responses in hypermetropic infants and children

Aims: Accommodation to overcome hypermetropia is implicated in emmetropisation. This study recorded accommodation responses in a wide range of emmetropising infants and older children with clinically significant hypermetropia to assess common characteristics and differences. Methods: A PlusoptiXSO4 photorefractor in a laboratory setting was used to collect binocular accommodation data from participants viewing a detailed picture target moving between 33cm and 2m. 38 typically developing infants were studied between 6-26 weeks of age and were compared with cross-sectional data from children 5-9 years of age with clinically significant hypermetropia (n=15), corrected fully accommodative strabismus (n=14) and 27 age-matched controls. Results: Hypermetropes of all ages under-accommodated compared to controls at all distances, whether corrected or not (p<0.00001) and lag related to manifest refraction. Emmetropising infants under-accommodated most in the distance, while the hypermetropic patient groups underaccommodated most for near. Conclusions: Better accommodation for near than distance is demonstrated in those hypermetropic children who go on to emmetropise. This supports the approach of avoiding refractive correction in such children. In contrast, hypermetropic children referred for treatment for reduced distance visual acuity are not likely to habitually accommodate to overcome residual hypermetropia left by an under-correction.

Stereo and motion parallax cues in human 3D vision: can they vanish without a trace?

In an immersive virtual reality environment, subjects fail to notice when a scene expands or contracts around them, despite correct and consistent information from binocular stereopsis and motion parallax, resulting in gross failures of size constancy (A. Glennerster, L. Tcheang, S. J. Gilson, A. W. Fitzgibbon, & A. J. Parker, 2006). We determined whether the integration of stereopsis/motion parallax cues with texture-based cues could be modified through feedback. Subjects compared the size of two objects, each visible when the room was of a different size. As the subject walked, the room expanded or contracted, although subjects failed to notice any change. Subjects were given feedback about the accuracy of their size judgments, where the “correct” size setting was defined either by texture-based cues or (in a separate experiment) by stereo/motion parallax cues. Because of feedback, observers were able to adjust responses such that fewer errors were made. For texture-based feedback, the pattern of responses was consistent with observers weighting texture cues more heavily. However, for stereo/motion parallax feedback, performance in many conditions became worse such that, paradoxically, biases moved away from the point reinforced by the feedback. This can be explained by assuming that subjects remap the relationship between stereo/motion parallax cues and perceived size or that they develop strategies to change their criterion for a size match on different trials. In either case, subjects appear not to have direct access to stereo/motion parallax cues.

Can misalignments in typical infants be used as a model for infantile esotropia?

PURPOSE. To investigate the nature of early ocular misalignments in human infants to determine whether they can provide insight into the etiology of esotropia and, in particular, to examine the correlates of misalignments. METHODS. A remote haploscopic photorefraction system was used to measure accommodation and vergence in 146 infants between 0 and 12 months of age. Infants underwent photorefraction immediately after watching a target moving between two of five viewing distances (25, 33, 50, 100, and 200 cm). In some instances, infants were tested in two conditions: both eyes open and one eye occluded. The resultant data were screened for instances of large misalignments. Data were assessed to determine whether accommodative, retinal disparity, or other cues were associated with the occurrence of misalignments. RESULTS. The results showed that there was no correlation between accommodative behavior and misalignments. Infants were more likely to show misalignments when retinal disparity cues were removed through occlusion. They were also more likely to show misalignments immediately after the target moved from a near to a far position in comparison to far-to-near target movement. DISCUSSION. The data suggest that the prevalence of misalignments in infants of 2 to 3 months of age is decreased by the addition of retinal disparity cues to the stimulus. In addition, target movement away from the infant increases the prevalence of misalignments. These data are compatible with the notion that misalignment are caused by poor sensitivity to targets moving away from the infant and support the theory that some forms of strabismus could be related to failure in a system that is sensitive to the direction of motion.

Psychosocial impact of visual impairment in working-age adults

Future research is required into the prevalence of loneliness, anxiety and depression in adults with visual impairment, and to evaluate the effectiveness of interventions for improving psychosocial well-being such as counselling, peer support and employment programmes.

Self-organized 40Hz synchronization in a physiological theory of EEG

We present evidence that large-scale spatial coherence of 40 Hz oscillations can emerge dynamically in a cortical mean field theory. The simulated synchronization time scale is about 150 ms, which compares well with experimental data on large-scale integration during cognitive tasks. The same model has previously provided consistent descriptions of the human EEG at rest, with tranquilizers, under anesthesia, and during anesthetic-induced epileptic seizures. The emergence of coherent gamma band activity is brought about by changing just one physiological parameter until cortex becomes marginally unstable for a small range of wavelengths. This suggests for future study a model of dynamic computation at the edge of cortical stability.

Modeling the effects of anesthesia on the electroencephalogram

Changes to the electroencephalogram (EEG) observed during general anesthesia are modeled with a physiological mean field theory of electrocortical activity. To this end a parametrization of the postsynaptic impulse response is introduced which takes into account pharmacological effects of anesthetic agents on neuronal ligand-gated ionic channels. Parameter sets for this improved theory are then identified which respect known anatomical constraints and predict mean firing rates and power spectra typically encountered in human subjects. Through parallelized simulations of the eight nonlinear, two-dimensional partial differential equations on a grid representing an entire human cortex, it is demonstrated that linear approximations are sufficient for the prediction of a range of quantitative EEG variables. More than 70 000 plausible parameter sets are finally selected and subjected to a simulated induction with the stereotypical inhaled general anesthetic isoflurane. Thereby 86 parameter sets are identified that exhibit a strong “biphasic” rise in total power, a feature often observed in experiments. A sensitivity study suggests that this “biphasic” behavior is distinguishable even at low agent concentrations. Finally, our results are briefly compared with previous work by other groups and an outlook on future fits to experimental data is provided.

The effects of retinoic acid on human corneal stromal keratocytes cultured in vitro under serum-free conditions

Purpose: Retinoic acid (RA) is a metabolite of vitamin A that plays a fundamental role in the development and function of the human eye. The purpose of this study was to investigate the effects of RA on the phenotype of corneal stromal keratocytes maintained in vitro for extended periods under serum-free conditions. Methods: Keratocytes isolated from human corneas were cultured up to 21 days in serum-free media supplemented with RA or DMSO vehicle. The effects of RA and of its removal after treatment on cell proliferation and morphology were evaluated. In addition, the expression of keratocyte markers was quantified at the transcriptional and protein levels by quantitative PCR and immunoblotting or ELISA, respectively. Furthermore, the effects of RA on keratocyte migration were tested using scratch assays. Results: Keratocytes cultured with RA up to 10×10-6 M showed enhanced proliferation and stratification, and reduced mobility. RA also promoted the expression of keratocyte-characteristic proteoglycans such as keratocan, lumican, and decorin, and increased the amounts of collagen type-I in culture while significantly reducing the expression of matrix metalloproteases 1, 3, and 9. RA effects were reversible, and cell phenotype reverted to that of control after removal of RA from media. Conclusions: RA was shown to control the phenotype of human corneal keratocytes cultured in vitro by regulating cell behaviour and extracellular matrix composition. These findings contribute to our understanding of corneal stromal biology in health and disease, and may prove useful in optimizing keratocyte cultures for applications in tissue engineering, cell biology, and medicine.

Change in convergence and accommodation after two weeks of eye exercises in typical young adults

Abstract: Introduction Although eye exercises appear to help heterophoria, convergence insufficiency and intermittent strabismus, true treatment effects can be confounded by placebo, practice and encouragement factors. This study assessed objective changes in vergence and accommodation responses in typical naïve young adults after two weeks of exercises compared to control conditions to assess the extent of treatment effects occur above other factors. Methods 156 asymptomatic young adults were randomly assigned to 6 exercise groups or 2 no-treatment groups. Treatment targeted i) accommodation, ii)vergence, iii) both, iv) convergence>accommodation, v)accommodation>convergence, or vi) a placebo. All were re-tested under identical conditions, except for the second control group who were additionally encouraged during testing. Objective accommodation and vergence were assessed to a range of targets moving in depth containing combinations of blur, disparity and proximity/looming cues. Results Response gain improved more for less naturalistic targets where more improvement was possible. Convergence exercises improved vergence for near across all targets (P=.035). Mean accommodation changed similarly,but non-significantly. No other treatment group differed significantly from the non-encouraged control group, while encouraging effort produced significantly increased vergence (P=.004) and accommodation (P=.005) gains in the other control group. Conclusions True treatment effects were small, only significantly better after vergence exercises to a non-accommodative target, and were rarely related to response they were designed to improve. Exercising accommodation without convergence made no difference to accommodation to cues containing detail. Additional effort improved objective responses the most, so should be controlled carefully in research, and considered when auditing treatment.

Information architecture for healthcare organizations: the case of a NHS Hospital in UK

Healthcare organizations are known for their complex and intense information environment. Healthcare information is facilitated via heterogeneous information systems or paper-based sources. Access to the right information under increasing time pressure is extremely challenging. This paper proposes an information architecture for healthcare organizations. It facilitates the provision of the right information to the right person in the right place and time tailored to their requirements. It adapts an abductive reasoning research approach. Organizational semiotics serves as its theoretical underpinning, guiding the data collection process through direct observation in the ophthalmology outpatient clinics of a UK hospital. It results the norm and information objects that form the information architecture. This is modeled by Archimate. The contribution of the information architecture can be seen from organizational, social and technical perspective. It clearly shows how information is facilitated within a healthcare organization, reducing duplicated data entry, and guiding the future technological implementation.

Screening for convergence insufficiency using the CISS is not indicated in young adults

Aim This paper presents Convergence Insufficiency Symptom Survey (CISS) and orthoptic findings in a sample of typical young adults who considered themselves to have normal eyesight apart from weak spectacles. Methods The CISS questionnaire was administered,followed by a full orthoptic evaluation, to 167 university undergraduate and postgraduate students during the recruitment phase of another study. The primary criterion for recruitment to this study was that participants‘feltthey had normal eyesight'. A CISS score of ≥21 was used to define‘significant’symptoms, and convergence insufficiency (CI) was defined as convergence≥8cm from the nose with a fusion range <15Δ base-out with small or no exophoria. Results The group mean CISS score was 15.4. In all, 17(10%) of the participants were diagnosed with CI, but 11(65%) of these did not have significant symptoms. 41(25%) participants returned a‘high’CISS score of ≥21 but only 6 (15%) of these had genuine CI. Sensitivity of the CISS to detect CI in this asymptomatic sample was 38%; specificity 77%; positive predictive value 15%; and negative predictive value 92%. The area under a receiver operating characteristic curve was 0.596 (95% CI 0.46 to 0.73). Conclusions‘Visual symptoms’are common in young adults, but often not related to any clinical defect, while true CI may be asymptomatic. This study suggests that screening for CI is not indicated

Disparity-driven vs blur-driven models of accommodation and convergence in binocular vision and intermittent strabismus

Background. Current models of concomitant, intermittent strabismus, heterophoria, convergence and accommodation anomalies are either theoretically complex or incomplete. We propose an alternative and more practical way to conceptualize clinical patterns. Methods. In each of three hypothetical scenarios (normal; high AC/A and low CA/C ratios; low AC/A and high CA/C ratios) there can be a disparity-biased or blur-biased “style”, despite identical ratios. We calculated a disparity bias index (DBI) to reflect these biases. We suggest how clinical patterns fit these scenarios and provide early objective data from small illustrative clinical groups. Results. Normal adults and children showed disparity bias (adult DBI 0.43 (95%CI 0.50-0.36), child DBI 0.20 (95%CI 0.31-0.07) (p=0.001). Accommodative esotropes showed less disparity-bias (DBI 0.03). In the high AC/A and low CA/C scenario, early presbyopes had mean DBI of 0.17 (95%CI 0.28-0.06), compared to DBI of -0.31 in convergence excess esotropes. In the low AC/A and high CA/C scenario near exotropes had mean DBI of 0.27, while we predict that non-strabismic, non-amblyopic hyperopes with good vision without spectacles will show lower DBIs. Disparity bias ranged between 1.25 and -1.67. Conclusions. Establishing disparity or blur bias, together with knowing whether convergence to target demand exceeds accommodation or vice versa explains clinical patterns more effectively than AC/A and CA/C ratios alone. Excessive bias or inflexibility in near-cue use increases risk of clinical problems. We suggest clinicians look carefully at details of accommodation and convergence changes induced by lenses, dissociation and prisms and use these to plan treatment in relation to the model.

Emergence of spatially heterogeneous burst suppression in a neural field model of electrocortical activity

Burst suppression in the electroencephalogram (EEG) is a well-described phenomenon that occurs during deep anesthesia, as well as in a variety of congenital and acquired brain insults. Classically it is thought of as spatially synchronous, quasi-periodic bursts of high amplitude EEG separated by low amplitude activity. However, its characterization as a “global brain state” has been challenged by recent results obtained with intracranial electrocortigraphy. Not only does it appear that burst suppression activity is highly asynchronous across cortex, but also that it may occur in isolated regions of circumscribed spatial extent. Here we outline a realistic neural field model for burst suppression by adding a slow process of synaptic resource depletion and recovery, which is able to reproduce qualitatively the empirically observed features during general anesthesia at the whole cortex level. Simulations reveal heterogeneous bursting over the model cortex and complex spatiotemporal dynamics during simulated anesthetic action, and provide forward predictions of neuroimaging signals for subsequent empirical comparisons and more detailed characterization. Because burst suppression corresponds to a dynamical end-point of brain activity, theoretically accounting for its spatiotemporal emergence will vitally contribute to efforts aimed at clarifying whether a common physiological trajectory is induced by the actions of general anesthetic agents. We have taken a first step in this direction by showing that a neural field model can qualitatively match recent experimental data that indicate spatial differentiation of burst suppression activity across cortex.