Title: Can the diagnostic accuracy of newborn eye screening for congenital cataract be improved with digital dual-light source imaging? The Digital Imaging vs Ophthalmoscopy (DIvO)study
Funder: Medical Research Council

Abstract: Cloudiness of the lens of the eye, called a cataract, is the commonest cause of avoidable child blindness in the world and affects 3 per 10,000 UK infants. Cataracts are present in both eyes in more than half of the babies affected. Surgery is required by 10 weeks of age to prevent permanent visual impairment at this critical time of vision and brain development. All UK babies are examined (screened) for cataract twice within the first 8 weeks of life during the Newborn and Infant Physical Examination but late diagnosis continues to be a problem, causing avoidable visual impairment in some affected children._x000D_ _x000D_ Two types of eye screening error can occur: failing to detect a cataract in an affected child (false-negative) or mistakenly suggesting that there is a cataract (false positive) triggering urgent unnecessary referral, parental anxiety and wasted NHS resources. Of the 145 families in our parent involvement group, half reported that their babies’ cataracts were not detected at screening and felt that their child’s vision had suffered as a result. Others have described “days of total panic” after a false positive screening test. Their experiences are shared at www.youtube.com/watch?v=1foGdYwe7eg._x000D_ _x000D_ Eye screening is currently performed by midwives and doctors shining a bright white light torch (an ophthalmoscope) into the eye to assess the reddish reflected light (red-reflex), similar to “red eye” seen in flash photos. Cataract causes a dark shadow on the red-reflex. However, the test can be difficult because the bright light causes the pupils to constrict and the babies to forcefully shut their eyes. The assessment is particularly difficult in ethnic minority infants since eye pigmentation affects the hue and brightness of the red-reflex. _x000D_ _x000D_ This study aims to test if using a specially designed hand-held digital imaging device is more accurate than using the ophthalmoscope for detecting cataracts during newborn eye screening. Early studies have indicated that using infrared light may improve the accuracy of cataract assessment. The no-touch imaging device painlessly images the eye’s reflection firstly to infrared light and then to a brief white light flash. Its infrared light causes no pupil constriction or avoidance response and the reflection is bright and consistent regardless of the baby’s ethnicity. Its brief white flash and immediate imaging allows a photo of the red-reflex to be captured before the pupil has time to constrict. _x000D_ _x000D_ To compare the accuracy of the existing screening test and digital imaging, parents’ permission will be sought to enrol 140,000 newborn babies born in maternity units across the UK during the two year study period. All babies will have both the current ophthalmoscope red-reflex screening test and additional digital eye imaging with the study device. Babies who have a potential abnormality on either screening test will be referred for specialist examination to determine the diagnosis._x000D_ _x000D_ A more accurate screening test could result in savings, both in terms of prevented life-long disability and in reduced costs to the NHS and society. This study will allow a future estimation of what these savings might be and whether changing to a digital imaging screening service in the UK might be justified. The result may be a change in the UK neonatal eye screening guidelines but also, potentially, an impact on eye screening world-wide to prevent childhood blindness from cataract.

Lay abstract: Congenital cataract is the main treatable cause of global childhood blindness. ‘Red-reflex’ assessment with an ophthalmoscope during the UK Newborn and Infant Physical Examination (NIPE) screening programme enables early detection and timely surgery, preventing permanent visual impairment._x000D_ _x000D_ Evidence for red-reflex screening accuracy is lacking but surveys suggest a high false negative and positive rate, particularly in minority ethnic babies. Recently, an imaging device (ID) has been developed; this is a hand-held digital camera incorporating co-axial dual LED (Light Emitting Diode) illumination. Directed at the eye from arm’s length, it automatically sequences digital reflections to infrared (IR) and white light. Superiority of IR imaging to ophthalmoscopic red-reflex assessment (O) has been demonstrated in cataract enriched childhood cohorts.(1)_x000D_ We aim to determine whether the sensitivity and specificity of newborn eye screening is better with the ID than with the existing O assessment, potentially improving the accuracy of the UK NIPE screening programme._x000D_ _x000D_ _x000D_ Methods_x000D_ This is a prospective population-based study on healthy, term newborn babies. 140,000 consecutive babies will be recruited from at least 13 large maternity units prior to their discharge home. Both the existing (O) and new (ID) test will be undertaken once only, with each test undertaken by different qualified screeners masked to the other’s results. _x000D_ All screeners will have standardised pre-study training and regular review. A 10% random sample of study images will be reviewed by an ophthalmologist for validation. Babies with abnormal assessment in either or both screening tests will be referred for ophthalmic examination, the usual standard care for a ‘screen positive’ baby. _x000D_ NHS Digital database record linkage at study’s end will identify all recruited babies subsequently diagnosed with cataract. Relative sensitivity and specificity will be calculated using discordant screening test results. An estimate of absolute sensitivity and specificity will be made following expert image review in those babies with double negative screening in whom cataract was subsequently diagnosed (since cataract can develop in infancy). Differences in diagnostic accuracy with ethnicity and screener experience and test usability will be determined._x000D_ _x000D_ Timelines _x000D_ Safety testing of the ID to enable UK trial use will be completed by March 2021. Patient recruitment will start in June 2021 and last 18 months. NHS Digital data will be requested in April 2023 to enable relative and absolute sensitivity and specificity to be calculated by close of the study in June 2023. _x000D_ _x000D_ Impact / dissemination_x000D_ Dissemination to Public Health bodies, midwifery organisations and the public has already started via invited national and international lectures and television broadcasts. The Ante-natal and Newborn Research Advisory Committee has formally supported the project, intending to include the study results as part of its policy review and potential NHS adoption. Future publications and invited lectures are expected. An application for an NIHR AI in Health and Care grant to develop the diagnostic capability of the device is planned. Potentially, screening with ID could replace current ophthalmoscopic red-reflex screening, improving screening accuracy both in the UK and internationally to reduce the global burden of preventable childhood blindness.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE