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1.
Diabet Med ; 38(4): e14425, 2021 04.
Article in English | MEDLINE | ID: mdl-33064854

ABSTRACT

AIMS: To investigate diabetic retinopathy screening attendance and trends in certified vision impairment caused by diabetic eye disease. METHODS: This was a retrospective study of attendance in three urban UK diabetic eye screening programmes in England. A survival analysis was performed to investigate time from diagnosis to first screen by age and sex. Logistic regression analysis of factors influencing screening attendance during a 15-month reporting period was conducted, as well as analysis of new vision impairment certifications (Certificate of Vision Impairment) in England and Wales from 2009 to 2019. RESULTS: Of those newly registered in the Routine Digital Screening pathway (n = 97 048), 80% attended screening within the first 12 months and 88% by 36 months. Time from registration to first eye screening was longer for people aged 18-34 years, and 20% were unscreened after 3 years. Delay in first screen was associated with increased risk of referable retinopathy. Although 95% of participants (n = 291 296) attended during the 15-month reporting period, uptake varied considerably. Younger age, social deprivation, ethnicity and duration of diabetes were independent predictors of non-attendance and referable retinopathy. Although the last 10 years has seen an overall reduction in vision impairment certification attributable to diabetic eye disease, the incidence of vision impairment in those aged <35 years was unchanged. CONCLUSIONS: Whilst the majority of participants are screened in a timely manner, there is considerable variation in uptake. Young adults, have sub-optimal attendance, and levels of vision impairment in this population have not changed over the last 10 years. There is an urgent need to explore barriers to/enablers of attendance in this group to inform policy initiatives and tailored interventions to address this issue.


Subject(s)
Diabetes Mellitus/epidemiology , Diabetic Retinopathy/diagnosis , Mass Screening/trends , Patient Compliance/statistics & numerical data , Vision Disorders/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Diabetes Mellitus/diagnosis , Diabetic Retinopathy/epidemiology , England/epidemiology , Female , Humans , Male , Mass Screening/methods , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Patient Participation/statistics & numerical data , Retrospective Studies , Vision Disorders/etiology , Vision Screening/methods , Vision Screening/trends , Young Adult
2.
Diabet Med ; 35(10): 1308-1319, 2018 10.
Article in English | MEDLINE | ID: mdl-29790594

ABSTRACT

AIMS: To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely to influence attendance. METHODS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the 'grey literature' for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance. RESULTS: Sixty-nine primary studies were included. We identified six theoretical domains ['environmental context and resources' (75% of included studies), 'social influences' (51%), 'knowledge' (51%), 'memory, attention, decision processes' (50%), 'beliefs about consequences' (38%) and 'emotions' (33%)] as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community-level media coverage acted as enablers. CONCLUSIONS: Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance.


Subject(s)
Communication Barriers , Diabetic Retinopathy/diagnosis , Health Knowledge, Attitudes, Practice , Patient Participation , Attitude of Health Personnel , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/psychology , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/psychology , Gray Literature/statistics & numerical data , Guideline Adherence , Humans , Professional Role
3.
BMJ Open ; 6(10): e011934, 2016 10 25.
Article in English | MEDLINE | ID: mdl-27798000

ABSTRACT

OBJECTIVES: To explore views of all stakeholders (patients, optometrists, general practitioners (GPs), commissioners and ophthalmologists) regarding the operation of community-based enhanced optometric services. DESIGN: Qualitative study using mixed methods (patient satisfaction surveys, semi-structured telephone interviews and optometrist focus groups). SETTING: A minor eye conditions scheme (MECS) and glaucoma referral refinement scheme (GRRS) provided by accredited community optometrists. PARTICIPANTS: 189 patients, 25 community optometrists, 4 glaucoma specialist hospital optometrists (GRRS), 5 ophthalmologists, 6 GPs (MECS), 4 commissioners. RESULTS: Overall, 99% (GRRS) and 100% (MECS) patients were satisfied with their optometrists' examination. The vast majority rated the following as 'very good'; examination duration, optometrists' listening skills, explanations of tests and management, patient involvement in decision-making, treating the patient with care and concern. 99% of MECS patients would recommend the service. Manchester optometrists were enthusiastic about GRRS, feeling fortunate to practise in a 'pro-optometry' area. No major negatives were reported, although both schemes were limited to patients resident within certain postcode areas, and some inappropriate GP referrals occurred (MECS). Communication with hospitals was praised in GRRS but was variable, depending on hospital (MECS). Training for both schemes was valuable and appropriate but should be ongoing. MECS GPs were very supportive, reporting the scheme would reduce secondary care referral numbers, although some MECS patients were referred back to GPs for medication. Ophthalmologists (MECS and GRRS) expressed very positive views and widely acknowledged that these new care pathways would reduce unnecessary referrals and shorten patient waiting times. Commissioners felt both schemes met or exceeded expectations in terms of quality of care, allowing patients to be seen quicker and more efficiently. CONCLUSIONS: Locally commissioned schemes can be a positive experience for all involved. With appropriate training, clear referral pathways and good communication, community optometrists can offer high-quality services that are highly acceptable to patients, health professionals and commissioners.


