Publications by authors named "James W Bainbridge"

Article Synopsis
  • Angiogenesis is a factor in neovascular age-related macular degeneration, and current treatments often fail over time, highlighting the need for new therapies.
  • Researchers discovered that a peptide called QM107, linked to syndecan-2 and CD148, effectively inhibits angiogenesis in various models, including a pre-clinical model of this eye condition.
  • QM107 shows low toxicity, negligible inflammation, and stable performance in the eye, making it a promising alternative or complementary treatment for patients unresponsive to existing therapies.
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Background: Macular holes cause severe impairment of sight. With the aim of improving the outcome of surgery for macular holes, particularly larger macular holes (those measuring over 400 μm), a variable period of face-down positioning may be advised. This review is an update of a Cochrane Review published in 2011.

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Background: Endophthalmitis is a sight-threatening emergency that requires prompt diagnosis and treatment. The condition is characterised by purulent inflammation of the intraocular fluids caused by an infective agent. In exogenous endophthalmitis, the infective agent is foreign and typically introduced into the eye through intraocular surgery or open globe trauma.

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Opticin is an extracellular glycoprotein present in the vitreous. Its antiangiogenic properties offer the potential for therapeutic intervention in conditions such as proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the hypothesis that intravitreal administration of recombinant human opticin can safely protect against the development of pathological angiogenesis and promote its regression.

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Gliosis is a complex process comprising upregulation of intermediate filament (IF) proteins, particularly glial fibrillary acidic protein (GFAP) and vimentin, changes in glial cell morphology (hypertrophy) and increased deposition of inhibitory extracellular matrix molecules. Gliosis is common to numerous pathologies and can have deleterious effects on tissue function and regeneration. The role of IFs in gliosis is controversial, but a key hypothesized function is the stabilization of glial cell hypertrophy.

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Background: Epiretinal membrane is an abnormal sheet of avascular fibrocellular tissue that develops on the inner surface of the retina. Epiretinal membrane can cause impairment of sight as a consequence of progressive distortion of retinal architecture.

Objectives: To determine the effects of surgery compared to no intervention for epiretinal membrane.

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The Rpe65-deficient dog has been important for development of translational therapies of Leber congenital amaurosis type 2 (LCA2). The purpose of this study was to provide a comprehensive report of the natural history of retinal changes in this dog model. Rpe65-deficient dogs from 2 months to 10 years of age were assessed by fundus imaging, electroretinography (ERG) and vision testing (VT).

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Purpose: To provide data on visual acuity (VA) outcomes and prognostic factors of microincision (23-gauge) vitrectomy surgery (MIVS) for retained lens fragments after complicated cataract surgery.

Design: Retrospective, interventional case series from 2012 to 2017.

Methods: Precataract surgery and intraoperative (vitrectomy) parameters, postvitrectomy complications, and best-corrected visual acuities (BCVAs) were identified.

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Purpose: To describe the nystagmus characteristics of subjects with molecularly confirmed CNGB3-associated achromatopsia and report the spectral domain optical coherence tomography (SD-OCT) findings in these individuals.

Methods: Adults and children with CNGB3-achromatopsia underwent visual acuity testing, ocular motility assessments, video nystagmography, and SD-OCT imaging. Qualitative assessment of foveal structure was performed by grading SD-OCT images into one of five categories.

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Purpose: We study the relationship between retinal vessel oxygenation and the spatial distribution of retinal nonperfusion using ultrawide field angiography in eyes with retinal vascular diseases.

Methods: This prospective single center study recruited 57 eligible eyes from 44 patients with retinal vascular diseases. Retinal oximetry measurements were obtained using the Oxymap T1 device to determine the arteriovenous (AV) difference.

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Importance: Threshold of retinal nonperfusion for the development of proliferative diabetic retinopathy (PDR) is unclear.

Objectives: To identify a threshold of retinal nonperfusion for the presence of retinal neovascularization and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy (NPDR), PDR, neovascularization of the optic disc (NVD), and retinal neovascularization elsewhere (NVE).

Design, Setting, And Participants: This cross-sectional image analysis study was performed between September 24, 2018, and October 24, 2018, at a multicenter national study in the United Kingdom.

