Publications by authors named "Alex J Shortt"

Purpose: To investigate if human oral mucosal fibroblasts (HOMF) from patients with limbal stem cell deficiency (LSCD) can be used as an autologous feeder layer to support the culture of epithelial cells for potential clinical use.

Methods: HOMF were isolated from oral mucosal biopsies obtained from the following groups of patients with LSCD: aniridia, mucous membrane pemphigoid (MMP), Stevens-Johnson syndrome (SJS), and ectodermal dysplasia (ED). The ability of these cells to support the culture of human limbal epithelial cells (HLE) was compared to that of HOMF from non-LSCD donors and 3T3s commonly used to culture epithelial cells for use in the clinic to treat LSCD.

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Objectives: To understand the incidence, causes, management and outcomes of intentional (assault) and unintentional severe ocular chemical injuries (SOCI) at an urban tertiary referral centre in the UK.

Design: Retrospective observational study.

Setting: A London tertiary referral ophthalmic centre, Moorfields Eye Hospital.

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Purpose: To analyze the short-term (up to 1 month) clinical outcomes in patients undergoing corneal laser refractive surgery and the impact on dry eye disease (DED) metrics and corneal nerves using in vivo confocal microscopy (IVCM).

Methods: The unaided distance visual acuity, corrected distance visual acuity, and spherical equivalent refraction (SEQ) were determined in 16 and 13 patients undergoing FS-LASIK and SMILE, respectively. DED metrics assessed were Ocular Surface Disease Index, Dry Eye Questionnaire 5-items (DEQ-5), tear film osmolarity, tear meniscus height, noninvasive keratograph breakup time (NIKBUT), ocular staining, and meibomian gland atrophy.

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Background: Corneal endothelial transplantation has become the gold standard for the treatment of corneal endothelial dysfunctions, replacing full thickness transplantation, known as penetrating keratoplasty. Corneal endothelial transplantation has been described using two different techniques: Descemet's membrane endothelial keratoplasty (DMEK) and Descemet's stripping automated endothelial keratoplasty (DSAEK). Both are still performed worldwide.

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Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation.

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Limbal epithelial stem cell (LESC) deficiency can cause blindness. Transplantation of cultured human limbal epithelial cells (hLE) on human amniotic membrane (HAM) can restore vision but clinical graft manufacture can be unreliable. We have developed a reliable and robust tissue equivalent (TE) alternative to HAM, Real Architecture for 3D Tissue (RAFT).

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Purpose: Cultured human limbal epithelial cells (HLECs) have shown promise in the treatment of limbal stem cell deficiency but little is known about their survival, behavior, and long-term fate after transplantation. The aim of this research was to evaluate, in vitro, quantum dot (Qdot) technology as a tool for tracking transplanted HLECs.

Methods: In vitro cultured HLECs were labeled with Qdot nanocrystals.

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Aim Of The Study: To develop a clinical grade fibrin gel for the culture of oral mucosal epithelial cells (OMEC) intended for ocular surface reconstruction in the treatment of limbal stem cell deficiency (LSCD).

Materials And Methods: Transparent fibrin gels composed of fibrinogen and thrombin were developed for the culture of epithelial cells. Oral mucosa was harvested from the buccal region of healthy volunteers and cultured as explants on fibrin gels.

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Limbal epithelial stem cells (LESCs) are essential to maintain the transparent ocular surface required for vision. Despite great advances in our understanding of ocular stem cell biology over the last decade, the exact location of the LESC niche remains unclear. In the present study we have used in vitro clonal analysis to confirm that limbal crypts provide a niche for the resident LESCs.

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Background: Fuchs endothelial dystrophy (FED) is a condition in which there is premature degeneration of corneal endothelial cells. When the number of endothelial cells is reduced to a significant degree, fluid begins to accumulate within the cornea. As a result, the cornea loses its transparency and the individual suffers a reduction in vision.

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Limbal stem cell deficiency (LSCD) is an eye disorder in which the stem cells responsible for forming the surface skin of the cornea are destroyed by disease. This results in pain, loss of vision, and a cosmetically unpleasant appearance. Many new treatments, including stem cell therapies, are emerging for the treatment of this condition, but assessment of these new technologies is severely hampered by the lack of biomarkers for this disease or validated tools for assessing its severity.

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Background: Myopia (also known as short-sightedness or near-sightedness) is an ocular condition in which the refractive power of the eye is greater than is required, resulting in light from distant objects being focused in front of the retina instead of directly on it. The two most commonly used surgical techniques to permanently correct myopia are photorefractive keratectomy (PRK) and laser-assisted in-situ keratomileusis (LASIK).

Objectives: To compare the effectiveness and safety of LASIK and PRK for correction of myopia by examining post-treatment uncorrected visual acuity, refractive outcome, loss of best spectacle-corrected visual acuity, pain scores, flap complications in LASIK, subepithelial haze, adverse events, quality of life indices and higher order aberrations.

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Current treatments for reversible blindness caused by corneal endothelial cell failure involve replacing the failed endothelium with donor tissue using a one donor-one recipient strategy. Due to the increasing pressure of a worldwide donor cornea shortage there has been considerable interest in developing alternative strategies to treat endothelial disorders using expanded cell replacement therapy. Protocols have been developed which allow successful expansion of endothelial cells in vitro but this approach requires a supporting material that would allow easy transfer of cells to the recipient.

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Objective: To investigate the outcome of a modified anterior approach surgical procedure for the correction of primary upper eyelid retraction in thyroid eye disease.

Methods: A retrospective review of 52 consecutive cases (in 32 patients) of anterior-approach graded upper lid lowering for the treatment of primary eyelid retraction, carried out at Moorfields Eye Hospital between 2006-2009 was conducted. Measurements of upper margin-reflex distance (MRD), upper lid skin crease height and skin fold height were taken from clinical records and photographs.

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Introduction Or Background: Corneal opacity is a common cause of blindness. The majority of cases result from ulceration and scarring following infection or trauma, but in a proportion corneal epithelial stem cell (SC) deficiency leads to an inability to maintain a healthy corneal surface.

Sources Of Data: This review includes systematic reviews and individual case series of treatments for corneal epithelial SC deficiency.

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Background: Fuchs endothelial dystrophy (FED), first described by Ernst Fuchsis in 1910, is a condition in which there is premature degeneration of corneal endothelial cells. When the number of endothelial cells is reduced to a significant degree fluid begins to accumulate within the cornea. As a result the cornea loses its transparency and the individual suffers a reduction in vision.

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The corneal epithelium is maintained by the limbal epithelial stem cells (LESCs). In this study, an in vitro model is proposed for the investigation of cell-cell interactions involving LESC maintenance. Imaging of the limbal niche demonstrated close spatial arrangement between basal limbal epithelial cells within putative LESC niche structures and fibroblasts in the stroma.

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The term ex vivo cultured limbal epithelial transplantation (CLET) refers to the process of culturing a sheet of human limbal epithelium in the laboratory and transplanting this sheet back onto the limbal stem cell-deficient cornea of the same patient or another recipient. This emerging technology represents one of the earliest successes in regenerative medicine. CLET is, at present, best suited to patients who have unilateral total limbal stem cell deficiency arising from chemical injury and who are suitable for autologous cell culture and transplantation.

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Background/aims: To compare ophthalmic viscoelastic devices (OVDs) in protecting the cornea from endothelial cell loss during cataract surgery.

Methods: A systematic review yielded 21 randomised controlled trials including 1769 patients. OVDs were classified according to the Arshinoff classification.

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Human amniotic membrane (HAM) is employed as a substrate for the ex-vivo expansion of limbal epithelial cells (LECs) used to treat corneal epithelial stem cell deficiency in humans. The optimal method of HAM preparation for this purpose is unknown. This study evaluated the ability of different preparations of stored HAM to serve as substrates for LEC expansion ex-vivo.

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Objective: To determine, using objective measures, the outcome of ex vivo cultured limbal epithelial stem cell (LESC) transplantation performed in compliance with good manufacturing practice using a novel culture system without 3T3 feeder cells.

Design: Prospective, noncomparative, interventional case series.

Participants: Ten eyes of 10 patients with profound LESC deficiency arising from chemical injury (4 eyes), aniridia (3 eyes), ectodermal dysplasia (1 eye), Reiger's anomaly with Pax6 haploinsufficiency (1 eye), and unknown cause (1 eye).

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The complex mechanisms by which transforming growth factor beta (TGFbeta) regulate re-epithelialisation following injury of stratified epithelia are not fully understood. TGFbeta signals via binding to distinct receptors activating downstream effectors, including Smads which initiate transcription of target genes. However, studies have shown that TGFbeta can also signal independently of Smads through MAPK pathways, demonstrating the diversity of TGFbeta signalling.

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Ex vivo cultured limbal epithelial stem cells have been used successfully to treat corneal limbal stem cell deficiency. We identified 17 reports of the application of this novel cell-based therapy in humans. In addition we identified four reports of the use of culture oral mucosal epithelial cells to treat limbal stem cell deficiency.

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