Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
Pharmaceutics ; 15(5)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37242686

RESUMO

Real-time measurement is important in modern dissolution testing to aid in parallel drug characterisation and quality control (QC). The development of a real-time monitoring platform (microfluidic system, a novel eye movement platform with temperature sensors and accelerometers and a concentration probe setup) in conjunction with an in vitro model of the human eye (PK-Eye™) is reported. The importance of surface membrane permeability when modelling the PK-Eye™ was determined with a "pursing model" (a simplified setup of the hyaloid membrane). Parallel microfluidic control of PK-Eye™ models from a single source of pressure was performed with a ratio of 1:6 (pressure source:models) demonstrating scalability and reproducibility of pressure-flow data. Pore size and exposed surface area helped obtain a physiological range of intraocular pressure (IOP) within the models, demonstrating the need to reproduce in vitro dimensions as closely as possible to the real eye. Variation of aqueous humour flow rate throughout the day was demonstrated with a developed circadian rhythm program. Capabilities of different eye movements were programmed and achieved with an in-house eye movement platform. A concentration probe recorded the real-time concentration monitoring of injected albumin-conjugated Alexa Fluor 488 (Alexa albumin), which displayed constant release profiles. These results demonstrate the possibility of real-time monitoring of a pharmaceutical model for preclinical testing of ocular formulations.

2.
J Glaucoma ; 32(3): 171-177, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36375094

RESUMO

PRCIS: ß-radiation is a neglected antiscarring therapy with past concerns for safety. This report found it safe and efficacious when used as an adjuvant to trabeculectomy surgery in 101 people (135 eyes) over 20 years. PURPOSE: ß-radiation has been used as an adjunct to prevent scarring in trabeculectomy surgery for many decades. Safety concerns were raised with the use of high doses on the bare sclera. Moorfields Eye Hospital has a large cohort of patients who have received ß-radiation therapy. We report a review of the long-term safety and efficacy. METHODS: Cases undertaken between August 1992 and August 1996 were reviewed. Those with records available for postoperative review of more than 5 years were included. Failure (reintervention/>21 mm Hg on 2 successive occasions) and any complication previously reported in association with ß-radiation were the primary outcomes. RESULTS: In total, 292 operations using ß-radiation were recorded and 101 people (135 eyes) with trabeculectomy surgery and postoperative follow-up for over 4.5 years were included. The median follow-up period was 22.5 years. At the final follow-up, 48 (48%) single eyes per person had failed and 20/51 (51%) eyes with primary open angle glaucoma had cataract surgery. Other complications were rare and associated with copathology. CONCLUSION: In glaucoma patients at risk of scarring and failure after trabeculectomy, as an antiscarring adjuvant, a 750 cGY dose of ß-radiation was found to be safe and efficacious in the long term.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Trabeculectomia , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Cicatriz/prevenção & controle , Cicatriz/cirurgia , Pressão Intraocular , Glaucoma/cirurgia , Glaucoma/tratamento farmacológico , Resultado do Tratamento , Estudos Retrospectivos , Seguimentos
3.
Eye (Lond) ; 36(6): 1281-1287, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34155365

RESUMO

BACKGROUND: Perimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research. METHODS: Experts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish 'agreement'. Divergence of opinions was investigated and resolved where possible through further iterations. RESULTS: 7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75-7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally. Panel members highlighted the importance of informing decisions based upon individual circumstances-from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing. CONCLUSIONS: There is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals' lifetime, highlighting the need for further research.


Assuntos
Glaucoma , Testes de Campo Visual , Criança , Consenso , Glaucoma/diagnóstico , Glaucoma/terapia , Humanos , Reprodutibilidade dos Testes , Pesquisa , Transtornos da Visão/diagnóstico , Testes de Campo Visual/métodos , Campos Visuais
4.
BMJ Open ; 11(9): e050992, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518270

RESUMO

OBJECTIVE: We aim to systematically assess and compare corneal endothelial cell density (ECD) loss in patients with glaucoma following glaucoma surgery and cataract surgery. INTRODUCTION: Corneal ECD loss may occur due to intraoperative surgical trauma in glaucoma surgery or postoperatively with chronic endothelial cell trauma or irritation. Corneal oedema and decompensation after aqueous shunt glaucoma surgery has been reported but the long-term ECD loss is still unknown. INCLUSION CRITERIA: Trabeculectomy, glaucoma filtration surgery or microinvasive glaucoma surgery in adults with ocular hypertension, primary and secondary open angle glaucoma, normal tension glaucoma and angle-closure glaucoma. Participants with pre-existing corneal disease will be excluded. Glaucoma laser treatments and peripheral iridotomy will be excluded. The outcomes include preoperative and postoperative corneal ECD, percentage change of corneal ECD and adverse events. METHODS: We will conduct an electronic database search for randomised controlled trials, prospective non-randomised studies, observational studies in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and The International Prospective Register of Systematic Reviews (PROSPERO). Eligibility criteria will include quantitative articles published after and including the year 2000, written in English and containing data on ECD loss. Two independent reviewers will screen titles and abstracts and extract data from full texts, reporting outcomes according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction of key characteristics will be completed using customised forms. Methodological quality will be assessed using the Joanna Briggs Institute critical appraisal forms. ETHICS AND DISSEMINATION: Ethics approval is not required for this review, as it will only include published data. Findings will be published in a peer-reviewed journal and disseminated across ophthalmic networks. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020192303.


Assuntos
Catarata , Glaucoma de Ângulo Aberto , Glaucoma , Trabeculectomia , Células Endoteliais , Glaucoma/cirurgia , Humanos , Revisões Sistemáticas como Assunto
5.
Lancet Glob Health ; 9(4): e489-e551, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33607016
6.
Pharmaceutics ; 12(10)2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33096803

RESUMO

Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

7.
BMJ Open ; 10(9): e036689, 2020 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-32895273

RESUMO

INTRODUCTION: Vision impairment (VI) places a burden on individuals, health systems and society in general. In order to support the case for investing in eye health services, an updated cost of illness study that measures the global impact of VI is necessary. To perform such a study, a systematic review of the literature is needed. Here we outline the protocol for a systematic review to describe and summarise the costs associated with VI and its major causes. METHODS AND ANALYSIS: We will systematically search in Medline (Ovid) and the Centre for Reviews and Dissemination database which includes the National Health Service Economics Evaluation Database. No language or geographical restriction will be applied. Additional literature will be identified by reviewing the references in the included studies and by contacting field experts. Grey literature will be considered. The review will include any study published from 1 January 2000 to November 2019 that provides information about costs of illness, burden of disease and/or loss of well-being in participants with VI due to an unspecified cause or due to one of the seven leading causes globally.Two reviewers will independently screen studies and extract relevant data from included studies. Methodological quality of economic studies will be assessed based on the British Medical Journal checklist for economic submissions adapted to costs of illness studies. This protocol has been prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols and has been published prospectively in Open Science Framework. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as primary data will not be collected in this review. The findings of this study will be disseminated through peer-reviewed publications, stakeholder meetings and inclusion in the ongoing Lancet Global Health Commission on Global Eye Health. REGISTRATION DETAILS: https://osf.io/9au3w (DOI 10.17605/OSF.IO/6F8VM).


Assuntos
Projetos de Pesquisa , Medicina Estatal , Causalidade , Análise Custo-Benefício , Atenção à Saúde , Humanos , Metanálise como Assunto , Literatura de Revisão como Assunto
9.
Eye (Lond) ; 34(12): 2163-2174, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32587389

RESUMO

The processes involved in ocular fibrosis after disease or ocular tissue injury, including surgery play an important part in the development or failure of treatment of most blinding diseases. Ocular fibrosis is one of the biggest areas of unmet need in ophthalmology. Effective anti-scarring therapies could potentially revolutionise the management of many diseases like glaucoma worldwide. The response of a quiescent or activated conjunctiva to glaucoma surgery and aqueous flow with different stimulatory components and the response to different interventions and future therapeutics is a paradigm for scarring prevention in other parts of the eye and orbit. Evolution in our understanding of molecular and cellular mechanisms in ocular fibrosis is leading to the introduction of new and re-purposed therapeutic agents, targeting a wide range of key processes. This review provides current and futures perspectives on different approaches to conjunctival fibrosis following glaucoma surgery and highlights the challenges faced in implementing these therapies with maximal effect and minimal side effects.


Assuntos
Túnica Conjuntiva , Glaucoma , Cegueira , Túnica Conjuntiva/patologia , Fibrose , Amigos , Glaucoma/patologia , Glaucoma/prevenção & controle , Humanos
10.
Br J Ophthalmol ; 104(12): 1690-1696, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32139502

RESUMO

BACKGROUND/AIMS: This work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes. METHODS: This was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints). RESULTS: 127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and ≥8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=-0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=-0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures. CONCLUSION: In post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression.


Assuntos
Fluoruracila/farmacologia , Glaucoma de Ângulo Aberto/fisiopatologia , Pressão Intraocular/fisiologia , Trabeculectomia , Campos Visuais/fisiologia , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/terapia , Humanos , Imunossupressores/farmacologia , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Estudos Retrospectivos , Singapura/epidemiologia , Fatores de Tempo , Tonometria Ocular
11.
Mol Ther ; 28(3): 820-829, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-31981492

RESUMO

Glaucoma is a common cause of blindness, yet current therapeutic options are imperfect. Clinical trials have invariably shown that reduction in intraocular pressure (IOP) regardless of disease subtype prevents visual loss. Reducing ciliary body aqueous humor production can lower IOP, and the adeno-associated virus ShH10 serotype was identified as able to transduce mouse ciliary body epithelium following intravitreal injection. Using ShH10 to deliver a single vector CRISPR-Cas9 system disrupting Aquaporin 1 resulted in reduced IOP in treated eyes (10.4 ± 2.4 mmHg) compared with control (13.2 ± 2.0 mmHg) or non-injected eyes (13.1 ± 2.8 mmHg; p < 0.001; n = 12). Editing in the aquaporin 1 gene could be detected in ciliary body, and no off-target increases in corneal or retinal thickness were identified. In experimental mouse models of corticosteroid and microbead-induced ocular hypertension, IOP could be reduced to prevent ganglion cell loss (32 ± 4 /mm2) compared with untreated eyes (25 ± 5/mm2; p < 0.01). ShH10 could transduce human ciliary body from post-mortem donor eyes in ex vivo culture with indel formation detectable in the Aquaporin 1 locus. Clinical translation of this approach to patients with glaucoma may permit long-term reduction of IOP following a single injection.


Assuntos
Aquaporina 1/genética , Corpo Ciliar/metabolismo , Edição de Genes , Terapia Genética , Glaucoma/genética , Glaucoma/terapia , Animais , Aquaporina 1/metabolismo , Sequência de Bases , Sistemas CRISPR-Cas , Dependovirus/genética , Expressão Gênica , Marcação de Genes , Terapia Genética/métodos , Vetores Genéticos/genética , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Camundongos , Retina/metabolismo , Retina/patologia , Transdução Genética , Transgenes
12.
Clin Transl Sci ; 13(1): 14-25, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568666

RESUMO

Glaucoma is the leading cause of irreversible blindness with over 70 million people affected worldwide. The surgical management of glaucoma aims to lower intraocular pressure by increasing aqueous outflow facility. The latest manufacturing techniques have allowed for the development of a number of novel implantable devices to improve safety and outcomes of glaucoma surgery. These are collectively referred to as minimally invasive glaucoma surgery (MIGS) devices and are among the smallest devices implanted in the human body. This review discusses the design criterion and constraints as well as the user requirements for MIGS devices. We review how recent devices have attempted to meet these challenges and give our opinion as to the necessary characteristics for the development of future devices.