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Purpose: To longitudinally characterize structural retinal changes in achromatopsia (ACHM) over extended follow-up.

Methods: Fifty molecularly confirmed ACHM subjects underwent serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Foveal structure on SD-OCT was graded and compared for evidence of progression, and foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness were serially measured.

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Purpose: The purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy.

Methods: This is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks.

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Purpose: To study the effects of different axial lengths on ultra-widefield imaging to determine the presence of distortion in images despite software correction and calculate an enlargement factor based on angular location.

Design: Experimental image analysis study.

Study Objects: Three 3-dimensional printed model eyes simulating eyes with axial lengths of 22, 24, and 26 mm.

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This case series examines a noninvasive method of measuring and differentiating collateral and new vessels of the optic disc.

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Purpose: To review the definition of ischaemic central retinal vein occlusion (CRVO) and stratify the risk of neovascular complication based on wider areas of visible retinal non-perfusion.

Design: Retrospective consecutive case series and image analysis study.

Methods: Setting: Moorfields Eye Hospital, London, United Kingdom.

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Purpose: Retinal epithelium-specific protein 65 kDa (RPE65)-deficient dogs are a valuable large animal model species that have been used to refine gene augmentation therapy for Leber congenital amaurosis type-2 (LCA2). Previous studies have suggested that retinal degeneration in the dog model is slower than that observed in humans. However, the area centralis of the dog retina is a cone and rod photoreceptor rich region comparable to the human macula, and the effect of RPE65 deficiency specifically on this retinal region, important for high acuity vision, has not previously been reported.

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Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retinal vasculature and retinal pigmented epithelial (RPE)-choroid respectively. Vascular endothelial growth factor (VEGF-A), a key regulator of angiogenesis and permeability, is the target of most pharmacological interventions of DR.

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The vascular endothelial growth factor (VEGF) isoform VEGF165 stimulates vascular growth and hyperpermeability. Whereas blood vessel growth is essential to sustain organ health, chronic hyperpermeability causes damaging tissue edema. By combining in vivo and tissue culture models, we show here that VEGF165-induced vascular leakage requires both VEGFR2 and NRP1, including the VEGF164-binding site of NRP1 and the NRP1 cytoplasmic domain (NCD), but not the known NCD interactor GIPC1.

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Hypoxia inducible factors (HIFs) are ubiquitously expressed transcription factors important for cell homeostasis during dynamic oxygen levels. Myeloid specific HIFs are crucial for aspects of myeloid cell function, including their ability to migrate into inflamed tissues during autoimmune disease. This contrasts with the concept that accumulation of myeloid cells at ischemic and hypoxic sites results from a lack of chemotactic responsiveness.

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Myeloid cells make a pivotal contribution to tissue homeostasis during inflammation. Both tissue-specific resident populations and infiltrating myeloid cells can cause tissue injury through aberrant activation and/or dysregulated activity. Reliable identification and quantification of myeloid cells within diseased tissues is important to understand pathological inflammatory processes.

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The impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pathways and myeloid cell populations involved in this increased neovascular response, we characterized the immune status of murine choroid and retina during aging and in the context of experimental CNV.

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Purpose: Biallelic mutations in AIPL1 cause Leber congenital amaurosis (LCA), a devastating retinal degeneration characterized by the loss or severe impairment of vision within the first few years of life. AIPL1 is highly polymorphic with more than 50 mutations and many more polymorphisms of uncertain pathogenicity identified. As such, it can be difficult to assign disease association of AIPL1 variations.

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Restored rod visual function after gene therapy can be established unequivocally by demonstrating that, after dark adaptation, spectral sensitivity has the shape characteristic of rods and that this shape collapses to a cone-like shape before rods have recovered after an intense bleach. We used these tests to assess retinal function in eight young adults and children with early-onset severe retinal dystrophy from Phase II of a clinical gene-therapy trial for RPE65 deficiency that involved the subretinal delivery of a recombinant adeno-associated viral vector carrying RPE65. We found substantial improvements in rod sensitivity in two participants: dark-adapted spectral sensitivity was rod-like after treatment and was cone-like before rods had recovered after a bleach.

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