Award Title: Early Recognition of Raised Intracranial Pressure in Craniosynostosis using Handheld Optical Coherence Tomography
Funder: Department of Health and Social Care

Abstract: Research question Can handheld optical coherence tomography (HH-OCT) improve early recognition of raised intracranial pressure (ICP) in craniosynostosis? Background Craniosynostosis is characterised by premature closure of cranial sutures. This may cause raised ICP, which can lead to optic atrophy, developmental delay, blindness and death if left untreated.1 Prevalence is 3.1-7.2 in 10,000 live births and rising.2 Treatment for those believed to be at risk of raised ICP involves surgical expansion of the skull vault, which carries risks including disability and death. Currently, there is no agreed protocol over who to treat and when; a popular option is prophylactic vault expansion for all patients with multisuture and syndromic craniosynostosis1, but this may represent unnecessary surgery for many infants. Aims and objectives To evaluate whether HH-OCT improves sensitivity/specificity for detecting raised ICP in craniosynostosis, compared to the current clinical protocol, involving neurosurgical and ophthalmic examinations and visual evoked potentials. Additionally, to characterise and quantitatively analyse HH-OCT changes and develop a management algorithm for craniosynostosis. Methods A diagnostic accuracy cohort study will be conducted at GOSH. 260 patients with craniosynostosis will be recruited. Clinical examination, visual evoked potentials (VEP) and HH-OCT will be performed. Patients with signs of raised ICP will be referred for surgery, during which intracranial measurement of ICP will be done. Raised ICP will be defined as that over 20mmHg. Sensitivity and specificity of HH-OCT for predicting raised ICP will be analysed. Timelines for delivery This study will take place over three years. Year 1 will include a systematic review of literature, recruitment and data analysis. Year 2 will consist of data collection and analysis, as well as presentation and publication of preliminary data and interesting cases. Year 3 will include finishing data collection and analysis, development of the management algorithm, thesis writing and dissemination of findings. Anticipated impact and dissemination This world-first study could optimise management of infants with craniosynostosis if OCT can recognise raised ICP earlier than existing methods. It could protect infants from unnecessary operations where not required. Finally, it could improve understanding of the pathophysiological mechanism between raised ICP and the eye. Findings will be disseminated via scientific journals, conference presentations, social media and local and national press. If successful, the treatment algorithm could be incorporated into clinical management guidelines.

Lay Abstract: Craniosynostosis is a condition where a baby's skull does not grow properly. It happens when the joining parts of the baby's skull called 'sutures' close before their head has fully formed. As a result, babies with craniosynostosis usually have an unevenly shaped head. The condition affects about 1 in 2000 babies. It can be very severe and can cause vision loss, learning disabilities, blindness and death, if not treated appropriately. Many babies with craniosynostosis need surgical treatment. This involves making the skull bigger to prevent rising pressure in the skull. It is important that doctors recognise rising pressure in the skull because too much pressure can lead to problems with the brain and vision. However, it is very hard for doctors to measure this so some babies may have risky surgery without the need for it. I want to look at a special technique called optical coherence tomography (OCT) to see if this can identify babies who are at risk of rising pressure in the brain. OCT is a scanning device that looks at the structure of the eye in amazingly minute detail. Up until recently, we could not use this technique on babies because they could not cooperate with the large table-mounted device for adults. However, our team are now using a hand-held OCT device that only takes a few seconds to scan the eye. I want to use the device to look for early changes in parts of the eye (the optic nerve and the retina). These changes could predict if a baby is at risk of rising pressure in the skull. My study will take place at Great Ormond Street Hospital - an international centre of excellence for child healthcare and the largest of only four centres in the UK treating craniosynostosis. My study will involve seeking consent from parents in craniosynostosis clinics. I will then scan the babies' eyes with handheld OCT to see if there are any changes in the eyes to suggest that there might be rising pressure in the skull. Finally, I will compare my results with the actual pressure measure in the operating theatre to see how good OCT is at predicting rising pressure in the skull. I will involve patients, families and members of the public in Expert Advisory Group meetings twice per year where I will provide study updates and seek feedback. I will work with our press teams to share my findings via newspapers, radio and television. I will work with the craniosynostosis charities Face Value and Headlines to publish significant news items via their websites. I will share findings on social media including Facebook and Twitter. Finally, I will present at clinical conferences and publish in scientific journals. My study has the potential to radically improve the care that babies with craniosynostosis receive. I hope to dramatically improve patient outcomes, including quality of vision and quality of life. I aim to improve early referral for those children who need surgery, whilst also protecting other children from unnecessary surgery when it is not required. If successful, the findings could feed into national clinical guidelines for craniosynostosis.

Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: REPRODUCTIVE HEALTH AND CHILDBIRTH;MUSCULOSKELETAL