Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Validity of the Red Reflex Exam in the Newborn Eye Screening Test Cohort

Cassie A. Ludwig, MD, MS; Natalia F. Callaway, MD, MS; Mark S. Blumenkranz, MD; Douglas R. Fredrick, MD; Darius M. Moshfeghi, MD

Abstract

BACKGROUND AND OBJECTIVE:

The validity of the red reflex exam has yet to be tested against new methods of wide-angle imaging that may improve early detection of neonatal ocular pathology. The authors aimed to determine the validity of the pediatrician's red reflex exam using 130° wide-angle external and fundus digital imaging as a gold standard.

PATIENTS AND METHODS:

This was a prospective cohort study of 194 healthy, term newborns enrolled in the Newborn Eye Screening Test study at Lucile Packard Children's Hospital from July 25, 2013, to July 25, 2014. Red reflex screening was performed by a pediatrician in the newborn nursery and wide-angle fundus digital imaging was performed by a neonatal intensive care unit-certified nurse. The main outcome measure was the validity of the pediatrician's red reflex exam (unweighted kappa [κ] statistic, sensitivity, specificity).

RESULTS:

Compared to no subjects with abnormal red reflex exams reported in the pediatrician's notes, 49 subjects demonstrated one or multiple ocular abnormalities on 130° wide-angle fundus imaging (κ = 0.00). The pediatrician's red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%–7.3%) and specificity of 100.0% (95% CI, 97.5%–100.0%) for the detection of ocular abnormalities.

CONCLUSION:

This study demonstrates the ability of wide-angle fundus imaging to detect fundus abnormalities not otherwise identified by standard newborn red reflex screening prior to hospital discharge.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:103–110.]

Abstract

BACKGROUND AND OBJECTIVE:

The validity of the red reflex exam has yet to be tested against new methods of wide-angle imaging that may improve early detection of neonatal ocular pathology. The authors aimed to determine the validity of the pediatrician's red reflex exam using 130° wide-angle external and fundus digital imaging as a gold standard.

PATIENTS AND METHODS:

This was a prospective cohort study of 194 healthy, term newborns enrolled in the Newborn Eye Screening Test study at Lucile Packard Children's Hospital from July 25, 2013, to July 25, 2014. Red reflex screening was performed by a pediatrician in the newborn nursery and wide-angle fundus digital imaging was performed by a neonatal intensive care unit-certified nurse. The main outcome measure was the validity of the pediatrician's red reflex exam (unweighted kappa [κ] statistic, sensitivity, specificity).

RESULTS:

Compared to no subjects with abnormal red reflex exams reported in the pediatrician's notes, 49 subjects demonstrated one or multiple ocular abnormalities on 130° wide-angle fundus imaging (κ = 0.00). The pediatrician's red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%–7.3%) and specificity of 100.0% (95% CI, 97.5%–100.0%) for the detection of ocular abnormalities.

CONCLUSION:

This study demonstrates the ability of wide-angle fundus imaging to detect fundus abnormalities not otherwise identified by standard newborn red reflex screening prior to hospital discharge.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:103–110.]

Introduction

Early detection of neonatal ocular pathology is critical to avoid permanent preventable vision loss. The 2016 American Academy of Pediatrics (AAP) policy statement and clinical report recommend red reflex testing in addition to external inspection of lids and eyes for all newborns.1,2 Pupil examination and visual acuity fix-and-follow response are recommended prior to 6 months of age, whereas photoscreening and handheld autorefraction for amblyogenic refractive error are recommended in children 6 months to 3 years of age.1–3 This policy replaced the 2008 AAP policy statement solely recommending an examination of the red reflex of the eyes by a trained pediatrician or primary care physician prior to discharge from the neonatal nursery and during all routine health visits.4 Recommendations in Sweden, Israel, and Brazil similarly emphasize the red reflex exam as a critical component of the newborn ocular exam.5–8 Though the current policy may improve compliance with necessary components of the anterior segment examination in newborns, posterior segment screening relies on the pediatrician's red reflex exam until 6 months of age or greater.

Red reflex testing has the potential to detect cataracts, glaucoma, retinoblastoma, retinal abnormalities, systemic diseases with ocular manifestations, and high refractive errors.4 However, sensitivity and specificity of the red reflex exam may vary by severity of eye disease. When Li et al. simulated retinoblastoma detection by the red reflex exam using model practice eyes with discs varying in size and location, they found a range in tumor detection of 16% (95% CI, 2%–31%) to 96% (95% CI, 93%–98%) depending on pupil dilation, observer orientation and tumor diameter.9 It is possible that the exam itself is too crude to detect subtle retinal abnormalities.

In spite of standardized neonatal ophthalmic examinations, a cohort of children continues to have vision and eye disorders that go undetected.10,11 In pursuit of a means to fill the gap of undetected eye disease, several researchers are exploring the use of wide-angle fundus digital imaging.12–14 This study aimed to evaluate the validity of the red reflex exam using 130° wide-angle fundus imaging as a gold standard. We hypothesized that the red reflex exam has poor sensitivity for detecting potentially visually threatening ocular pathology.

Patients and Methods

Study Design

The Newborn Eye Screening Test (NEST) study is a prospective cohort study that aims to evaluate the efficacy and outcomes of a telemedicine screening initiative for human newborns.14 NEST is conducted at Lucile Packard Children's Hospital (LPCH) at Stanford University School of Medicine. Images were taken by a neonatal intensive care unit (NICU)-certified nurse, after which they were immediately available for remote review by a pediatric vitreoretinal specialist at Byers Eye Institute telemedicine reading center. Parents, obstetrician delivery notes, pediatrician progress notes, and pediatrician discharge summaries were used to obtain demographic, maternal, pregnancy, delivery, and newborn characteristics. All pediatrician progress notes and pediatrician discharge summaries prior to each newborn's first hospital discharge were reviewed prospectively, and any report of ocular abnormalities detected on red reflex exam was noted.

Study Participants

The study includes newborns in the NEST cohort who were screened from July 25, 2013, to July 25, 2014. Universal newborn screening was offered to all infants born at LPCH who did not receive retinopathy of prematurity (ROP) screening. Exclusion criteria were patients who were bilaterally anophthalmic, patients without images or medical charts available for review, patients with infectious conjunctivitis, and patients deemed too unstable for exam by their attending pediatrician. Overall, 830 subjects were approached, and 202 newborns were ultimately consented and screened (3,024 images) with 202 right eyes and 201 left eyes imaged. The remainder of subjects approached declined screening for their newborns, most commonly for the following reasons: “Don't want to bother baby,” “Believe it is not necessary for the child,” and “Concern about adverse effects.”14 There was no statistically significant difference in gender or delivery method between screened and unscreened cohorts. However, the cohorts differed in self-identified ethnicity (Chi-squared test = 14.53; P = .0001), with 41.8% (84 of 201) of the screened cohort identifying as Hispanic or Latino as compared to 27.5% of the unscreened cohort (171 of 622). Seven subjects did not report self-identified ethnicity.

Imaging Protocol

A NICU-certified nurse was trained by a certified ophthalmic photographer as well as the overseeing pediatric vitreoretinal specialist prior to initiating screening. The NICU nurse used a RetCam III 130° lens (Clarity Medical Systems, Pleasanton, CA) to obtain wide-angle external and fundus images of all infants enrolled in the NEST study. Feedings were discontinued 2 hours pre- and post-exam in accordance with aspiration precaution guidelines. Each subject's eyes were dilated with 2.5% phenylephrine and 1% tropicamide 30 minutes to 60 minutes prior to examination. Infants were monitored for signs of apnea or distress. A topical anesthetic 0.5% proparacaine was administered in each eye prior to examination. A sterile lid speculum was used to provide adequate exposure for photography, and 2.5% hydroxypropyl methylcellulose was used to couple the digital camera lens to the infant's cornea. Digital images were taken by the nurse and stored on the camera's computer hard drive as well as input into the NEST telemedicine database management system.

The goal was to obtain an external/facies image as well as six focused images in each eye using the 130° lens: 1) iris image, 2) optic nerve centered, 3) optic nerve superior, 4) optic nerve inferior, 5) optic nerve nasal, and 6) optic nerve temporal. The infant was observed by the NICU nurse for any adverse outcomes following screening. Parents were contacted via secure healthcare messaging and/or phone call about any abnormalities requiring ophthalmic referral within 48 hours of screening.

Variables

Mention of a pediatrician's conduct of the red reflex exam in addition to the results of the red reflex exam were obtained from pediatrician progress notes and pediatrician discharge summaries prior to newborn discharge. The red reflex was recorded as reported if “red reflex” was mentioned unless the author stated, “Red reflex exam deferred.” The red reflex exam was recorded as “did not report” if it was absent from all notes prior to the infant's first discharge or if the exam was reported as “deferred” and was otherwise absent in all notes prior to discharge. None of the notes included mention of referral to an ophthalmologist or included notes written by a referred ophthalmologist.

Outcomes

The primary outcome of this study was validity of the pediatrician's red reflex exam in detecting posterior segment abnormalities using retinal image photography as the gold standard in the NEST study. Validity was measured by sensitivity, specificity, and the unweighted kappa statistic (κ), or the agreement beyond what would be expected by chance. Our secondary aim was to determine the prevalence of the conduct of the red reflex exam.

Statistical Analysis

All data were analyzed by the authors (CAL, NFC) using Statistical Analysis Software (SAS) Enterprise Guide version 6.1 (Cary, NC). Newborns were first separated by their classifications of normal exam findings versus abnormal exam findings. Percent overall agreement was then calculated for each type of abnormality noted. Cohen's unweighted κ was calculated to assess agreement between the pediatrician's red reflex exam and RetCam III screening beyond what would be expected by chance. κ ranges from −1.00 to +1.00. A value of 0.81 to 1.00 can be considered “almost perfect,” whereas a value of 0.00 can be considered “poor,” and a value between 0.00 and 0.21 can be considered “slight.” Sensitivity, specificity, positive predictive value, and negative predictive value were then calculated for each type of abnormality noted.

Ethics

Research was performed ethically and in accordance with the Stanford University School of Medicine Institutional Review Board. Written informed consent was obtained from the parent of an infant participating in NEST screening and the study was conducted in a HIPAA-compliant fashion. All image acquisition and transmittal was handled with strict attention to the confidentiality of personal data in accordance with the Data Protection Act of 1998 and Access to Health Records of 1990.

The images were stored on a secure, encrypted, HIPAA-compliant server. Study data were collected and managed using REDCap electronic data capture tools hosted at Stanford University.15 REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing 1) an intuitive interface for validated data entry, 2) audit trails for tracking data manipulation and export procedures, 3) automated export procedures for seamless data downloads to common statistical packages, and 4) procedures for importing data from external sources.

Results

Participants

During the 1-year study period, 202 newborns who met inclusion criteria for NEST study participation were screened out of 830 approached. The baseline characteristics of the screened cohort are shown in Table 1 and are described in additional detail by Callaway et al.14 No adverse outcomes (bradycardia, allergic reactions, corneal abrasions) were reported at the time of exam or at 1-year follow-up.

Demographic Data for Newborns Screened by Wide-Field Digital Imaging With or Without Standard Red Reflex Exam Screening

Table 1:

Demographic Data for Newborns Screened by Wide-Field Digital Imaging With or Without Standard Red Reflex Exam Screening

The red reflex exam was conducted in 194 of 202 (96%) newborns. Of the eight newborns who did not undergo a red reflex exam, three were found to have retinal hemorrhages, three had macular hemorrhages, and two had optic nerve flame hemorrhages. There was no significant difference between newborns who received red reflex exam screening and those who did not receive red reflex exam screening in terms of sex, birth weight, chronological age at exam, self-identified ethnicity, self-identified race, and delivery method.

Those screened by both exams included 92 (47.4%) females and 102 (52.6%) males, 118 (60.8%) who were delivered vaginally and 76 (39.2%) who were delivered by cesarean section. The average weight at birth was 3,310 grams (range: 2,010 to 4,510 g) and median estimated gestational age was 39.3 weeks (interquartile range [IQR]: 38.1 weeks to 40.0 weeks). The median chronological age in hours at exam was 40.2 hours (IQR: 33.3 hours to 53.2 hours). The parents of 82 of 194 (42.3%) newborns identified their newborn as Hispanic or Latino, 66 of 121 (54.5%) as white, 45 of 121 (37.2%) as Asian, nine of 121 (7.41%) as Native Hawaiian or Pacific Islander, and one of 121 (0.8%) as black or African-American.

Validity of the Pediatrician's Newborn Ocular Assessment

Whereas 49 out of 194 (25.3%) subjects screened by both modalities demonstrated one or multiple posterior segment abnormalities on 130° wide-angle fundus imaging, as shown in Figure 1, no subjects had abnormal posterior segment findings reported in any pediatrician notes prior to discharge (κ = 0.00; number needed to screen [NNS] = 4). Based on fundus imaging, 36 subjects were found to have retinal hemorrhages, 31 had macular hemorrhages (NNS = 7), 26 had optic nerve flame hemorrhages, four had grouped pigmentation, four had choroidal nevus in the macula, two had choroidal nevus elsewhere in the retina, one had choroidal pigmentation, one had albinotic appearance of the choroid, one had polar bear tracks, one had pigmentary retinopathy, and one had focal depigmentation of the retinal pigmented epithelium.

Abnormal posterior segment findings. (A) Extensive white-centered extrafoveal hemorrhages, subretinal foveal hemorrhage, and flame hemorrhages; (B) albinotic appearing retina; (C) choroidal pigmentation; and (D) nasal polar bear tracks

Figure.

Abnormal posterior segment findings. (A) Extensive white-centered extrafoveal hemorrhages, subretinal foveal hemorrhage, and flame hemorrhages; (B) albinotic appearing retina; (C) choroidal pigmentation; and (D) nasal polar bear tracks

Table 2 compares pediatrician red reflex exam findings in all notes prior to newborn discharge to ophthalmic abnormalities on 130° wide-angle fundus imaging. The unweighted kappa coefficient was not statistically significant for all abnormalities grouped together (κ = 0.00) or for any one abnormality individually. The percent overall agreement between the pediatrician's red reflex exam and fundus imaging ranged from 81.4% to 99.5% for any one abnormality.

Agreement Between the Red Reflex Exam and Wide-Angle Fundus Digital Image Screening (N = 194)a

Table 2:

Agreement Between the Red Reflex Exam and Wide-Angle Fundus Digital Image Screening (N = 194)

Table 3 demonstrates the sensitivity, specificity, positive predictive value, and negative predictive value of the pediatrician's red reflex exam as compared to 130° wide-angle fundus imaging. The pediatrician's red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%–7.3%) and specificity of 100.0% (95% CI, 97.5%–100.0%) for the detection of any pathology. For any single pathology, sensitivity of the pediatrician's ocular assessment was 0.0%, and specificity was 100.0%, positive predictive value could not be calculated, and negative predictive value ranged from 81.4% to 99.5%.

Validity of Findings From the Red Reflex Exam Compared With Wide-Angle Fundus Digital Imaging (N = 194)

Table 3:

Validity of Findings From the Red Reflex Exam Compared With Wide-Angle Fundus Digital Imaging (N = 194)

Discussion

The NEST study reveals that a significant number of posterior segment abnormalities are missed by pediatricians' red reflex exam. These included potentially visually threatening abnormalities such as macular hemorrhages. Agreement was low between pediatricians' red reflex exam and 130° wide-angle fundus imaging in detection of posterior segment pathology (κ = 0.00). The number of patients needed to screen to detect any posterior segment abnormality with wide-angle imaging as compared to a pediatricians' red reflex exam was four, and to detect potentially visually threatening abnormalities was seven — both much lower than the 878 needed to screen to detect hearing loss in the United States.16 Specificity of the pediatrician's newborn ocular assessment was 100% for each type of ocular pathology due to an absence of false-positive red reflex exams. However, sensitivity was 0%, indicating a predominance of false-negative red reflex exams. The inability of the pediatrician's red reflex exam to detect posterior segment newborn pathology in our study is consistent with prior reports of pathology missed by traditional vision screening.9,17,18

Secondary aims of this study were to determine the prevalence of the conduct of the red reflex exam to assess compliance with screening standards. Assuming notes included all exams performed, not all subjects received the 2016 AAP recommended screening exam as 4% of newborns in the NEST cohort did not undergo red reflex exam prior to discharge.19 When performed, no abnormalities were detected through this exam technique, including retinal hemorrhages detected in 18.6% of newborns by digital imaging.

Although the small sample size of the NEST cohort limited the amount of visually threatening pathology identified, data from larger studies demonstrate the ability of wide-angle digital imaging to detect such pathology. In a study utilizing wide-field digital imaging to screen 3,573 healthy full-term newborns in China, researchers detected abnormal eye exams in 871 newborns (24.4%), and visually threatening ocular abnormalities in 107 newborns (2.99%).12 These included severe optic nerve cupping (0.08%), congenital cataracts (0.06%), and retinal masses (0.065%). A similar study including 1,021 term infants in India revealed 48 newborns with ocular abnormalities (4.7%), nine of whom required medical or surgical intervention (0.89%).13 Abnormalities requiring intervention in this study included posterior uveitis with linear perivasculitis (0.49%), salt-and-pepper retinopathy that prompted cardiac and auditory referral (0.10%), posterior synechia evaluated for an intrauterine infection (0.10%), unilateral cataract (0.10%), and retinoblastoma (0.10%).

Potentially visually threatening abnormalities detected in the NEST cohort included macular hemorrhages. Data on long-term vision outcomes of macular hemorrhages are limited and conflicting.20–22 Although the vast majority of birth hemorrhages resolve without sequelae, delayed resorption of macular hemorrhages from beneath the internal limiting membrane has the potential to obscure vision during a critical period of vision development.23 In future studies, we aim to determine the role that macular hemorrhages, particularly those missed on red reflex exam, may play in the development of amblyopia.

The benefits of newborn wide-angle digital imaging are manifold, but must be balanced against the cost of implementation. Additional studies must be performed to review in detail the cost-effectiveness of universal newborn screening — weighing the benefit of the detection of preventable visually significant pathology against the cost of the equipment, labor, reading centers, and potential morbidity associated with a dilated exam required for screening. This is critical for dense bilateral cataracts that require operation within the first 14 weeks of life as well as retinoblastoma requiring prompt treatment.24,25 Imaging can also be performed by nurses, reserving in-person pediatric ophthalmologist exams for infants with visually significant pathology. Training nurses to both capture and interpret images could add to the cost-effectiveness of the screening modality. Predictive modeling should also be performed to determine whether a higher-risk cohort exists among all newborns that might further increase the cost-effectiveness of imaging.

The strengths of this study are that the NEST cohort will continue to be monitored longitudinally for changes in vision that may be related to pathology detected with digital ophthalmic imaging. This cohort derived from the NEST study includes an ethnically diverse population, increasing the generalizability of its results. Limitations include the use of pediatricians' red reflex exam information from notes recorded in the LPCH electronic medical record system. It is possible that ophthalmic exam maneuvers were performed but not recorded leading to underestimation of the prevalence of the red reflex exam. It is also possible that the red reflex exam was not performed but recorded in some instances due to the use of electronic medical record templates leading to an overestimation of the prevalence of the red reflex exam. Additionally, the study's small sample size limits the findings on both the red reflex exam and wide-angle digital imaging.

The study design notably places the pediatrician's red reflex at a disadvantage as pediatricians were unaware a priori that their exams were being compared to wide-field digital imaging exams to capture typical red reflex exam practices. Therefore, overall low detection rate of congenital ocular pathology may be the result of noncompliance, low sensitivity of the red reflex exam, inadequate technique, or a combination of these. The present study detected both noncompliance and low sensitivity of the red reflex exam, but it was not designed to identify inadequate technique. A prospective study in which training was provided to both pediatricians and those conducting imaging would eliminate this potential source of bias.

The authors present the results of a large, population-based cohort study examining the validity of the pediatric red reflex exam as compared to digital fundoscopic imaging. With 4 million live births per year and 31 recommended vision screens during the course of each child's first 21 years of life, the 92,000 pediatricians in the United States are expected to perform approximately 128 million red reflex exams each year.2,19 Though the current standard for neonatal vision screening in the United States emphasizes the red reflex exam of the newborn, this study demonstrates a lack of sensitivity of the exam in detecting potentially visually threatening posterior segment pathology as compared to wide-angle digital imaging. Therefore, the NEST study demonstrates a potential role for wide-angle fundus digital imaging in the detection of neonatal ocular pathology otherwise missed by the pediatrician's red reflex exam.

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Demographic Data for Newborns Screened by Wide-Field Digital Imaging With or Without Standard Red Reflex Exam Screening

Characteristica Red Reflex Exam (n = 194) No Red Reflex Exam (n = 8) No. Missing Unadjusted P Valueb

Gender
  Female 92/194 (47) 4 (50) 0 1.00
  Male 102/194 (53) 4 (50)

Low Birth Weight (< 2,500 g)
  Yes 13/194 (7) 8 (100) 0 1.00
  No 181/194 (93) 0 (0)

Chronological Age at Exam
  < 24 hours 16/194 (8) 0 (0) 0 .28
  24–47.9 hours 108/194 (56) 7 (88)
  48–71.9 hours 46/194 (24) 0 (0)
  ≥ 72 hours 24/194 (12) 1 (13)

Self-Identified Ethnicity
  Not Hispanic or Latino 111/194 (58) 6 (75) 0 .47
  Hispanic or Latino 82/194 (42) 2 (25)

Self-Identified Race
  White/Caucasian 66/121 (55) 3/6 (50) 75 .81
  Asian 45/121 (37) 3/6 (50)
  Black or Africa-American 1/121 (1) 0/6 (0)
  Native Hawaiian or Pacific Islander 9/121 (7) 0/6 (0)

Delivery Method
  Vaginal 118/194 (61) 7/8 (88) 0 .16
  Cesarean section 76/194 (39) 1/8 (13)

Agreement Between the Red Reflex Exam and Wide-Angle Fundus Digital Image Screening (N = 194)a

No. Present According to Red Reflex Exam No. Present According to Imaging Unweighted κ Statisticb Overall Agreement

No Abnormalities 194/194 (100) 145/194 (75) 0.0 145/194 (75)c

Any Abnormality 0/194 (0) 49/194 (25)

Macula
  Macular hemorrhage 0/194 (0) 31/194 (16) 0.0 163/194 (84)
  Choroidal nevus 0/194 (0) 4/194 (2) 0.0 190/194 (98)
  Choroidal pigmentation 0/194 (0) 1/194 (1) 0.0 193/194 (99)
  Albinotic appearance 0/194 (0) 1/194 (1) 0.0 193/194 (99)

Retina
  Retinal hemorrhage 0/194 (0) 36/194 (19) 0.0 158/194 (81)
  Choroidal nevus 0/194 (0) 2/194 (1) 0.0 192/194 (99)
  Pigmentation, grouped 0/194 (0) 4/194 (2) 0.0 190/194 (98)
  Polar bear tracks 0/194 (0) 1/194 (1) 0.0 193/194 (99)
  Pigmentary retinopathy 0/194 (0) 1/194 (1) 0.0 193/194 (99)
  Focal depigmentation of RPE 0/194 (0) 1/194 (1) 0.0 193/194 (99)

Optic Nerve
  Flame hemorrhage 0.0 (0) 26/194 (13) 0.0 168/194 (87)

Validity of Findings From the Red Reflex Exam Compared With Wide-Angle Fundus Digital Imaging (N = 194)

Sensitivity, % (95% CI) Specificity, % (95% CI) PPV, % (95% CI)a NPV, % (95% CI)

Any Abnormality 0.0 (0.0–7.3) 100.0 (97.5–100.0) - 74.7 (68.0–80.7)

Macula
  Macular hemorrhage 0.0 (0.0–11.0) 100.0 (97.8–100.0) - 84.0 (78.1–88.9)
  Choroidal nevus 0.0 (0.0–49.0) 100.0 (98.1–100.0) - 97.9 (94.8–99.4)
  Choroidal pigmentation 0.0 (0.0–79.4) 100.0 (98.1–100.0) - 99.5 (97.2–100.0)
  Albinotic appearance 0.0 (0.0–79.4) 100.0 (98.1–100.0) - 99.5 (97.2–100.0)

Retina
  Retinal hemorrhage 0.0 (0.0–9.6) 100.0 (97.7–100.0) - 81.4 (75.3–86.7)
  Choroidal nevus 0.0 (0.0–65.8) 100.0 (98.1–100.0) - 99.0 (96.3–99.9)
  Pigmentation, grouped 0.0 (0.0–49.0) 100.0 (98.1–100.0) - 97.9 (94.8–99.4)
  Polar bear tracks 0.0 (0.0–79.4) 100.0 (98.1–100.0) - 99.5 (97.2–100.0)
  Pigmentary retinopathy 0.0 (0.0–79.4) 100.0 (98.1–100.0) - 99.5 (97.2–100.0)
  Focal depigmentation of RPE 0.0 (0.0–79.4) 100.0 (98.1–100.0) - 99.5 (97.2–100.0)

Optic Nerve
  Flame hemorrhage 0.0 (0.0–12.9) 100.0 (97.8–100.0) - 86.6 (81.0–91.1)
Authors

From Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA.

The material under consideration was presented at the Association for Research in Vision and Ophthalmology in Denver on May 3, 2015.

The authors report no relevant financial disclosures.

Dr. Moshfeghi did not participate in the editorial review of this manuscript.

Editor's Note: Clarity Medical Systems, the original manufacturer of the RetCam III Imaging System mentioned in this study, has since been acquired by Natus Medical Incorporated.

This study was funded by a grant for the Giannini Foundation with additional support for both Natalia F. Callaway and Cassie A. Ludwig from a TL1 Clinical Research Training Program of the Stanford Clinical and Translational Science Award to Spectrum (NIH TL1 TR 001084). The Research Electronic Data Capture (REDCap) database tool hosted by Stanford University is maintained by the Stanford Center for Clinical Informatics grant support (Stanford CTSA award number UL1 RR025744 from NIH/NCRR).

The authors are grateful for the help of Andrew Martin, PhD (Stanford Center for Clinical Informatics), who provided database design and management.

Address correspondence to Darius M. Moshfeghi, MD, Professor of Ophthalmology, Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, 2452 Watson Court, Room 2277, Palo Alto, CA 94303; email: dariusm@stanford.edu.

Received: April 07, 2017
Accepted: August 02, 2017

10.3928/23258160-20180129-04

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