Subject(s)
Attitude of Health Personnel , Community Health Services , Delivery of Health Care/methods , Eye Diseases , Optometry , Patient Satisfaction , Professional Role , England , Eye Diseases/diagnosis , General Practitioners , Glaucoma , Humans , Ophthalmologists , Optometrists , Referral and Consultation
4.
BMJ Open ; 6(8): e011832, 2016 08 10.
Article in English | MEDLINE | ID: mdl-27515757

ABSTRACT

BACKGROUND: The establishment of minor eye conditions schemes (MECS) within community optometric practices provides a mechanism for the timely assessment of patients presenting with a range of acute eye conditions. This has the potential to reduce waiting times and avoid unnecessary referrals to hospital eye services (HES). OBJECTIVE: To evaluate the clinical effectiveness, impact on hospital attendances and patient satisfaction with a minor eye service provided by community optometrists. METHODS: Activity and outcome data were collected for 12 months in the Lambeth and Lewisham MECS. A patient satisfaction questionnaire was given to patients at the end of their MECS appointment. A retrospective difference-in-differences analysis of hospital activity compared changes in the volume of referrals by general practitioners (GPs) from a period before (April 2011-March 2013) to after (April 2013-March 2015) the introduction of the scheme in Lambeth and Lewisham relative to a neighbouring area (Southwark) where the scheme had not been commissioned. Appropriateness of case management was assessed by consensus using clinical members of the research team. RESULTS: A total of 2123 patients accessed the scheme. Approximately two-thirds of patients (67.5%) were referred by their GP. The commonest reasons for patients attending for a MECS assessment were 'red eye' (36.7% of patients), 'painful white eye' (11.1%) and 'flashes and floaters' (10.2%). A total of 64.1% of patients were managed in optometric practice and 18.9% were referred to the HES; of these, 89.2% had been appropriately referred. First attendances to HES referred by GPs reduced by 26.8% (95% CI -40.5% to -13.1%) in Lambeth and Lewisham compared to Southwark. CONCLUSIONS: The Lambeth and Lewisham MECS demonstrates clinical effectiveness, reduction in hospital attendances and high patient satisfaction and represents a successful collaboration between commissioners, local HES units and primary healthcare providers.


Subject(s)
Community Health Services , Delivery of Health Care , Eye Diseases/diagnosis , Optometry , Patient Satisfaction , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Eye Diseases/therapy , Female , Humans , Infant , Male , Middle Aged , Ophthalmology , Referral and Consultation , State Medicine , United Kingdom , Young Adult
5.
Eye (Lond) ; 30(9): 1160-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27518543

ABSTRACT

Childhood cataract is an avoidable cause of visual disability worldwide and is a priority for VISION 2020: The Right to Sight. There is a paucity of information about the burden of cataract in children and the aim of this review is to assess the global prevalence of childhood cataract. The methodology for the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search for studies reporting estimates of prevalence or incidence of cataract among children (aged<18 years) at any global location using the Cochrane Library, Medline and Embase up to January 2015. No restrictions were imposed based on language or year of publication. Study quality was assessed using a critical appraisal tool designed for systematic reviews of prevalence. Twenty prevalence and four incidence studies of childhood cataract from five different geographical regions were included. The overall prevalence of childhood cataract and congenital cataract was in the range from 0.32 to 22.9/10000 children (median=1.03) and 0.63 to 9.74/10000 (median=1.71), respectively. The incidence ranged from 1.8 to 3.6/10000 per year. The prevalence of childhood cataract in low-income economies was found to be 0.42 to 2.05 compared with 0.63 to 13.6/10000 in high-income economies. There was no difference in the prevalence based on laterality or gender. This review highlights substantial gaps in the epidemiological knowledge of childhood cataract worldwide, particularly from low and lower middle-income economies. More studies are needed using standard definitions and case ascertainment methods with large enough sample sizes.


Subject(s)
Cataract/epidemiology , Global Health/statistics & numerical data , Adolescent , Cataract/congenital , Cataract Extraction/statistics & numerical data , Child , Child, Preschool , Databases, Factual , Humans , Incidence , Infant , Infant, Newborn , Prevalence
7.
BMJ Open ; 4(5): e004781, 2014 May 29.
Article in English | MEDLINE | ID: mdl-24875489

ABSTRACT

OBJECTIVES: To explore the views of optometrists, general practitioners (GPs) and ophthalmologists regarding the development and organisation of community-based enhanced optometric services. DESIGN: Qualitative study using free-text questionnaires and telephone interviews. SETTING: A minor eye conditions scheme (MECS) and a glaucoma referral refinement scheme (GRRS) are based on accredited community optometry practices. PARTICIPANTS: 41 optometrists, 6 ophthalmologists and 25 GPs. RESULTS: The most common reason given by optometrists for participation in enhanced schemes was to further their professional development; however, as providers of 'for-profit' healthcare, it was clear that participants had also considered the impact of the schemes on their business. Lack of fit with the 'retail' business model of optometry was a frequently given reason for non-participation. The methods used for training and accreditation were generally thought to be appropriate, and participating optometrists welcomed the opportunities for ongoing training. The ophthalmologists involved in the MECS and GRRS expressed very positive views regarding the schemes and widely acknowledged that the new care pathways would reduce unnecessary referrals and shorten patient waiting times. GPs involved in the MECS were also very supportive. They felt that the scheme provided an 'expert' local opinion that could potentially reduce the number of secondary care referrals. CONCLUSIONS: The results of this study demonstrated strong stakeholder support for the development of community-based enhanced optometric services. Although optometrists welcomed the opportunity to develop their professional skills and knowledge, enhanced schemes must also provide a sufficient financial incentive so as not to compromise the profitability of their business.


Subject(s)
Attitude of Health Personnel , Community Health Services/organization & administration , General Practice , Ophthalmology , Optometry , England , Humans , Qualitative Research , Referral and Consultation , Surveys and Questionnaires
8.
Eye (Lond) ; 26(7): 967-71, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22562188

ABSTRACT

INTRODUCTION: We have established one model for community care of glaucoma clinic patients. Community optometrists received training and accreditation in glaucoma care. Once qualified they alternated between running half day glaucoma clinics in their own High Street practices and assisting in a hospital-based glaucoma clinic session. This paper reports the cost of this model. METHODS: Micro-costing was undertaken for the hospital clinic. A consensus meeting was held to agree costs for community clinics involving all optometrists in the project along with representatives of the multiple chain optometry practices who had participated. Costs to patients both indirect and direct were calculated following structured interviews of 197 patients attending hospital clinics and 194 attending community clinics. RESULTS: The estimated cost per patient attendance to the hospital clinic was £63.91 and the estimated cost per attendance to the community clinic was £145.62. For patients the combined direct and indirect cost to attend the hospital clinic was £6.15 and the cost to attend the community clinic £5.91. DISCUSSION: The principal reason for the higher cost in the community clinic was higher overhead costs in the community. Re-referral to the hospital system only occurred for 9% of patients and was not a large contribution to the increased cost. Time requested to next appointment was similar for the two clinics. Sensitivity analysis shows a strong effect of increasing patients seen per clinic. It would, however, require 25 patients to be seen per clinician per day in the community in order to make the costs comparable.


Subject(s)
Community Health Services/economics , Glaucoma/economics , Health Care Costs , Optometry/economics , Outpatient Clinics, Hospital/economics , Cost of Illness , England , Female , Glaucoma/therapy , Humans , Longitudinal Studies , Male , Optometry/education
9.
Eye (Lond) ; 24(9): 1509-14, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20467448

ABSTRACT

PURPOSE: To develop a competency framework, using a modified Delphi methodology, for optometrists with a specialist interest in glaucoma, which would provide a basis for training and accreditation. METHODS: A modified iterative Delphi technique was used using a 16-member panel consisting almost exclusively of sub-specialist optometrists and ophthalmologists. The first round involved scoring the relevance of a draft series of competencies using a 9-point Likert scale with a free-text option to modify any competency or suggest additional competencies. The revised framework was subjected to a second round of scoring and free-text comment. The Delphi process was followed by a face-to-face structured workshop to debate and agree the final framework. The version of the framework agreed at the workshop was sent out for a 4-month period of external stakeholder validation. RESULTS: There was a 100% response to round 1 and an 94% response to round 2. All panel members attended the workshop. The final version of the competency framework was validated by a subsequent stakeholder consultation and contained 19 competencies for the diagnosis of glaucoma and 7 further competencies for monitoring and treatment. CONCLUSIONS: Application of a consensus methodology consisting of a modified Delphi technique allowed the development of a competency framework for glaucoma specialisation by optometrists. This will help to shape the development of a speciality curriculum and potentially could be adapted for other healthcare professionals.


Subject(s)
Clinical Competence , Glaucoma , Optometry/education , Specialization , Accreditation , Delphi Technique , Education, Medical, Continuing/organization & administration , Humans
10.
Eye (Lond) ; 24(6): 999-1005, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19960038

ABSTRACT

AIM: To investigate the costs to patients attending hospital-based glaucoma clinics. METHODS: A patient-based costs questionnaire was developed and completed for patients attending six ophthalmology units across London (Ealing General Hospital, St Georges Hospital, Mile End Hospital, Upney Centre Barking, St Ann's Hospital and the Royal London Hospital). The questionnaire considered age, sex, ethnicity as well as patient-based costs, opportunity costs, and companion costs. All patients visiting for review or appointments were approached non-selectively. A total of 100 patients were sampled from each unit. RESULTS: The mean age of the full sample was 69.6 years (SD 12.6), with little variation between sites (68.5-71.8 years). There was an almost equal sex distribution (male (298 (50.6%)). There was no major difference in occupational distribution between sites. The majority of people came to hospital by bus (40%) or car (26%). Female patients went slightly more by cab or car, whereas male patients went slightly more by foot or train. There was some variability in transport method by site. The data showed that the Royal London hospital had the highest mean cost per visit (pound16.20), whereas St Georges had the lowest (pound12.90). Upney had the second highest mean cost per visit (pound15.20), whereas Ealing and St Ann's had similar mean costs of (pound13.25) and (pound13), respectively. Travel costs accounted for about one-fifth of the total patient's costs. For all glaucoma clinics, total societal costs were higher than the sum of patients' costs because of the high frequency of companions. A surprising finding was that two-thirds of the population (392 or 66.6%) reported no qualification-considerably higher than the national census statistics for the same population. CONCLUSIONS: To our knowledge this paper presents direct and indirect patient costs in attending hospital glaucoma units for the first time. It highlights the significance of opportunity costs when considering health-care interventions as they amount to a third or more of the total costs of patient attendances to clinics.


Subject(s)
Glaucoma/economics , Health Expenditures , Outpatient Clinics, Hospital/economics , Aged , Aged, 80 and over , Cost of Illness , Female , Humans , London , Male , Middle Aged , Surveys and Questionnaires , Transportation/economics , Transportation/statistics & numerical data , Travel/economics
11.
Br J Ophthalmol ; 86(11): 1259-61, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12386084

ABSTRACT

BACKGROUND/AIMS: Disturbances of colour vision are a frequently reported sign of digoxin toxicity. The aim of this study was to investigate the incidence of acquired colour vision deficiency in elderly hospitalised patients receiving maintenance digoxin therapy. METHODS: 30 patients (mean age 81.3 (SD 6.1) years) receiving digoxin were tested using a battery of colour vision tests (Ishihara, AO Hardy Rand Rittler plates, City tritan test, Lanthony tritan album, and the Farnsworth D15). These were compared to an age matched control group. Serum digoxin concentrations were determined from venous blood samples. RESULTS: Slight to moderate red-green impairment was found in approximately 20-30% of patients taking digitalis, and approximately 20% showed a severe tritan deficiency. There was no correlation between colour vision impairment and serum digoxin level. CONCLUSIONS: Formal colour vision testing of elderly patients taking digitalis showed a high incidence of colour deficiency, suggesting that impairment of retinal function can occur even at therapeutic drug levels. As a result, colour vision testing in this population would have limited value for the detection of drug toxicity.


Subject(s)
Cardiotonic Agents/adverse effects , Color Vision Defects/chemically induced , Digoxin/adverse effects , Aged , Aged, 80 and over , Cardiotonic Agents/blood , Color Perception Tests , Color Vision Defects/blood , Digoxin/blood , Female , Humans , Male
12.
J Neurocytol ; 30(1): 35-44, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11577244

ABSTRACT

Evidence from a variety of sources suggests that pericytes have contractile properties and may therefore function in the regulation of capillary blood flow. However, it has been suggested that contractility is not a ubiquitous function of pericytes, and that pericytes surrounding true capillaries apparently lack the machinery for contraction. The present study used a variety of techniques to investigate the expression of contractile proteins in the pericytes of the CNS. The results of immunocytochemistry on cryosections of brain and retina, retinal whole-mounts and immunoblotting of isolated brain capillaries indicate strong expression of the smooth muscle isoform of actin (alpha-SM actin) in a significant number of mid-capillary pericytes. Immunogold labelling at the ultrastructural level showed that alpha-SM actin expression in capillaries was exclusive to pericytes, and endothelial cells were negative. Compared to alpha-SM actin, non-muscle myosin was present in lower concentrations. By contrast, smooth muscle myosin isoforms, were absent. Pericytes were strongly positive for the intermediate filament protein vimentin, but lacked desmin which was consistently found in vascular smooth muscle cells. These results add support for a contractile role in pericytes of the CNS microvasculature, similar to that of vascular smooth muscle cells.


Subject(s)
Blood-Brain Barrier/physiology , Contractile Proteins/analysis , Pericytes/chemistry , Actins/analysis , Animals , Calcium-Binding Proteins/analysis , Cytoskeleton , Desmin/analysis , Immunoenzyme Techniques , Male , Microcirculation , Microfilament Proteins , Microscopy, Immunoelectron , Pericytes/ultrastructure , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Rats , Rats, Sprague-Dawley , Retinal Vessels/chemistry , Retinal Vessels/cytology , Smooth Muscle Myosins/analysis , Vimentin/analysis , Calponins
13.
Cells Tissues Organs ; 169(1): 1-11, 2001.
Article in English | MEDLINE | ID: mdl-11340256

ABSTRACT

Pericytes are perivascular cells with multifunctional activities which are now being elucidated. The functional interaction of pericytes with endothelial cells (EC) is now being established, using current molecular and cytochemical techniques. The detailed morphology of the pericyte has been well described. Pericytes extend long cytoplasmic processes over the surface of the EC, the two cells making interdigitating contacts. At points of contact, communicating gap junctions, tight junctions and adhesion plaques are present. Pericytes appear to show both structural and functional heterogeneity. The coverage of EC by pericytes varies considerably between different microvessel types and the location of pericytes on the microvessel is not random but appears to be functionally determined. Interaction between pericytes and EC is important for the maturation, remodelling and maintenance of the vascular system via the secretion of growth factors or modulation of the extracellular matrix. There is also evidence that pericytes are involved in the transport across the blood-brain barrier and the regulation of vascular permeability. The long-standing view that pericytes are the microvessel equivalent of larger vessel smooth muscle cells and are contractile is being reassessed using current methods. An important role for pericytes in pathology, and neuropathology in particular, has been indicated in hypertension, diabetic retinopathy, Alzheimer's disease, multiple sclerosis and CNS tumour formation.


Subject(s)
Pericytes , Animals , Cell Communication , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/pathology , Humans , Microcirculation/pathology , Pericytes/cytology , Pericytes/pathology , Pericytes/physiology
14.
Brain Res Bull ; 52(1): 1-12, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10779695

ABSTRACT

The blood-brain barrier (BBB) has been much more extensively investigated than the blood-nerve barrier (BNB). Nevertheless it is clear that there are both similarities and differences in the molecular and morphophysiological characteristics of the two barrier systems. A number of enzymes, transporters and receptors have been investigated at both the BNB and BBB, as well as in the perineurium of peripheral nerves, which is also a metabolically active diffusion barrier. While there have been few systematic comparisons of the distribution of these molecules in both the BNB and BBB, it is apparent from the data available, reviewed in this article, that their distribution also supports the concept of the BNB and BBB having some features in common but also showing distinct identities. These similarities and differences cannot simply be accounted for by the presence of the inductive influences of astrocytes at the BBB and absence at the BNB. Whether the Schwann cell also has the capacity to induce some BNB properties remains to be determined.


Subject(s)
Blood-Brain Barrier/physiology , Capillary Permeability/physiology , Carrier Proteins/metabolism , Enzymes/metabolism , Nervous System/metabolism , Receptors, Cell Surface/metabolism , Animals , Humans
15.
J Anat ; 196 ( Pt 1): 55-60, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10697288

ABSTRACT

There is evidence that the endothelial cell (EC) glycocalyx is a significant determinant of vascular permeability, acting as a charge-size filter to permeant molecules. We have therefore examined its oligosaccharide composition in 3 classes of microvessel with differing permeabilities. EC in rat brain, retina and myocardium were labelled with a panel of lectins and subjected to a semiquantitative analysis. Surprisingly, no substantial differences were evident for any lectin labelling between the 3 microvessel types despite their marked morphophysiological diversity. In particular, all showed substantial sialic acid expression, with Maackia amurensis (MAA) labelling sialic acid in an alpha2-3 linkage to beta-galactose and Sambucus nigra (SNA) recognising sialic acid in an alpha2-6 linkage to beta-galactose. Arachis hypogaea (PNA) binding after neuraminidase digestion indicated the presence of Gal beta1-3GalNAc attached to terminal sialic acid. The results therefore show that the sequences NeuNAc alpha2-3Gal beta1-3GalNAc and NeuNAc alpha2-6Gal beta1-3GalNAc are strongly expressed in the 3 microvessel types irrespective of their permeability properties. This homogeneity suggests that these lectin ligands may be involved in a common set of EC functions, e.g. cell:cell and cell:matrix interactions. However, we cannot rule out the possibility that glycocalyx differences may exist between vessels in the paracellular cleft which may alter its filtration properties.


Subject(s)
Brain/anatomy & histology , Heart/anatomy & histology , Retina/anatomy & histology , Animals , Cerebrovascular Circulation , Endothelium, Vascular/anatomy & histology , Lectins/metabolism , Male , Microcirculation , Rats , Rats, Wistar
16.
Anat Embryol (Berl) ; 199(6): 509-17, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10350131

ABSTRACT

A number of major properties of endothelial cells (EC) at the blood-brain barrier (BBB) have been shown to be astrocyte-dependent. Whether analogous properties at the blood-nerve barrier (BNB) are induced and maintained by Schwann cells has not been investigated. As a preliminary investigation we have undertaken a comparative study of six EC membrane markers at the BBB and BNB and perineurium. Employing immunoblotting and immunocytochemistry the relative distribution between rat brain cortex and sciatic nerve was determined for the glucose transporter (GLUT-1), the transferin receptor (OX-26), the endothelial barrier antigen (EBA) and the OX-47 antigen. Using enzyme cytochemistry the same comparison was made for gamma-glutamyl transpeptidase (GGTP) and alkaline phosphatase. By immunocytochemistry GLUT-1 was uniformly strongly represented in brain EC, nerve EC and perineurium. OX-26 was strongly positive in brain EC but present only in trace quantities in nerve EC and perineurium. EBA similarly showed strong positivity in brain EC and trace amounts in nerve EC but was absent from perineurium. OX-47 was present moderately in brain EC and perineurium but absent from nerve EC. Quantitative immunoblotting of brain and sciatic nerve homogenates showed statistically significant differences in the level of expression of EBA and OX-26 between the two tissues. Enzyme cytochemistry showed that GGTP was strongly positive in brain EC but absent from nerve EC and perineurium. Alkaline phosphatase stained strongly in brain and nerve EC and was absent from perineurium. In summary the six membrane markers were heterogeneously represented in nerve compared with brain. This pattern of distribution in the nerve cannot simply be accounted for by the absence of astrocytes and their inductive influences. Any inductive influences of Schwann cells require investigation.


Subject(s)
Antigens, CD , Antigens, Neoplasm , Antigens, Surface , Avian Proteins , Biomarkers/analysis , Blood Proteins , Blood-Brain Barrier , Cerebral Cortex/blood supply , Endothelium, Vascular/metabolism , Sciatic Nerve/blood supply , Alkaline Phosphatase/metabolism , Animals , Basigin , Blotting, Western , Cell Membrane/metabolism , Endothelium, Vascular/cytology , Glucose Transporter Type 1 , Immunoenzyme Techniques , Membrane Glycoproteins/metabolism , Microcirculation , Monosaccharide Transport Proteins/metabolism , Mucin-1/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Transferrin/metabolism , gamma-Glutamyltransferase/metabolism
17.
Graefes Arch Clin Exp Ophthalmol ; 237(2): 117-24, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9987628

ABSTRACT

BACKGROUND: A study was carried out to ascertain, in ophthalmologically normal subjects, the short-term effects of dipivefrin hydrochloride 0.1% on visual performance and make comparisons with pilocarpine. METHODS: Twelve normal volunteers aged 20-26 years attended on three occasions. One eye, randomly selected, received one drop of either pilocarpine 2%, dipivefrin or saline 0.9%. High- and low-contrast LogMAR acuity at 6 m and pupil diameter (measured by infra-red pupillometry) were recorded at baseline (T0) and at intervals up to 90 min following instillation of drops. Program 30-2 of the Humphrey Visual Field Analyzer (HFA) was run at T0 and at 60 min after treatment instillation (T60). Saline was always instilled at visit 1, to allow for learning effects. On visits 2 and 3 either pilocarpine or dipivefrin was randomly instilled into the treated eye. RESULTS: Pilocarpine significantly worsened the field global indices mean deviation (P < 0.001) and pattern standard deviation (P < 0.01) compared with T0. There was no significant change with dipivefrin. A significant (P = 0.01) pupil dilation from 5.44 mm (SD 0.79) at T0 to 6.19 mm (SD 1.09) at T90 occurred with dipivefrin. Pilocarpine caused significant miosis. No significant changes in LogMAR values were found with dipivefrin. Pilocarpine significantly (P < 0.01) increased LogMAR values (i.e. reduced acuity) compared with dipivefrin. At T30 the mean increase in LogMAR was 0.76 (SD 0.30) for high and 0.83 (SD 0.11) for low contrast. By T90 recovery of acuity was virtually complete. CONCLUSIONS: In normals dipivefrin causes mydriasis but does not affect the central visual field global indices (as assessed by STATPAC), or high- and low-contrast LogMAR acuity. Pilocarpine adversely affects the visual field and both measures of acuity. Knowledge of these effects is of value in glaucoma therapy and when monitoring the progression of visual loss.


Subject(s)
Epinephrine/analogs & derivatives , Miotics/pharmacology , Mydriatics/pharmacology , Pilocarpine/pharmacology , Pupil/drug effects , Visual Acuity/drug effects , Visual Fields/drug effects , Adult , Cross-Over Studies , Double-Blind Method , Epinephrine/administration & dosage , Epinephrine/pharmacology , Female , Humans , Male , Miotics/administration & dosage , Mydriatics/administration & dosage , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/pharmacology , Pilocarpine/administration & dosage , Visual Field Tests
18.
Anat Embryol (Berl) ; 199(1): 29-34, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9924932

ABSTRACT

Pial microvessels have several important blood-brain barrier (BBB) characteristics in common with cerebral microvessels, despite lacking their astrocytic ensheathment. We have therefore determined whether they have the same distribution of two enzymes, gamma-glutamyl transpeptidase (GGTP) and alkaline phosphatase, both of which are known to be astrocyte-dependent. GGTP was absent from all rat pial microvessels but strongly present in brain cortical capillaries. Alkaline phosphatase was heterogeneously expressed in pial microvessels, including capillaries, but strongly positive in brain cortical capillaries. Diffusible, inductive factors produced by astrocytes could account for these differences in enzyme distribution between the two vessel types. Furthermore, differences in expression between the two markers may reflect their differing sensitivities to the astrocytic factors. Caution is urged in the common usage of the pial microvessel as a model system in BBB studies.


Subject(s)
Alkaline Phosphatase/biosynthesis , Capillaries/enzymology , Cerebral Cortex/blood supply , Pia Mater/blood supply , gamma-Glutamyltransferase/biosynthesis , Animals , Arterioles/enzymology , Cerebral Cortex/enzymology , Endothelium, Vascular/enzymology , Endothelium, Vascular/ultrastructure , Histocytochemistry , Microscopy, Electron , Pericytes/enzymology , Pericytes/ultrastructure , Pia Mater/enzymology , Rats , Rats, Sprague-Dawley , Venules/enzymology
19.
Histochem J ; 30(1): 51-60, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9539207

ABSTRACT

The oligosaccharide chains of cell surface and extracellular matrix glycoconjugates are essential for the biological properties of these molecules. We have, therefore, investigated carbohydrate residues in the rat cornea using biotinylated lectin-gold probes. Fixed corneas were removed and embedded in Lowicryl HM20 or LR White. Ultrathin sections were incubated in one of the lectins: Triticum vulgare (WGA), Canavalia ensiformis (Con A), Griffonia simplicifolia (GS-1), Limax flavus (LFA) and Allomyrina dichotoma (Allo A), followed by streptavidin-gold, or the sections were incubated in cationic colloidal gold. Semi-quantification of gold labelling was determined for corneal endothelium, Descemet's membrane, stroma and epithelium from electron micrographs. WGA and Con A binding sites were expressed either moderately or strongly throughout the cornea, suggesting a preponderance of alpha-mannose and N-acetylglucosamine residues. A particular concentration of these sugars was found in Descemet's membrane. In contrast, GS-1 (specific for alpha-galactose) and Allo A (specific for beta-galactose) labelled all regions weakly. Sialic acid residues, as defined by LFA labelling and the expression of neuraminidase-sensitive cationic colloidal gold binding sites, were sparsely distributed throughout the stroma, Descemet's membrane and endothelium. In contrast, sialoglycoconjugates were found in significant concentrations in the epithelium. Electron microscopy proved useful in providing new information on the cellular and subcellular localization of these lectin binding sites.


Subject(s)
Cornea/ultrastructure , Glycoconjugates/isolation & purification , Histocytochemistry/methods , Acrylic Resins , Animals , Cornea/chemistry , Extracellular Matrix/chemistry , Extracellular Matrix/ultrastructure , Gold , Histocytological Preparation Techniques , Lectins , Male , Rats , Rats, Sprague-Dawley
20.
Ophthalmic Physiol Opt ; 18(5): 393-400, 1998 Sep.
Article in English | MEDLINE | ID: mdl-10023471

ABSTRACT

Several topical ocular local anaesthetics are available in preservative-free unit-dose applicators. There is little comparative data as to the efficacy and tolerability of these drugs. The purpose of this study was to compare the tolerability, and the depth and duration of corneal anaesthesia following instillation of one drop of 0.4% oxybuprocaine (benoxinate), 0.5% amethocaine, or 0.5% proxymetacaine. The tolerability of each anaesthetic was assessed using a linear ten point arbitrary comfort scale. A group of 14 healthy male subjects, with a wide variation in iris pigment levels, participated in the study (mean age 26.6 years, range 18-40 years). Corneal sensitivity was measured using a slit-lamp mounted Cochet-Bonnet aesthesiometer prior to instillation, and at 1, 2, 5, 10, 15, 20 and 30 min after instillation, and continued if necessary until corneal sensitivity had returned to pre-instillation levels. For each anaesthetic, complete anaesthesia occurred within 1 min of instillation and a return to baseline sensitivity levels occurred by 45 min. No significant difference in anaesthesia was found between the drugs at each time point. Tolerability profiles indicated that proxymetacaine was significantly better tolerated than either amethocaine (p < 0.01) or oxybuprocaine (benoxinate) (p < 0.001). There was considerable inter-subject variability in the duration of anaesthesia, and practitioners should be alert to this when allowing patients to leave the practice following the production of corneal anaesthesia. There seems little to choose clinically between the three active agents as regards clinical effectiveness. Proxymetacaine was significantly better tolerated than either amethocaine or oxybuprocaine.


Subject(s)
Anesthetics, Local/adverse effects , Cornea/drug effects , Ophthalmic Solutions/adverse effects , Administration, Topical , Adolescent , Adult , Anesthetics, Local/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Male , Ophthalmic Solutions/administration & dosage , Pain/prevention & control , Pain Measurement , Time Factors , Touch/drug effects
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