{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:57:25Z","timestamp":1781344645089,"version":"3.54.1"},"update-to":[{"DOI":"10.3310\/nihropenres.13370.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000}}],"reference-count":12,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/open-government-licence\/version\/3\/"}],"funder":[{"DOI":"10.13039\/501100001922","name":"Efficacy and Mechanism Evaluation Programme","doi-asserted-by":"publisher","award":["NIHR130628"],"award-info":[{"award-number":["NIHR130628"]}],"id":[{"id":"10.13039\/501100001922","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns3:p>Abstract Background Congenital cataract is the commonest cause of preventable child blindness in the world. It affects 1: 3000 babies, 60% of whom will have bilateral disease. Although screening of the newborn red-reflex with an ophthalmoscope is recommended, there are questions over this technique's accuracy, particularly in non-specialist hands. Several studies in enriched paediatric eye clinic populations have demonstrated superior accuracy when a digital image of the the eye's reflection to infrared light is evaluated. Aim This study uses a prototype infrared digital camera to test the hypothesis that the sensitivity and specificity of newborn screening using evaluation of the \"infrared-reflex\" image is superior to the standard red-reflex examination using ophthalmoscopy. Methods 140,000 newborn babies will be recruited into the study from at least 13 maternity units in England over an 18 month period. Babies will have both the standard red-reflex assessment and evaluation of the infrared-reflex using a prototype device. Since specialist gold-standard evaluation of every participant is impractical, bespoke data linkage requests to NHS England will be made. Data from the red-reflex evaluation and the presence of codes relating to cataract diagnosis and\/or treatment in Hospital Episode Statistics (HES) will be retrieved for each participant a minimum of 6 months after their birth. This data will be used to calculate relative and absolute sensitivity and specificity for each screening test and comparison of accuracy using the McNemar test. Secondary outcome measures will include comparison of accuracy in different ethnic groups and screener usability scores. Anticipated impact Confirmation of the hypothesis will support development of a commercial screening device and the possible revision of newborn screening recommendations. Trial registration The study is registered with clinicaltrials.gov: NCT05282147.<\/ns3:p>","DOI":"10.3310\/nihropenres.13370.2","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:19:06Z","timestamp":1779470346000},"page":"25","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Can the diagnostic accuracy of newborn eye screening for congenital cataract be improved with digital imaging? The Digital Imaging versus Ophthalmoscopy (DIvO) study"],"prefix":"10.3310","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-8884","authenticated-orcid":false,"given":"Louise","family":"Allen","sequence":"first","affiliation":[{"name":"Ophthalmology Department Cambridge N\/A CB2 0QQ Cambridge University Hospitals NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Bain","sequence":"additional","affiliation":[{"name":"Cambridge Clinical Trials Unit Cambridge CB2 0QQ Cambridge University Hospitals NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Rose","sequence":"additional","affiliation":[{"name":"Midwifery Department Cambridge CB1 1PT Anglia Ruskin University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2528-1040","authenticated-orcid":false,"given":"Simon","family":"Bond","sequence":"additional","affiliation":[{"name":"Cambridge Clinical Trials Unit Cambridge CB2 0QQ Cambridge University Hospitals NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5718-9209","authenticated-orcid":false,"given":"Jugnoo","family":"Rahi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology London Great Ormond Street Hospital for Children"},{"name":"Population , Policy and Practice Dept London WC1N 1EH UCL GOS Institute of Child health"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1160-1169","DOI":"10.1038\/eye.2016.156 5023808","article-title":"Global prevalence of childhood cataract: a systematic review.","volume":"30","author":"S Sheeladevi","year":"2016","journal-title":"Eye (Lond)."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"28564","DOI":"10.1038\/srep28564","article-title":"Prevalence and epidemiological characteristics of congenital cataract: a systematic review and meta-analysis.","volume":"6","author":"X Wu","year":"2016","journal-title":"Sci Rep."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e1-e8","DOI":"10.1016\/j.jaapos.2015.01.013","article-title":"Global Challenges in the Management of Congenital Cataract: Proceedings of the 4th International Congenital Cataract Symposium held on March 7, 2014, New York, New York.","volume":"19","author":"P Lenhart","year":"2015","journal-title":"J AAPOS."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"192-196.e4","DOI":"10.1016\/j.jpeds.2016.08.048","article-title":"Sensitivity and Specificity of Red Reflex Test in Newborn Eye Screening.","volume":"179","author":"M Sun","year":"2016","journal-title":"J Pediatr."},{"key":"ref5","first-page":"1444-1448","article-title":"British Congenital Cataract Interest Group: Measuring and interpreting the incidence of congenital ocular anomalies: lessons from a national study of congenital cataract in the UK.","volume":"42","author":"J Rahi","year":"2001","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1-5","DOI":"10.1258\/shorts.2010.010036","article-title":"The role of education in the promotion of red reflex assessments.","volume":"1","author":"W Muen","year":"2010","journal-title":"JRSM Short Rep."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"F389-F393","DOI":"10.1136\/adc.2007.122465","article-title":"The value of the postnatal examination in improving child health.","volume":"93","author":"K Green","year":"2008","journal-title":"Arch Dis Child Fetal Neonatal Ed."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"364-366","DOI":"10.1136\/adc.78.4.364","article-title":"A survey of paediatricians' practice and training in routine infant eye examination.","volume":"78","author":"J Rahi","year":"1998","journal-title":"Arch Dis Child."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1471-1476","DOI":"10.1136\/bjophthalmol-2014-306394","article-title":"Risks and outcomes associated with primary intraocular lens implantation in children under 2 years of age: the IoLunder2 cohort study.","volume":"99","author":"A Solebo","year":"2015","journal-title":"Br J Ophthalmol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1865-1870","DOI":"10.1038\/s41433-019-0509-9","article-title":"The infrared reflex: a potential new method for congenital cataract screening.","volume":"33","author":"A Duret","year":"2019","journal-title":"Eye (Lond)."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1347-1353","DOI":"10.1038\/s41433-020-1019-5","article-title":"Red reflex examination in reproductive and child health clinics for early detection of paediatric cataract and ocular media disorders: cross-sectional diagnostic accuracy and feasibility studies from Kilimanjaro, Tanzania.","volume":"35","author":"F Mndeme","year":"2021","journal-title":"Eye (Lond)."},{"key":"ref12","author":"L Allen","year":"2023","journal-title":"DIvO study."}],"container-title":["NIHR Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:29:07Z","timestamp":1781342947000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":12,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.13370.2","relation":{"has-version":[{"id-type":"doi","id":"10.3310\/nihropenres.13370.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.3310\/nihropenres.15624.r40594","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.15624.r40594","asserted-by":"object"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.14501.r29282, Anthony T. Moore, Department of Ophthalmology, University of California San Francisco, San Francisco, California, 12 Jun 2023, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v1#referee-response-29282","order":0,"name":"referee-response-29282","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Louise Allen<\/b>; \n<i>Posted: 15 Jun 2023<\/i>; The authors thank Professor Moore for his review of the DIvO study protocol and agree that improving the early detection of congenital cataract is of global importance in preventing treatable childhood blindness. Many of the participating maternity hospitals will be located in cities, chosen both because of their high birthrate and the level of ethnic diversity in the population they serve. &nbsp; A very large number of babies will be recruited to the study and, given the pressure on ophthalmic and maternity services, we are using linkage to diagnostic and procedure codes in HES data as the gold-standard. Although not currently specified in the protocol, we agree that data linkage should occur at least 12 months after screening in order to reduce the risk of missing late cataract presentations. The babies screened early in the recruitment period will have up to 24 months of HES data collection. This will maximise the accuracy in determing the absolute sensitivity and specificity of each screening test.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2#referee-comment-3253","order":1,"name":"referee-comment-3253","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.14501.r29283, Alistair R. Fielder, Department of Optometry & Visual Science, City University of London, London, England, 12 Jun 2023, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v1#referee-response-29283","order":2,"name":"referee-response-29283","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Louise Allen<\/b>; \n<i>Posted: 15 Jun 2023<\/i>; The authors thank Professor Fielder for his review of the study protocol and for the important points he makes.  For statistical power, we need to recruit 67 babies with cataract and this may require the screening of more than 140,000 babies. Being able to review the neocam images of eyes with a suspected abnormality on screening will enable us to keep a tally of cataracts detected and will determine the end-point of the recruitment period.&nbsp;&nbsp;  \n<b>Timing of assessments:<\/b> Most babies are discharged by 24 hours: we have taken the time period for assessment of within 72 hours of birth because this is the NIPE standard. We agree the vast majority of babies may spend less than 24 hours in the maternity unit. We have discussed the logistics of having two different screeners undertake parallel NIPE and neocam screening ward rounds with each participating unit and all can comply. Given the pressures on staffing, we are seeking to enrol and consent the majority of parents online antenatally so that parents will have had time to consider whether to participate at a less stressful time and the workload for staff on the delivery ward is minimised.&nbsp;  Why not undertake neocam screening at 6-8 week check?: The reasons why we feel the neocam check should take place at the neonatal&nbsp; physical examination are as follows:  In our experience the 6-8 week check is often delayed until 9 weeks to coincide with vaccinations, this potentially leaves very little time to organise onward specialist referral. The findings from the 6-8 week infant physical examination are not uploaded to a national database or audited. This study relies on data linkage with the S4N database to collect the red-reflex evaluations, therefore the neonatal screening timepoint has to be used.&nbsp; Babies for the NIPE check are concentrated in one place for the neonatal examination and then disperse to GP surgeries for the infant examination. It would not be feasible to&nbsp;train thousands of GP practice staff and provide the number of prototype cameras required.&nbsp;  \n<b>The two tests:<\/b> Risk of contamination between evalutions: The protocol states that different screeners will be undertaking the standard red-reflex test and neocam screening. Specific site training will&nbsp; underline the importance of the screeners not discussing the results with the parents or each other until both evaluations are uploaded. We are pragmatic about the order in which the assessments are undertaken to give pressurised staff more flexibility.  False positives and false negatives: Figure 2. (study flow chart) shows the method of identifying false positives and false negatives from either evaluation. Each evaluation will be compared to the gold-standard (drawn from data linkage) to give the number of false positive and negatives for each screening test. These figures will be used for the sensitivity and specifity calculations.&nbsp; There may be occasions when both tests are falsely negative. In these cases diagnostic and procedure codes relating to cataract will be present in the HES data retrieved 12 or months after screening. It is possible that, in these cases, the cataract developed after birth. An expert panel, drawn from the Trial Steering Committee will review the neocam images in these cases to determine if there was any indication of cataract in the neonatal period.&nbsp; &nbsp; \n<b>Bench Testing:<\/b> The neocam device has had quite extensive testing in childhood populations. Correct use is important to the capture of good quality images. Just as with red-reflex assessment, the screening evaluation requires an &quot;on-axis&quot; examination at the correct distance. Some modifications have been made in version 2 of the prototype to promote its correct use. It is possible and an interesting thought that a future device could take a series of images co-axially and then at eccentric angles to enable an experienced clinician to determine the location of the cataract in the lens.&nbsp;  This study does not include a health economic evaluation but it will provide the data to determine if the potential improvement in visual outcomes due to earlier detection and intervention warrant a change in the screening recommendations.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2#referee-comment-3254","order":3,"name":"referee-comment-3254","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15624.r40594, Cinantya Paramita, Suryanti Tsang, Universitas Dian Nuswantoro, Semarang, Central Java, 13 Jun 2026, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-25\/v2#referee-response-40594","order":4,"name":"referee-response-40594","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the National Institute for Health Research (NIHR) (Grant Reference Number NIHR130628). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This open access work is licensed under the Open Government Licence v3.0.","order":0,"name":"copyright-info","label":"Copyright"}]}}