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.

Cue combination for 3D location judgements

Cue combination rules have often been applied to the perception of surface shape but not to judgements of object location. Here, we used immersive virtual reality to explore the relationship between different cues to distance. Participants viewed a virtual scene and judged the change in distance of an object presented in two intervals, where the scene changed in size between intervals (by a factor of between 0.25 and 4). We measured thresholds for detecting a change in object distance when there were only 'physical' (stereo and motion parallax) or 'texture-based' cues (independent of the scale of the scene) and used these to predict biases in a distance matching task. Under a range of conditions, in which the viewing distance and position of the tarte relative to other objects was varied, the ration of 'physical' to 'texture-based' thresholds was a good predictor of biases in the distance matching task. The cue combination approach, which successfully accounts for our data, relies on quite different principles from those underlying geometric reconstruction.

Latitude and longitude vertical disparities

The literature on vertical disparity is complicated by the fact that several different definitions of the term “vertical disparity” are in common use, often without a clear statement about which is intended or a widespread appreciation of the properties of the different definitions. Here, we examine two definitions of retinal vertical disparity: elevation-latitude and elevation-longitude disparities. Near the fixation point, these definitions become equivalent, but in general, they have quite different dependences on object distance and binocular eye posture, which have not previously been spelt out. We present analytical approximations for each type of vertical disparity, valid for more general conditions than previous derivations in the literature: we do not restrict ourselves to objects near the fixation point or near the plane of regard, and we allow for non-zero torsion, cyclovergence, and vertical misalignments of the eyes. We use these expressions to derive estimates of the latitude and longitude vertical disparities expected at each point in the visual field, averaged over all natural viewing. Finally, we present analytical expressions showing how binocular eye position—gaze direction, convergence, torsion, cyclovergence, and vertical misalignment—can be derived from the vertical disparity field and its derivatives at the fovea.

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.

A novel Bayesian approach to drug design with simple and complex enzymes: Use with lens aldehyde dehydrogenase and the glyoxalase pathway

Purpose: Acquiring details of kinetic parameters of enzymes is crucial to biochemical understanding, drug development, and clinical diagnosis in ocular diseases. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. Methods: We have developed Bayesian utility functions to minimise kinetic parameter variance involving differentiation of model expressions and matrix inversion. These have been applied to the simple kinetics of the enzymes in the glyoxalase pathway (of importance in posttranslational modification of proteins in cataract), and the complex kinetics of lens aldehyde dehydrogenase (also of relevance to cataract). Results: Our successful application of Bayesian statistics has allowed us to identify a set of rules for designing optimum kinetic experiments iteratively. Most importantly, the distribution of points in the range is critical; it is not simply a matter of even or multiple increases. At least 60 % must be below the KM (or plural if more than one dissociation constant) and 40% above. This choice halves the variance found using a simple even spread across the range.With both the glyoxalase system and lens aldehyde dehydrogenase we have significantly improved the variance of kinetic parameter estimation while reducing the number and costs of experiments. Conclusions: We have developed an optimal and iterative method for selecting features of design such as substrate range, number of measurements and choice of intermediate points. Our novel approach minimises parameter error and costs, and maximises experimental efficiency. It is applicable to many areas of ocular drug design, including receptor-ligand binding and immunoglobulin binding, and should be an important tool in ocular drug discovery.

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.

Independent and reciprocal accommodation in anisometropic amblyopia

Accommodation is considered to be a symmetrical response and to be driven by the least ametropic and nonamblyopic eye in anisometropia. We report the case of a 4-year-old child with anisometropic amblyopia who accommodates asymmetrically, reliably demonstrating normal accommodation in the nonamblyopic eye and antiaccommodation of the amblyopic eye to near targets. The abnormal accommodation of the amblyopic eye remained largely unchanged during 7 subsequent testing sessions undertaken over the course of therapy. We suggest that a congenital dysinnervation syndrome may result in relaxation of accommodation in relation to near cues and might be a hitherto unconsidered additional etiological factor in anisometropic amblyopia.

Decreased accommodation during decompensation of distance exotropia

Objective. Disparity cues can be a major drive to accommodation via the CA/C (convergence accommodation to convergence) linkage but, on decompensation of exotropia, disparity cues are extinguished by suppression, so this drive is lost. This study investigated accommodation and vergence responses to disparity, blur and proximal cues in a group of distance exotropes aged between 4-11 years both during decompensation and when exotropic. Methods. 19 participants with distance exotropia were tested using a PlusoptiXSO4 photorefractor set in a remote haploscopic device which assessed simultaneous vergence and accommodation to a range of targets incorporating different combinations of blur, disparity and proximal cues at four fixation distances between 2m and 33cm. Responses on decompensation were compared to those from the same children when their deviation was controlled. Results. Manifest exotropia was more common in the more impoverished cue conditions. When decompensated for near, mean accommodation gain for the all-cue (naturalistic) target reduced significantly (p<0.0001), with resultant mean under-accommodation of 2.33D at 33cm. The profile of near cues usage changed after decompensation, with blur and proximity driving residual responses, but these remaining cues did not compensate for loss of accommodation caused by the removal of disparity. Conclusions. Accommodation often reduces on decompensation of distance exotropia as the drive from convergence is extinguished, providing a further reason to try to prevent decompensation for near.

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.

Psychophysics of emotion: the QUEST for emotional attention

To investigate the mechanisms involved in automatic processing of facial expressions, we used the QUEST procedure to measure the display durations needed to make a gender decision on emotional faces portraying fearful, happy, or neutral facial expressions. In line with predictions of appraisal theories of emotion, our results showed greater processing priority of emotional stimuli regardless of their valence. Whereas all experimental conditions led to an averaged threshold of about 50 ms, fearful and happy facial expressions led to significantly less variability in the responses than neutral faces. Results suggest that attention may have been automatically drawn by the emotion portrayed by face targets, yielding more informative perceptions and less variable responses. The temporal resolution of the perceptual system (expressed by the thresholds) and the processing priority of the stimuli (expressed by the variability in the responses) may influence subjective and objective measures of awareness, respectively.

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.