Lid wiper epitheliopathy Efron, Nathan; Brennan, Noel A.; Morgan, Philip B. ...
Progress in retinal and eye research,
July 2016, 2016-Jul, 2016-07-00, 20160701, Letnik:
53
Journal Article
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Some recent research has resulted in a hypothesis that there is a common 'lid wiper' region that is apposite to the ocular surface or anterior lens surface (where contact lenses are worn), ...responsible for spreading tears during blinking. In the upper eyelid, it extends about 0.6 mm from the crest of the sharp posterior (inner) lid border (i.e. the mucocutaneous junction, or line of Marx) to the subtarsal fold superiorly and from the medial upper punctum to the lateral canthus horizontally. Histologically, it is seen as an epithelial elevation comprising of stratified epithelium with a transitional conjunctival structure of (moving posteriorly) squamous cells then cuboidal cells, with some parakeratinised cells and goblet cells. Lid wiper epitheliopathy (LWE) denotes staining of the lid wiper observed after instillation of dyes such as fluorescein, rose bengal or lissamine green. There have been some reports of higher rates of LWE in dry eye patients and contact lens wearers, but others have failed to find such associations. The primary cause of LWE is thought to be increased friction between the lid wiper and ocular or anterior contact lens surface due to inadequate lubrication, which could be caused by dry eye and may be exacerbated by factors such as abnormal blinking patterns, poor contact lens surface lubricity and adverse environmental influences. Recent evidence suggests that LWE is associated with sub-clinical inflammation. LWE has the potential to provide the missing mechanistic link between clinical observation and symptoms associated with dry eye and contact lens wear. Clinical and fundamental research into LWE is still in its infancy and in many instances equivocal; however, it is an idea that provides a potentially important new avenue for further investigation of anterior eye discomfort associated with ocular dryness and contact lens wear.
Dry eye disease (DED) is a growing public health concern affecting quality of life and visual function, with a significant socio-economic impact. It is characterised by the loss of homoeostasis, ...resulting in tear film instability, hyperosmolarity and inflammation of the ocular surface. If the innate immune response is unable to cope with internal bodily or environmental adverse conditions, the persistent, self-maintaining vicious circle of inflammation leads to the chronic form of the disease. Treatment of DED should be aimed at the restoration of the homoeostasis of the ocular surface system. A proper diagnostic approach is fundamental to define the relevance and importance of each of the DED main pathogenic factors, namely tear film instability, epithelial damage and inflammation. Consideration also needs to be given concerning two other pathogenic elements: lid margin changes and nerve damage. All the factors that maintain the vicious circle of DED in the patient's clinical presentation have to be considered and possibly treated simultaneously. The treatment should be long-lasting and personalised since it has to be adapted to the different clinical conditions observed along the course of the disease. Since DED treatment is frequently unable to provide fast and complete relief from symptoms, empathy with patients and willingness to explain to them the natural history of the disease are mandatory to improve patients' compliance. Furthermore, patients should be instructed about the possible need to increase the frequency and/or change the type of treatment according to the fluctuation of symptoms, following a preplanned rescue regimen.
•Evaluation of green roofs for stormwater management at urban basin scale.•Green roofs cause peak flow and volume reduction in the urban drainage network.•Green roofs are more effective during ...frequent storms of smaller magnitude.•Non-linear reduction of outlet peak flow if network mainly at maximum convey capacity.•Effectiveness may increase with spatially heterogeneous implementation.
Urbanization modifies the hydrologic cycle, resulting in increased runoff rates, volumes, and peak flows in the drainage network. In this paper, the implementation of green roofs as source control solutions for mitigating the impacts of urbanization is analysed at the urban catchment scale. The hydrologic-hydraulic response of a 2 km2 urban basin is investigated under various implementation scenarios and rainfall characteristics. In particular, a distributed hydrologic model is employed to assess the impact of 4 spatially homogeneous installations of green roofs (25%, 50%, 75%, 100% of roofs area converted) when forced by 6 storms differing in both duration and return period. In addition, a spatially heterogeneous configuration is tested, with green roofs concentrated where the drainage network is more prone to high degrees of filling. Results show that implementing green roofs at the urban watershed scale can be considered a valuable strategy to reduce both flow peak and volume in urban drainage networks, although the approach is more effective for frequent storms of smaller magnitude. In addition, it is found that the urban system may respond non-linearly to the extent of green roofs implementation in terms of peak flow reduction at the network outlet, and that non-linearity is mainly related to the network being close to its flow convey capability. Finally, planning redevelopment efforts on the basis of local insufficiencies in network convey capacity has the potential of increasing the effectiveness of Low Impact Development solutions.
Glutamatergic hyperactivity in the nucleus striatum, the main basal ganglia input, has been involved in the progression of Parkinson's disease (PD) and the onset of L-Dopa-induced dyskinesias (LIDs). ...Abnormalities in the spiny projection neurons excitability and firing, and in the overactivity of glutamate transmission found in animal models of PD, pointed to the synaptic dysfunctions as a primary target to counteract alterations before overt neurodegeneration, conferring a key role to striatal glutamatergic transmission in the early phases of the disease. The present paper provides an overview of the evidence that glutamatergic overactivity is a critical mechanism underlying different PD-associated striatal alterations in early and advanced symptomatic stages of the disease. These aberrant changes, under L-Dopa therapy, lead to a more complex synaptopathy that involves other neurotransmitter systems and persistent modifications to generate LIDs. The review discusses the main changes in glutamatergic functions found in PD preclinical models and clinical studies and an update of the current pharmacological strategies to modulate the glutamatergic systems at the pre- and postsynaptic levels will be provided.
•Glutamate-mediated excitatory signals play a key role in the basal ganglia circuitry.•Excessive glutamatergic transmission in the striatum is implicated in the progression of PD and in the emergence of LIDs.•DA levels reduction leads to alterations in firing activity patterns in tPD striatum of experimental models and patients.•Blunting excessive glutamate transmission is a therapeutic strategy to normalize neurotransmitter synaptic levels.
•A simulation-optimization model was proposed to optimize a LID scenario.•Optimal solutions on various runoff reduction levels were found at different costs.•Thresholds from which the return of ...investment was not significant were identified.•Enhancements to the model are needed to develop a reliable LID design method.
High rates of soil imperviousness, intensified by urbanization, have been contributing strongly to the occurrence of floods all over the world. To mitigate these impacts, Low Impact Development (LID) techniques seek to preserve the hydrology of urban catchments closer to pre-development conditions by using distributed stormwater control systems. Nevertheless, the application of these techniques is associated with a variety of challenges, including the design of the LID controls, due to the significant number of variables involved and the need to attend to multiple objectives simultaneously. In this context, the application of hydrologic simulation models integrated with optimization techniques has been recently explored as an alternative to assist in planning LID scenarios. This work aims to verify the applicability of an adaptation of the Genetic Algorithm NSGA-II, together with the hydrologic model SWMM, to assist the optimal design of a LID scenario seeking to reduce the stormwater runoff and the total costs on different return periods. This scenario has considered the combined implementation of permeable pavements, green roofs and bioretention cells. The results showed that the model was capable of finding a great variety of optimal solutions on various levels of runoff reduction, at different costs, for all return periods considered. Regarding the applicability of the optimization model as a LID design method, some limitations were found related to practical applications and possible oversizing of the subjacent layers of the LIDs. Therefore, suggestions on how to improve the model have been made to solve the identified problems.
The ocular surface is continually exposed to the environment and as a consequence to different types of microbes, but whether there is a normal microbiota of the ocular surface remains unresolved. ...Using traditional microbial culture techniques has shown that <80% of swabs of the conjunctiva yield cultivable microbes. These usually belong to the bacterial types of the coagulase-negative staphylococci, Propionibacterium sp., with low frequency of isolation of bacteria such as Staphylococcus aureus, Micrococcus sp., Gram-negative bacteria or fungi. Even when these are grown, the numbers of colony forming units (cfu) per swab of the conjunctiva is usually much less than 100 cfu. Swabs of the lid more commonly result in microbial growth, of the same species as from the conjunctiva and slightly higher cfu. Contact lenses have also been cultured, and they yield similar microbial types. Microbes can be isolated from the ocular surface almost immediately after birth. The advent of molecular techniques for microbial identification based on 16S rRNA sequencing has opened up the possibility of determining whether there are non-cultivable microbes that can colonise the ocular surface. Additionally, use of these techniques with cross-sectional and longitudinal studies may help to understand whether the ocular surface harbours its own unique microbiota, or whether the microbiota are only transiently present.
•It is unknown whether the ocular surface contains a normal microbiota.•Culture of the conjunctiva yields small numbers of bacteria but not on all occasions.•Molecular techniques may establish whether the ocular surface has a unique microbiota.
Levodopa (L-DOPA) administration remains the gold standard therapy for Parkinson's disease (PD). Despite several pharmacological advances in the use of L-DOPA, a high proportion of chronically ...treated patients continues to suffer disabling involuntary movements, namely, L-DOPA-induced dyskinesias (LIDs). As part of the effort to stop these unwanted side effects, the present study used a rodent model to identify and manipulate the striatal outflow circuitry responsible for LIDs. To do so, optogenetic technology was used to activate separately the striatal direct (D1R- expressing) and indirect (D2R- expressing) pathways in a mouse model of PD. Firstly, D1-cre or A2a-cre animals received unilateral injections of neurotoxin 6-hydroxydopamine (6-OHDA) to simulate the loss of dopamine observed in PD patients. The effects of independently stimulating each pathway were tested to see if experimental dyskinesias could be induced. Secondly, dopamine depleted A2a-cre animals received systemic L-DOPA to evoke dyskinetic movements. The ability of indirect pathway optogenetic stimulation to suppress pre-established LIDs was then tested. Selective manipulation of direct pathway evoked optodyskinesias both in dopamine depleted and intact animals, but optical inhibition of these neurons failed to suppress LIDs. On the other hand, selective activation of indirect striatal projection neurons produced an immediate and reliable suppression of LIDs. Thus, a functional dissociation has been found here whereby activation of D1R- and D2R-expressing projection neurons evokes and inhibits LIDs respectively, supporting the notion of tight interaction between the two striatal efferent systems in both normal and pathological conditions. This points to the importance of maintaining an equilibrium in the activity of both striatal pathways to produce normal movement. Finally, the ability of selective indirect pathway optogenetic activation to block the expression of LIDs in an animal model of PD sheds light on intrinsic mechanisms responsible for striatal-based dyskinesias and identifies a potential therapeutic target for suppressing LIDs in PD patients.
•Activation of indirect striatal pathway suppressed L-DOPA-induced dyskinesias.•Direct pathway stimulation evoked optodyskinesias both in dopamine depleted and intact mice.•Optogenetic inhibition of striatal direct pathway failed to suppress LIDs.•L-DOPA priming potentiates optodyskinesias.•Direct pathway activation increased Fos-B only in dopamine depleted animals.
To define and quantify the upper lid contour by adapting Bézier curves with a newly developed software in normal subjects, assessing their reliability.
Fifty eyes of 50 healthy patients with no ...ocular pathology were included in this study from October 2020 to November 2020. All measurements were performed on Bézier curves adjusted to the upper lid contour. An original software was used to measure the radial and vertical midpupil-to-lid margin distances (MPLD), temporal-to-nasal (T/N) ratios, contour peak location and grade of superposition (GS) and asymmetry (GA) indexes. We calculated differences in the variables measured regarding age, gender or the side of the eye being assessed.
The mean Bézier curve showed an excellent level of inter-rater reliability (intraclass correlation coefficient of 0.99). The median GS index of each eyelid to the mean Bézier curve was 95.4%, 8.5 IQR, and the median GA index was 3%, 3.4 IQR. The mean contour peak location was -0.35 mm, SD 0.45. Overall, the mean central MPLD was 4.1 mm, SD 0.6. No significant differences were found between male and female patients in variables derived from Bézier curves.
Bézier curves may become a very useful tool for the assessment of upper lid contour, contour peak and symmetry. GS and GA indexes, along with the T/N area ratio are potential outcomes for this purpose. All current variables can be obtained just from one single Bézier curve measurement. Our results offer an in-depth exhaustive description of these variables and their distribution in the normal population.
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