Ultra-high resolution optical coherence tomography (UHR-SD OCT) in infants and children: characterisation of normal and abnormal foveal development

The recent development of optical coherence tomography (OCT) provides pictures of the back of the eye (the retina) with the precision of a microscope in living people. This has contributed to significant progress in the diagnosis and treatment of retinal diseases in adults. However, OCT is not currently clinically available for young children.
The normal retina is not mature at birth and undergoes significant changes until about 45 months leading to visual improvement. We aim to visualise for the first time changes in the retina from birth to 6 years of age using a newly developed hand-held OCT device, comparing also results in older children and adults. OCTs will be performed in a large amount of children with normal eyes and in children with developmental eye problems which can occur, for example, in albinism (pigment deficiency), colour blindness or other genetic problems. We will investigate whether retinal development is "arrested" or slowed down after birth in these patients.
We aim to determine whether OCT images can assist in the diagnosis and prediction of vision in preverbal infants and of the vision developing later in life. We hope that this study will help to understand the cause of nystagmus, involuntary eye movements frequently occurring in children with retinal problems.
We anticipate that our study will be an important step in validating and providing access of OCT in newborns, infants and young children. The data we aim to acquire from normal children will also lay the ground to investigate other diseases using OCT such as retinal problems of premature children, glaucoma or retinitis pigmentosa. To examine retinal structures in vivo in small children with high precision will be an important component of evaluating and timing imminent gene therapy, for example in achromatopsia.

Recently, optical coherence tomography (OCT) has significantly improved diagnosis and therapy of retinal diseases in adults. However, OCT is not yet available clinically for infants and young children. Histological studies suggest that the fovea develops until at least 45 months of age but this has never been visualised in vivo. We aim to use a recently developed handheld ultra-high resolution spectral domain OCT (UHR-SD OCT) designed for children to (i) characterise normal and abnormal development of the fovea, (ii) improve early diagnosis of infants and children with foveal hypoplasia, (iii) better understand mechanisms of nystagmus and (iv) estimate or predict later visual acuity by also characterising eye movements in nystagmus.
Approximately 320 OCT images of control subjects and patients with idiopathic infantile nystagmus (IIN), albinism, PAX6 mutations and achromatopsia will be obtained using cross-sectional and longitudinal sampling (from birth to 6 years of age, in 10-12 year old children, and in young adults).
OCTs will be obtained using a spectral domain handheld OCT (3.2micro meter resolution, 1000 A-scans x 100 B-scans, 10x10mm, Bioptigen Inc, NC)
Analysis will include measurements of the thickness of the nerve fiber layer, all processing and photoreceptor layers and retinal pigment epithelium. Foveal grading will be based on total retinal thickness, foveal pit depth, and widening of the outer nuclear and outer segment layers at the fovea.

Eye movements of children with nystagmus will be recorded with head free high resolution infrared oculography (EyeLink 1000) suitable for infants and children. Eye movement characteristics such as amplitude, frequency, intensity, foveation characteristics and waveform will be analysed using Spike 2 Software.
We anticipate that this study will help establish OCT as a key investigational and diagnostic tool for children.

We anticipate that this research will benefit children with retinal diseases by giving them access to a new technology called optical coherence tomography. So far this technique has mainly be used in adults, where it has had an enormous impact on diagnosis and treatment. Infants will benefit from this research through better diagnosis, assessment of visual potential and possible prediction of visual acuity later in life. The results of this study will be immediately applicable for clinical purposes and further research. Giving children access to retinal imaging in-vivo will also improve methods for selecting suitable patients and determining the best ages for treatment as well as monitoring results of imminent gene therapies. We will also create databases of patients' pheno- and genotype and make possible trials in genetic therapy immediately available to these patients. Patients with diseases like glaucoma in childhood, retinopathy of prematurity, any retinal or optic nerve disorders will also potentially benefit from this study. For example, it is extremely difficult to monitor glaucoma in early childhood as subjective measurements such as visual fields are not feasible and not precise. The objective monitoring of the retinal nerve fibre layer would be extremely important in childhood glaucoma. Normative data and advance in techniques in acquisition and analysis of data obtained in the proposed study will contribute to examine several childhood diseases. Proving that the method of the handheld OCT is suitable clinically for children is likely to increase production of such instruments by several companies in the field. This is likely to improve the quality of these instruments and reduce costs. A successful study will also improve the likelihood of relevant medical charities to raise funds for this research.