Assuntos
Cirurgia Filtrante/instrumentação , Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Desenho de Prótese , Humanos
13.
PLoS One ; 14(10): e0221715, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647822

RESUMO

Clinical grading systems following glaucoma filtration surgery do not include any effects of the bleb on the intra-ocular pressure and are relatively subjective, therefore carrying the risk of inter and/or intra-observer variability. The main objective of the study is to quantify and model the effect of subconjunctival bleb on flow pressure for assessment of clinical grading following glaucoma surgery. Subconjunctival bleb was created by inserting a tube into ex vivo rabbit eyes via an ab externo approach through the anterior chamber and exiting into the subconjunctival space. Sterile dyed water was injected through the tube into the developing bleb. For the in vitro approach a silicone bleb was created by clamping a circular silicone sheet, injecting dyed water through a fixed resistance outlet tube. Photographic measurements of the bleb height, planform area and pressure were taken as a function of time. Clinical blebs were also collected over a few months. Mathematical algorithm software was used to build the bleb model. Bleb height and volume increase as pressure in the bleb increases. The bleb planform area tended to a constant determined by the section of conjunctiva prior to shunt insertion. These increases were in accordance with the bleb model developed in the Appendix. They show that the pressure in the bleb is related to the resistance of the outflow. The linearity of clinical grading systems is reviewed and a new grading approach is proposed. The pressure in the bleb has a strong dependence on bleb extent, height and a weak dependence on conjunctival thickness. The pressure in a bleb can be estimated from bleb height, radius, and flow rate inlet in agreement with the bleb flow model. These results provide support for an improved bleb categorization system.


Assuntos
Túnica Conjuntiva , Cirurgia Filtrante , Glaucoma , Pressão Intraocular , Animais , Humanos , Coelhos , Algoritmos , Túnica Conjuntiva/fisiopatologia , Modelos Animais de Doenças , Drenagem/instrumentação , Drenagem/métodos , Cirurgia Filtrante/instrumentação , Cirurgia Filtrante/métodos , Glaucoma/fisiopatologia , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Cicatrização/fisiologia
14.
Transl Vis Sci Technol ; 8(3): 58, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31293813

RESUMO

PURPOSE: Minimally invasive glaucoma surgery (MIGS) devices that drain into the subconjunctival space can be inserted via an ab externo or ab interno approach. Limited experimental data exists as to the impact of either technique on intraocular pressure (IOP) control. We performed microfluidic studies by using ex vivo rabbit eyes to assess the effect of each approach on outflow resistance of a subconjunctival drainage device for IOP control. METHODS: A microfluidic experiment system was designed, consisting of a controlled reservoir of water connected to a pressure pump/flow sensor. The flow rate of water was fixed at 2 µl/min to simulate aqueous humor production. The pressure readings for each approach were recorded at a frequency of 1 Hz. A baseline reading was made before tube insertion into the eye (PEEK tube length set to aim for an initial outflow resistance of 5 to 10 mm Hg/µL/min) followed by measurements for a cumulative 2-ml volume entering the subconjunctival space. Results were adjusted for water viscosity at 37°C and reported as outflow resistance (mm Hg/µL/min ± standard error of mean). RESULTS: Outflow resistance via the ab interno approach was 90.4% higher than with the ab externo approach being measured at 0.80 ± 0.11 mm Hg/µL/min and 0.42 ± 0.05 mm Hg/µL/min, respectively. Bleb formation was observed to be less predictable with the ab interno approach. CONCLUSIONS: The ab interno approach demonstrated greater outflow resistance and less predictable bleb formation than the ab externo approach. These results have implications for long-term IOP control and success depending on the approach to device insertion and could be an important consideration for future MIGS devices. TRANSLATIONAL RELEVANCE: The effect of the ab interno versus ab externo approach of a MIGS device inserted into the subconjunctival space was assessed. The ab interno approach demonstrated greater outflow resistance and less predictable bleb formation that may have implications for the development of future MIGS devices.

15.
BMJ Open ; 9(2): e025077, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30796124

RESUMO

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.


Assuntos
Bancos de Espécimes Biológicos/estatística & dados numéricos , Oftalmopatias/epidemiologia , Macula Lutea/anatomia & histologia , Tomografia de Coerência Óptica , Adulto , Idoso , Etnicidade , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Reino Unido/epidemiologia , Acuidade Visual
16.
J Glaucoma ; 28(5): e75-e76, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30676408

RESUMO

PURPOSE: The aim of this study was to present a case of a Baerveldt glaucoma implant lumen being completely occluded with a 3-0 Supramid stent suture. PATIENT AND METHODS: The patient underwent Baerveldt glaucoma implant surgery with placement of an intraluminal 3-0 Supramid stent suture that acts to restrict flow across the device and reduce the risk of postoperative hypotony. Following suturing of the implant to the sclera, the device was flow tested. No flow was observed through the device tube and a significant ballooning of the tube diameter occurred with increased pressure on the device. The device was explanted from the eye and replaced with a different implant without further postoperative complication. The explanted device was assessed using custom microfluidic equipment in an in vitro environment. RESULTS: This phenomenon occurred despite using several different batches of the 3-0 Supramid stent suture and the device had to be removed and replaced with another device without complication. In vitro microfluidic assessment of the device demonstrated no flow across the device tube despite over 150 mm Hg of pressure being exerted on the device. CONCLUSIONS: We hypothesize that the blockage occurred at the junction between the device tube and plate and that the ballooning phenomenon observed was due to a defect in the tube wall. This case highlights the importance of flow testing all glaucoma drainage devices before insertion given the variation in manufacturing conditions to avoid the risk of intraoperative complications.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto/cirurgia , Complicações Intraoperatórias , Falha de Prótese/etiologia , Suturas/efeitos adversos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Nylons , Estudos Retrospectivos , Tonometria Ocular
17.
Eur J Hum Genet ; 26(11): 1713-1718, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30089822

RESUMO

1. NAME OF THE DISEASE (SYNONYMS): Primary congenital glaucoma (PCG). Glaucoma, congenital (GLC). 2. OMIM# OF THE DISEASE: 231300- GLC3A. 600975- GLC3B. 613085- GLC3C. 613086- GLC3D. 617272- GLC3E. 3. NAME OF THE ANALYSED GENES OR DNA/CHROMOSOME SEGMENTS: CYP1B1. LTBP2. MYOC. FOXC1. TEK. 4. OMIM# OF THE GENE(S): CYP1B1 MIM# 601771. LTBP2 MIM# 602091. MYOC MIM# 601652. FOXC1 MIM# 601090. TEK MIM# 600221. Review of the analytical and clinical validity, as well as of the clinical utility of DNA-based testing for variants in the CYP1B1, LTBP2 and MYOC gene(s) in ⊠ diagnostic, ⊠ predictive and ⊠ prenatal settings and for ⊠ risk assessment in relatives.


Assuntos
Testes Genéticos/métodos , Glaucoma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Citocromo P-450 CYP1B1/genética , Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Fatores de Transcrição Forkhead/genética , Glaucoma/congênito , Glaucoma/patologia , Glicoproteínas/genética , Humanos , Proteínas de Ligação a TGF-beta Latente/genética , Receptor TIE-2/genética
19.
RSC Adv ; 8(62): 35787-35793, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35547916

