Exploration of the artificial eye process in children with Retinoblastoma: addressing the psychological impact and potential for technological advancement.

Background: Retinoblastoma (Rb) is the result of genes becoming mutated and can be hereditary (predominately unilateral and unifocal) or non-hereditary (predominately bilateral and multifocal). 70% of unilateral Rb requires enucleation and thus a lifetime supply of artificial eyes. Aim: To explore the artificial eye process in children with a diagnosis of Rb to address the psychological impact and potential technological improvements that can be made to the current process. Methods: A qualitative approach was used consisting of one study and three components. Firstly, a qualitative questionnaire of artificial eye prosthetists (AEP) perspective of the process. Secondly, an Interpretative Phenomenological Study (IPA) to understand the lived experience of the fitting process of artificial eyes in 13-16 year olds and parents of children with a diagnosis of Rb. Thirdly, a transfer of knowledge between the equipment and tools used in the assessment stage by AEP’s and maxillofacial prosthetists (MP). Findings: Component 1 highlighted the distress of the process experienced by the child patient and their parents as well as the role of parents and the AEP which can act as a barrier and facilitator to the process. Component 2 revealed a potential link between the way artificial eyes are fitted and the psychological wellbeing of the patient and their parents. Component 3 suggested that the tools and equipment used by MP’s have the potential to be utilised in the artificial eye process. Conclusion: This thesis demonstrates an original and significant contribution to knowledge in exploring the psychological impact of the artificial eye process in children with a diagnosis of Rb and the continual need to investigate the capabilities of technology for its potential incorporation into the process. The common theme running throughout this thesis was that of an intrinsic link between human and technological factors in creating an effective service. The findings contribute to both the Rb and ophthalmology literature: highlighting the needs and requirements for the progression of artificial eye services and the treatment and care of children with a diagnosis of Rb

The neuroregenerative effects of topical decorin on the injured mouse cornea

BACKGROUND: The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury. METHODS: Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea. RESULTS: At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin. CONCLUSIONS: Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury

The Importance of Incorporating Technological Advancements into the Prosthetic Eye Development: A Perspective Commentary

Application of technology into healthcare has typically been targeted to high demand illnesses and treatments. However, with an increasing need to meet patient’s expectations combined with increased accessibility and reduced costs, smaller healthcare fields are starting to investigate its function and usability. Services have historically been led by skills and expertise, and recent developments are being seen by ocularists in the field of prosthetic eyes who acknowledge the potential benefit from technological advancement. Utilising the technologies recently investigated in maxillofacial prosthesis can start the evolutionary process where products are continually re-designed and re-developed to achieve excellent patient outcome and satisfaction levels

Qualitative exploration of health professionals' experiences of communicating positive newborn bloodspot screening results for nine conditions in England.

OBJECTIVE: To explore health professionals' experiences of communicating positive newborn bloodspot screening (NBS) results, highlight differences, share good practice and make recommendations for future research. DESIGN: Qualitative exploratory design was employed using semi-structured interviews SETTING: Three National Health Service provider organisations in England PARTICIPANTS: Seventeen health professionals involved in communicating positive newborn bloodspot screening results to parents for all nine conditions currently included in the newborn bloodspot screening programme in England. RESULTS: Findings indicated variation in approaches to communicating positive newborn bloodspot screening results to parents, largely influenced by resources available and the lack of clear guidance. Health professionals emphasised the importance of communicating results to families in a way that is sensitive to their needs. However, many challenges hindered communication including logistical considerations; difficulty contacting the family and other health professionals; language barriers; parental reactions; resource considerations; lack of training; and insufficient time. CONCLUSION: Health professionals invest a lot of time and energy trying to ensure communication of positive newborn bloodspot screening results to families is done well. However, there continues to be great variation in the way these results are communicated to parents and this is largely influenced by resources available but also the lack of concrete guidance. How best to support health professionals undertaking this challenging and emotive task requires further exploration. We recommend evaluation of a more cohesive approach that meets the needs of parents and staff while being sensitive to the subtleties of each condition. TRIAL REGISTRATION NUMBER: ISRCTN15330120

A multiple sclerosis-like disorder in patients with OPA1 mutations.

We describe three unrelated patients presenting with a spinal cord syndrome and neuroimaging features consistent with multiple sclerosis (MS). All harbored a pathogenic OPA1 mutation. Although the neurological phenotype resembled neuromyelitis optica (NMO), anti-aquaporin 4 antibodies were not detected and the disorder followed a slow progressive course. The coincidental occurrence of OPA1 mutations and an MS-like disorder is likely to have modulated the phenotypic manifestations of both disorders, but unlike the previously reported association of Leber hereditary optic neuropathy and MS (Harding disease), the optic neuropathy in patients with OPA1 mutations and an MS-like disorder can be mild with a good visual prognosis.PYWM is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK), and also receives funding from Fight for Sight (UK), the UK National Institute of Health Research (NIHR) as part of the Rare Diseases Translational Research Collaboration, and the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. PFC is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/ Z), and a UK NIHR Senior Investigator. PFC receives additional support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943), the Medical Research Council (UK) Centre for Translational Muscle Disease research (G0601943), and EU FP7 TIRCON

Ocular development after highly effective modulator treatment early in life

Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF. All HEMT are known to be able pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of HEMT in young rats demonstrated infant cataracts, and case reports have reported the presence of congenital cataracts in early life exposure to HEMT. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of healthy and abnormal lens development in the context of HEMT exposure during pregnancy and breastfeeding, and raises questions that remain unanswered