Photo-screening for Retinoblastoma: A Proof-of-Concept Study

Photo-screening for Retinoblastoma: A Proof-of-Concept Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Photo-screening for Retinoblastoma: A Proof-of-Concept Study Vijitha S Vempuluru, Ganesh Babu Jonnadula, Shrikant Bharadwaj, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1464972/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: The potential of Infrared (IR) photo-screening for detection of retinoblastoma has not been assessed. This study aimed to assess the IR reflex formed across the pupil in eyes with retinoblastoma (RB), vis-à-vis eyes with no intraocular tumor. Methods: Central gaze IR-reflex assessment in eyes with and without RB. Results: Of 30 eyes from 21 subjects, 20 eyes had RB and 10 eyes had no tumors. Image frames were extracted from IR video recordings of 30 eyes, of which 71 central gaze images were eligible for measurement of pixel intensity (0 to 255). Of these, 49 images had RB and 22 images had no tumor. The mean pixel intensity (MPI) within the pupil, in images of eyes with RB was 115 (median, 92; range, 38 to 254), in images of eyes with no tumor was 73 (median, 68; range, 26 to 125) and the difference was statistically significant (Odds ratio 1.018; 95 % CI: 1.004 – 1.032; p, .010;) on bivariate analysis. Of 57 images from eyes with RB, 35 were captured with un-dilated pupils and 22 with dilated pupils. The MPI in images from un-dilated eyes with RB was 107 (median, 79; range, 38 to 254), in images from dilated eyes with RB was 128 (median, 114; range, 46 to 215). However, the difference was not statistically significant (Odds ratio 1.006; 95 % CI: 0.996– 1.015; p, .248). Conclusion: Technology combining IR imaging and MPI measurement within the pupil can translate into a potential tool for early detection of RB. Eye Cancer Children Retinoblastoma Screening Infrared IR imaging Figures Figure 1 Figure 2 Introduction Retinoblastoma accounts for approximately 3% of solid tumors of infancy. 1 It is the most common malignant intraocular tumor of childhood with an incidence of 1 in 15,000 to 20,000 live births. 2 – 5 Although the management of this devastating disease has evolved greatly resulting in improved survival, globe and vision salvage, the scenario is not uniform across the globe. 6 , 7 Children diagnosed with retinoblastoma fare better in high income countries than in middle and low income countries due to early detection of the disease in the former. 7 Late presentation of Retinoblastoma is common in middle and low income countries, due to lack of universal screening norms. 8 Various methods have been employed in screening for retinoblastoma in children which include red reflex examination, Bruckner’s test, universal fundus examination in neonates to list a few. 8 Red reflex is the most commonly used screening methods for intraocular pathology with its scope for detection of intraocular tumors being limited greatly by pupillary dilatation and expertise of examiner. 9 Infrared spectrum of light has been utilized widely for photorefraction, amblyopia and congenital cataract screening in children, 10 – 12 but has not been explored for detection of intraocular tumors. Longer wavelengths of light cause delayed and lesser pupillary constriction, 13 thus offering a larger pupillary area for assessment. In a first of its kind study, it was attempted to understand the infrared reflex pattern in eyes with retinoblastoma and establish its potential role in the development of a simple screening tool for early detection of retinoblastoma. Materials And Methods This was a prospective study conducted at the LV Prasad Eye Institute, Hyderabad, India and approval from Institutional Review Board was obtained. The study adhered to the tenets of Declaration of Helsinki. Children diagnosed with retinoblastoma and their siblings routinely screened for retinoblastoma at Operation Eyesight Universal Institute for Eye Cancer, LV Prasad Eye Institute were recruited for the study after obtaining informed consent from the parents/ caretakers from August 2020 to December 2020. Clinical details recorded included age of the subject, presence or absence of retinoblastoma, activity and location of the intraocular tumor. Infrared videography was perform by a custom designed photorefraction device at the Visual Optics Laboratory of the Brien Holden Institute of Optometry and Vision Sciences, L V Prasad Eye Institute. The photoreflex from eyes with retinoblastoma and normal eyes was obtained from viewing distance of 1m in a semi-dark room. IR light of 850nm was shone into the eye and the reflected light that formed the photoreflex across the pupils was obtained before instillation of any eye drops in all subjects and after the eyes were dilated using a cycloplegic agent (1% Cyclopentolate HCl eye drops) whenever feasible, subject to cooperation of the child. IR videography was performed at 30fps sampling rate and the video clips were saved for analysis. Individual frames in various gazes were captured from the video recordings and only central gaze images of acceptable quality were analyzed further using Image J software (version 1.53e). Each image was converted into an 8-bit file after which the pupillary area was manually marked with precision using the selection tool. The ‘gray value’ within the pupillary area was measured to obtain the mean pixel intensity ( 0 to 255). Data was recorded in Microsoft Excel for Mac (Version 16.41). Descriptive data was expressed as mean, median, range and proportions. Mean pixel intensity was compared between images with and without retinoblastoma. In images with retinoblastoma, the mean pixel intensity was compared prior to and after dilatation. Statistical analysis was performed using SPSS (IBM SPSS Statistics, Version 23). Data was checked for normality and compared between the groups by Mann-Whitney U test followed by bivariate analysis. 95% confidence intervals were obtained and a p-value of < .05 was considered statistically significant. Results Twenty-one subjects were included in the study. Thirty eyes of 21 subjects were satisfactorily imaged. Mean age of subjects of eyes with retinoblastoma was 6 years (median, 4 years; range, 1 to 17 years) and mean age of subjects of eyes with no tumor was 3 years (median, 2 years; range, 1 to 6 years). Of 30 eyes, 20 eyes had retinoblastoma and 10 eyes had no tumor. Tumor characteristics are listed in Table 1 . From the infrared video recordings of 30 eyes, 74 central gaze images were extracted. Image characteristics are detailed in Table 2 . Table 1 Tumor characteristics of eyes with retinoblastoma Feature Eyes with RB (n = 20) Status of tumors Active Regressed 8 12 Location of tumor Posterior pole Posterior pole + Equator Posterior pole + Equator + Periphery Posterior pole + Equator + Periphery Equator + Periphery 8 3 7 1 1 Table 2 Distribution of analysed images Parameter Number of images (N = 71) Images from eyes with retinoblastoma Undilated Dilated 49 31 18 Images from eyes with no intraocular tumor Undilated Dilated 22 14 8 The mean pixel intensity of the images from eyes with retinoblastoma and no tumor were compared (Figs. 1 & 2 , Table 3 ). The mean pixel intensity in eyes with retinoblastoma was 115 (median, 92; range 38 to 254), in eyes with no tumor was 74 (median 68, range 26 to 125) and the difference was statistically significant (Odds ratio 1.018; 95% CI: 1.004–1.032; p, .010;) on bivariate analysis. Receiver Operating Characteristic Curve was plotted and the area under the curve was found to be 0.689 (p, .011; 95% CI, 0.555–0.824). At an arbitrary cut off of 60 mean pixel intensity, the sensitivity was 82% and specificity was 50% (Fig. 2 ). Table 3 Comparison of mean pixel intensity in images from a normal eye and those with retinoblastoma Mean Pixel intensity No tumor N = 17 RB N = 57 RB, un-dilated N = 31 RB, dilated N = 18 Mean 73 114 107 128 Median 68 92 80 114 Range 26–125 38–254 38–254 46–215 IQR 39–108 69–150 63–136 91–175 Odds Ratio (95% Confidence interval) p-value* 1.018 (1.004–1.032) 0.010 1.006 (0.996–1.015) 0.248 RB: retinoblastoma; *Bivariate analysis In eyes with retinoblastoma, the mean pixel intensity was compared between un-dilated and pharmacologically dilated eyes. Although the mean pixel intensity was greater in pharmacologically dilated eyes, the difference was not significant (Figs. 1 & 2 , Table 3 ). Discussion Red reflex examination is a commonly used and simple technique for detection of intraocular pathology in infants and children. 9 It involves illuminating the pupil from a light source such as ophthalmoscope or retinoscope and observing the light reflected off the retina which illuminates the pupil. 9 Feasibility of red reflex examination can be affected by pupil size and its validity by expertise of the examiner, method or equipment. 9 Screening employing infrared light, referred to as photo-screening, on the other hand, have gained popularity and shown to be useful in detection of refractive errors, amblyopia and congenital cataracts. 10 – 12 This study aimed to establish the utility of infrared reflex assessment in early detection of retinoblastoma. In agreement with the testing hypothesis of altered infrared reflex in eyes with retinoblastoma when compared to eyes with no tumor, the mean pixel intensity in the former was noted to be higher (Table 3 ). The mean pixel intensity, however, varied in eyes in retinoblastoma as well, from as low as 26 to as high as 254. This difference (in central gaze) can be accounted for by the location and size of the tumor. Notably, since tumors in younger children are posteriorly located more often, 14 central gaze image may suffice for detection of small tumors. Further, assessment of infrared reflex in all directions of gaze can aid detection of peripheral tumors. Pupillary dilatation being one of the limiting factors for conventional red reflex assessment, the effect of this parameter on the mean pixel intensity in eyes with retinoblastoma was assessed. There was no statistically significant difference in mean pixel intensity between un-dilated and pharmacologically dilated eyes with retinoblastoma. Thus, infrared light provides sufficient pupillary area for infrared reflex assessment sans pupillary dilatation, rendering it ideal for rapid screening in a community. Technique employed in this study i.e. measurement of mean pixel intensity for assessing the infrared reflex is simple and differs from conventional photo-screening devices where the pattern of infrared reflex is evaluated. Further, need for subjective interpretation by an observer as in conventional screening methods can be obviated by automation of the mean pixel intensity calculation. This study has certain limitations. Firstly, quality of infrared video recordings was subject to cooperation of the children, thus only a small fraction of image frames were eligible for analysis. Secondly, image frames from non-central gazes were excluded to ensure uniformity in comparison with non-tumor images. Further, sub-group comparisons based on location of tumor, gaze position and mean pixel intensity could not be performed due to small numbers. Despite its limitations this study provides evidence that infrared reflex in eyes with retinoblastoma has a significantly different mean pixel intensity than eyes with no intraocular tumor. Extrapolating its use at a community level, this technology can be employed to devise a portable screening tool equipped with automatic mean pixel intensity image capture and pixel intensity measurement software that subsequently generates of an output for referral if an abnormal reflex is noted. In conclusion, t his proof-of-concept study establishes that infrared pupillary reflex assessment with pixel intensity measurement holds promise for development of a point of care screening tool for early detection of retinoblastoma. Future directions include validation in a larger population and incorporation of this technology into a hand-held device for utilization at the community level. Declaration Support provided by The Operation Eyesight Universal Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India. The funders had no role in the preparation, review or approval of the manuscript. No conflicting relationship exists for any author. References Allen-Rhoades W, Whittle SB, Rainusso N. Pediatric Solid Tumors of Infancy: An Overview. Pediatr Rev 2018;39:57-67. Usmanov RH, Kivelä T. Predicted Trends in The Incidence of Retinoblastoma in the Asia-Pacific Region. Asia Pac J Ophthalmol 2014;3:151–7. Tamboli A, Podgor MJ, Horm, JW. The Incidence of Retinoblastoma in the United States: 1974 through 1985. Arch Ophthalmol 1990;108:128–32. Seregard S, Lundell G, Svedberg H, Kivelä T. Incidence of Retinoblastoma From 1958 To 1998 Ii Northern Europe: Advantages of Birth Cohort Analysis. Ophthalmology 2004; 111:1228–32. MacCarthy A, Birch JM, Draper GJ, et al. Retinoblastoma in Great Britain 1963–2002. Br J Ophthalmol 2009;93:33–7. Kaliki S, Ji X, Zou Y, et al. Lag Time Between Onset of First Symptom and Treatment of Retinoblastoma: An International Collaborative Study of 692 Patients from 10 Countries. Cancers (Basel) 2021;13:1956. Tomar AS, Finger PT, Gallie B, et al. American Joint Committee on Cancer Ophthalmic Oncology Task Force. Global Retinoblastoma Treatment Outcomes: Association with National Income Level. Ophthalmology 2021;128:740-53. Vempuluru VS, Kaliki S. Screening for Retinoblastoma: A Systematic Review of Current Strategies. Asia Pac J Ophthalmol (Phila) 2021;10:192-9.` Nguyen M, Blair K. Red Reflex. [Updated 2021 Sep 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553139/ Sravani NG, Nilagiri VK, Bharadwaj SR. Photorefraction Estimates of Refractive Power Varies with the Ethnic Origin of Human Eyes. Sci Rep 2015;5:7976. D'Souza H, Kun A, Martinson S, et al. The Positive Predictive Value of Photoscreening Devices for Amblyogenic Conditions. J AAPOS 2021;11:S1091-8531(21)00566-8. Duret A, Humphries R, Ramanujam S, et al. The Infrared Reflex: A Potential New Method for Congenital Cataract Screening. Eye (Lond) 2019;33:1865-70. Bonmati-Carrion MA, Hild K, Isherwood CM, et al. Effect of Single and Combined Monochromatic Light on the Human Pupillary Light Response. Front Neurol 2018;9:1019. Abramson DH, Gombos DS. The Topography of Bilateral Retinoblastoma Lesions. Retina 1996;16:232–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1464972","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":91983763,"identity":"e89f621c-b044-4e8c-83b3-de1b625b9e44","order_by":0,"name":"Vijitha S Vempuluru","email":"","orcid":"","institution":"LV Prasad Eye Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Vijitha","middleName":"S","lastName":"Vempuluru","suffix":""},{"id":91983765,"identity":"a953a53f-7263-49a1-be32-ca10b6d2b221","order_by":1,"name":"Ganesh Babu Jonnadula","email":"","orcid":"","institution":"LV Prasad Eye Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ganesh","middleName":"Babu","lastName":"Jonnadula","suffix":""},{"id":91983767,"identity":"97d7bab7-fad7-49ff-ba1b-0fcc8cd6248f","order_by":2,"name":"Shrikant Bharadwaj","email":"","orcid":"","institution":"LV Prasad Eye Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shrikant","middleName":"","lastName":"Bharadwaj","suffix":""},{"id":91983768,"identity":"3fdd6842-e2eb-4732-9893-6de8a9805775","order_by":3,"name":"Swathi Kaliki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACCQbmhoMNBiAmD8OBDwwMCURoYYRqYeNhODiDWC2MDQwQLcw8xGiRbD/YeHBGQV1i//zeg4dt2+zy+NkbGD98zMGtRZonseHgBoPDiTOO8SUczm1LLpbsOcAsOXMbbi1yDEAtDwwO5DYc4zEAamFO3HAjgY2ZF58W/ocgLXW580FaLNvqCWuRlgA7jDl3A0gLY9thwlokZwBtmWFwuH7jsRyDgz3njifO7DnYjNcvEueTD3/s+VNnLHf4jPGHH2XVif3szQc/fMSjBRUwsoHJBmLVg8AfUhSPglEwCkbBSAEA+HReO5WOwrAAAAAASUVORK5CYII=","orcid":"","institution":"LV Prasad Eye Institute","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Swathi","middleName":"","lastName":"Kaliki","suffix":""}],"badges":[],"createdAt":"2022-03-18 09:29:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1464972/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1464972/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19446632,"identity":"523db314-3098-418e-ba8d-bf33cda94e58","added_by":"auto","created_at":"2022-03-21 18:57:46","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":633256,"visible":true,"origin":"","legend":"\u003cp\u003eClinical photograph showing the infrared reflex in imaged eyes\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e(A) \u003c/strong\u003eCentral gaze infrared image of the right eye of a child with no intraocular tumor\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e(B)\u003c/strong\u003e Central gaze infrared image of the right eye of a child with retinoblastoma\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e(C) \u003c/strong\u003eCentral gaze infrared image of the right eye of a child with retinoblastoma before pupillary dilatation\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e(D)\u003c/strong\u003e Central gaze infrared image of the right eye of the same child with retinoblastoma after pharmacological pupillary dilatation.\u003c/p\u003e","description":"","filename":"Figure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-1464972/v1/7a5bb5617ee30e39d4302dcf.jpeg"},{"id":19446985,"identity":"c90aa81e-0156-48c7-825b-979198d43863","added_by":"auto","created_at":"2022-03-21 19:00:46","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":507694,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A): \u003c/strong\u003eReceiver Operating Characteristic Curve with an area under the curve 0.689 (p=.011) under non-parametric assumption; null hypothesis: true area=0.5.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e(B):\u003c/strong\u003e Box plot depicting the Mean Pixel Intensity distribution in eyes with no tumor versus retinoblastoma (RB)\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e(C):\u003c/strong\u003e Box plot depicting the Mean Pixel Intensity distribution in undilated versus dilated eyes with retinoblastoma (RB)\u003c/p\u003e","description":"","filename":"Figure2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-1464972/v1/3a6bc1122ed6a503a9cc3f4e.jpeg"},{"id":19736121,"identity":"43371dae-105f-49d9-94a0-6428e45fe141","added_by":"auto","created_at":"2022-03-29 13:59:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":357900,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1464972/v1/effa7a1c-b679-4692-b606-87bc08dd3e4b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Photo-screening for Retinoblastoma: A Proof-of-Concept Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRetinoblastoma accounts for approximately 3% of solid tumors of infancy.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e It is the most common malignant intraocular tumor of childhood with an incidence of 1 in 15,000 to 20,000 live births.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Although the management of this devastating disease has evolved greatly resulting in improved survival, globe and vision salvage, the scenario is not uniform across the globe.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Children diagnosed with retinoblastoma fare better in high income countries than in middle and low income countries due to early detection of the disease in the former.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Late presentation of Retinoblastoma is common in middle and low income countries, due to lack of universal screening norms.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eVarious methods have been employed in screening for retinoblastoma in children which include red reflex examination, Bruckner\u0026rsquo;s test, universal fundus examination in neonates to list a few.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Red reflex is the most commonly used screening methods for intraocular pathology with its scope for detection of intraocular tumors being limited greatly by pupillary dilatation and expertise of examiner.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eInfrared spectrum of light has been utilized widely for photorefraction, amblyopia and congenital cataract screening in children,\u003csup\u003e\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e but has not been explored for detection of intraocular tumors. Longer wavelengths of light cause delayed and lesser pupillary constriction,\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e thus offering a larger pupillary area for assessment. In a first of its kind study, it was attempted to understand the infrared reflex pattern in eyes with retinoblastoma and establish its potential role in the development of a simple screening tool for early detection of retinoblastoma.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eThis was a prospective study conducted at the LV Prasad Eye Institute, Hyderabad, India and approval from Institutional Review Board was obtained. The study adhered to the tenets of Declaration of Helsinki. Children diagnosed with retinoblastoma and their siblings routinely screened for retinoblastoma at Operation Eyesight Universal Institute for Eye Cancer, LV Prasad Eye Institute were recruited for the study after obtaining informed consent from the parents/ caretakers from August 2020 to December 2020.\u003c/p\u003e \u003cp\u003eClinical details recorded included age of the subject, presence or absence of retinoblastoma, activity and location of the intraocular tumor. Infrared videography was perform by a custom designed photorefraction device at the Visual Optics Laboratory of the Brien Holden Institute of Optometry and Vision Sciences, L V Prasad Eye Institute. The photoreflex from eyes with retinoblastoma and normal eyes was obtained from viewing distance of 1m in a semi-dark room. IR light of 850nm was shone into the eye and the reflected light that formed the photoreflex across the pupils was obtained before instillation of any eye drops in all subjects and after the eyes were dilated using a cycloplegic agent (1% Cyclopentolate HCl eye drops) whenever feasible, subject to cooperation of the child. IR videography was performed at 30fps sampling rate and the video clips were saved for analysis. Individual frames in various gazes were captured from the video recordings and only central gaze images of acceptable quality were analyzed further using Image J software (version 1.53e). Each image was converted into an 8-bit file after which the pupillary area was manually marked with precision using the selection tool. The \u0026lsquo;gray value\u0026rsquo; within the pupillary area was measured to obtain the mean pixel intensity ( 0 to 255).\u003c/p\u003e \u003cp\u003eData was recorded in Microsoft Excel for Mac (Version 16.41). Descriptive data was expressed as mean, median, range and proportions. Mean pixel intensity was compared between images with and without retinoblastoma. In images with retinoblastoma, the mean pixel intensity was compared prior to and after dilatation. Statistical analysis was performed using SPSS (IBM SPSS Statistics, Version 23). Data was checked for normality and compared between the groups by Mann-Whitney U test followed by bivariate analysis. 95% confidence intervals were obtained and a p-value of \u0026lt;\u0026thinsp;.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTwenty-one subjects were included in the study. Thirty eyes of 21 subjects were satisfactorily imaged. Mean age of subjects of eyes with retinoblastoma was 6 years (median, 4 years; range, 1 to 17 years) and mean age of subjects of eyes with no tumor was 3 years (median, 2 years; range, 1 to 6 years). Of 30 eyes, 20 eyes had retinoblastoma and 10 eyes had no tumor. Tumor characteristics are listed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. From the infrared video recordings of 30 eyes, 74 central gaze images were extracted. Image characteristics are detailed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTumor characteristics of eyes with retinoblastoma\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFeature\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEyes with RB (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eStatus of tumors\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eActive\u003c/p\u003e\n \u003cp\u003eRegressed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocation of tumor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePosterior pole\u003c/p\u003e\n \u003cp\u003ePosterior pole\u0026thinsp;+\u0026thinsp;Equator\u003c/p\u003e\n \u003cp\u003ePosterior pole\u0026thinsp;+\u0026thinsp;Equator\u0026thinsp;+\u0026thinsp;Periphery\u003c/p\u003e\n \u003cp\u003ePosterior pole\u0026thinsp;+\u0026thinsp;Equator\u0026thinsp;+\u0026thinsp;Periphery\u003c/p\u003e\n \u003cp\u003eEquator\u0026thinsp;+\u0026thinsp;Periphery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDistribution of analysed images\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of images (N\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eImages from eyes with retinoblastoma\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eUndilated\u003c/p\u003e\n \u003cp\u003eDilated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eImages from eyes with no intraocular tumor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eUndilated\u003c/p\u003e\n \u003cp\u003eDilated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eThe mean pixel intensity of the images from eyes with retinoblastoma and no tumor were compared (Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e \u0026amp; \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The mean pixel intensity in eyes with retinoblastoma was 115 (median, 92; range 38 to 254), in eyes with no tumor was 74 (median 68, range 26 to 125) and the difference was statistically significant (Odds ratio 1.018; 95% CI: 1.004\u0026ndash;1.032; p, .010;) on bivariate analysis. Receiver Operating Characteristic Curve was plotted and the area under the curve was found to be 0.689 (p, .011; 95% CI, 0.555\u0026ndash;0.824). At an arbitrary cut off of 60 mean pixel intensity, the sensitivity was 82% and specificity was 50% (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of mean pixel intensity in images from a normal eye and those with retinoblastoma\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean Pixel\u003c/p\u003e\n \u003cp\u003eintensity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo tumor\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;17\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRB\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;57\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRB, un-dilated\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eRB, dilated\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;18\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u0026ndash;125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u0026ndash;254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u0026ndash;254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e46\u0026ndash;215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u0026ndash;108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69\u0026ndash;150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u0026ndash;136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e91\u0026ndash;175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003cp\u003e(95% Confidence interval)\u003c/p\u003e\n \u003cp\u003ep-value*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.018\u003c/p\u003e\n \u003cp\u003e(1.004\u0026ndash;1.032)\u003c/p\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" \u003e\n \u003cp\u003e1.006\u003c/p\u003e\n \u003cp\u003e(0.996\u0026ndash;1.015)\u003c/p\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eRB: retinoblastoma; *Bivariate analysis\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eIn eyes with retinoblastoma, the mean pixel intensity was compared between un-dilated and pharmacologically dilated eyes. Although the mean pixel intensity was greater in pharmacologically dilated eyes, the difference was not significant (Figs. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e \u0026amp; \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRed reflex examination is a commonly used and simple technique for detection of intraocular pathology in infants and children.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e It involves illuminating the pupil from a light source such as ophthalmoscope or retinoscope and observing the light reflected off the retina which illuminates the pupil.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Feasibility of red reflex examination can be affected by pupil size and its validity by expertise of the examiner, method or equipment.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Screening employing infrared light, referred to as photo-screening, on the other hand, have gained popularity and shown to be useful in detection of refractive errors, amblyopia and congenital cataracts.\u003csup\u003e\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e This study aimed to establish the utility of infrared reflex assessment in early detection of retinoblastoma.\u003c/p\u003e \u003cp\u003eIn agreement with the testing hypothesis of altered infrared reflex in eyes with retinoblastoma when compared to eyes with no tumor, the mean pixel intensity in the former was noted to be higher (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The mean pixel intensity, however, varied in eyes in retinoblastoma as well, from as low as 26 to as high as 254. This difference (in central gaze) can be accounted for by the location and size of the tumor. Notably, since tumors in younger children are posteriorly located more often,\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e central gaze image may suffice for detection of small tumors. Further, assessment of infrared reflex in all directions of gaze can aid detection of peripheral tumors.\u003c/p\u003e \u003cp\u003ePupillary dilatation being one of the limiting factors for conventional red reflex assessment, the effect of this parameter on the mean pixel intensity in eyes with retinoblastoma was assessed. There was no statistically significant difference in mean pixel intensity between un-dilated and pharmacologically dilated eyes with retinoblastoma. Thus, infrared light provides sufficient pupillary area for infrared reflex assessment sans pupillary dilatation, rendering it ideal for rapid screening in a community.\u003c/p\u003e \u003cp\u003eTechnique employed in this study i.e. measurement of mean pixel intensity for assessing the infrared reflex is simple and differs from conventional photo-screening devices where the pattern of infrared reflex is evaluated. Further, need for subjective interpretation by an observer as in conventional screening methods can be obviated by automation of the mean pixel intensity calculation.\u003c/p\u003e \u003cp\u003eThis study has certain limitations. Firstly, quality of infrared video recordings was subject to cooperation of the children, thus only a small fraction of image frames were eligible for analysis. Secondly, image frames from non-central gazes were excluded to ensure uniformity in comparison with non-tumor images. Further, sub-group comparisons based on location of tumor, gaze position and mean pixel intensity could not be performed due to small numbers.\u003c/p\u003e \u003cp\u003eDespite its limitations this study provides evidence that infrared reflex in eyes with retinoblastoma has a significantly different mean pixel intensity than eyes with no intraocular tumor. Extrapolating its use at a community level, this technology can be employed to devise a portable screening tool equipped with automatic mean pixel intensity image capture and pixel intensity measurement software that subsequently generates of an output for referral if an abnormal reflex is noted.\u003c/p\u003e \u003cp\u003eIn conclusion, \u003cb\u003et\u003c/b\u003ehis proof-of-concept study establishes that infrared pupillary reflex assessment with pixel intensity measurement holds promise for development of a point of care screening tool for early detection of retinoblastoma. Future directions include validation in a larger population and incorporation of this technology into a hand-held device for utilization at the community level.\u003c/p\u003e"},{"header":"Declaration","content":"\u003cp\u003eSupport provided by The Operation Eyesight Universal Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India. The funders had no role in the preparation, review or approval of the manuscript.\u003c/p\u003e\n\u003cp\u003eNo conflicting relationship exists for any author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAllen-Rhoades W, Whittle SB, Rainusso N. Pediatric Solid Tumors of Infancy: An Overview. Pediatr Rev 2018;39:57-67.\u003c/li\u003e\n \u003cli\u003eUsmanov RH, Kivelä T. Predicted Trends in The Incidence of Retinoblastoma in the Asia-Pacific Region. Asia Pac J Ophthalmol 2014;3:151\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eTamboli A, Podgor MJ, Horm, JW. The Incidence of Retinoblastoma in the United States: 1974 through 1985. Arch Ophthalmol 1990;108:128\u0026ndash;32.\u003c/li\u003e\n \u003cli\u003eSeregard S, Lundell G, Svedberg H, Kivelä T. Incidence of Retinoblastoma From 1958 To 1998 Ii Northern Europe: Advantages of Birth Cohort Analysis. Ophthalmology 2004; 111:1228\u0026ndash;32.\u003c/li\u003e\n \u003cli\u003eMacCarthy A, Birch JM, Draper GJ, et al. Retinoblastoma in Great Britain 1963\u0026ndash;2002. Br J Ophthalmol 2009;93:33\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eKaliki S, Ji X, Zou Y, et al. Lag Time Between Onset of First Symptom and Treatment of Retinoblastoma: An International Collaborative Study of 692 Patients from 10 Countries. Cancers (Basel) 2021;13:1956.\u003c/li\u003e\n \u003cli\u003eTomar AS, Finger PT, Gallie B, et al. American Joint Committee on Cancer Ophthalmic Oncology Task Force. Global Retinoblastoma Treatment Outcomes: Association with National Income Level. Ophthalmology 2021;128:740-53.\u003c/li\u003e\n \u003cli\u003eVempuluru VS, Kaliki S. Screening for Retinoblastoma: A Systematic Review of Current Strategies. Asia Pac J Ophthalmol (Phila) 2021;10:192-9.`\u003c/li\u003e\n \u003cli\u003eNguyen M, Blair K. Red Reflex. [Updated 2021 Sep 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: \u003ca href=\"https://www.ncbi.nlm.nih.gov/books/NBK553139/\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK553139/\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eSravani NG, Nilagiri VK, Bharadwaj SR. Photorefraction Estimates of Refractive Power Varies with the Ethnic Origin of Human Eyes. Sci Rep 2015;5:7976.\u003c/li\u003e\n \u003cli\u003eD\u0026apos;Souza H, Kun A, Martinson S, et al. The Positive Predictive Value of Photoscreening Devices for Amblyogenic Conditions. J AAPOS 2021;11:S1091-8531(21)00566-8.\u003c/li\u003e\n \u003cli\u003eDuret A, Humphries R, Ramanujam S, et al. The Infrared Reflex: A Potential New Method for Congenital Cataract Screening. Eye (Lond) 2019;33:1865-70.\u003c/li\u003e\n \u003cli\u003eBonmati-Carrion MA, Hild K, Isherwood CM, et al. Effect of Single and Combined Monochromatic Light on the Human Pupillary Light Response. Front Neurol 2018;9:1019.\u003c/li\u003e\n \u003cli\u003eAbramson DH, Gombos DS. The Topography of Bilateral Retinoblastoma Lesions. Retina 1996;16:232\u0026ndash;9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Eye, Cancer, Children, Retinoblastoma, Screening, Infrared, IR imaging ","lastPublishedDoi":"10.21203/rs.3.rs-1464972/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1464972/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e The potential of Infrared (IR) photo-screening for detection of retinoblastoma has not been assessed. This study aimed to assess the IR reflex formed across the pupil in eyes with retinoblastoma (RB), vis-à-vis eyes with no intraocular tumor.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Central gaze IR-reflex assessment in eyes with and without RB.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Of 30 eyes from 21 subjects, 20 eyes had RB and 10 eyes had no tumors. Image frames were extracted from IR video recordings of 30 eyes, of which 71 central gaze images were eligible for measurement of pixel intensity (0 to 255). Of these, 49 images had RB and 22 images had no tumor. The mean pixel intensity (MPI) within the pupil, in images of eyes with RB was 115 (median, 92; range, 38 to 254), in images of eyes with no tumor was 73 (median, 68; range, 26 to 125) and the difference was statistically significant (Odds ratio 1.018; 95 % CI: 1.004 – 1.032; p, .010;) on bivariate analysis. Of 57 images from eyes with RB, 35 were captured with un-dilated pupils and 22 with dilated pupils. The MPI in images from un-dilated eyes with RB was 107 (median, 79; range, 38 to 254), in images from dilated eyes with RB was 128 (median, 114; range, 46 to 215). However, the difference was not statistically significant (Odds ratio 1.006; 95 % CI: 0.996– 1.015; p, .248).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Technology combining IR imaging and MPI measurement within the pupil can translate into a potential tool for early detection of RB.\u003c/p\u003e","manuscriptTitle":"Photo-screening for Retinoblastoma: A Proof-of-Concept Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-21 18:57:44","doi":"10.21203/rs.3.rs-1464972/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3791d7e4-6b5b-4a6f-be5f-7a1172720463","owner":[],"postedDate":"March 21st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-03-29T13:59:14+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-21 18:57:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1464972","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1464972","identity":"rs-1464972","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}