Smartphone Ophthalmoscope of Lens Vascularity to Estimate Gestational Age

Smartphone Ophthalmoscope Lens Vascularity Estimated Gestational Age (SOLVE-GA)

The purpose of this study is to develop a novel, highly automated method of gestational age estimation at delivery combining anterior lens capsule vascularity (ALCV) and biophysical parameters appropriate for use in low income countries. The specific aims of the proposed study are: (1) To develop an algorithm to predict gestational age at delivery from 26 to 42 weeks' gestation with ALCV and key biophysical parameters (2)To evaluate the performance of ALCV and biophysical parameter-based gestational age estimates. Specifically, we hypothesize that the accuracy of the predictive algorithm will be comparable to commonly used measures of gestational age dating (±2 days) and have better precision (±14 days) than commonly used measures of gestational age dating.

Study Overview

• Status: Completed
• Conditions: Gestational Age

Detailed Description

Postnatal gestational age dating methods are needed in low/middle income settings as ultrasound is often unavailable, last menstrual dates uncertain, and physical/neurological scoring complex. The disappearance of anterior lens capsule vascularity (ALCV), a normal embryological process, has a high correlation with gestational age at delivery among preterm neonates. We will use an observational method-comparison study to establish the validity of smartphone ophthalmoscope ALCV gestational age estimates among preterm infants at delivery compared to the referent standard of ultrasound gestational age estimates. Study objectives and methods include the following: Objective 1. Develop an ALCV biomarker dataset from smartphone ophthalmoscope images using automated image analysis software. The dataset will include image features including: vessel quantity, lens clearing, tortuosity, vessel thickness, and branching angles and coefficients. Methods: (1) capture ALCV images via smartphone ophthalmoscope within 24 hours of delivery, and (2) segment ALCV images using software developed for the assessment of retinal vasculature. Proposed software will convert images into graphs and automatically find the vasculature based on the Dijkstra's shortest-path algorithm. The proposed software is tested for video-indirect neonatal ophthalmoscope images. Objective 2. Develop an algorithm to predict gestational age at delivery from 26 to 42 weeks' gestation with the ALCV biomarker dataset combined with key neonatal biophysical measures. Methods: (1) conduct descriptive and univariate analyses of predictors and assess linear model assumptions, and (2) fit a constrained linear regression model by selecting and shrinking estimated model coefficients from a fully specified model in the original sample to optimize predictive accuracy and model parsimony. Objective 3. Assess the performance of ALCV gestational age estimates compared to referent standard ultrasound estimates. Methods: (1) compare distributions of gestational age and the mean difference in days between dating methods, (2) test agreement between dating methods using Lin's concordance correlation coefficient and Bland-Altman plots with limits of agreement (3) internally validate test agreement using a bootstrap procedure for optimism correction of the agreement statistics. All statistical analyses will be performed in SAS 9.4 (SAS, Cary, North Carolina, USA).

• Study Type: Observational
• Enrollment (Actual): 252

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92345
      • Loma Linda University Children's Hospital
  • Iowa
    • Iowa City, Iowa, United States, 45542
      • University of Iowa Children's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-2200
      • University of North Carolina at Chapel Hill North Carolina Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Singleton live births between 26 and 42 weeks' gestation (determined by first or early-second trimester ultrasound dating)

Description

Inclusion Criteria:

• Gestational age 260/7 to 426/7 weeks (based on antenatal ultrasound <20 weeks gestation)

  • Chronological age <24 hours
  • Consent of the patient's parents or legal guardians

Exclusion Criteria:

• Fused eyelids
• Corneal opacity or cataract
• Obstetrical ultrasound performed at <20 weeks' gestation not performed/not available
• Known genetic/congenital anomalies
• Known coagulopathies
• Patients who, in the opinion of the attending physician or clinical study staff, are too medically unstable to participate in the study safely

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Preterm and term neonates; A. Preterm and term neonates B. Singleton live births between 26 and 42 weeks gestation (determined by first of early-second trimester ultrasound dating) at three referral hospitals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anterior lens capsule vascularity estimated gestational age	The gestational age is estimated by eye lens vascularity measurement	Within 24 hours of delivery

Collaborators and Investigators

• Sponsor: RTI International
• Collaborators: University of Iowa; Duke University; University of North Carolina, Chapel Hill; Loma Linda University
• Investigators: Principal Investigator: Jennifer Griffin, Ph.D. M.P.H., RTI International

Publications and helpful links

General Publications

• Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, Kinney M, Lawn J; Born Too Soon Preterm Birth Action Group. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health. 2013;10 Suppl 1(Suppl 1):S2. doi: 10.1186/1742-4755-10-S1-S2. Epub 2013 Nov 15.
• Altman, D. G. and J. M. Bland (1983).
• Bland, J. M. and D. G. Altman (2010).
• Concato, J., P. Peduzzi, T. R. Holford and A. R. Feinstein (1995). Estrada, R., C. Tomasi, M. T. Cabrera, D. K. Wallace, S. F. Freedman and S. Farsiu (2011).
• Estrada R, Tomasi C, Cabrera MT, Wallace DK, Freedman SF, Farsiu S. Exploratory Dijkstra forest based automatic vessel segmentation: applications in video indirect ophthalmoscopy (VIO). Biomed Opt Express. 2012 Feb 1;3(2):327-39. doi: 10.1364/BOE.3.000327. Epub 2012 Jan 18.
• Hittner HM, Gorman WA, Rudolph AJ. Examination of the anterior vascular capsule of the lens: II. Assessment of gestational age in infants small for gestational age. J Pediatr Ophthalmol Strabismus. 1981 Mar-Apr;18(2):52-4. doi: 10.3928/0191-3913-19810301-12.
• Hittner HM, Hirsch NJ, Rudolph AJ. Assessment of gestational age by examination of the anterior vascular capsule of the lens. J Pediatr. 1977 Sep;91(3):455-8. doi: 10.1016/s0022-3476(77)81324-3.
• Nagpal J, Kumar A, Ramji S. Anterior lens capsule vascularity in evaluating gestation in small for gestation neonates. Indian Pediatr. 2004 Aug;41(8):817-21.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): November 30, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: January 20, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): January 17, 2018
• Last Update Submitted That Met QC Criteria: January 12, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Preterm; Gestational Age; Anterior Lens Capsule Vascularity; Method-comparison
• Other Study ID Numbers: OPP1119360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No