RESUMO

An antibody mimetic known as Fab-PEG-Fab (FpF) is a stable bivalent molecule that may have some potential therapeutic advantages over IgG antibodies due to differences in their binding kinetics as determined by surface plasmon resonance. Here we describe the thermodynamic binding properties to vascular endothelial growth factor (VEGF) of the FpF antibody mimetics derived from bevacizumab and ranibizumab. Bevacizumab is an IgG antibody and ranibizumab is an antibody fragment (Fab). Both are used clinically to target VEGF to inhibit angiogenesis. FpFbeva displayed comparable binding affinity (KD) and binding thermodynamics (ΔH = -25.7 kcal mole-1 and ΔS = 14 kcal mole-1) to bevacizumab (ΔH = -25 kcal mole-1, ΔS = 13.3 kcal mole-1). FpFrani interactions with VEGF were characterised by large favourable enthalpy (ΔH = -42 kcal mole-1) and unfavourable entropy (ΔS = 31 kcal mole-1) changes compared to ranibizumab (ΔH = -18.5 kcal mole-1 and ΔS = 6.7 kcal mole-1), which being a Fab, is mono-valent. A large negative entropy change resulting in binding of bivalent FpF to homodimer VEGF might be due to the conformational change of the flexible regions of the FpF upon ligand binding. Mono-valent Fab (i.e. ranibizumab or the Fab derived from bevacizumab) displayed a larger degree of freedom (smaller unfavourable entropy) upon binding to homodimer VEGF. Our report describes the first comprehensive enthalpy and entropy compensation analysis for FpF antibody mimetics. While the FpFs displayed similar thermodynamics and binding affinity to the full IgG (i.e. bevacizumab), their enhanced protein stability, slower dissociation rate and lack of Fc effector functions could make FpF a potential next-generation therapy for local tissue-targeted indications.

20.
JAMA Ophthalmol ; 136(2): 155-161, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29285534

RESUMO

Importance: There is limited evidence to support the development of guidance for visual field testing in children with glaucoma. Objective: To compare different static and combined static/kinetic perimetry approaches in children with glaucoma. Design, Setting, and Participants: Cross-sectional, observational study recruiting children prospectively between May 2013 and June 2015 at 2 tertiary specialist pediatric ophthalmology centers in London, England (Moorfields Eye Hospital and Great Ormond Street Hospital). The study included 65 children aged 5 to 15 years with glaucoma (108 affected eyes). Main Outcomes and Measures: A comparison of test quality and outcomes for static and combined static/kinetic techniques, with respect to ability to quantify glaucomatous loss. Children performed perimetric assessments using Humphrey static (Swedish Interactive Thresholding Algorithm 24-2 FAST) and Octopus combined static tendency-oriented perimetry/kinetic perimetry (isopter V4e, III4e, or I4e) in a single sitting, using standardized clinical protocols, administered by a single examiner. Information was collected about test duration, completion, and quality (using automated reliability indices and our qualitative Examiner-Based Assessment of Reliability score). Perimetry outputs were scored using the Aulhorn and Karmeyer classification. One affected eye in 19 participants was retested with Swedish Interactive Thresholding Algorithm 24-2 FAST and 24-2 standard algorithms. Results: Sixty-five children (33 girls [50.8%]), with a median age of 12 years (interquartile range, 9-14 years), were tested. Test quality (Examiner-Based Assessment of Reliability score) improved with increasing age for both Humphrey and Octopus strategies and were equivalent in children older than 10 years (McNemar test, χ2 = 0.33; P = .56), but better-quality tests with Humphrey perimetry were achieved in younger children (McNemar test, χ2 = 4.0; P = .05). Octopus and Humphrey static MD values worse than or equal to -6 dB showed disagreement (Bland-Altman, mean difference, -0.70; limit of agreement, -7.74 to 6.35) but were comparable when greater than this threshold (mean difference, -0.03; limit of agreement, -2.33 to 2.27). Visual field classification scores for static perimetry tests showed substantial agreement (linearly weighted κ, 0.79; 95% CI, 0.65-0.93), although 25 of 80 (31%) were graded with a more severe defect for Octopus static perimetry. Of the 7 severe cases of visual field loss (grade 5), 5 had lower kinetic than static classification scores. Conclusions and Relevance: A simple static perimetry approach potentially yields high-quality results in children younger than 10 years. For children older than 10 years, without penalizing quality, the addition of kinetic perimetry enabled measurement of far-peripheral sensitivity, which is particularly useful in children with severe visual field restriction.


Assuntos
Algoritmos , Glaucoma/diagnóstico , Testes de Campo Visual/métodos , Campos Visuais/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Glaucoma/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA