Punctal plug: a medical device to treat dry eye syndrome and for sustained drug delivery to the eye

Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Tracking the Links to Social Functioning: Asperger Syndrome and Gaze Patterns

The application of Eye Tracking (ET) to the study of social functioning in Asperger Syndrome (AS) provides a unique perspective into social attention and cognition in this atypical neurodevelopmental group. Research in this area has shown how ET can capture social attention atypicalities within this group, such as diminished fixations to the eye region when viewing still images and movie clips; increased fixation to the mouth region; reduced face gaze. Issues exist, however, within the literature, where the type (static/dynamic) and the content (ecological validity) of stimuli used appear to affect the nature of the gaze patterns reported. Objectives: Our research aims were: using the same group of adolescents with AS, to compare their viewing patterns to age and IQ matched typically developing (TD) adolescents using stimuli considered to represent a hierarchy of ecological validity, building from static facial images; through a non-verbal movie clip; through verbal footage from real-life conversation; to eye tracking during real-life conversation. Methods: Eleven participants with AS were compared to 11 TD adolescents, matched for age and IQ. In Study 1, participants were shown 2 sets of static facial images (emotion faces, still images taken from the dynamic clips). In Study 2, three dynamic clips were presented (1 non-verbal movie clip, 2 verbal footage from real-life conversation). Study 3 was an exploratory study of eye tracking during a real-life conversation. Eye movements were recorded via a HiSpeeed (240Hz) SMI eye tracker fitted with chin and forehead rests. Various methods of analysis were used, including a paradigm for temporal analysis of the eye movement data. Results: Results from these studies confirmed that the atypical nature of social attention in AS was successfully captured by this paradigm. While results differed across stimulus sets,
collectively they demonstrated how individuals with AS failed to focus on the most socially relevant aspects of the various stimuli presented. There was also evidence that the eye movements of the AS group were atypically affected by the presence of motion and verbal information. Discriminant Function Analysis demonstrated that the ecological validity of stimuli was an important factor in identifying atypicalities associated with AS, with more accurate classifications of AS and TD groups occurring for more naturalistic stimuli (dynamic rather than static). Graphical analysis of temporal sequences of eye movements revealed the atypical manner in which AS participants followed interactions within the dynamic stimuli. Taken together with data on the order of gaze patterns, more subtle atypicalities were detected in the gaze behaviour of AS individuals towards more socially pertinent regions of the dynamic stimuli. Conclusions: These results have potentially important implications for our understanding of deficits in Asperger Syndrome, as they show that, with more naturalistic stimuli, subtle differences in social attention can be detected that

Spontaneous and cued gaze-following in autism and Williams syndrome

Background: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and Autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people.

Methods: We used eye tracking to explore how individuals with WS and Autism attended to, and subsequently interpreted, an actor’s eye gaze cue within a social scene. Images were presented for three seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye-gaze in each condition was analyzed by ANOVA and accuracy of identification was compared with t-tests.

Results: Participants with WS allocated more gaze time to face and eyes than their matched controls both with and without being asked to identify the item being looked at; while participants with Autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets, while those with Autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls.

Conclusions: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and Autism are characterised by atypicalities of social attention that impact upon socio-cognitive expertise but importantly the type of atypicality is syndrome-specific.

Plateau iris syndrome associated with multiple ciliary body cysts:Report of 3 cases

Objective: To describe plateau iris syndrome associated with multiple neuroepithelial cysts of the pars plicata. Methods: Case reports of 3 patients with plateau iris syndrome who were found to have multiple bilateral ciliary body cysts on ultrasound biomicroscopic examination. Results: Ultrasound biomicroscopy revealed classic features of plateau iris syndrome in each patient but also showed multiple neuroepithelial cysts of the ciliary body in each eye. Conclusion: Plateau iris syndrome may be associated with multiple ciliary body cysts.

The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon Lefevre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early,onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p. V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 mu moles/mg/min vs. 1,678.7 +/- SD 527.2 mu moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. (C) 2004 Wiley-Liss, Inc.

Eye Spy Private High: Re-conceptualizing High Policing Theory

This paper contests traditional analyses of high policing, suggesting that it needs to be decoupled (in theoretical terms) from its umbilical linkage to public actors and the preservation and augmentation of state authority. Arguing that conventional conceptualizations of high policing fail to acknowledge the role of private actors, we adopt the term `private high policing' to more accurately reflect the complexity of this paradigm. In particular, we note a long legacy of protecting dominant interests within corporate power structures, as well as increased involvement in outsourced security services for Western states. This has reached its zenith in the recent conflict/reconstruction efforts in Iraq. Eschewing conventional notions of the `proxy' debate, we propose a more complex relationship of obfuscation whereby both public and private high policing actors cross-permeate and coalesce in the pursuit of symbiotic state and corporate objectives.

Effects of amisulpride, risperidone and chlorpromazine on auditory and visual latent inhibition, prepulse inhibition, executive function and eye movements in healthy volunteers.

In view of the evidence that cognitive deficits in schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed a trend to disrupt visual latent inhibition. Although amisulpride did not affect eye movements, both risperidone and chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the risperidone group, correlated with drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and akathisia they produce. The effect risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following amisulpride was similar in nature to that which would be expected with amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of schizophrenia.

Neurobiological model of visuo-spatial cognition in young Williams Syndrome children: measures of dorsal-stream and frontal function

We examine hypotheses for the neural basis of the profile of visual cognition in young children with Williams syndrome (WS). These are: (a) that it is a consequence of anomalies in sensory visual processing; (b) that it is a deficit of the dorsal relative to the ventral cortical stream; (c) that it reflects deficit of frontal function, in particular of fronto-parietal interaction; (d) that it is related to impaired function in the right hemisphere relative to the left. The tests reported here are particularly relevant to (b) and (c). They form part of a more extensive programme of investigating visual, visuospatial, and cognitive function in large group of children with WS children, aged 8 months to 15 years. To compare performance across tests, avoiding floor and ceiling effects, we have measured performance in children with WS in terms of the ‘age equivalence’ for typically developing children. In this paper the relation between dorsal and ventral function was tested by motion and form coherence thresholds respectively. We confirm the presence of a subgroup of children with WS who perform particularly poorly on the motion (dorsal) task. However, such performance is also characteristic of normally developingchildren up to 5 years: thus the WS performance may reflect an overall persisting immaturity of visuospatial processing which is particularly evident in the dorsal stream. Looking at the performance on the global coherence tasks of the entire WS group, we find that there is also a subgroup who have both high form and motion coherence thresholds, relative to the performance of children of the same chronological age and verbal age on the BPVS, suggesting a more general global processing deficit. Frontal function was tested by a counterpointing task, ability to retrieve a ball from a ‘detour box’, and the Stroop-like ‘day-night’ task, all of which require inhibition of a familiar response. When considered in relation to overall development as indexed by vocabulary, the day-night task shows little specific impairment, the detour box shows a significant delay relative to controls, and the counterpointing task shows a marked and persistent deficit in many children. We conclude that frontal control processes show most impairment in WS when they are associated with spatially directed responses, reflecting a deficit of fronto-parietal processing. However, children with WS may successfully reduce the effect of this impairment by verbally mediated strategies. On all these tasks we find a range of difficulties across individual children and a small subset of WS who show very good performance, equivalent to chronological age norms of typically developing children. Neurobiological models of visuo-spatial cognition in children with WS p.4 Overall, we conclude that children with WS have specific processing difficulties with tasks involving frontoparietal circuits within the spatial domain. However, some children with WS can achieve similar performance to typically developing children on some tasks involving the dorsal stream, although the strategies and processing may be different in the two groups.